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)
A class of cell surface leukotriene receptors with a preference for leukotriene B4. Leukotriene B4 receptor activation influences chemotaxis, chemokinesis, adherence, enzyme release, oxidative bursts, and degranulation in polymorphonuclear leukocytes. There are at least two subtypes of these receptors. Some actions are mediated through the inositol phosphate and diacylglycerol second messenger systems.
(2S-(2 alpha,3 beta(1E,3E,5Z,8Z)))-3-(1,3,5,8-Tetradecatetraenyl)oxiranebutanoic acid. An unstable allylic epoxide, formed from the immediate precursor 5-HPETE via the stereospecific removal of a proton at C-10 and dehydration. Its biological actions are determined primarily by its metabolites, i.e., LEUKOTRIENE B4 and cysteinyl-leukotrienes. Alternatively, leukotriene A4 is converted into LEUKOTRIENE C4 by glutathione-S-transferase or into 5,6-di-HETE by the epoxide-hydrolase. (From Dictionary of Prostaglandins and Related Compounds, 1990)
Cell-surface receptors that bind LEUKOTRIENES with high affinity and trigger intracellular changes influencing the behavior of cells. The leukotriene receptor subtypes have been tentatively named according to their affinities for the endogenous leukotrienes LTB4; LTC4; LTD4; and LTE4.
A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.
The conjugation product of LEUKOTRIENE A4 and glutathione. It is the major arachidonic acid metabolite in macrophages and human mast cells as well as in antigen-sensitized lung tissue. It stimulates mucus secretion in the lung, and produces contractions of nonvascular and some VASCULAR SMOOTH MUSCLE. (From Dictionary of Prostaglandins and Related Compounds, 1990)
A biologically active principle of SRS-A that is formed from LEUKOTRIENE D4 via a peptidase reaction that removes the glycine residue. The biological actions of LTE4 are similar to LTC4 and LTD4. (From Dictionary of Prostaglandins and Related Compounds, 1990)
One of the biologically active principles of SRS-A. It is generated from LEUKOTRIENE C4 after partial hydrolysis of the peptide chain, i.e., cleavage of the gamma-glutamyl portion. Its biological actions include stimulation of vascular and nonvascular smooth muscle, and increases in vascular permeability. (From Dictionary of Prostaglandins and Related Compounds, 1990)
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.
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)
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.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
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.
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.
Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively.
Scaffolding proteins that play an important role in the localization and activation of 5-LIPOXYGENASE.
A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated.
Arachidonic acids are polyunsaturated fatty acids, specifically a type of omega-6 fatty acid, that are essential for human nutrition and play crucial roles in various biological processes, including inflammation, immunity, and cell signaling. They serve as precursors to eicosanoids, which are hormone-like substances that mediate a wide range of physiological responses.
(5Z)-(15S)-11 alpha-Hydroxy-9,15-dioxoprostanoate:NAD(P)+ delta(13)-oxidoreductase. An enzyme active in prostaglandin E and F catabolism. It catalyzes the reduction of the double bond at the 13-14 position of the 15-ketoprostaglandins and uses NADPH as cofactor. EC 1.3.1.48.
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).
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.
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.
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.
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.- .
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.
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.
The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.
Zymosan is a polysaccharide derived from the cell walls of Saccharomyces cerevisiae, commonly used in research as an immunostimulant to induce inflammation and study phagocytosis, complement activation, and oxidative burst in neutrophils and macrophages.
A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights.
Chemical substances that attract or repel cells. The concept denotes especially those factors released as a result of tissue injury, microbial invasion, or immunologic activity, that attract LEUKOCYTES; MACROPHAGES; or other cells to the site of infection or insult.
Quinolines are heterocyclic aromatic organic compounds consisting of a two-nitrogened benzene ring fused to a pyridine ring, which have been synthesized and used as building blocks for various medicinal drugs, particularly antibiotics and antimalarials.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
Phenylpropionates are a class of organic compounds, including certain drugs such as ephedrine and pseudoephedrine, which contain a phenylethanoic acid structure with a propionate substitution.
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.
Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin.
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.
Usually high-molecular-weight, straight-chain primary alcohols, but can also range from as few as 4 carbons, derived from natural fats and oils, including lauryl, stearyl, oleyl, and linoleyl alcohols. They are used in pharmaceuticals, cosmetics, detergents, plastics, and lube oils and in textile manufacture. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
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)
