Cyclooxygenase 2: An inducibly-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes and INFLAMMATION. It is the target of COX2 INHIBITORS.Cyclooxygenase 1: A constitutively-expressed subtype of prostaglandin-endoperoxide synthase. It plays an important role in many cellular processes.Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.Cyclooxygenase 2 Inhibitors: A subclass of cyclooxygenase inhibitors with specificity for CYCLOOXYGENASE-2.Prostaglandin-Endoperoxide Synthases: Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.Dinoprostone: The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.NitrobenzenesAnti-Inflammatory Agents, Non-Steroidal: Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects.Lipoxygenase Inhibitors: Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES.Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis.Sulfonamides: A group of compounds that contain the structure SO2NH2.Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Thromboxane B2: A stable, physiologically active compound formed in vivo from the prostaglandin endoperoxides. It is important in the platelet-release reaction (release of ADP and serotonin).Arachidonic AcidsMembrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Flurbiprofen: An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting CARBONIC ANHYDRASE.Lipoxygenase: An enzyme of the oxidoreductase class primarily found in PLANTS. It catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives.6-Ketoprostaglandin F1 alpha: The physiologically active and stable hydrolysis product of EPOPROSTENOL. Found in nearly all mammalian tissue.Eicosanoids: A class of compounds named after and generally derived from C20 fatty acids (EICOSANOIC ACIDS) that includes PROSTAGLANDINS; LEUKOTRIENES; THROMBOXANES, and HYDROXYEICOSATETRAENOIC ACIDS. They have hormone-like effects mediated by specialized receptors (RECEPTORS, EICOSANOID).Epoprostenol: A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension (HYPERTENSION, PULMONARY).Masoprocol: A potent lipoxygenase inhibitor that interferes with arachidonic acid metabolism. The compound also inhibits formyltetrahydrofolate synthetase, carboxylesterase, and cyclooxygenase to a lesser extent. It also serves as an antioxidant in fats and oils.Aspirin: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)Piroxicam: A cyclooxygenase inhibiting, non-steroidal anti-inflammatory agent (NSAID) that is well established in treating rheumatoid arthritis and osteoarthritis and used for musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily.Thromboxane A2: An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt.Intramolecular Oxidoreductases: Enzymes of the isomerase class that catalyze the oxidation of one part of a molecule with a corresponding reduction of another part of the same molecule. They include enzymes converting aldoses to ketoses (ALDOSE-KETOSE ISOMERASES), enzymes shifting a carbon-carbon double bond (CARBON-CARBON DOUBLE BOND ISOMERASES), and enzymes transposing S-S bonds (SULFUR-SULFUR BOND ISOMERASES). (From Enzyme Nomenclature, 1992) EC 5.3.Receptors, Prostaglandin E: Cell surface receptors which bind prostaglandins with a high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin E receptors prefer prostaglandin E2 to other endogenous prostaglandins. They are subdivided into EP1, EP2, and EP3 types based on their effects and their pharmacology.Thromboxane-A Synthase: An enzyme found predominantly in platelet microsomes. It catalyzes the conversion of PGG(2) and PGH(2) (prostaglandin endoperoxides) to thromboxane A2. EC 5.3.99.5.Naproxen: An anti-inflammatory agent with analgesic and antipyretic properties. Both the acid and its sodium salt are used in the treatment of rheumatoid arthritis and other rheumatic or musculoskeletal disorders, dysmenorrhea, and acute gout.Arachidonate 5-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 5-hydroperoxyarachidonate (5-HPETE) which is rapidly converted by a peroxidase to 5-hydroxy-6,8,11,14-eicosatetraenoate (5-HETE). The 5-hydroperoxides are preferentially formed in leukocytes.Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase.Meclofenamic Acid: A non-steroidal anti-inflammatory agent with antipyretic and antigranulation activities. It also inhibits prostaglandin biosynthesis.Hydroxyeicosatetraenoic Acids: Eicosatetraenoic acids substituted in any position by one or more hydroxy groups. They are important intermediates in a series of biosynthetic processes leading from arachidonic acid to a number of biologically active compounds such as prostaglandins, thromboxanes, and leukotrienes.ThiazinesProstaglandins G: A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. Most frequently encountered member of this group is the prostaglandin G2.Seminal Vesicles: A saclike, glandular diverticulum on each ductus deferens in male vertebrates. It is united with the excretory duct and serves for temporary storage of semen. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)5,8,11,14-Eicosatetraynoic Acid: A 20-carbon unsaturated fatty acid containing 4 alkyne bonds. It inhibits the enzymatic conversion of arachidonic acid to prostaglandins E(2) and F(2a).Dinoprost: A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine: A dual inhibitor of both cyclooxygenase and lipoxygenase pathways. It exerts an anti-inflammatory effect by inhibiting the formation of prostaglandins and leukotrienes. The drug also enhances pulmonary hypoxic vasoconstriction and has a protective effect after myocardial ischemia.Prostaglandins E: (11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating various physiological activities.SulfonesVasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Lactones: Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Phospholipases A: Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.Prostaglandin H2: A cyclic endoperoxide intermediate produced by the action of CYCLOOXYGENASE on ARACHIDONIC ACID. It is further converted by a series of specific enzymes to the series 2 prostaglandins.Phospholipases A2: Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES.Enzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Sulindac: A sulfinylindene derivative prodrug whose sulfinyl moiety is converted in vivo to an active NSAID analgesic. Specifically, the prodrug is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This helps to maintain constant blood levels with reduced gastrointestinal side effects.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system.8,11,14-Eicosatrienoic Acid: A 20-carbon-chain fatty acid, unsaturated at positions 8, 11, and 14. It differs from arachidonic acid, 5,8,11,14-eicosatetraenoic acid, only at position 5.Ketorolac: A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is an NSAID and is used principally for its analgesic activity. (From Martindale The Extra Pharmacopoeia, 31st ed)Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Vasoconstriction: The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates. These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids. The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- .Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Receptors, Thromboxane: Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems.Prostaglandin D2: The principal cyclooxygenase metabolite of arachidonic acid. It is released upon activation of mast cells and is also synthesized by alveolar macrophages. Among its many biological actions, the most important are its bronchoconstrictor, platelet-activating-factor-inhibitory, and cytotoxic effects.Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Receptors, Prostaglandin E, EP4 Subtype: A subtype of prostaglandin E receptors that specifically couples to GS ALPHA GTP-BINDING PROTEIN SUBUNITS and subsequently activates ADENYLYL CYCLASES. The receptor may also signal through the activation of PHOSPHATIDYLINOSITOL 3-KINASE.Receptors, Prostaglandin E, EP1 Subtype: A subtype of prostaglandin E receptors that specifically couples to GTP-BINDING PROTEIN ALPHA SUBUNIT, GQ and the subsequently activates TYPE C PHOSPHOLIPASES. Additional evidence has shown that the receptor can act through a calcium-dependent signaling pathway.Prostaglandin Antagonists: Compounds that inhibit the action of prostaglandins.Leukotriene B4: The major metabolite in neutrophil polymorphonuclear leukocytes. It stimulates polymorphonuclear cell function (degranulation, formation of oxygen-centered free radicals, arachidonic acid release, and metabolism). (From Dictionary of Prostaglandins and Related Compounds, 1990)Calcimycin: An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.Prostaglandins H: A group of physiologically active prostaglandin endoperoxides. They are precursors in the biosynthesis of prostaglandins and thromboxanes. The most frequently encountered member of this group is the prostaglandin H2.HydrazinesSalicylates: The salts or esters of salicylic acids, or salicylate esters of an organic acid. Some of these have analgesic, antipyretic, and anti-inflammatory activities by inhibiting prostaglandin synthesis.Tolmetin: A non-steroidal anti-inflammatory agent (ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL) similar in mode of action to INDOMETHACIN.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Receptors, Prostaglandin E, EP2 Subtype: A subtype of prostaglandin E receptors that specifically couples to GS ALPHA GTP-BINDING PROTEIN SUBUNITS and subsequently activates ADENYLYL CYCLASES.Interleukin-1: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Nitric Oxide Synthase Type II: A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.PeroxidasesReceptors, Prostaglandin: Cell surface receptors that bind prostaglandins with high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin receptor subtypes have been tentatively named according to their relative affinities for the endogenous prostaglandins. They include those which prefer prostaglandin D2 (DP receptors), prostaglandin E2 (EP1, EP2, and EP3 receptors), prostaglandin F2-alpha (FP receptors), and prostacyclin (IP receptors).12-Hydroxy-5,8,10,14-eicosatetraenoic Acid: A lipoxygenase metabolite of ARACHIDONIC ACID. It is a highly selective ligand used to label mu-opioid receptors in both membranes and tissue sections. The 12-S-HETE analog has been reported to augment tumor cell metastatic potential through activation of protein kinase C. (J Pharmacol Exp Ther 1995; 274(3):1545-51; J Natl Cancer Inst 1994; 86(15):1145-51)Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Platelet Aggregation: The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS.Ketoprofen: An IBUPROFEN-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis.Ketorolac Tromethamine: A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity.Nitroarginine: An inhibitor of nitric oxide synthetase which has been shown to prevent glutamate toxicity. Nitroarginine has been experimentally tested for its ability to prevent ammonia toxicity and ammonia-induced alterations in brain energy and ammonia metabolites. (Neurochem Res 1995:200(4):451-6)Vasodilator Agents: Drugs used to cause dilation of the blood vessels.15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid: A stable prostaglandin endoperoxide analog which serves as a thromboxane mimetic. Its actions include mimicking the hydro-osmotic effect of VASOPRESSIN and activation of TYPE C PHOSPHOLIPASES. (From J Pharmacol Exp Ther 1983;224(1): 108-117; Biochem J 1984;222(1):103-110)Biological Factors: Endogenously-synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.SRS-A: A group of LEUKOTRIENES; (LTC4; LTD4; and LTE4) that is the major mediator of BRONCHOCONSTRICTION; HYPERSENSITIVITY; and other allergic reactions. Earlier studies described a "slow-reacting substance of ANAPHYLAXIS" released from lung by cobra venom or after anaphylactic shock. The relationship between SRS-A leukotrienes was established by UV which showed the presence of the conjugated triene. (From Merck Index, 11th ed)Receptors, Prostaglandin E, EP3 Subtype: A subtype of prostaglandin E receptors that specifically couples to GTP-BINDING PROTEIN ALPHA SUBUNIT, GI and subsequently inhibits ADENYLYL CYCLASES.Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Vasoconstrictor Agents: Drugs used to cause constriction of the blood vessels.Receptors, Thromboxane A2, Prostaglandin H2: A subclass of eicosanoid receptors that have specificity for THROMBOXANE A2 and PROSTAGLANDIN H2.Microsomes: Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Anti-Inflammatory Agents: Substances that reduce or suppress INFLAMMATION.Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries.Quinacrine: An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Prostaglandins F: (9 alpha,11 alpha,13E,15S)-9,11,15-Trihydroxyprost-13-en-1-oic acid (PGF(1 alpha)); (5Z,9 alpha,11,alpha,13E,15S)-9,11,15-trihydroxyprosta-5,13-dien-1-oic acid (PGF(2 alpha)); (5Z,9 alpha,11 alpha,13E,15S,17Z)-9,11,15-trihydroxyprosta-5,13,17-trien-1-oic acid (PGF(3 alpha)). A family of prostaglandins that includes three of the six naturally occurring prostaglandins. All naturally occurring PGF have an alpha configuration at the 9-carbon position. They stimulate uterine and bronchial smooth muscle and are often used as oxytocics.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Gastric Mucosa: Lining of the STOMACH, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. The surface cells produce MUCUS that protects the stomach from attack by digestive acid and enzymes. When the epithelium invaginates into the LAMINA PROPRIA at various region of the stomach (CARDIA; GASTRIC FUNDUS; and PYLORUS), different tubular gastric glands are formed. These glands consist of cells that secrete mucus, enzymes, HYDROCHLORIC ACID, or hormones.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Phospholipases A2, Cytosolic: A subcategory of phospholipases A2 that occur in the CYTOSOL.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Stomach Ulcer: Ulceration of the GASTRIC MUCOSA due to contact with GASTRIC JUICE. It is often associated with HELICOBACTER PYLORI infection or consumption of nonsteroidal anti-inflammatory drugs (NSAIDS).Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Hydroxyprostaglandin Dehydrogenases: Catalyzes reversibly the oxidation of hydroxyl groups of prostaglandins.Mesenteric Arteries: Arteries which arise from the abdominal aorta and distribute to most of the intestines.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Lipoxins: Trihydroxy derivatives of eicosanoic acids. They are primarily derived from arachidonic acid, however eicosapentaenoic acid derivatives also exist. Many of them are naturally occurring mediators of immune regulation.Fatty Acids, Unsaturated: FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.Mice, Inbred C57BLKinetics: The rate dynamics in chemical or physical systems.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Sodium Salicylate: A non-steroidal anti-inflammatory agent that is less effective than equal doses of ASPIRIN in relieving pain and reducing fever. However, individuals who are hypersensitive to ASPIRIN may tolerate sodium salicylate. In general, this salicylate produces the same adverse reactions as ASPIRIN, but there is less occult gastrointestinal bleeding. (From AMA Drug Evaluations Annual, 1992, p120)Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated.Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in PLATELETS.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Isoxazoles: Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.omega-N-Methylarginine: A competitive inhibitor of nitric oxide synthetase.Peroxides: A group of compounds that contain a bivalent O-O group, i.e., the oxygen atoms are univalent. They can either be inorganic or organic in nature. Such compounds release atomic (nascent) oxygen readily. Thus they are strong oxidizing agents and fire hazards when in contact with combustible materials, especially under high-temperature conditions. The chief industrial uses of peroxides are as oxidizing agents, bleaching agents, and initiators of polymerization. (From Hawley's Condensed Chemical Dictionary, 11th ed)Group IV Phospholipases A2: A cytosolic phospholipase A2 group that plays an important role in the release of free ARACHIDONIC ACID, which in turn is metabolized to PROSTAGLANDINS by the CYCLOOXYGENASE pathway and to LEUKOTRIENES by the 5-LIPOXYGENASE pathway.Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Alprostadil: A potent vasodilator agent that increases peripheral blood flow.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities.Prostaglandins I: A class of cyclic prostaglandins that contain the 6,9-epoxy bond. Endogenous members of this family are biosynthesized enzymatically from PROSTAGLANDIN ENDOPEROXIDES.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.ThiazolesChromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.Linoleic Acid: A doubly unsaturated fatty acid, occurring widely in plant glycosides. It is an essential fatty acid in mammalian nutrition and is used in the biosynthesis of prostaglandins and cell membranes. (From Stedman, 26th ed)Nitroprusside: A powerful vasodilator used in emergencies to lower blood pressure or to improve cardiac function. It is also an indicator for free sulfhydryl groups in proteins.Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Indoprofen: A drug that has analgesic and anti-inflammatory properties. Following reports of adverse reactions including reports of carcinogenicity in animal studies it was withdrawn from the market worldwide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p21)Isoprostanes: A series of prostaglandin-like compounds that are produced by the attack of free-radical species on unsaturated fatty acids, especially ARACHIDONIC ACID, of cellular MEMBRANES. Once cleaved from the lipid membrane by the action of phospholipases they can circulate into various bodily fluids and eventually be excreted. Although these compounds resemble enzymatically synthesized prostaglandins their stereoisometric arrangement is usually different than the "naturally occurring" compounds.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Proadifen: An inhibitor of drug metabolism and CYTOCHROME P-450 ENZYME SYSTEM activity.Intestinal Mucosa: Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI.Edema: Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Eicosanoic Acids: 20-carbon saturated monocarboxylic acids.Prostaglandin Endoperoxides, Synthetic: Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds.Endothelium-Dependent Relaxing Factors: Paracrine substances produced by the VASCULAR ENDOTHELIUM with VASCULAR SMOOTH MUSCLE relaxation (VASODILATION) activities. Several factors have been identified, including NITRIC OXIDE and PROSTACYCLIN.Receptors, Epoprostenol: Cell surface receptors for EPOPROSTENOL. They are coupled to HETEROTRIMERIC G-PROTEINS.Colonic Neoplasms: Tumors or cancer of the COLON.Diflunisal: A salicylate derivative and anti-inflammatory analgesic with actions and side effects similar to those of ASPIRIN.Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-.Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects.Aorta: The main trunk of the systemic arteries.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Prostaglandin Endoperoxides: Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Catechols: A group of 1,2-benzenediols that contain the general formula R-C6H5O2.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Carrageenan: A water-soluble extractive mixture of sulfated polysaccharides from RED ALGAE. Chief sources are the Irish moss CHONDRUS CRISPUS (Carrageen), and Gigartina stellata. It is used as a stabilizer, for suspending COCOA in chocolate manufacture, and to clarify BEVERAGES.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Microcirculation: The circulation of the BLOOD through the MICROVASCULAR NETWORK.Platelet Activating Factor: A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.Regional Blood Flow: The flow of BLOOD through or around an organ or region of the body.Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans.Pulmonary Circulation: The circulation of the BLOOD through the LUNGS.Vascular Resistance: The force that opposes the flow of BLOOD through a vascular bed. It is equal to the difference in BLOOD PRESSURE across the vascular bed divided by the CARDIAC OUTPUT.Nitric Oxide Donors: A diverse group of agents, with unique chemical structures and biochemical requirements, which generate NITRIC OXIDE. These compounds have been used in the treatment of cardiovascular diseases and the management of acute myocardial infarction, acute and chronic congestive heart failure, and surgical control of blood pressure. (Adv Pharmacol 1995;34:361-81)Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy-5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in NEUTROPHILS and LYMPHOCYTES.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).ZymosanInflammation Mediators: The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Analgesics, Non-Narcotic: A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Arginine: An essential amino acid that is physiologically active in the L-form.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Anticarcinogenic Agents: Agents that reduce the frequency or rate of spontaneous or induced tumors independently of the mechanism involved.Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Endocannabinoids: Fatty acid derivatives that have specificity for CANNABINOID RECEPTORS. They are structurally distinct from CANNABINOIDS and were originally discovered as a group of endogenous CANNABINOID RECEPTOR AGONISTS.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.AcetophenonesPhenol: An antiseptic and disinfectant aromatic alcohol.Furans: Compounds with a 5-membered ring of four carbons and an oxygen. They are aromatic heterocycles. The reduced form is tetrahydrofuran.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.