The minor fragment formed when C5 convertase cleaves C5 into C5a and COMPLEMENT C5B. C5a is a 74-amino-acid glycopeptide with a carboxy-terminal ARGININE that is crucial for its spasmogenic activity. Of all the complement-derived anaphylatoxins, C5a is the most potent in mediating immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE), smooth MUSCLE CONTRACTION; HISTAMINE RELEASE; and migration of LEUKOCYTES to site of INFLAMMATION.
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).
Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic.
INFLAMMATION of PLEURA, the lining of the LUNG. When PARIETAL PLEURA is involved, there is pleuritic CHEST PAIN.
20-carbon saturated monocarboxylic acids.
Compounds with a core of fused benzo-pyran rings.
Important polyunsaturated fatty acid found in fish oils. It serves as the precursor for the prostaglandin-3 and thromboxane-3 families. A diet rich in eicosapentaenoic acid lowers serum lipid concentration, reduces incidence of cardiovascular disorders, prevents platelet aggregation, and inhibits arachidonic acid conversion into the thromboxane-2 and prostaglandin-2 families.
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.
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.
A derivative of complement C5a, generated when the carboxy-terminal ARGININE is removed by CARBOXYPEPTIDASE B present in normal human serum. C5a des-Arg shows complete loss of spasmogenic activity though it retains some chemotactic ability (CHEMOATTRACTANTS).
Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
Phospholipases that hydrolyze one of the acyl groups of phosphoglycerides or glycerophosphatidates.
Effective in the initiation of protein synthesis. The initiating methionine residue enters the ribosome as N-formylmethionyl tRNA. This process occurs in Escherichia coli and other bacteria as well as in the mitochondria of eucaryotic cells.
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.
The rate dynamics in chemical or physical systems.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).
C5 plays a central role in both the classical and the alternative pathway of COMPLEMENT ACTIVATION. C5 is cleaved by C5 CONVERTASE into COMPLEMENT C5A and COMPLEMENT C5B. The smaller fragment C5a is an ANAPHYLATOXIN and mediator of inflammatory process. The major fragment C5b binds to the membrane initiating the spontaneous assembly of the late complement components, C5-C9, into the MEMBRANE ATTACK COMPLEX.
Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR.
A family of G-protein-coupled receptors that was originally identified by its ability to bind N-formyl peptides such as N-FORMYLMETHIONINE LEUCYL-PHENYLALANINE. Since N-formyl peptides are found in MITOCHONDRIA and BACTERIA, this class of receptors is believed to play a role in mediating cellular responses to cellular damage and bacterial invasion. However, non-formylated peptide ligands have also been found for this receptor class.
Phospholipases that hydrolyze the acyl group attached to the 2-position of PHOSPHOGLYCERIDES.
Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes.
The forcing into the skin of liquid medication, nutrient, or other fluid through a hollow needle, piercing the top skin layer.
Drugs that are used to treat asthma.
The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions.
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.
The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cell-surface receptors on the neutrophil.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
Cytotaxins liberated from normal or invading cells that specifically attract eosinophils; they may be complement fragments, lymphokines, neutrophil products, histamine or other; the best known is the tetrapeptide ECF-A, released mainly by mast cells.
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.
FATTY ACIDS in which the carbon chain contains one or more double or triple carbon-carbon bonds.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.
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.
The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects.
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.
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.
Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes.
Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.
Cell surface proteins that bind eicosanoids with high affinity and trigger intracellular changes influencing the behavior of cells. Among the eicosanoid receptors are receptors for the prostaglandins, thromboxanes, and leukotrienes.
(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.
An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.
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.
The movement of cells or organisms toward or away from a substance in response to its concentration gradient.
Cell surface proteins that bind LIPOXINS with high affinity and trigger intracellular changes influencing the behavior of cells.
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.
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).
The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).
Exudates are fluids, CELLS, or other cellular substances that are slowly discharged from BLOOD VESSELS usually from inflamed tissues. Transudates are fluids that pass through a membrane or squeeze through tissue or into the EXTRACELLULAR SPACE of TISSUES. Transudates are thin and watery and contain few cells or PROTEINS.
A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.
Round, granular, mononuclear phagocytes found in the alveoli of the lungs. They ingest small inhaled particles resulting in degradation and presentation of the antigen to immunocompetent cells.
The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type.