Mechanisms of prostaglandin E2 release by intact cells expressing cyclooxygenase-2: evidence for a 'two-component' model. (1/1887)

Prostaglandin (PG) release in cells expressing constitutive cyclooxygenase-1 is known to be regulated by liberation of arachidonic acid by phospholipase A2 followed by metabolism by cyclooxygenase. However, the relative contribution of phospholipase A2 to the release of PGs in cells expressing cyclooxygenase-2 is not clear. We addressed this question by using radioimmunoassay to measure PGE2 release by human cells (A549) induced to express cyclooxygenase-2 (measured by Western blot analysis) by interleukin-1beta. Cells were either unstimulated or stimulated with agents known to activate phospholipase A2 (bradykinin, Des-Arg10-kallidin, or the calcium ionophore A23187) or treated with exogenous arachidonic acid. When cells were treated to express cyclooxygenase-2, the levels of PGE2 released over 15 min were undetectable; however, in the same cells stimulated with bradykinin, A23187, or arachidonic acid, large amounts of prostanoid were produced. Using selective inhibitors/antagonists, we found that the effects of bradykinin were mediated by B2 receptor activation and that prostanoid release was due to cyclooxygenase-2, and not cyclooxygenase-1, activity. In addition, we show that the release of PGE2 stimulated by either bradykinin, A23187, or arachidonic acid was inhibited by the phospholipase A2 inhibitor arachidonate trifluoromethyl ketone. Hence, we have demonstrated that PGE2 is released by two components: induction of cyclooxygenase-2 and supply of substrate, probably via activation of phospholipase A2. This is illustrated in A549 cells by a clear synergy between the cytokine interleukin-1beta and the kinin bradykinin.  (+info)

Inhibition of prostaglandin synthesis up-regulates cyclooxygenase-2 induced by lipopolysaccharide and peroxisomal proliferators. (2/1887)

Primary cultures of fetal hepatocytes expressed cyclooxygenase-2 (COX-2) upon stimulation with bacterial lipopolysaccharide (LPS) or peroxisomal proliferators. This enzyme was active and a good correlation between the mRNA levels, the amount of protein, and the synthesis of prostaglandin E2 was observed. However, when cells were incubated in the presence of indomethacin or the COX-2-specific inhibitor NS398, the amount of COX-2 protein increased 5-fold after activation with LPS and 2-fold after treatment with clofibrate. This up-regulation of COX-2 was not observed at the mRNA level. The mechanism of protein accumulation might involve either a direct stabilization of the enzyme by the inhibitors or the absence of prostaglandins involved in the regulation of its turnover. Among the prostaglandins assayed, only 15-deoxy-Prostaglandin J2 exerted a statistically significant decrease in the COX-2 levels in cells stimulated with LPS or LPS plus NS398. The accumulation of COX-2 in the presence of inhibitors was also observed in peritoneal macrophages treated under identical conditions. These results indicate that COX-2 protein accumulates after enzyme inhibition, and because removal of the inhibitors restored the enzyme activity, suppression of treatment with reversible COX-2 inhibitors may cause a transient overproduction of prostaglandins.  (+info)

Characterization of the analgesic and anti-inflammatory activities of ketorolac and its enantiomers in the rat. (3/1887)

The marked analgesic efficacy of ketorolac in humans, relative to other nonsteroidal anti-inflammatory drugs (NSAIDs), has lead to speculation as to whether additional non-NSAID mechanism(s) contribute to its analgesic actions. To evaluate this possibility, we characterized (R,S)-ketorolac's pharmacological properties in vivo and in vitro using the nonselective cyclooxygenase (COX) inhibitors [indomethacin (INDO) and diclofenac sodium (DS)] as well as the selective COX-2 inhibitor, celecoxib, as references. The potency of racemic (R,S)-ketorolac was similar in tests of acetic acid-induced writhing, carrageenan-induced paw hyperalgesia, and carrageenan-induced edema formation in rats; ID50 values = 0.24, 0. 29, and 0.08 mg/kg, respectively. (R,S)-ketorolac's actions were stereospecific, with (S)-ketorolac possessing the biological activity of the racemate in the above tests. The analgesic potencies for (R,S)-, (S)-, and (R)-ketorolac, INDO, and DS were highly correlated with their anti-inflammatory potencies, suggesting a common mechanism. (R,S)-ketorolac was significantly more potent than INDO or DS in vivo. Neither difference in relative potency of COX inhibition for (R,S)-ketorolac over INDO and DS nor activity of (S)-ketorolac at a number of other enzymes, channels, or receptors could account for the differences in observed potency. The distribution coefficient for (R,S)-ketorolac was approximately 30-fold less than for DS or INDO, indicating that (R,S)-ketorolac is much less lipophilic than these NSAIDs. Therefore, the physicochemical and pharmacokinetics properties of (R,S)-ketorolac may optimize the concentrations of (S)-ketorolac at its biological target(s), resulting in greater efficacy and potency in vivo.  (+info)

Oxidative bioactivation of the lactol prodrug of a lactone cyclooxygenase-2 inhibitor. (4/1887)

The lactol derivative of a lactone cyclooxygenase-2 inhibitor (DFU) was evaluated in vivo and in vitro for its potential suitability as a prodrug. DFU-lactol was found to be 10 to 20 times more soluble than DFU in a variety of aqueous vehicles. After administration of DFU-lactol at 20 mg kg-1 p.o. in rats, a Cmax of 7.5 microM DFU was reached in the plasma. After oral administration, the ED50s of DFU-lactol in the carrageenan-induced paw edema and lipopolysaccharide-induced pyresis assays in rats are comparable with the ED50s observed when dosing with DFU. Incubations of DFU-lactol with rat and human hepatocytes demonstrated that the oxidation of DFU-lactol can be mediated by liver enzymes and that a competing pathway is direct glucuronidation of the DFU-lactol hydroxyl group. Assays with subcellular fractions from rat liver indicated that most of the oxidation of DFU-lactol occurs in the cytosolic fraction and requires NAD(P)+. Human liver cytosol can also support the oxidation of DFU-lactol to DFU when NAD(P)+ is added to the incubations. Fractionation of human liver cytosolic proteins showed that at least three enzymes are capable of efficiently effecting the oxidation of DFU-lactol to DFU. Incubations with commercially available dehydrogenases suggest that alcohol and hydroxysteroid dehydrogenases are involved in this oxidative process. These data together suggest that lactols may represent useful prodrugs for lactone-containing drugs.  (+info)

Inhibition of cyclooxygenase-2 expression by 4-trifluoromethyl derivatives of salicylate, triflusal, and its deacetylated metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid. (5/1887)

The therapeutic potential of drugs that block the induction of cyclooxygenase-2 has been emphasized. When two 4-trifluoromethyl salicylate derivatives [2-acetoxy-4-trifluoromethyl-benzoic acid (triflusal) and its deacetylated metabolite 2-hydroxy-4-trifluoromethylbenzoic acid (HTB)] were compared with aspirin and sodium salicylate as cyclooxygenase-2 (COX-2) inhibitors, we observed that in bacterial lipopolysaccharide-activated human blood, triflusal, aspirin, and HTB, but not sodium salicylate, inhibited COX-2-mediated prostaglandin E2 (PGE2) production (IC50 = 0.16, 0.18, 0.39, and >10 mM, respectively). However, only triflusal and aspirin inhibited purified COX-2 enzyme. To test this apparent discrepancy, we realized that HTB and triflusal (but neither aspirin nor salicylate) produced a concentration-dependent inhibition of COX-2 protein expression in peripheral human mononuclear cells. This observation was further confirmed in a rat air pouch model in vivo, in which both aspirin and triflusal inhibited PGE2 production (ID50 = 18.9 and 11.4 mg/kg p.o., respectively) but only triflusal-treated animals showed a decrease in COX-2 expression. This different behavior may be, at least in part, due to the ability of HTB and triflusal to block the activation of the transcription factor nuclear factor-kappaB to a higher extent than aspirin and sodium salicylate. Thus, in addition to inhibiting the COX-2 activity at therapeutic concentrations, triflusal is able to block through its metabolite HTB the expression of new enzyme, and hence the resumption of PGE2 synthesis. Triflusal and HTB may exert beneficial effects in processes in which de novo COX-2 expression is involved and, in a broader sense, in pathological situations in which genes under nuclear factor-kappaB control are up-regulated.  (+info)

Cyclo-oxygenase-2 mediates P2Y receptor-induced reactive astrogliosis. (6/1887)

Excessive cyclo-oxygenase-2 (COX-2) induction may play a role in chronic neurological diseases characterized by inflammation and astrogliosis. We have previously identified an astroglial receptor for extracellular nucleotides, a P2Y receptor, whose stimulation leads to arachidonic acid (AA) release, followed, 3 days later, by morphological changes resembling reactive astrogliosis. Since COX-2 may be upregulated by AA metabolites, we assessed a possible role for COX-2 in P2Y receptor-mediated astrogliosis. A brief challenge of rat astrocytes with the ATP analogue alpha,beta-methylene ATP (alpha,beta(me)ATP) resulted, 24 h later, in significantly increased COX-2 expression. The selective COX-2 inhibitor NS-398 completely abolished alpha,beta(me)ATP-induced astrocytic activation. Constitutive astroglial COX-1 or COX-2 did not play any role in purine-induced reactive astrogliosis. PGE2, a main metabolite of COX-2, also induced astrocytic activation. These data suggest that a P2Y receptor mediates reactive astrogliosis via induction of COX-2. Antagonists selective for this receptor may counteract excessive COX-2 activation in both acute and chronic neurological diseases.  (+info)