Dietary effect of EPA-rich and DHA-rich fish oils on the immune function of Sprague-Dawley rats. (1/1250)

The dietary effect of fish oils (FOs) rich in eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on the immune function of Sprague-Dawley rats was compared with that of safflower oil. After 3 weeks of feeding at the 10% level of a dietary fat, the IgG and IgM production by splenocytes and IgG production by mesenteric lymph node (MLN) lymphocytes were significantly higher in the FO-fed rats, while no significant difference was found in IgA or IgE productivity by both the spleen and MLN lymphocytes. In the FO-fed rats, peritoneal exudate cells released a lower amount of LTB4, reflecting their lower arachidonic acid level, and a higher amount of LTB5, reflecting their higher EPA level in phospholipids. On these EPA-rich FO exerted a stronger effect than DHA-rich FO immune functions.  (+info)

Leukotriene binding, signaling, and analysis of HIV coreceptor function in mouse and human leukotriene B4 receptor-transfected cells. (2/1250)

The mouse leukotriene B4 receptor (m-BLTR) gene was cloned. Membrane fractions of human embryonic kidney 293 cells stably expressing m-BLTR demonstrated a high affinity and specific binding for leukotriene B4 (LTB4, Kd = 0.24 +/- 0.03 nM). In competition binding experiments, LTB4 was the most potent competitor (Ki = 0.23 +/- 0.05 nM) followed by 20-hydroxy-LTB4 (Ki = 1.1 +/- 0.2 nM) and by 6-trans-12-epi-LTB4 and LTD4 (Ki > 1 microM). In stably transfected Chinese hamster ovary cells, LTB4 inhibited forskolin-activated cAMP production and induced an increase of intracellular calcium, suggesting that this receptor is coupled to Gi- and Go-like proteins. In Xenopus laevis melanophores transiently expressing m-BLTR, LTB4 induced the aggregation of pigment granules, confirming the inhibition of cAMP production induced by LTB4. BLT receptors share significant sequence homology with chemokine receptors (CCR5 and CXCR4) that act as human immunodeficiency virus (HIV) coreceptors. However, among the 16 HIV/SIV strains tested, the human BLT receptor did not act as a coreceptor for virus entry into CD4-expressing cells based on infection and cell-cell fusion assays. In 5-lipoxygenase-deficient mice, the absence of leukotriene B4 biosynthesis did not detectably alter m-BLT receptor binding in membranes obtained from glycogen-elicited neutrophils. Isolation of the m-BLTR gene will form the basis of future experiments to elucidate the selective role of LTB4, as opposed to cysteinyl-leukotrienes, in murine models of inflammation.  (+info)

Differential regulation of beta1 integrins by chemoattractants regulates neutrophil migration through fibrin. (3/1250)

Chemoattractants differ in their capacity to stimulate neutrophils to adhere to and to migrate through matrices containing fibrin. Formyl methionyl leucyl phenylalanine (fMLP) stimulates neutrophils to adhere closely to, but not to migrate into, fibrin gels. Leukotriene B4 (LTB4) stimulates neutrophils to adhere loosely to and to migrate through fibrin gels. We report that alpha5beta1 integrins regulate the different migratory behaviors on fibrin gels of neutrophils in response to these chemoattractants. fMLP, but not LTB4, activated neutrophil beta1 integrins, as measured by binding of mAb 15/7 to an activation epitope on the beta1 integrins. Antibodies or peptides that block alpha5beta1 integrins prevented fMLP-stimulated neutrophils from forming zones of close apposition on fibrin and reversed fMLP's inhibitory effect on neutrophil chemotaxis through fibrin. In contrast, neither peptides nor antibodies that block beta1 integrins affected the capacity of LTB4-stimulated neutrophils to form zones of loose apposition or to migrate through fibrin gels. These results suggest that chemoattractants generate at least two different messages that direct neutrophils, and perhaps other leukocytes, to accumulate at specific anatomic sites: a general message that induces neutrophils to crawl and a specific message that prepares neutrophils to stop when they contact appropriate matrix proteins for activated beta1 integrins.  (+info)

Effects of petrosaspongiolide M, a novel phospholipase A2 inhibitor, on acute and chronic inflammation. (4/1250)

The marine product petrosaspongiolide M is a novel inhibitor of phospholipase A2 (PLA2), showing selectivity for secretory PLA2 versus cytosolic PLA2, with a potency on the human synovial enzyme (group II) similar to that of manoalide. This compound was more potent than manoalide on bee venom PLA2 (group III) and had no effect on group I enzymes (Naja naja and porcine pancreatic PLA2). Inhibition of PLA2 was also observed in vivo in the zymosan-injected rat air pouch, on the secretory enzyme accumulated in the pouch exudate. Petrosaspongiolide M decreased carrageenan paw edema in mice after the oral administration of 5, 10, or 20 mg/kg. This marine metabolite (0.01-1.0 micromol/pouch) induced a dose-dependent reduction in the levels of prostaglandin (PG)E2, leukotriene B4, and tumor necrosis factor-alpha in the mouse air pouch injected with zymosan 4 h after the stimulus. It also had a weaker effect on cell migration. The inflammatory response of adjuvant arthritis was reduced by petrosaspongiolide M, which also inhibited leukotriene B4 levels in serum and PGE2 levels in paw homogenates. In contrast with indomethacin, this marine compound did not reduce PGE2 levels in stomach homogenates. Petrosaspongiolide M is a new inhibitor of secretory PLA2 in vitro and in vivo, with anti-inflammatory properties in acute and chronic inflammation.  (+info)

The effects of phosphodiesterase type 4 inhibitors on tumour necrosis factor-alpha and leukotriene B4 in a novel human whole blood assay. (5/1250)

1. The aim of this study was to assess the inhibitory activities of phosphodiesterase type 4 (PDE4) inhibitors on tumour necrosis factor-alpha (TNF-alpha) and leukotriene B4 (LTB4) production in a novel human whole blood assay. 2. Lipopolysaccharide (LPS) stimulation of human whole blood caused a time dependent increase in TNF-alpha and prostaglandin E2 (PGE2) plasma levels. Inhibition of LPS-induced TNF-alpha by the selective PDE4 inhibitor RP73401 was proportionally enhanced with endogenous PGE2 (maximal after 24 h). In contrast, blocking endogenous PGE2 production with indomethacin in blood stimulated with LPS for 24 h decreased the potency of RP73401 to that observed with a 4 h LPS incubation. 3. Non-selective and selective PDE4 inhibitors showed greater inhibition of LPS-induced TNF-alpha after 24 h compared to 4 h. Stereoselectivity was only achieved in the 24 h method. 4. LPS-stimulation of whole blood for either 30 min or 24 h followed by N-formyl-Met-Leu-Phe (fMLP) activation resulted in low plasma LTB4 levels. Combination of both treatments resulted in a greater than 7 fold increase in plasma LTB4 levels. Inhibition of the double LPS and fMLP-activated LTB4 production was observed with non-selective and PDE4-selective inhibitors. Their LTB4 inhibitory potencies were similar to that observed in the 24 h LPS-induced TNF-alpha assay. Thus, stimulation of human whole blood with two LPS stimulations followed by fMLP gives rise to both TNF-alpha and LTB4 and their inhibition by various compounds can be assessed in the same blood sample. 5. Calcium ionophore (A23187) stimulation of whole blood resulted in plasma LTB4 levels similar to the double LPS and fMLP method. Inhibition of A23187-induced LTB4 biosynthesis was also achieved by PDE4-selective inhibitors as well as the direct 5-lipoxygenase (5-LO) inhibitor L-739,010. 6. These results confirm the anti-inflammatory properties of PDE4 inhibitors. Thus, this novel human whole blood can be used to assess the biochemical efficacy of PDE4 inhibitors in human subjects.  (+info)