Curcumin inhibits cyclooxygenase-2 transcription in bile acid- and phorbol ester-treated human gastrointestinal epithelial cells. (7/1887)

We investigated whether curcumin, a chemopreventive agent, inhibited chenodeoxycholate (CD)- or phorbol ester (PMA)-mediated induction of cyclooxygenase-2 (COX-2) in several gastrointestinal cell lines (SK-GT-4, SCC450, IEC-18 and HCA-7). Treatment with curcumin suppressed CD- and PMA-mediated induction of COX-2 protein and synthesis of prostaglandin E2. Curcumin also suppressed the induction of COX-2 mRNA by CD and PMA. Nuclear run-offs revealed increased rates of COX-2 transcription after treatment with CD or PMA and these effects were inhibited by curcumin. Treatment with CD or PMA increased binding of AP-1 to DNA. This effect was also blocked by curcumin. In addition to the above effects on gene expression, we found that curcumin directly inhibited the activity of COX-2. These data provide new insights into the anticancer properties of curcumin.  (+info)

Angiotensin II attenuates renal cortical cyclooxygenase-2 expression. (8/1887)

We have previously shown that in rat renal cortex, cyclooxygenase-2 (COX-2) expression is localized to cTALH cells in the region of the macula densa, and that dietary salt restriction increases COX-2 expression. Administration of the angiotensin converting inhibitor, captopril, further increased COX-2 mRNA and renal cortical COX-2 immunoreactivity, with the most pronounced expression in the macula densa. Administration of an AT1 receptor antagonist, losartan, also significantly increased cortical COX-2 mRNA expression and COX-2 immunoreactivity. Mutant mice homozygous for both Agtr1a and Agtr1b null mutations (Agtr1a-/-,Agtr1b-/-) demonstrated large increases in immunoreactive COX-2 expression inthe cTALH/macula densa. To determine whether increased COX-2expression in response to ACE inhibition mediated increases in renin production, rats were treated with captopril for one week with or without the specific COX-2 inhibitor, SC58236. Plasma renin activity increased significantly in the captropril group, and this increase was significantly inhibited by simultaneous treatment with SC58236. Thus, these studies indicated that angiotensin II inhibitors augment upregulation of renal cortical COX-2 in states of volume depletion, suggesting that negative feedback by the renin-angiotensin system modulates renal cortical COX-2 expression and that COX-2 is a mediator of increased renin production in response to inhibition of angiotension II production.  (+info)