Aminopeptidase B is structurally related to leukotriene-A4 hydrolase but is not a bifunctional enzyme with epoxide hydrolase activity. (6/1250)

Aminopeptidase B (Ap B; EC 3.4.11.6) is a zinc-binding protein that contains the consensus sequence HEXXHX18E (324-347), conserved among the M1 family of metallopeptidases. To determine if these putative zinc-binding residues (His324, His328 and Glu347) and the active-site Glu325 are essential for the enzyme activity, we replaced the histidines with tyrosines and the glutamic acid residues with alanines using site-directed mutagenesis. The cDNAs were expressed in Escherichia coli, and the resulting recombinant proteins, named H324Y, E325A, H328Y and E347A, were purified to apparent homogeneity. None of the expressed mutated proteins showed aminopeptidase activity. The E325A enzyme contained 1 mol of zinc per mol of protein, and the other three mutants, H324Y, H328Y and E347A, did not contain significant amounts of zinc, as determined by atomic absorption spectrometry. From sequence-homology searches, Ap B is known to be closely related to leukotriene (LT)-A4 hydrolase (EC 3.3.2.6). We examined human placental Ap B and recombinant rat Ap B, both of which had been purified previously [Fukasawa, Fukasawa, Kanai, Fujii and Harada (1996) J. Biol. Chem. 271, 30731-30735], to determine whether or not they had epoxide hydrolase activities. However, neither enzyme hydrolysed LTA4 into LTB4. We then replaced some amino acids in the domain of the rat enzyme similar to the LTA4-binding site of LTA4 hydrolase. However, these mutants, Y408F, N409S and NE409-410SS also did not possess any epoxide hydrolase activity. We concluded that Ap B is an M1-family zinc metallopeptidase without epoxide hydrolase activity.  (+info)

Polyisoprenyl phosphate (PIPP) signaling regulates phospholipase D activity: a 'stop' signaling switch for aspirin-triggered lipoxin A4. (7/1250)

It is of wide interest to understand how opposing extracellular signals (positive or negative) are translated into intracellular signaling events. Receptor-ligand interactions initiate the generation of bioactive lipids by human neutrophils (PMN), which serve as signals to orchestrate cellular responses important in host defense and inflammation. We recently identified a novel polyisoprenyl phosphate (PIPP) signaling pathway and found that one of its components, presqualene diphosphate (PSDP), is a potent negative intracellular signal in PMN that regulates superoxide anion generation by several stimuli, including phosphatidic acid. We determined intracellular PIPP signaling by autocoids with opposing actions on PMN: leukotriene B4 (LTB4), a potent chemoattractant, and lipoxin A4 (LXA4), a 'stop signal' for recruitment. LTB4 receptor activation initiated a rapid decrease in PSDP levels concurrent with activation of PLD and cellular responses. In sharp contrast, activation of the LXA4 receptor reversed LTB4-initiated PSDP remodeling, leading to an accumulation of PSDP and potent inhibition of both PLD and superoxide anion generation. Thus, an inverse relationship was established for PSDP levels and PLD activity with two PMN ligands that evoke opposing responses. In addition, PSDP directly inhibited both isolated human recombinant (Ki = 6 nM) and plant (Ki = 20 nM) PLD. Together, these findings link PIPP remodeling to intracellular regulation of PMN function and suggest a role for PIPPs as lipid repressors in signal transduction, a novel mechanism that may also explain aspirin's suppressive actions in vivo in cell signaling.  (+info)

Fish macrophages express a cyclo-oxygenase-2 homologue after activation. (8/1250)

In mammals, the increased generation of prostaglandins (PG) during the onset of inflammatory responses and activation of immune cell types has been attributed to the induction of a novel cyclo-oxygenase (COX) isoform, termed COX-2, which is distinct from the well-characterized constitutive activity (COX-1). Goldfish (Carassius auratus) macrophages exposed to bacterial lipopolysaccharide and leucocyte-derived macrophage-activating factor(s) showed a significant increase in the generation of the major COX product, PGE2, within the first 6 h of stimulation. The selective COX-2 inhibitor, NS398, inhibited this elevated generation of PGE, whereas the basal level of this product synthesized by unstimulated macrophages was unaffected by such exposure. PGE generation by goldfish macrophages was similarly inhibited by the glucocorticoid, dexamethasone, and an inhibitor of protein synthesis, cycloheximide, suggesting that this stimulation may be due to an inducible enzyme equivalent to mammalian COX-2. The complete coding sequence of rainbow trout (Oncorhynchus mykiss) COX-2 was obtained by PCR. The gene contains a 61 bp 5'-untranslated region (UTR), a 1821 bp open reading frame and a 771 bp 3'UTR containing multiple copies of an mRNA instability motif (ATTTA). The predicted translation product had high homology to known mammalian and chicken COX-2 (83-84%) and COX-1 (77%) sequences. Reverse-transcriptase PCR with cDNA from control and bacterially challenged fish revealed that trout COX-2 expression was not constitutive but could be induced. Overall, these studies show for the first time that the inducible isoform of COX has a long evolutionary history, probably dating back to the evolution of fish over 500 million years ago.  (+info)

Leukotriene B4 (LTB4) is a type of lipid mediator called eicosanoid, which is derived from arachidonic acid through the 5-lipoxygenase pathway. It is primarily produced by neutrophils, eosinophils, monocytes, and macrophages in response to various stimuli such as infection, inflammation, or injury. LTB4 acts as a potent chemoattractant and activator of these immune cells, playing a crucial role in the recruitment and activation of neutrophils during acute inflammatory responses. It also enhances the adhesion of leukocytes to endothelial cells, contributing to the development of tissue damage and edema. Dysregulation of LTB4 production has been implicated in several pathological conditions, including asthma, atherosclerosis, and cancer.

Leukotriene B4 (LTB4) receptors are a type of G protein-coupled receptor that bind to and are activated by the lipid mediator Leukotriene B4. There are two main types of LTB4 receptors, named BLT1 and BLT2.

BLT1 is highly expressed in cells of the immune system such as neutrophils, eosinophils, monocytes, and dendritic cells, and it mediates many of the pro-inflammatory effects of LTB4, including chemotaxis, adhesion, and activation of these cells.

BLT2 is more widely expressed in various tissues, including the skin, lung, and intestine, and it has been shown to play a role in a variety of physiological and pathological processes, such as pain sensation, wound healing, and cancer progression.

Overall, LTB4 receptors are important targets for the development of therapies aimed at modulating inflammation and immune responses.

Leukotriene A4 (LTA4) is a lipid mediator derived from arachidonic acid, which is released from membrane phospholipids by the action of phospholipase A2. LTA4 is synthesized in the cell through the 5-lipoxygenase pathway and serves as an intermediate in the production of other leukotrienes (LB4, LTC4, LTD4, LTE4) that are involved in inflammation, bronchoconstriction, increased vascular permeability, and recruitment of leukocytes.

Leukotriene A4 is an unstable compound with a short half-life, which can be converted to Leukotriene B4 (LTB4) by the enzyme LTA4 hydrolase or to Leukotriene C4 (LTC4) by the addition of glutathione through the action of LTC4 synthase. These leukotrienes play a significant role in the pathophysiology of asthma, allergies, and other inflammatory diseases.