After the doctor knows what kind of arthritis youve, he or she will talk with you about the best way to treat it. The doctor may give you a prescription for medicine that will help with the pain, stiffness, and inflammation. The good news is that now there is a way to stop your pain with a medication . Celebrex is a nonsteroidal anti-inflammatory drug (NSAID), specifically a COX-2 inhibitor, which relieves pain and swelling inflammation). It represents a huge breakthrough in the treatment of soreness, inflammation, and stiffness of arthritis. Celebrex is thought to fight pain and swelling by inhibiting the effect of a natural enzyme called COX-2. Unlike the older medicines, however, it does not interfere with an identical substance, called COX-1, which puts a protective effect on the lining of the stomach. Celebrex wont make the stomach bleeding and also sores that traditional nonsteroidal anti-inflammatory drugs (NSAIDs) might ...
Several studies suggest that cyclooxygenase-2 contributes to the delayed progression of ischemic brain damage. In this study we examined whether the highly selective cyclooxygenase-2 inhibitor DFU reduces neuronal damage when administered several hours after 5 min of transient forebrain ischemia in gerbils. The extent of ischemic injury was assessed behaviorally by measuring the increases in locomotor activity and by histopathological evaluation of the extent of CA1 hippocampal pyramidal cell injury 7 days after ischemia. DFU treatment (10 mg/kg, p.o.) significantly reduced hippocampal neuronal damage even if the treatment is delayed until 12 h after ischemia. These results suggest that selective cyclooxygenase-2 inhibitors may be a valuable therapeutic strategy for ischemic brain injury. ...
Patients with arthritis taking a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID) appear to have a lower risk of adverse gastrointestinal events compared with those on a nonselective NSAID
This study demonstrated dose-related excess mortality associated with the use of NSAIDs in patients with prior MI. There was a trend for increased risk of rehospitalization for MI, although the dose-related response in risk was not as clear as for death.. The VIGOR study was the first to report increased cardiovascular risk associated with the selective COX-2 inhibitors.1 Since then, several studies,5,6,8,12,23 although not all,2,24-26 have confirmed the findings. Several recently published observational studies have also indicated an increased cardiovascular risk associated with the nonselective NSAIDs.7-9,13. The present study is the first to address the risk of all NSAIDs in a selected population of post-MI patients. These patients are elderly, are frequently treated with NSAIDs, and have a high risk of additional cardiovascular events. Many of the randomized trials have excluded these patients. The results of the present study indicate acute or subacute effects of both the selective COX-2 ...
Celecoxib and rofecoxib belong to a new class of NSAIDs that specifically inhibits COX-2. They have a significant anti-inflammatory and analgesic properties but are far less toxic than traditional NSAIDs, which inhibit both COX-1 and COX-2 (20 , 21) . However, not all COX-2 inhibitors share the same anticancer effects. The predictive discrepancy between the in vitro growth inhibitions of celecoxib and rofecoxib may be indicative of the difference in their mechanism of action. The present study provides the first direct comparison of the in vitro anticancer effects of the two clinically available COX-2 inhibitors.. The antiproliferative effect of celecoxib was noted to particularly inhibit the growth of the transformed but not the growth of the normal cells. Exposure to 10 μm celecoxib, for 72 h, inhibited transformed cell growth by 50% but had very little effect on the growth of normal cells (Fig. 1)⇓ . The IC50s of celecoxib ranges between 5 and 20 μm across this entire panel of cell lines. ...
Preclinical CRO PhysioStim is expected to complete its range of cardiovascular safety studies and create a new alliance to answer upcoming CiPA guidelines
Synonyms for COX 2 inhibitor in Free Thesaurus. Antonyms for COX 2 inhibitor. 8 words related to Cox-2 inhibitor: anti-inflammatory, anti-inflammatory drug, Celebrex, celecoxib, rofecoxib, Vioxx, Bextra, valdecoxib. What are synonyms for COX 2 inhibitor?
The size of the PCR products from cyclooxygenase-1 and cyclooxygenase-2 are 524 and 583 base pairs, respectively. The specificity of the PCR reaction for cyclooxygenase-1 and cyclooxygenase-2 complementary deoxyribonucleic acid (cDNA) was confirmed by digestion of PCR products by sequence-specific restriction enzymes (cyclooxygenase-1: Sac I and Sma I; cyclooxygenase-2: Pst I and Nco I). For quantitation of cyclooxygenase-1 and cyclooxygenase-2 mRNA levels, the Escherichia coli plasmid pT2M containing specific internal standards for cyclooxygenase-1 and cyclooxygenase-2 was constructed by internal deletion of sequences: The truncated fragments (320 base pairs) from cyclooxygenase-1 and cyclooxygenase-2 PCR products were incorporated into the E. coli cloning plasmid pBSII SK(+)(Stratagene, La Jolla, CA) at the EcoR I and Kpn I restriction sites and multiplied as plasmids in an E. coli strain Dh5 alpha. Plasmid solutions were adjusted to 1 x 104molecules/micro liter after double digestion by ...
Meloxicam (under the brand name Mobicox) is a new arthritis drug. Unlike other COX-II selective nonsteroidal anti-inflammatory drugs (NSAID) known as coxibs, Meloxicam, an oxicam COX-2 selective NSAID, is a unique class of COX-II selective NSAIDs that appear to not carry the same risk of blood clots that other coxibs have.
Varas-Lorenzo, C., Castellsague, J., Stang, M. R., Perez-Gutthann, S., Aguado, J. and Rodriguez, L. A. G. (2009), The use of selective cyclooxygenase-2 inhibitors and the risk of acute myocardial infarction in Saskatchewan, Canada . Pharmacoepidem. Drug Safe., 18: 1016-1025. doi: 10.1002/pds.1815 ...
Objective:To identify factors that influence prescribers in their selection and use of cyclo-oxygenase-2 (COX-2) selective inhibitors as opposed to non-selective non-steroidal anti-inflammatory...
This is the first study to demonstrate that a selective COX-2 inhibitor on top of standard therapy improves endothelial function and reduces markers of inflammation and oxidative stress in patients with coronary artery disease. Recognition that COX-2 is an inducible enzyme particularly associated with inflammation led to the development of selective COX-2 inhibitors that offer comparable efficacy and fewer unwanted side effects attributable to COX-1 inhibition, gastric ulceration in particular.1,2 Gastrointestinal safety of selective COX-2 inhibitors, however, may come at the cost of increased cardiovascular events, as suggested by the results of the VIGOR trial.5 Cardiovascular safety of coxibs was additionally challenged by studies in mice deficient in the PGI2 or TXA2 receptor.10 PGI2 receptor-deficient animals showed enhanced injury-induced vascular proliferation and platelet activation that was abolished in mice deficient of both PGI2 and TXA2 receptor, suggesting that PGI2 inhibition with ...
Selective COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration, and is the main feature of celecoxib, rofecoxib and other members of this drug class. After several COX-2 inhibiting drugs were approved for marketing, data from clinical trials revealed that COX-2 inhibitors caused a significant increase in heart attacks and strokes, with some drugs in the class having worse risks than others. Rofecoxib (commonly known as Vioxx) was taken off the market in 2004 because of these concerns and celecoxib and traditional NSAIDs received boxed warnings on their labels. Many COX-2-specific inhibitors have been removed from the U.S. market. As of December 2011, only Celebrex (generic name is celecoxib) is still available for purchase in the United States. Some COX-2 inhibitors are used in a single dose to treat pain after ...
When we considered all the randomised trial data, selective COX 2 inhibitors were associated with a highly significant 1.4-fold increased risk of serious vascular events, largely due to a twofold increased risk of myocardial infarction. Although we found no significant excesses in the incidence of stroke or vascular death, the confidence intervals for each were wide, so we could not exclude a clinically important excess. If, as some people have suggested (on the basis of the delayed divergence of survival curves), the hazard emerges only after a year or 18 months,4 5 then combining short term and long term trials might underestimate the effects of long term exposure to a selective COX 2 inhibitor. We were not able to assess time dependent variation in the rate ratio because we sought numbers of events and person time only for the whole period of follow-up in each trial. However, as figure 2 clearly shows, when all the long term trials are considered, the summary rate ratio is similar to that ...
Introduction Cyclooxygenase-2 (COX-2) is frequently over-expressed in primary breast cancer. In transgenic breast cancer models, over-expression of COX-2 leads to tumour formation while COX-2...
TY - JOUR. T1 - What Did Safe Mean To Prescribes Of Selective Cox-2 Inhibitors?. AU - McGettigan, Patricia. AU - Peel, Roseanne. AU - Stokes, Barrie J.. AU - Henderson, Kim M.. AU - Whitaker, Diana. AU - Henry, David A. PY - 2009. Y1 - 2009. N2 - Introduction: Among vulnerable individuals, cyclo-oxygenase-2(COX-2) inhibition increases the risk of cardiovascular thromboticevents. Promotional safety messages led to channeling of selectiveCOX-2 inhibitors to individuals with gastrointestinal risks.Aims: We investigated whether this was associated with inappropriatechanneling of COX-2 inhibitors to patients at risk of cardiovascular events.Methods: Case-control study, August 2003-October 2006. Cases:patients admitted to hospital with acute coronary syndrome (ACS, myocardial infarction/unstable angina) (n = 814). Controls:Patients admitted for reasons other than acute vascular ischaemia, heartfailure, renal failure, or upper gastro-intestinal ulceration/bleeding(n = 1500). Structured interviews ...
COX-2 preferentially leads to synthesis of prostacyclin which have anti-platelet aggregation effects. COX-1 preferentially leads to synthesis of thromboxane which induces platelet aggregation. One would then expect COX-1 inhibition to cause more blood-thinning than COX-2 inhibition. This is the reason COX-2 inhibitors are associated with increased risk of cardiovascular events (by inhibiting prostacyclin synthesis without inhibiting thromboxane synthesis). However, Celebrex is not as selective a COX-2 inhibitor as other coxibs such as rofecoxib (which was removed from the market in 2004), and has minor activity against COX-1 ...
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Etodolac (Lodine) is a COX inhibitor with an IC50 of 53.5 nM. Find all the information about Etodolac (Lodine) for cell signaling research.
This trial assessed the safety and efficacy of a single dose of lumiracoxib 400 mg compared to placebo and to a single dose of celecoxib 200mg. It also assessed safety and efficacy of 400mg lumiracoxib administered once a day for 7 days compared to placebo and to 200 mg celecoxib twice daily ...
Experts discuss the use of firocoxib in horses, including benefits of selective COX-2 inhibition, FDA restrictions, and the importance of proper dosing.
The present meta--analysis attempted to assess whether an unfavourable cardiovascular risk profile could be identified in the case of two COX2 selective inhibitors (COXIBs), namely celecoxib and etoricoxib. Based on the data from the literature, our
3. COX-2 inhibitors, including celecoxib (brand name Celebrex). Two drugs in this class have been withdrawn from the market because of cardiovascular toxicity: rofecoxib (brand name Vioxx), and valdecoxib (brand name Bextra). These drugs are a special class of NSAID that were developed to be safer for the stomach, but have the same risk as other NSAIDs for kidney damage ...
COX-2 inhibitors, including celecoxib (brand name Celebrex). Two drugs in this class have already been withdrawn from the market because of cardiovascular toxicity: rofecoxib (brand name Vioxx), and valdecoxib (brand name Bextra). These drugs are a special class of NSAID and were developed to be safer for the stomach, but have the same risk as other NSAIDs do for kidney damage ...
Professor Mitchell added: "This review shows us that despite the large scale use of NSAIDs and COX-2 inhibitors for a number of years, we still need more information on their benefits and potential risks and that more research needs to be done in this area. Looking at existing evidence, however, it would seem COX-2 inhibitors may be the best option for some patients. They are as effective as traditional NSAIDs, but with less gastric side effects than some older drugs ...
Priva-Celecoxib: Celecoxib belongs to the group of medications called selective COX-2 inhibitors, which is a kind of nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs work by reducing a substance in the body that leads to inflammation (swelling) and pain.
Riva-Celecoxib: Celecoxib belongs to the group of medications called selective COX-2 inhibitors, which is a kind of nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs work by reducing a substance in the body that leads to inflammation (swelling) and pain.
Celecoxib belongs to the group of medications called selective COX-2 inhibitors, which is a kind of nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs work by reducing a substance in the body that leads to inflammation (swelling) and pain.
Celecoxib belongs to the group of medications called selective COX-2 inhibitors, which is a kind of nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs work by reducing a substance in the body that leads to inflammation (swelling) and pain.
Get this from a library! Nimesulide--actions and uses. [K D Rainsford;] -- Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) which acts as a cyclooxygenase- 2 inhibitor but also has other novel pharmacological features which account for its effect in the control ...
Modelled structure of COX-1 and COX-2.Comparison of modelled structures with their template structures revealed the active sites of located in the enzymes. (A)
ab120295 NS 398, COX-2 inhibitor (CAS番号: 123653-11-2) 分子量: 314.36 化学式: C13H18N2O5S COX-2 阻害剤 アブカムの高純度な生理活性物質(アゴニスト・アンタゴニスト・アクティベーター・阻害剤)
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Interaction with platelet function by non-steroidal anti-inflammatory drugs (NSAIDs) is related to the inhibition of cyclo-oxygenase-1 (COX-1). In pat
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The use of cyclo-oxygenase 2 selective nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of acute myocardial infarction (AMI). The association between the risks of AMI with nonselective NSAIDs is less clear. We reviewed the published evidence and assessed the risk of AMI with nonselective NSAIDs. We performed a meta-analysis of all studies containing data from population databases that compared the risk of AMI in NSAID users with that in non-users or remote NSAID users. The primary outcome was objectively confirmed AMI. Fourteen studies met predefined criteria for inclusion in the meta-analysis. Nonselective NSAIDs as a class was associated with increased AMI risk (relative AMI risk 1.19, 95% confidence interval [CI] 1.08 to 1.31). Similar findings were found with diclofenac (relative AMI risk 1.38, 95% CI 1.22-1.57) and ibuprofen (relative AMI risk 1.11, 95% CI 1.06 to 1.17). However, this effect was not observed with naproxen (relative AMI risk 0.99, 95% CI 0.88-1.11). In
Celecoxib is a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID). It is used to treat the pain and inflammation of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute pain in adults, painful menstruation, and juvenile rheumatoid arthritis in people two years or older.. Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID). It works by reducing hormones that cause inflammation and pain in the body.. Celecoxib is used to treat pain or inflammation caused by many conditions such as arthritis, ankylosing spondylitis, and menstrual pain.. Celecoxib is used to treat juvenile rheumatoid arthritis in children who are at least 2 years old. It is also used in the treatment of hereditary polyps in the colon.. Celebrex was one of Pfizers "best-selling drugs, amounting to more than $2.5 billion in sales [by 2012], and was prescribed to 2.4 million" people in 2011. By 2012, 33 million Americans had taken Celebrex. As of 2015, the cost for a typical month of medication in the ...