Leukotriene receptors are a type of cell surface receptor that bind to and are activated by leukotrienes, which are lipid mediators derived from arachidonic acid. These receptors play an important role in the inflammatory response and are involved in various physiological and pathophysiological processes, including bronchoconstriction, increased vascular permeability, and recruitment of inflammatory cells.

There are two main types of leukotriene receptors: CysLT1 and CysLT2. The CysLT1 receptor has a high affinity for the cysteinyl leukotrienes LTC4, LTD4, and LTE4, while the CysLT2 receptor has a lower affinity for these ligands. Activation of the CysLT1 receptor leads to smooth muscle contraction, increased vascular permeability, and recruitment of inflammatory cells, while activation of the CysLT2 receptor is associated with vasoconstriction and bronchodilation.

Leukotriene receptors are found on various cell types, including immune cells (e.g., eosinophils, mast cells), airway smooth muscle cells, endothelial cells, and epithelial cells. They play a key role in the pathogenesis of asthma and other allergic diseases, as well as in the development of inflammation in response to infection or tissue injury.

Drugs that target leukotriene receptors, such as montelukast (a CysLT1 receptor antagonist), are used in the treatment of asthma and allergic rhinitis. These drugs work by blocking the activation of leukotriene receptors, thereby reducing inflammation and bronchoconstriction.

Leukotriene antagonists are a class of medications that work by blocking the action of leukotrienes, which are chemicals released by the immune system in response to an allergen or irritant. Leukotrienes cause airway muscles to tighten and inflammation in the airways, leading to symptoms such as wheezing, shortness of breath, and coughing. By blocking the action of leukotrienes, leukotriene antagonists can help relieve these symptoms and improve lung function. These medications are often used to treat asthma and allergic rhinitis (hay fever). Examples of leukotriene antagonists include montelukast, zafirlukast, and pranlukast.

Leukotriene C4 (LTC4) is a type of lipid mediator called a cysteinyl leukotriene, which is derived from arachidonic acid through the 5-lipoxygenase pathway. It is primarily produced by activated mast cells and basophils, and to a lesser extent by eosinophils, during an allergic response or inflammation.

LTC4 plays a crucial role in the pathogenesis of asthma and other allergic diseases by causing bronchoconstriction, increased vascular permeability, mucus secretion, and recruitment of inflammatory cells to the site of inflammation. It exerts its effects by binding to cysteinyl leukotriene receptors (CysLT1 and CysLT2) found on various cell types, including airway smooth muscle cells, bronchial epithelial cells, and immune cells.

LTC4 is rapidly metabolized to Leukotriene D4 (LTD4) and then to Leukotriene E4 (LTE4) by enzymes such as gamma-glutamyl transpeptidase and dipeptidases, which are present in the extracellular space. These metabolites also have biological activity and contribute to the inflammatory response.

Inhibitors of 5-lipoxygenase or leukotriene receptor antagonists are used as therapeutic agents for the treatment of asthma, allergies, and other inflammatory conditions.

Leukotriene E4 (LTE4) is a biological mediator derived from the arachidonic acid pathway, which plays a significant role in the inflammatory response. It is a type of leukotriene that is synthesized from leukotriene C4 (LTC4) and leukotriene D4 (LTD4) via the action of enzymes such as gamma-glutamyl transpeptidase and dipeptidases.

LTE4 is a potent bronchoconstrictor, meaning it can cause narrowing of the airways in the lungs, and it also has chemotactic properties that attract inflammatory cells such as eosinophils to sites of inflammation. It is involved in the pathogenesis of asthma and other allergic diseases, where it contributes to bronchoconstriction, increased vascular permeability, and mucus production.

LTE4 can be measured in urine as a biomarker of airway inflammation, particularly in patients with asthma. Increased levels of LTE4 in the urine have been associated with more severe asthma symptoms, poorer lung function, and increased risk of exacerbations.

Leukotriene D4 (LTD4) is a biological mediator derived from arachidonic acid, which is released from membrane phospholipids by the action of phospholipase A2. It is one of the cysteinyl leukotrienes (cys-LTs), along with LTC4 and LTE4, that are produced in the body through the 5-lipoxygenase pathway.