A dermally deliverable pharmaceutical composition comprises at least one selective cyclooxygenase-2 (COX-2) inhibitory drug or prodrug thereof solubilized in a pharmaceutically acceptable carrier that comprises a low molecular weight monohydric alcohol, and exhibits a skin permeation rate of the therapeutic agent at least equal to that exhibited by a reference solution of the therapeutic agent in 70% aqueous ethanol. A method of effecting targeted delivery of a selective COX-2 inhibitory drug to a site of pain and/or inflammation in a subject comprises topically administering such a composition to skin of the subject, preferably at a locus overlying or adjacent to the site of pain and/or inflammation. A method of effecting systemic treatment of a subject having a COX-2 mediated disorder comprises transdermally administering such a composition, preferably by contacting the composition with an area of skin of the subject not greater than about 400 cm2.
Third generation aromatase inhibitors (AIs) are more effective than tamoxifen in the treatment of estrogen receptor (ER) positive breast cancer. However, long-term use of AIs commonly results in resistance. We examined whether compound JCC76{Cyclohexanecarboxylic acid [3-(2,5-dimethyl-benzyloxy)-4-(methanesulfonyl-methyl-amino)-phenyl]-amide}, an analog of Cyclooxygenase-2 (COX-2) inhibitor nimesulide, can inhibit the growth of AI-insensitive breast cancer cells and the mechanisms by which the compound affects cell proliferation. LTEDaro (long term estrogen deprived MCF-7aro cell) cells, which are a model for AI resistance, were used in this study. JCC76 effectively inhibited LTEDaro cell proliferation with an IC(50) of 2.75 ± 0.31 μM. Further investigations reveal that the compound significantly induced apoptosis in LTEDaro cells by decreasing pAKT, BCL-2 and pBad protein levels, which were all up regulated in the cells after long term estrogen deprivation. LTEDaro tumor size and weight were
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The Food and Drug Administration on Nov. 21 granted orphan drug designation to rofecoxib (TRM-201), a cyclooxygenase 2-selective nonsteroidal anti-inflammatory
Medications from several classes have been shown to have moderate, mostly short-term benefits for patients with low back pain. Acetaminophen (Tylenol®) is a slightly weaker pain medication than non-steroidal anti-inflammatories (NSAIDs). However, acetaminophen is generally safer and less costly. Acetaminophen can cause liver enzyme elevations at dosages of 4 g (4,000 mg)/day even in healthy adults. The clinical significance of the liver enzyme elevation is uncertain.. NSAIDs can be selective, or non-selective. Advil® and Motrin® (ibuprofen); and Aleve® (naproxen) are examples of over-the-counter non-selective NSAIDs. Celebrex® is the only selective NSAID available in the United States. Nonselective NSAIDs, while more effective than acetaminophen, are known to cause stomach and kidney problems. Selective NSAIDs such as Celebrex® and most non-selective NSAIDS also increase risk for heart attack. The lowest effective doses for the shortest periods necessary are recommended. If you ...
Several studies suggest that cyclooxygenase (COX)-2 plays a pivotal role in the progression of ischemic brain damage. In the present study, we investigated the effects of selective inhibition of COX-2 with nimesulide (12 mg/kg) and selective inhibition of COX-1 with valeryl salicylate (VAS, 12-120 mg/kg) on prostaglandin E2 (PGE2) levels, myeloperoxidase (MPO) activity, Evans Blue (EB) extravasation and infarct volume in a standardized model of transient focal cerebral ischemia in the rat. Postischemic treatment with nimesulide markedly reduced the increase in PGE2 levels in the ischemic cerebral cortex 24 h after stroke and diminished infarct size by 48 % with respect to vehicle-treated animals after 3 days of reperfusion. Furthermore, nimesulide significantly attenuated the blood-brain barrier (BBB) damage and leukocyte infiltration (as measured by EB leakage and MPO activity, respectively) seen at 48 h after the initial ischemic episode. These studies provide the first experimental evidence ...
Indications: RA, juvenile idiopathic arthritis, osteoarthritis, ankylosing spondylitis, spondyloarthropathy, gout, pain. Mechanism of Action: Anti-inflammatory and antiplatelet properties are mediated by the inhibition of COX enzymes and decreased production of prostaglandins. Drugs that inhibit COX-2 are anti-inflammatory because they decrease the formation of prostaglandins by activated cells. Drugs that inhibit COX-1 decrease the production of thromboxane and thus decrease platelet activation. Because COX-1 contributes to the maintenance of gastric mucosa, blocking COX-1 increases the risk of peptic ulceration. NSAIDs are classified according to whether they inhibit both COX-1 and COX-2 (nonselective NSAIDs) or whether they are more selective for COX-2 and spare COX-1 (COX-2 selective NSAIDs or coxibs). Nonacetylated salicylates such as salsalate are weak inhibitors of COX, and their mechanism of action is poorly understood.. Contraindications: Hypersensitivity to NSAIDs, GI ulceration, ...
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In this study, we analyzed a nationwide health insurance claims database and found an increased risk for ischemic and hemorrhagic stroke was evident for all selective and nonselective NSAIDs, particularly when used parenterally. Risk was highest for ketorolac as compared with other NSAIDs.. Four population-based studies in Denmark, the United Kingdom, the United States, and The Netherlands investigated nonselective NSAIDs, selective COX-2 inhibitors, and the risk of ischemic stroke.6-9 They found the ORs for ischemic stroke ranged from 1.2 to 1.7 for a variety of nonselective NSAIDs, including ibuprofen, indomethacin, diclofenac, and naproxen. A nested case-control study observed an exposure period as short as 14 days was associated with a significantly increased risk of ischemic stroke.6 In a prospective population-based cohort study, Haag and colleagues found use of any NSAID was related to the risk of hemorrhagic stroke with a hazard ratio of 2.03, albeit nonsignificant.8 Conflicting results ...
William Penn College. I. Ressel, MD: "Order Celecoxib on line amex".. Modulation of the MEP in biceps and triceps brachii by ulnar volleys in a long-suffering with a spinal lesion at the C6 C7 intersection purchase celecoxib 100 mg on line arthritis knee leg. The lesion (bristling level dotted graft) is presumed to horn in axons of PNs and on the whole to save the corticospinal projections to MNs and segmental INs order celecoxib 200mg on-line arthritis in neck and feet. Samples of averaged (20 sweeps) rectified in check (condensed lines) and conditioned (thin lines) MEPs (expressed as a interest of the backstage EMG) are illustrated inasmuch as the biceps at the 4 discount 200 mg celecoxib free shipping chinese medicine arthritis diet. Sway MEPs in triceps (here the lesion) had the same latency (в€ј13 ms) and alike resemble quarter on both sides purchase tadapox discount, consistent with the relative sparing of the corticospinal projections to low-cervical MNs and segmental INs order ...
Purpose Non-selective (NSAIDs) and selective (COX-2) nonsteroidal anti-inflammatory drugs are commonly used for their analgesic and anti-inflammatory effects. Their role after orthopaedic surgery has...
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There are no restrictions on food, beverages, or activity while taking celecoxib unless otherwise directed by your doctor. Concomitant use of celecoxib with aspirin or other NSAIDs (e.g., ibuprofen, naproxen, etc.) may increase the occurrence of stomach and intestinal ulcers. Fluconazole (Diflucan) increases the concentration of celecoxib in the body by inhibiting the breakdown of celecoxib in the liver. Therefore, treatment with celecoxib should be initiated at the lowest recommended doses in patients who are taking fluconazole. Celecoxib increases the concentration of lithium (Eskalith) in the blood by 17%. Therefore, lithium therapy should be closely monitored during and after therapy with celecoxib. Persons, taking the anticoagulant (blood thinner) warfarin (Coumadin), should have their blood tested when initiating or changing celecoxib treatment, particularly in the first few days, for any changes in the effects of the anticoagulant. Persons, who drink more than 3 alcoholic beverages per ...
Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase (COX)-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX-2 is responsible for the chemopreventive efficacy of these agents. However, the precise mechanisms by which NSAIDs exert their antiproliferative effects are still a matter of debate. Numerous other studies have shown that NSAIDs can act through COX-independent mechanisms. This review provides a detailed description of the major COX-independent molecular targets of NSAIDs and discusses how these targets may be involved in their anticancer effects. Toxicities resulting from COX inhibition and the suppression of
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1. Health Technol Assess. 2008 Apr12(11):1-278, iii. Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib
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The results of this study demonstrate that single doses of celecoxib, a highly selective COX-2 inhibitor in vitro, are well tolerated by healthy volunteers. All doses inhibited LPS-stimulated monocyte PGE2 formation ex vivo, an index of COX-2 activity, to a degree that approximated that attained after 800 mg ibuprofen, a therapeutic dose of a nonselective, conventional NSAID. Although interindividual differences in response were apparent and the biochemical selectivity of Celecoxib for COX-2 was relative, rather than absolute, in humans, it did not influence TxA2-dependant platelet aggregation ex vivo. Surprisingly, celecoxib and ibuprofen had comparable suppressive effects on the excretion of PGI-M. Celecoxib also suppressed urinary 6-keto PGF1α. This implies a major role for COX-2 in the biosynthesis of both systemic and renal PGI2 under physiological conditions in young volunteers.. The two COX isoforms are distinct gene products prone to differential patterns of regulation (5-9, 13-17). ...
Our in vitro results revealed that, in HNSCC cells, the selective Cox-2 inhibitors led to the suppression of the EMT by restoring the expression of E-cadherin through the downregulation of its transcriptional repressors. Moreover, the extent of the effect of Cox-2 inhibition was shown to depend on the baseline expression levels of both E-cadherin and Cox-2 in each cell; i.e., tumor cells expressing lower E-cadherin and higher Cox-2 are expected to be more sensitive to Cox-2 inhibition in terms of the restoration of E-cadherin expression. Such a finding is consistent with a previous study of bladder cancer cells using another Cox-2 inhibitor, etodolac. In that study, etodolac upregulated E-cadherin expression only in T24 cells, which express the highest level of Cox-2 and the lowest level of E-cadherin; it did not do so in 5637 cells or K47 cells, which express a lower level of Cox-2 and a higher level of E-cadherin [42]. Interestingly, using the same three bladder cancer cell lines and three ...
We were not asleep at the wheel, we were actually engaged in reviewing a lot of data," Dr. Lourdes Villalba told a joint meeting of the Food and Drug Administrations arthritis advisory committee and its drug safety and risk management advisory committee, which are looking into Vioxx, Celebrex and Bextra. Celebrex and Bextra, made by Pfizer Inc., remain on the market, though some studies have also indicated they, too, may carry an added heart risk. Villalba, medical officer responsible for Vioxx at the FDAs Center for Drug Evaluation and Research, pointed out that a study done in 2000 comparing Vioxx with the painkiller naproxen, showed a higher rate of heart problems with Vioxx, but other studies had conflicting results. In discussions with Merck officials, she said, the company suggested naproxen might have a heart protective effect. Nonetheless, in 2002 the agency required an added warning on the Vioxx label urging caution in prescribing it for people with heart conditions. "We never bought ...
The results of a clinical trial (PRECISION)1 comparing the cardiovascular safety of the COX-2 selective NSAID celecoxib (Celebrex, and generics) with that of ibuprofen and naproxen, which are nonselective, have been described in the lay press in terms that may overestimate the safety of celecoxib.. NSAID PHARMACOLOGY - NSAIDs inhibit the enzyme cyclooxygenase (COX), which is required for synthesis of prostaglandins and thromboxane. COX-1 inhibition blocks the protective effect of prostaglandins on the gastric mucosa, which can cause gastrointestinal toxicity, and has an antiplatelet effect that can cause bleeding. COX-2 inhibition produces therapeutic anti-inflammatory and analgesic effects, but it has effects on vascular endothelium that can be prothrombotic.. Ibuprofen and naproxen inhibit COX-1 more than COX-2. The COX-2 selective NSAID rofecoxib (Vioxx), ... more ...
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15.3 deaths/100,000 NSAID/aspirin users, and hypothesis that anti-inflammatory effects are usu- that up to one third of all NSAID/aspirin deaths ally due to COX-2 inhibition and that adverse can be attributed to low-dose aspirin use.12 In an effects usually occur because of COX-1 inhibi- endoscopic evaluation of patients who had contin- tion, selective COX-2 inhibitors (celecoxib, rofe- uously used NSAIDs over the previous 6 months, coxib, valdecoxib, etc.) were developed to reduce gastroduodenal ulcers were detected in 24% of NSAID-associated GI toxicities.19 Several clinical patients, and approximately 1-2% of NSAID users trials showed a 41-57% reduction in the rate of developed ulcer-related complications (bleeding, GI toxicities with the use of selective COX-2 in- perforation, obstruction) annually.13,14 Notably, hibitors.20 However, the VIGOR trial raised the the majority of patients with NSAID-related GI issue of the cardiovascular safety of the coxibs complications did not have preceding ...
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Ive recently been experiencing a lot of joint pain. Its mostly my SI joints, fingers, and toes. Its feeling very much like it did years ago when the docs thought I had rheumatoid arthritis. Tylenol is doing nothing to touch the pain. So, I asked my gastro for something else. He said he normally gives IBD patients Tramadol, but he couldnt give it to me. Apparently, Tramadol and most SSRI antidepressants dont mix well. Its not to the point of needing narcotics yet. He prescribed Celebrex with the promise that I wouldnt take it every day. Celebrex is still an NSAID, but he says its better than the others. Does anyone else here take Celebrex for joint pain? If so, how often do you take it? Have you had any problems with GI bleeding, etc. with it ...
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Papers pp 619, 624. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce pain and improve function in people with mechanical and inflammatory arthropathies and are beneficial in many other conditions, but these benefits come at a price. In the United Kingdom, every year over 2000 people die as a result of upper gastrointestinal damage induced by NSAIDs, and these agents can also have unwanted effects on the lower bowel, lungs, kidneys, and cardiovascular system. Conversely, some NSAIDs may have useful antithrombotic actions and increasing evidence shows that they may inhibit the development of colonic neoplasia and other gastrointestinal cancers.1-3 The introduction of new anti-inflammatory agents, with more specific inhibitory effects on cyclo-oxygenase 2 (COX 2) pathways, promised equivalent efficacy with greater safety and tolerability.. Two large pivotal trials have been published, in which the efficacy and safety of the COX 2 inhibitors celecoxib and rofecoxib were compared with various ...
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Sandoz Celecoxib: Celecoxib belongs to the group of medications called selective COX-2 inhibitors, which is a kind of nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs work by reducing a substance in the body that leads to inflammation (swelling) and pain.
The aim of the study is to assess the influence of celecoxib on relapse-free survival in completely resected patients with poor prognosis indicated by metastatic involvement of intrapulmonary/hilar (pN1) or ipsilateral mediastinal (pN2) lymph nodes. Celecoxib, a selective oral COX-2 inhibitor, was found to exert significant anti-proliferative activity against a variety of tumor cell lines in vitro, including NSCLC. COX-2 is frequently up-regulated in NSCLC cell lines and archival tumor samples. Its high expression was also correlated with poor prognosis of the patients. A clinical trial addressing the role of celecoxib as adjuvant treatment in radically operated patients with high risk of relapse is warranted ...
1 Answer - Posted in: celebrex, rheumatoid arthritis, osteoarthritis, pain - Answer: Lesliea I have taken Celebrex off and on several times over the ...
1 Answer (question resolved) - Posted in: celebrex, pain, doctor - Answer: All celebrex would do would be to decrease inflamation. It surely wouldnt ...
See risks and benefits. Find dosing info for CELEBREX® (celecoxib) Capsules, a prescription treatment for relief of symptoms of OA, RA and acute pain in adults.
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Faculty/Faculty Disclosure: Martin Quan, MD Professor of Clinical Family Medicine David Geffen School of Medicine at UCLA Vice Chair for Academic Affairs UCLA Department of Family Medicine Los Angeles, CA Dr. Quan discloses that he has no real or apparent conflicts to report. Click Here to Read Supplement. ...
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) may confer a long-term risk of adverse cardiovascular events, a Danish population study found.
Nine popular painkillers - including traditional NSAIDs and cyclo-oxygenase-2 (COX-2) inhibitors - are associated with an increased risk of hospitalization for heart failure in adults, based on data from a case-control study of approximately 92,000 hospital admissions. The findings were published online Sept. 28 in BMJ. Read Entire Article: http://www.mdedge.com/ecardiologynews/article/114651/cardiology/heart-failure-risk-individual-nsaids-examined-study
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Deramaxx is a non-steroidal anti-inflammatory drug or NSAID that contains the active ingredient Deracoxib. It is primarily used in the control and management of moderate to severe pain as well as inflammation that typically occurs as a result of tissue injury such as after surgery and even osteoarthritis in dogs. Deramaxx should not be confused with Celebrex or celecoxib as the latter is primarily intended for pain and inflammation management in humans.. Deramaxx is a special formulation of a type of NSAIDs known as cyclooxygenase-2 (COX-2) inhibitors. These substances prevent the conversion of arachidonic acid into prostaglandins, thromboxane A2, and prostacyclin, 3 molecules that are largely considered in the scientific community as pro-inflammatory. Thromboxane A2 is involved in platelet aggregation that forms blood clots around injured tissues which can add to the overall inflammatory effect. Prostacyclin, on the other hand, increases the diameter of the blood vessels while also inhibiting ...
The objective of the present study was to elucidate the role of etoricoxib - a COX-2 selective NSAID, in fracture healing process, with a view to understand its role in the fracture repair process. Our study shows that mechanical strength, radiographic and morphological signs of healing were significantly decreased in etoricoxib group as compared to control group at 4, 8 and 12 weeks, although differences were not very significant at 12 weeks. These results point that bone healing is impaired by COX-2 selective NSAIDS, especially in early and intermediate stages of healing. These results are in agreement with the results of previous studies on coxibs by OConnor et al. [15], Goodman et al .[16] and Simon et al .[17] .Our study thus supports the hypothesis that COX-2 enzyme is integrally involved in the acute inflammatory response and is essential for fracture healing.. Our results are in direct contrast to the results of Gerstenfeld et al [13], Brown et al. [10] and Karachalios et al. [18] who ...
GI events for GLP-1 agonists are a common side effect; study finds fewer T2 patients on exenatide once-weekly reported gastrointestinal adverse events.
Vioxx is a COX-2 inhibitor that was recalled in September 2004. Since then, questions have arisen about the potential safety risks for other COX-2 inhibitors (Celebrex and Bextra), as well as for naproxen (another type of NSAID).
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Some Celebrex alternatives include other medications, surgery, and lifestyle changes. This eMedTV Web article explores possible alternatives if this medicine is not working for you or if you are concerned about unwanted side effects.
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etodolac definition: A nonsteroidal anti-inflammatory medicine, made use of especially for the treating osteoarthritis.; A nonsteroidal anti-inflammatory medication.; a nonsteroidal anti inflammatory…
S-2474 is an inhibitor of COX-2 and 5-lipoxygenase (5-LO), with IC50s of 11 nM and 27 μM for COX-2 and COX-1 in human intact cells, and used as a nonsteroidal anti-inflammatory drug. - Mechanism of Action & Protocol.
Use of prescribed nonsteroidal anti-inflammatory drugs (NSAIDs) may be tied to a higher risk of heart failure, according to research published online September 28 in The BMJ.
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Meloxicam vs. Celebrex: Differences, similarities, and which one is better for youDrug overview & main differences | Conditions treated | Efficacy | Insurance
therapy that was later replaced by NSAIDs by injection questions: ... therapy has been discontinued for the insertion of NSAIDs by injection . Finding inconsistency between the result of instrumental ... Tioside, Depalgos, low-molecular-weight-heparin, NSAIDs, Protelos, Combisartan, Lucen, Depalgos, Piroxicam, Tioside, heparin, .... ...
Arcoxia a non steriodal anti-flammatory drug, information about side effects, uses, active ingredient and taking Arcoxia with other medicines
Does Celebrex Cause Canker Sores. Recurring Canker Sores? - Effective Prevention that works! Ad Effective Prevention that works! 2 Month Cure. Moneyback Guarantee. Can Celebrex cause Mouth Sores? - Treato Can Celebrex cause Mouth Sores? Complete analysis from patient reviews and trusted online health resources, including first-hand experiences. Will you have Canker sores with Celebrex - ehealthme.com Could Celebrex cause Canker sores? We studied 98,692 Celebrex users who have side effects from FDA and eHealthme. Among them, 20 have Canker sores. See what we found. Celebrex Advanced Patient Information - Drugs.com Detailed drug Information for Celebrex. or sulfonamide-type drugs. Anaphylaxis can be life-threatening and requires immediate medical attention. sores, ulcers Celebrex mouth sores - Doctor answers on HealthcareMagic Celebrex mouth sores, I have never been proned to mouth sores or canker s and the does drinking a small amount of infectious pee cause mouth sores to drinker?? Does celebrex ...
In our aim to provide our erudite clients with the best research material with absolute in-depth information of the market, our new report on Global Non-steroidal Anti-inflammatory Drugs Market is confident in meeting their needs and expectations. The 2017 market research report on Global Non-steroidal Anti-inflammatory Drugs Market is an in-depth study and analysis of the market by our industry experts with unparalleled domain knowledge.. The report will shed light on many critical points and trends of the industry which are useful for our esteemed clients. The report covers a vast expanse of information including an overview, comprehensive analysis, definitions and classifications, applications, and expert opinions, among others. With the extent of information filled in the report, the presentation and style of the Global Non-steroidal Anti-inflammatory Drugs (NSAID) Market report is a noteworthy.. The Global Non-steroidal Anti-inflammatory Drugs (NSAID) Industry report provides key ...
Utilization of gastroprotective strategies for nonsteroidal anti-inflammatory drug-induced gastrointestinal events in a major teaching hospital Hooi Leng Lee,1 Siew Siang Chua,1 Sanjiv Mahadeva2 1Department of Pharmacy, 2Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia Background and purpose: Clinical guidelines recommend the prescribing of gastroprotective strategies in nonsteroidal anti-inflammatory drug (NSAID) users with risk factors for gastrointestinal (GI) ulcer or ulcer complications. However, these guidelines are not often translated into clinical practice. Therefore, the aim of this study was to investigate the utilization of gastroprotective strategies for NSAID-induced upper GI events in at-risk users in a major teaching hospital. Patients and methods: A cross-sectional, observational, pharmacy-based study was conducted in a major Asian institution with both primary and secondary health care services. This study involved the screening of
The relative risk for use of the cyclo-oxygenase-2 inhibitors celecoxib, rofecoxib, and for other non-steroidal anti-inflammatory drugs was assessed.. The doctors identified a total of 3083 cases of acute pancreatitis and 30,830 population controls.. For current use, the relative risk estimate for celecoxib was 1.4, and 1.3 for rofecoxib.. The overall relative risk for other non-steroidal anti-inflammatory drugs was 2.7.. However, the team noted substantial variation in risk between the individual drugs.. The highest relative risk was for diclofenac, and the lowest for naproxen.. Dr Sorensens team concluded, Cyclo-oxygenase-2 selective inhibitors are associated with a lower risk of acute pancreatitis than most other non-steroidal anti-inflammatory drugs. ...
OBJECTIVES: To investigate the cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs) and estimate the risk of hospital admission for heart failure with use of individual NSAIDs. DESIGN: Nested case-control study. SETTING: Five population based healthcare databases from four European countries (the Netherlands, Italy, Germany, and the United Kingdom). PARTICIPANTS:
TY - JOUR. T1 - Effect of nonsteroidal antiinflammatory drugs on fracture healing. T2 - a laboratory study in rats.. AU - Altman, R. D.. AU - Latta, L. L.. AU - Keer, R.. AU - Renfree, K.. AU - Hornicek, F. J.. AU - Banovac, K.. PY - 1995. Y1 - 1995. N2 - We studied the effects of two nonsteroidal antiinflammatory drugs (NSAIDs) on fracture healing in rats: ibuprofen (30 mg/kg/day) and indomethacin (1 mg/kg/day). Femoral fractures were induced via a three-point bending technique. NSAIDs were administered orally for 4 or 12 weeks. Control animals received no medication. In each group a minimum of six animals were killed at the following intervals: 2, 4, 6, 8, 10, and 12 weeks postfracture. Fracture healing was determined by mechanical testing and histologic evaluation. The bending strength of each fractured femur was expressed as a percentage of the strength of the intact, contralateral femur. Histologic evaluation was performed on serial longitudinal sections stained with hematoxylin and eosin ...
TY - CHAP. T1 - Non-steroidal anti-inflammatory drugs and increased risk of sudden cardiac death. AU - Hwang, Soyun M.. AU - Gilda, Jennifer E.. AU - Cui, Ziyou. AU - Gomes, Aldrin V. PY - 2013. Y1 - 2013. UR - http://www.scopus.com/inward/record.url?scp=84892089153&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84892089153&partnerID=8YFLogxK. M3 - Chapter. AN - SCOPUS:84892089153. SN - 9781626187863. SP - 123. EP - 167. BT - Sudden Cardiac Death: Epidemiology, Genetics and Predictive/Prevention Strategies. PB - Nova Science Publishers, Inc.. ER - ...
Reversible COX-1/COX-2 inhibition.. Topical.. No data.. Skin disorders.. Skin conditions, such as contact dermatitis. ... Thus, the COX2 inhibitors were developed to inhibit only the COX2 enzyme (traditional NSAIDs block both versions in general). ... Reversible COX-1/COX-2 inhibition.. PO, IM, IV, rectal.. No data.. Pain.. As per diclofenac. ... Irreversibly inhibits COX-1 and COX-2; hence inhibiting prostaglandin synthesis.. PO, IM, IV, rectal. Bioavailability = 80-100 ...
inhibitors). COX. (PTGS). *Salicylic acids: Aloxiprin. *Aspirin (acetylsalicylic acid). *Benorilate (benorylate). *Carbasalate ... At least two different types of cyclooxygenases, COX-1 and COX-2, are acted on by aspirin. Aspirin irreversibly inhibits COX-1 ... Blockade of COX-1 by aspirin apparently results in the upregulation of COX-2 as part of a gastric defense[96] and that taking ... "Cyclooxygenase-3 (COX-3): filling in the gaps toward a COX continuum?". Proceedings of the National Academy of Sciences of the ...
inhibitors). COX. (PTGS). *Salicylic acids: Aloxiprin. *Aspirin (acetylsalicylic acid). *Benorilate (benorylate). *Carbasalate ... InChI=1S/C17H15NO5/c1-11(19)18-13-7-9-14(10-8-13)23-17(21)15-5-3-4-6-16(15)22-12(2)20/h3-10H,1-2H3,(H,18,19) N ...
inhibitors). COX. (PTGS). *Salicylic acids: Aloxiprin. *Aspirin (acetylsalicylic acid). *Benorilate (benorylate). *Carbasalate ... COX-1 and COX-2) enzymes reversibly, which decreases production of proinflammatory prostaglandin precursors.[10][12] ... doi:10.1208/s12249-009-9367-2. PMC 2850498. PMID 20087696.. *^ Sarzi-Puttini, P; Atzeni, F; Lanata, L; Bagnasco, M (2013). " ... Ketoprofen, (RS)-2-(3-benzoylphenyl)-propionic acid (chemical formula C16H14O3) is one of the propionic acid class of ...
Most NSAIDs act as nonselective inhibitors of the enzyme cyclooxygenase (COX), inhibiting both the cyclooxygenase-1 (COX-1) and ... 978-0-9757919-2-9. .. [page needed] *^ a b c d e f g h i j k l m n o p q r s t Consumer Reports Health Best Buy Drugs (July ... ISBN 84-8174-340-2 *^ a b c d e f g h i j k l m n o p q Simone Rossi, ed. (2006). Australian medicines handbook 2006. Adelaide ... Licofelone acts by inhibiting LOX (lipooxygenase) & COX and hence known as 5-LOX/COX inhibitor ...
See also: Cyclooxygenase. Cyclooxygenase (COX) has two well-studied isoforms, called COX-1 and COX-2. COX-1 mediates the ... inhibitors). COX. (PTGS). *Salicylic acids: Aloxiprin. *Aspirin (acetylsalicylic acid). *Benorilate (benorylate). *Carbasalate ... Prostacyclin/thromboxane are produced by both COX-1 and COX-2, and rofecoxib suppresses just COX-2 enzyme, so there is no ... Discovery and development of cyclooxygenase 2 inhibitors. Footnotes[edit]. *^ Knox R (September 30, 2004), Merck Pulls ...
inhibitors). COX. (PTGS). *Salicylic acids: Aloxiprin. *Aspirin (acetylsalicylic acid). *Benorilate (benorylate). *Carbasalate ... InChI=1S/C13H11NO2/c15-13(16)11-8-4-5-9-12(11)14-10-6-2-1-3-7-10/h1-9,14H,(H,15,16) N ... 2] See also[edit]. *synthesis of Fenamic acid: C. F. H. Allen, G. H. W. McKee (1939). "Acridone". 2: 6. doi:10.15227/orgsyn. ... Jack DeRuiter, Principles of Drug Action 2, Fall 2002 1: Non-Steroidal Antiinflammatory Drugs (NSAIDS) ...
"Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal ... Phosphodiesterase-4 inhibitors[edit]. A first-in-class treatment option for the management of psoriatic arthritis, apremilast ... NSAIDs can irritate the stomach and intestine, and long-term use can lead to gastrointestinal bleeding.[11][12] Coxibs (COX-2 ... Biologics prescribed for psoriatic arthritis are TNF-α inhibitors, including infliximab, etanercept, golimumab, certolizumab ...
Vioxx was designed as a selective inhibitor of the enzyme cyclooxygenase-2. Such compounds were expected to cause less ... Carrie Cox will be named Chairman of the Board of Directors. Cox formerly served as chair of Array BioPharma, Inc., CEO and ... Retrieved 2 February 2018.. *^ a b c d e f "US SEC: Form 10-K Merck & Co., Inc" (PDF). United States Securities and Exchange ... "Merck Melanoma Drug Is First PD-1 Inhibitor OK'd by FDA". Genetic Engineering & Biotechnology News. Retrieved 3 July 2015.. ...
Peres MF, Silberstein SD (2002). "Hemicrania continua responds to cyclooxygenase-2 inhibitors". Headache. 42 (6): 530-1. doi: ... 2, by G.S.Davis, and the incident has been cited in King's American Dispensatory (1898 and later editions) in the description ... Changing the 'cocktail' to include [for example] 10mls of .5% Marcaine and changing to 2% Lignocaine, whilst in theory should ... Davis, G.S. (1881). The Therapeutic Gazette, Volume 2. p. 54. King; Felter; Lloyd, John; Harvey Wickes; John Uri (1898). King's ...
It is also known for its release of the first bulk laxative, Metamucil, in 2002; Dramamine, for motion sickness; the COX-2 ... inhibitor Bextra; Ambien for insomnia; and NutraSweet (also known as aspartame), an artificial sweetener, in 2003. It was ...
inhibitors). COX. (PTGS). *Salicylic acids: Aloxiprin. *Aspirin (acetylsalicylic acid). *Benorilate (benorylate). *Carbasalate ... In Europe, use of selexipag together with strong inhibitors of the liver enzyme [CYP2C8], such as gemfibrozil, is ... 2-{4-[(5,6-diphenylpyrazin-2-yl)(propan-2-yl)amino]butoxy}-N-(methanesulfonyl)acetamide ...
inhibitors). COX. (PTGS). *Salicylic acids: Aloxiprin. *Aspirin (acetylsalicylic acid). *Benorilate (benorylate). *Carbasalate ... General chemical structures of 1,2-diacylglycerols (top) and 1,3-diacylglycerols (bottom), where R1 and R2 are fatty acid side ... a precursor of the endocannabinoid 2-arachidonoylglycerol. *an activator of a subfamily of transient receptor potential ... 2][3] with total annual sales of approximately USD 200 million in Japan since its introduction in the late 1990s till 2009.[2] ...
inhibitors). COX. (PTGS). *Salicylic acids: Aloxiprin. *Aspirin (acetylsalicylic acid). *Benorilate (benorylate). *Carbasalate ... Decreases inflammation, pain, and fever, probably through inhibition of cyclooxygenase (COX-2 inhibitor) activity and ... Angiotensin-converting enzyme (ACE) inhibitors: Antihypertensive effect of ACE inhibitors may be diminished. ... InChI=1S/C15H14O3/c1-11(15(16)17)12-6-5-9-14(10-12)18-13-7-3-2-4-8-13/h2-11H,1H3,(H,16,17) Y ...
inhibitors). COX. (PTGS). *Salicylic acids: Aloxiprin. *Aspirin (acetylsalicylic acid). *Benorilate (benorylate). *Carbasalate ... Mesalazine, also known as mesalamine or 5-aminosalicylic acid (5-ASA), is an aminosalicylate anti-inflammatory drug[2] used to ... InChI=1S/C7H7NO3/c8-4-1-2-6(9)5(3-4)7(10)11/h1-3,9H,8H2,(H,10,11) Y ...
COX-1 in COX-2. Zaviranje COX-1, na katerega celekoksob v terapevstkih odmerkih ne vpliva, povzroči inhibicijo proizvodnje ... Celekoksib okoli 10-20-krat močneje zavira COX-2 kot COX-1.[31][33] S polarno sulfonamidno stransko verigo se veže na ... 23,0 23,1 Guy Howes J. Selective COX-2 inhibitors, NSAIDs and cardiovascular events - is celecoxib the safest choice? Ther Clin ... Shi S, Klotz U (Mar 2008). "Clinical use and pharmacological properties of selective COX-2 inhibitors.". European journal of ...
... a COX inhibitor, as well as of other COX-inhibiting nonsteroidal anti-inflammatory drugs (NSAIDs), have been found to slightly ... de Pedro M, Baeza S, Escudero MT, Dierssen-Sotos T, Gómez-Acebo I, Pollán M, Llorca J (2015). "Effect of COX-2 inhibitors and ... Cyclooxygenase-2 (COX-2) overexpression in mammary gland tissue produces mammary gland hyperplasia as well as precocious ... Al-Salihi MA, Ulmer SC, Doan T, Nelson CD, Crotty T, Prescott SM, Stafforini DM, Topham MK (2007). "Cyclooxygenase-2 ...
... an important difference with reversible inhibitors. Furthermore, aspirin, while inhibiting the ability of COX-2 to form pro- ... At least two different types of cyclooxygenases, COX-1 and COX-2, are acted on by aspirin. Aspirin irreversibly inhibits COX-1 ... Warner, T D; Warner TD, Mitchell JA (2002). "Cyclooxygenase-3 (COX-3): filling in the gaps toward a COX continuum?". ... Blockade of COX-1 by aspirin apparently results in the upregulation of COX-2 as part of a gastric defense and that taking COX-2 ...
Among them are serotonin, a neurotransmitter; indometacin, a non-steroidal anti-inflammatory agent; L-761,066, a COX-2 ... inhibitor; and LY311727, an inhibitor of secretory phospholipase. Currently, one of the most interesting applications of the ... Huang, Yun-Sheng; Zhang, W.; Zhang, X.; Wang, J. (2010). "Manufacturing synthesis of 5-hydroxy-2-methyl-1H-indole". Research on ... Nenitzescu, C.D. (1929). "Derivatives of 2-methyl-5-hydroxyindole". Bull. Soc. Chim. Romania. 11: 37-43. Allen, G.; Pidacks, C ...
FitzGerald, Garret (2001). "COX-2 inhibitors and the cardiovascular system". Clin Exp Rheumatol. 19: S31-6. ... 2)-adrenoceptor antagonists". Br J Pharmacol. 164: 317-31. doi:10.1111/j.1476-5381.2011.01269.x. Hughes, J (1975). " ...
It is also known for its release of the first bulk laxative, Metamucil, in 1934; Dramamine, for motion sickness; the COX-2 ... inhibitors Celebrex and Bextra; Ambien for insomnia; and NutraSweet (also known as aspartame), an artificial sweetener, in 1965 ... which Searle developed and which became the first selective COX-2 inhibitor to be approved by the FDA on December 31, 1998. ...
It acts as a COX-2 inhibitor. European Public Assessment Report (EPAR): Trocoxil, European Medicines Agency Cox, S. R.; Lesman ... a long-acting COX-2 inhibitor, in young adult laboratory dogs". Journal of Veterinary Pharmacology and Therapeutics. 33 (5): ...
It acts as a COX-2 inhibitor. Reaction of the imine with TosMIC in the presence of potassium carbonate leads to what may be ... Activity Relationship of a New Series of COX-2 Selective Inhibitors: 1,5-Diarylimidazoles". Journal of Medicinal Chemistry. 46 ... viewed as 2+3 cycloaddition of the nitrogen analogue of a ketene to form the imidazole ring. "European Public Assessment Report ...
Zhang, J J.; Ding, E. L.; Song, Y (2006). "Adverse Effects of Cyclooxygenase-2 Inhibitors on Renal and Arrhythmia Events: Meta- ... It is a selective cyclooxygenase-2 inhibitor. Valdecoxib was manufactured and marketed under the brand name Bextra by G. D. ... FDA Alert on Bextra withdrawal Large systematic review of adverse renal and arrhythmia risk of valdcoxib and other COX-2 ... inhibitors, JAMA 2006. ... On September 2, 2009, the United States Department of Justice ...
Sudbø J, Ristimäki A, Sondresen JE, Kildal W, Boysen M, Koppang HS, Reith A, Risberg B, Nesland JM, Bryne M. Cyclooxygenase-2 ( ... Sudbø J. [Adverse effects of COX-2 inhibitors]. Tidsskr Nor Laegeforen. 2002 Jan 10;122(1):102-3. Sudbø J. [DNA ploidy analysis ... COX-2) expression in high-risk premalignant oral lesions. Oral Oncol. 2003 Jul;39(5):497-505. Retraction: Oral Oncol. 2007 Apr; ... 2006 Nov 2;355(18):1927. Sudbø J, Bryne M, Mao L, Lotan R, Reith A, Kildal W, Davidson B, Søland TM, Lippman SM. Molecular ...
Its structure is different from that of other COX-2 inhibitors, such as celecoxib: lumiracoxib is an analogue of diclofenac ( ... Shi, S; Klotz, U (March 2008). "Clinical use and pharmacological properties of selective COX-2 inhibitors". European Journal of ... Tacconelli S, Capone ML, Patrignani P (2004). "Clinical pharmacology of novel selective COX-2 inhibitors". Curr Pharm Des. 10 ( ... Lumiracoxib (rINN) is a carboxylic acid COX-2 selective inhibitor nonsteroidal anti-inflammatory drug, manufactured by Novartis ...
Yi, John S.; Cox, Maureen A.; Zajac, Allan J. T-cell exhaustion: characteristics, causes and conversion. Immunology. 2010-04, ... U.S. FDA Approved Immune-Checkpoint Inhibitors and Immunotherapies. Medical Writer Agency , 香港醫學作家 , MediPR , MediPaper Hong ... T细胞耗竭的直接原因包括持续的抗原刺激、以及CD4细胞的缺失[42]。长时间的抗原暴露和高病毒负载可以加重T细胞耗竭的程度
阿司匹林對COX-1的抑制似乎啟動了胃的防禦機制,使COX-2活性增強,[76] 若同時服用COX-2抑制劑,則會增加對胃黏膜的侵蝕。[77] 因此,當阿司匹林與任何「天然」的會抑制COX-2的補充劑(如大蒜提取物,薑黃素,越桔,松樹皮,銀杏,魚油,白藜 ... 血栓素
COX-2 inhibitors do not appear to affect platelet function or bleeding time at indicated dosages and may be preferable if risk ... Sharoni, Y. Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha-carotene or beta-carotene ... All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for ... COX-2 inhibitors, other NSAIDs, and cardiovascular risk; the seduction of common sense. JAMA. Riboli, E. Diet and gastric ...
... aspirin and other COX-1 inhibitors) are regularly prescribed to treat inflammatory and pain-related symptoms of rheumatoid ... The two COX isoforms appear to play different roles in neuroinflammation. COX-1 (inhibited only by traditional NSAIDs such as ... COX-1 and COX-2), which catalyze the synthesis of prostaglandins.. ... COX-2, but not COX-1, activity is necessary for the induction of perforant path long-term potentiation and spatial learning in ...
... an inhibitor of prostaglandin synthesis as well as Cox-1 and Cox-2, from Santa Cruz.Overnight delivery usa, Piroxicam - ... feldene 40 mg inyectable salep feldene piroksikam obat apa feldene 20 mg wiki.A 2 discount piroxicam 10mg without a ...
Naproxen 375 mg/1 TABLET may interact with some other drug or may have side effects as it is Cyclooxygenase Inhibitors [MoA], ... Medicine Uses Status - Cyclooxygenase Inhibitors [MoA],Nonsteroidal Anti-inflammatory Compounds [Chemical/Ingredient], ... The action of Naproxen 375 mg/1 TABLET is Cyclooxygenase Inhibitors [MoA],Nonsteroidal Anti-inflammatory Compounds [Chemical/ ... Naproxen & Naproxen uses - Cyclooxygenase Inhibitors [MoA],Nonsteroidal Anti-inflammatory Compounds [Chemical/Ingredient], ...
COX inhibitors have been shown to reduce the occurrence of cancers and pre-cancerous growths. The National Cancer Institute has ... Lau L, Hansford LM, Cheng LS, Hang M, Baruchel S, Kaplan DR, Irwin MS (Mar 2007). "Cyclooxygenase inhibitors modulate the p53/ ... Prostaglandins whose synthesis involves the cyclooxygenase-I enzyme, or COX-1, are responsible for maintenance and protection ... 170-fold more potent in inhibiting COX-1 than COX-2.[32] Studies of meloxicam 7.5 mg per day for 23 days find a level of ...
... Laurel J. Mengle-Gaw and Benjamin D. Schwartz ... Laurel J. Mengle-Gaw and Benjamin D. Schwartz, "Cyclooxygenase-2 inhibitors: promise or peril?," Mediators of Inflammation, vol ...
... inhibitors, both of which can irritate the digestive tract. At times additional drugs are co-prescribed with NSAIDs or COX-2 ... Cox 2 Inhibitor News and Research. RSS Cox-2 Inhibitors are nonsteroidal anti-inflammatory drugs used to relieve pain and ... The cyclooxygenase-2 enzyme is just such a protein, as the concentration of COX-2 is greater in cancer cells than in adjacent ... COX-2 inhibitor extends sunitinib activity in renal cell carcinoma The effectiveness of sunitinib for the treatment of renal ...
Two large pivotal trials have been published, in which the efficacy and safety of the COX 2 inhibitors celecoxib and rofecoxib ... Efficacy and safety of COX 2 inhibitors New data are encouraging but the risk:benefit ratio remains unclear ... with more specific inhibitory effects on cyclo-oxygenase 2 (COX 2) pathways, promised equivalent efficacy with greater safety ... Efficacy and safety of COX 2 inhibitors. BMJ 2002; 325 doi: https://doi.org/10.1136/bmj.325.7365.607 (Published 21 September ...
We also touch on the COX-1/COX-2 selectivity of NSAIDs, the localization of COX enzymes in kidneys, and clinical studies ... Selective cyclooxygenase-2 (COX-2) inhibitors have provided relief for patients suffering from chronic pain and other ... NSAIDs and the kidney revisited: are selective cyclooxygenase-2 inhibitors safe?. Eras J1, Perazella MA. ... Therefore, this article reviews the role of cyclooxygenase enzyme activity and associated prostaglandins in the kidney and the ...
Cox-2 inhibitor definition at Dictionary.com, a free online dictionary with pronunciation, synonyms and translation. Look it up ... cox-2 inhibitor in Medicine Expand. COX-2 inhibitor n. Any of a class of nonsteroidal anti-inflammatory drugs thought to have ...
Two related isoforms of the cyclo-oxygenase (COX) enzyme have been described: COX-1 (PGHS-1) and COX-2 (PGHS-2). COX-1 is ... COX-2 inhibitors and gastroduodenal toxicity: Major clinical trials. Author. Mark Feldman, MD, MACP, AGAF, FACG. Mark Feldman, ... COX-2 inhibitors. Lancet 1999; 353:307.. *Simon LS, Weaver AL, Graham DY, et al. Anti-inflammatory and upper gastrointestinal ... Other COX-2 inhibitors are available in some countries. Parecoxib is a prodrug that is converted to valdecoxib. Etoricoxib and ...
Hypertension and Cyclooxygenase-2 Inhibitors. Target: The Renal Medulla. Chuan-Ming Hao, Matthew D. Breyer ...
... is one type of COX-2 inhibitor used to treat inflammation and back pain. This article includes information about potential side ... See Understanding COX-2 Inhibitor Side Effects. Celebrex is still available, but with strong warnings, as are required for all ... See Safe Use of COX-2 Inhibitors and Other NSAIDs. However, many reports of heart attacks and stroke prompted the FDA to re- ... As a COX-2 inhibitor, celecoxib blocks an inflammation-promoting enzyme called COX-2. Medications known as COX-2 inhibitors ...
Sponsors of other COX-2 inhibitors will also be asked for updated safety data, including details of any studies underway. ... The local pattern of use indicated that users of COX-2 inhibitors were older, had other co-morbidities and were often on ... Prescribers can assist in monitoring the safety of all COX-2 inhibitors by reporting adverse events to the Centre for Adverse ... The Australian Prescriber journal has made available an advance publication of their article on the vascular effects of COX-2 ...
If a COX-2 inhibitor is considered necessary for a patient taking warfarin, the INR should be checked a few days after ... The interaction between COX-2 inhibitors and warfarin has now been included in the list of adverse reactions of current concern ... Reports of COX-2 and warfarin interaction: INR increase, haemorrhage. The New Zealand Centre for Adverse Reactions Monitoring ( ... If the INR increases, it may be possible to continue the selective COX-2 inhibitor by reducing the dose of warfarin.2,3 ...
In order to take advantage of both the COX-dependent and COX-independent benefits of NSAIDs and selective COX-2 inhibitors, ... One or more of these COX-independent effects could contribute to the antiangiogenic properties of NSAIDs and selective COX-2 ... a selective inhibitor of COX-2 was shown to potentiate the beneficial antitumor effects of ionizing radiation with no increase ... Some of the COX-independent mechanisms for NSAIDs and selective COX-2 inhibitors include activation of protein kinase G, ...
Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited, thus ... COX-2 inhibitors. Class Summary. Cyclooxygenase 2 (COX-2) inhibitors have a lower incidence of GI bleeding as compared with ... Primarily inhibits COX-2. COX-2 is considered an inducible isoenzyme, induced by pain and inflammatory stimuli. ... Their mechanism of action is not known, but they may inhibit cyclo-oxygenase activity and prostaglandin synthesis. Other ...
Make research projects and school reports about COX-2 inhibitor easy with credible articles from our FREE, online encyclopedia ... and pictures about COX-2 inhibitor at Encyclopedia.com. ... "COX-2 inhibitor." A Dictionary of Nursing. . Encyclopedia.com. ... COX-2 inhibitor n. an anti-inflammatory drug (see NSAID) that selectively blocks the action of the enzyme cyclo-oxygenase 2 ( ... COX-2 inhibitor A Dictionary of Nursing © A Dictionary of Nursing 2008, originally published by Oxford University Press 2008. ...
"By inhibiting COX-2 in human patients, we may have an option to delay the progression of lesions," said lead author Guido Eibl ... COX-2, an enzyme which causes inflammation, is no stranger to cancer researchers. Studies of breast, colon, and pancreatic ... COX-2 inhibitors delay pancreatic cancer precursors in mice. 03.08.2007. Nimesulide, a cyclooxygenase-2 (COX-2) inhibitor, ... To study the effects of COX-2 on PanIN progression, Dr. Eibl and colleagues focused on the KrasG12D mouse, an animal model that ...
... has a pretty funny take on the whole COX-2 inhibitor thing. Like this quote: A couple peoples hearts explode, and everyone ... The Onion, a satiric Web site, has a pretty funny take on the whole COX-2 inhibitor thing. Like this quote:. "A couple peoples ... The Onion on COX-2 inhibitors. Sue Pelletier 2 , Feb 22, 2005 ... Webinar] Meetings Master Classes 2019 Session 2: Getting to ...
... a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). Both prednisone and celecoxib decreased ... In contrast, nonspecific COX inhibitors showed a tendency towards a decreased rate of proteoglycan synthesis [18]. The in vitro ... There are two isoforms of the COX enzyme: COX-1, found in most tissues and constitutively expressed in normal cells, and COX-2 ... Nonspecific COX inhibitors did not demonstrate these findings but instead showed a tendency towards a lower synthesis rate of ...
Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti- ... Of 88,867 controls, 33% had been prescribed an NSAID and 6% had been prescribed a COX-2 inhibitor. Increased risks of adverse ... There is no evidence to back up claims that the new generation of anti-inflammatory drugs (COX-2 inhibitors) are less harmful ... These results suggest that COX-2 inhibitors may not be as safe as originally thought, although a possible confounding effect ...
Hydroxymethylglutaryl-CoA Reductase Inhibitors. Enzyme Inhibitors. Cyclooxygenase 2 Inhibitors. Cyclooxygenase Inhibitors. Anti ... Cyclo-oxygenase-2 (COX-2) is a key enzyme in the production of prostaglandins (PG), and evidence suggests that COX-2 plays an ... Statins and Selective Cyclooxygenase-2 Receptor Inhibitors in Blunt Chest Trauma. The recruitment status of this study is ... Aims: The current study aims at evaluating the beneficial effects of statins and COX-2 receptor inhibitors on ALI elicited by ...
... new findings suggest that COX-2 inhibitors may be beneficial for the prevention of renal damage in obesity-related Type II ... Protein expression of COX-1 and COX-2 in the kidney cortex, renal microvessels and glomeruli was studied. The levels of 6-keto ... Prostaglandins and thromboxane are formed by the enzymatic oxidation of arachidonic acid catalyzed by the cyclooxygenases, COX ... COX-2 regulation and its association with renal damage are not known in the Obese Zucker rat. A new study tests the hypothesis ...
Are selective COX 2 inhibitors superior to traditional non steroidal anti-inflammatory drugs? Adequate analysis of the CLASS ... Selective cyclo-oxygenase 2 (COX 2) inhibitors, including celecoxib (Celebrex) and rofecoxib (Vioxx), are hypothesised to have ... Are selective COX 2 inhibitors superior to traditional non steroidal anti-inflammatory drugs? ... Are selective COX 2 inhibitors superior to traditional non steroidal anti-inflammatory drugs? ...
  • Addition of PD98059, a MEK-1 inhibitor, suppressed ERK activation and significantly reversed these signaling events and apoptosis suggesting involvement of ERK in mediating these events. (aacrjournals.org)
  • In vivo apoptosis correlated with significant decrease in activation of protein kinase B/Akt, a cell survival signaling kinase, with increased expression of the proapoptotic protein Bax and decreased expression of the antiapoptotic protein Bcl-2. (aacrjournals.org)
  • Overexpression of COX-2 protein and PGE 2 during carcinogenesis is implicated in proliferation, invasion, apoptosis, immune suppression, and angiogenesis. (aacrjournals.org)
  • We found that a specific cyclooxygenase-2 (COX-2) inhibitor SC-236 similarly induced apoptosis in gastric cancer cells. (oup.com)
  • The re-emergence, in the recent years, of cyclooxygenase as a biological target in therapeutic areas other than inflammation is likely to require new optimized leads, particularly suited for the requirements of specific drug development programs. (eurekaselect.com)
  • These results suggest that selective cyclooxygenase-2 inhibitors may be a valuable therapeutic strategy for ischemic brain injury. (cogprints.org)
  • Cyclooxygenase-2 (COX-2) inhibitors are rapidly emerging as a new generation of therapeutic drug in combination with chemotherapy or radiation therapy for the treatment of cancer. (aacrjournals.org)
  • A dermally deliverable pharmaceutical composition comprises at least one selective cyclooxygenase-2 (COX-2) inhibitory drug or prodrug thereof solubilized in a pharmaceutically acceptable carrier that comprises a low molecular weight monohydric alcohol, and exhibits a skin permeation rate of the therapeutic agent at least equal to that exhibited by a reference solution of the therapeutic agent in 70% aqueous ethanol. (justia.com)
  • The present invention relates to pharmaceutical compositions containing a selective cyclooxygenase-2 (COX-2) inhibitory drug, in particular to such compositions that are suitable for administration to skin to provide a local or systemic therapeutic effect. (justia.com)
  • The therapeutic use of conventional COX inhibitors are limited due to drug associated side effects, including life threatening ulceration and renal toxicity. (google.com)
  • COX-2 inhibitors are used in the treatment of arthritis and acute gout. (encyclopedia.com)
  • Although some studies have reported mixed results with regard to the cardiovascular risk, 2-4 several recently published randomized trials and population-based studies have established an increased risk of acute myocardial infarction (MI) and thromboembolic events related to the use of most COX-2 inhibitors. (ahajournals.org)
  • The δ and κ opioid receptors are involved in the activity of COX-2 inhibitor on the facilitated state as well as acute pain at the spinal level, whereas the µ opioid receptor is related only to facilitated pain. (pubmedcentralcanada.ca)
  • Thus, µ, δ and κ opioid receptor antagonists were intrathecally administered to investigate the ability of opioid receptor subtype antagonists to reverse the antinociception induced by COX-2 inhibitor in the formalin test which shows an early phase of acute nociceptive response followed by a late phase response being related to more complex inflammatory reactions. (pubmedcentralcanada.ca)
  • Efficacy Assessment of Meloxicam, a Preferential Cyclooxygenase-2 Inhibitor, in Acute Coronary Syndromes Without ST-Segment Elevation. (acc.org)
  • Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis. (semanticscholar.org)
  • Accumulating evidence indicates the essential contribution of cyclooxygenase (COX)-2 and 5-lipoxygenase (5-LOX) to acute pancreatitis. (semanticscholar.org)
  • We studied the effects of flavocoxid, a plant-derived dual inhibitor of COX-2 and 5-LOX, in a model of caerulein (CER)-induced acute pancreatitis. (semanticscholar.org)
  • In addition, chamomile caused reduction in LPS-induced COX-2 mRNA and protein expression, without affecting COX-1 expression. (herbs.org)
  • In addition, COX-2 mRNA, matrix metalloproteinase (MMP)-9 mRNA, and tissue inhibitor of MMP (TIMP)-1 mRNA of cancer tissue were measured by means of real-time RT-PCR. (spandidos-publications.com)
  • Expression of COX-2 mRNA and MMP-9 mRNA correlated significantly (r=0.78, p=0.001), but there was no correlation between either COX-2 mRNA and TIMP-1 mRNA expression or between MMP-9 mRNA and TIMP-1 mRNA expression. (spandidos-publications.com)
  • J. Koistinaho, S. Koponen, P.H. Chan, Expression of cyclooxygenase-2 mRNA after global ischemia is regulated by AMPA receptors and glucocorticoids, Stroke 30 (1999) 1900-1906. (cogprints.org)
  • Renal cortex mRNA was isolated for determination of COX-2, eNOS, and CRP mRNA by real-time reverse-transcriptase polymerase chain reaction. (uzh.ch)
  • SP600125 did not downregulate IL-1-induced COX-2 mRNA expression when measured 2 h after addition of IL-1β but suppressed mRNA levels in the later time points suggesting post-transcriptional regulation. (uta.fi)
  • The treated foals showed a dramatic fold reduction in COX-2, TNF-ά (tumor necrosis factor), ILs-1β, -8, and -6 (interleukins, protein mediators between white blood cells) mRNA (messenger RNA), compared to the untreated controls. (noniresearch.org)
  • Also, the senescence associated increase of plasminogen activator inhibitor one mRNA amounts was not universaly noticed, getting selectively connected only with replicative senescence in both parental and bystander senescent cells. (cox2-inhibitors.com)
  • The regulator's remarks come close on the heels of comments by a U.S. advisory panel on Friday that Merck & Co Inc.'s withdrawn COX-2 inhibitor arthritis drug, Vioxx, was safe enough to rejoin Pfizer's rival pain relievers, Celebrex and Bextra, on the U.S. market. (laleva.org)
  • The cox-2 class is generally aimed at treating chronic pain of arthritis and other conditions. (cureresearch.com)
  • In rheumatoid arthritis, COX-2 inhibitors are not disease-modifying drugs. (thefreedictionary.com)
  • Do COX-2 inhibitors provide additional pain relief and anti-inflammatory effects in patients with rheumatoid arthritis who are on biological disease-modifying anti-rheumatic drugs and/or corticosteroids? (biomedcentral.com)
  • Although they provided great pain relief to millions of people who suffered from rheumatoid arthritis, menstrual cramps, and sports injuries, COX-2 inhibitors also had a number of side effects, including nausea, diarrhea, flatulence, abdominal pain, headache and insomnia. (legalinfo.com)
  • See 'COX-2 selective inhibitors: Adverse cardiovascular effects' . (uptodate.com)
  • In New Zealand, the Medicines Adverse Reactions Committee (MARC) had previously reviewed all significant data but found that the evidence for an association between any of the COX-2 inhibitors and increased cardiovascular events was inconclusive. (medsafe.govt.nz)
  • Medsafe and MARC have also monitored and reviewed published literature on adverse events in general with the COX-2 inhibitors. (medsafe.govt.nz)
  • Published data on cardiovascular events for all the COX-2 inhibitors, along with New Zealand case reports of adverse reactions and any other available unpublished data, will be reviewed by the MARC. (medsafe.govt.nz)
  • Prescribers can assist in monitoring the safety of all COX-2 inhibitors by reporting adverse events to the Centre for Adverse Reactions Monitoring (CARM) in Dunedin. (medsafe.govt.nz)
  • The interaction between COX-2 inhibitors and warfarin has now been included in the list of adverse reactions of current concern in order to encourage reporting of these adverse events and to gather more data about them. (medsafe.govt.nz)
  • Patients receiving celecoxib were more likely to report dyspepsia symptoms during treatment, though other adverse events were similar between the 2 groups. (thefreelibrary.com)
  • These agents may not be as durable as other drug classes in improving pulmonary hypertension, but the adverse-effect profile of phosphodiesterase inhibitors is often more favorable than prostaglandin or anti-endothelin therapies. (medscape.com)
  • Celebrex is the only COX-2 inhibitor that is still on the market in the U.S. since the others were pulled as a result of cardiovascular and other potential adverse reactions. (newsinferno.com)
  • According to Dr. Fendrick: 'The fact that cox-2 inhibitor drug users had higher rates of adverse GI events than nonusers comes as no surprise to me, Even a drug that might be safer than other alternatives doesn't mean that the drug is completely safe. (newsinferno.com)
  • COX-2 inhibitors also have been shown to cause adverse cardiovascular effects when administered at high doses over long durations. (bio-medicine.org)
  • Of course, if this is so, all of the hype and expense associated with the COX-2s was for naught and the only ones that benefited from the drugs were (and are) Merck and Pfizer, which have made tens of billions of dollars in profits from Vioxx, Celebrex, and Bextra. (newsinferno.com)
  • The German regulator said that COX-2 inhibitors-- the general category to which Arcoxia, Vioxx, Celebrex and Bextra belong -- should be taken only in the smallest possible effective dose and only as long as absolutely needed. (laleva.org)
  • 1 - 3 The introduction of new anti-inflammatory agents, with more specific inhibitory effects on cyclo-oxygenase 2 (COX 2) pathways, promised equivalent efficacy with greater safety and tolerability. (bmj.com)
  • In conjunction with the recent development of next generation, highly selective COX-2 inhibitors, they can be expected to lead to even greater efficacy of their use as adjuncts to various anticancer agents for the treatment of high-risk patients without compromising their quality of life. (aacrjournals.org)
  • These observations have led to the hypothesis that COX-2 expression mediates the enhanced prostanoid release, which characterizes the inflammatory response ( 21 ). (pnas.org)
  • However, while Cox-2 is associated with inflammation and pain , Cox-1 maintains the integrity of the gastric mucosa, mediates normal platelet function, and regulates renal blood flow. (thefreedictionary.com)
  • Some of these analogs retained COX-2 inhibitory activity, whereas many others didn't. (wikipedia.org)
  • Despite a failure to suppress TxA 2 -dependant platelet aggregation, celecoxib had a modest but significant inhibitory effect on serum TxB 2 4 hr after dosing. (pnas.org)
  • Of note, the simultaneous addition of SC-236 and CJ-13,610 resulted in a higher inhibitory profile on PGE2 biosynthesis than the dual COX/5-LO inhibitor licofelone. (sigmaaldrich.com)
  • PD98059 (an inhibitor of Erk1/2 pathway) suppressed IL-1-induced COX-2 expression and PGE2 production in a dose-dependent manner, and seemed to have an inhibitory effect on COX-2 activity. (uta.fi)
  • A method of effecting targeted delivery of a selective COX-2 inhibitory drug to a site of pain and/or inflammation in a subject comprises topically administering such a composition to skin of the subject, preferably at a locus overlying or adjacent to the site of pain and/or inflammation. (justia.com)
  • Selective COX-2 inhibitory drugs have therefore represented a major advance in the art. (justia.com)
  • Numerous compounds have been reported having therapeutically and/or prophylactically useful selective COX-2 inhibitory effect, and have been disclosed as having utility in treatment or prevention of specific COX-2 mediated disorders or of such disorders in general. (justia.com)
  • Other compounds reported to have therapeutically and/or prophylactically useful selective COX-2 inhibitory effect are substituted isoxazolyl benzenesulfonamides as reported in U.S. Pat. (justia.com)
  • In recent years, several additional intracellular components (besides COX-2) were discovered that appear to be important for mediating the anticancer effects of celecoxib in the absence of COX-2. (wikipedia.org)
  • Additional support for the idea that other targets besides COX-2 are important for celecoxib's anticancer effects has come from studies with chemically modified versions of celecoxib. (wikipedia.org)
  • To study the effects of COX-2 on PanIN progression, Dr. Eibl and colleagues focused on the KrasG12D mouse, an animal model that mimics the early stages of pancreatic cancer. (innovations-report.com)
  • Aims: The current study aims at evaluating the beneficial effects of statins and COX-2 receptor inhibitors on ALI elicited by blunt trauma to the chest. (clinicaltrials.gov)
  • Singh and colleagues point out that since these arrhythmia effects bypass COX-2, it is unclear if other COX-2 inhibitors would yield similar results. (newsinferno.com)
  • They also stress it is too early to speculate on human effects, although their results suggest Drosophilaâ€"one of the most valuable of organisms in biological research and has been used as a model research organism for almost a centuryâ€"are a valuable tool to investigate other COX-2 drugs. (newsinferno.com)
  • Cyclooxygenase-2 (COX-2) inhibitors and calcium influx inhibitors are agents which have previously shown to have cytostatic effects against tumor cells. (aacrjournals.org)
  • Pre-treatment with naltrexone diminished the analgesic effects of a COX-2 inhibitor, and its antinociception was abolished in rats made tolerant to the analgesic effects of morphine [ 4 ]. (pubmedcentralcanada.ca)
  • In the present study we investigated the effects of the inhibitors of mitogen-activated protein kinase (MAPK) pathways Erk1/2, p38, and JNK on COX-2 expression and prostaglandin E2 (PGE2) production in human chondrocytes. (uta.fi)
  • (1) in this issue of the Journal adds to the concerns surrounding the cardiovascular effects of cyclooxygenase (COX)-2 inhibitors. (onlinejacc.org)
  • Consequently, the effects of a COX inhibitor, acting high in this pathway, are likely to be complex. (onlinejacc.org)
  • There has been so much published about side effects of Cox-2 inhibitors that it is hard to keep up with the evolving story. (pmean.com)
  • Meta-analysis of Cyclooxygenase-2 Inhibitors and Their Effects on Blood Pressure. (pmean.com)
  • Tramadol is structurally closer to venlafaxine than to codeine and delivers analgesia by not only delivering "opioid-like" effects (through mild agonism of the mu receptor ) but also by acting as a weak but fast-acting serotonin releasing agent and norepinephrine reuptake inhibitor . (wikipedia.org)
  • If you have taken one of these COX-2 inhibitors and have suffered ill effects as a result, it may behoove you to contact an attorney in your area who specializing in pharmaceutical lawsuits. (legalinfo.com)
  • Cells tend to express a predominant isomerase (prostacyclin synthase, thromboxane synthase, PGE synthase, PGD synthase) closely coupled with COX, which largely determines which product is generated. (onlinejacc.org)
  • In this Letter, we provide the structure-activity relationships, optimization of design, testing criteria, and human half-life data for a series of selective COX-2 inhibitors. (rcsb.org)
  • Separate administration of 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC-236), a selective COX-2 inhibitor, and CJ-13,610, a 5-LO inhibitor, to carbon tetrachloride-treated mice significantly reduced fibrosis as revealed by the analysis of Sirius Red-stained liver sections without affecting necroinflammation. (sigmaaldrich.com)
  • Hematological profile of untreated or ionizing radiation-exposed cyclooxygenase-2-deficient mice. (semanticscholar.org)