LTD4 plays a significant role in the inflammatory response, particularly in the airways. It is a potent constrictor of bronchial smooth muscle, increases vascular permeability, and recruits eosinophils and other inflammatory cells to the site of inflammation. These actions contribute to the pathogenesis of asthma and allergic rhinitis.

LTD4 exerts its effects by binding to cys-LT receptors (CysLT1 and CysLT2) found on various cell types, including smooth muscle cells, endothelial cells, and inflammatory cells. The activation of these receptors leads to a cascade of intracellular signaling events that result in the observed biological responses.

Inhibitors of 5-lipoxygenase or cys-LT receptor antagonists are used as therapeutic agents for the treatment of asthma and allergic rhinitis, targeting the actions of LTD4 and other cys-LTs to reduce inflammation and bronchoconstriction.

Arachidonate 5-Lipoxygenase (also known as ALOX5 or 5-LO) is a type of enzyme involved in the biosynthesis of leukotrienes, which are important inflammatory mediators. It catalyzes the conversion of arachidonic acid, a polyunsaturated fatty acid, to 5-hydroperoxyeicosatetraenoic acid (5-HPETE), which is then converted to leukotriene A4 (LTA4). LTA4 is a precursor for the synthesis of other leukotrienes, such as LTB4, LTC4, LTD4, and LTE4. These lipid mediators play key roles in various physiological and pathophysiological processes, including inflammation, immune response, and allergic reactions.

The gene encoding arachidonate 5-lipoxygenase is located on human chromosome 10 (10q11.2). Mutations in this gene have been associated with several diseases, such as severe congenital neutropenia, recurrent infections, and increased risk of developing asthma and other allergic disorders. Inhibitors of arachidonate 5-lipoxygenase are used as therapeutic agents for the treatment of inflammatory conditions, including asthma and rheumatoid arthritis.

"SRS-A" is an older abbreviation for "Slow-Reacting Substance of Anaphylaxis," which refers to a group of molecules called "leukotrienes." Leukotrienes are mediators of inflammation and play a key role in the pathogenesis of asthma and other allergic diseases. They are produced by mast cells and basophils upon activation, and cause bronchoconstriction, increased vascular permeability, and mucus production.

The term "SRS-A" is not commonly used in modern medical literature, as it has been largely replaced by the more specific names of its individual components: LTC4, LTD4, and LTE4. These leukotrienes are now collectively referred to as the "cysteinyl leukotrienes."

Leukotrienes are a type of lipid mediator derived from arachidonic acid, which is a fatty acid found in the cell membranes of various cells in the body. They are produced by the 5-lipoxygenase (5-LO) pathway and play an essential role in the inflammatory response. Leukotrienes are involved in several physiological and pathophysiological processes, including bronchoconstriction, increased vascular permeability, and recruitment of immune cells to sites of injury or infection.

There are four main types of leukotrienes: LTB4, LTC4, LTD4, and LTE4. These molecules differ from each other based on the presence or absence of specific chemical groups attached to their core structure. Leukotrienes exert their effects by binding to specific G protein-coupled receptors (GPCRs) found on the surface of various cells.

LTB4 is primarily involved in neutrophil chemotaxis and activation, while LTC4, LTD4, and LTE4 are collectively known as cysteinyl leukotrienes (CysLTs). CysLTs cause bronchoconstriction, increased mucus production, and vascular permeability in the airways, contributing to the pathogenesis of asthma and other respiratory diseases.

In summary, leukotrienes are potent lipid mediators that play a crucial role in inflammation and immune responses. Their dysregulation has been implicated in several disease states, making them an important target for therapeutic intervention.

Neutrophils are a type of white blood cell that are part of the immune system's response to infection. They are produced in the bone marrow and released into the bloodstream where they circulate and are able to move quickly to sites of infection or inflammation in the body. Neutrophils are capable of engulfing and destroying bacteria, viruses, and other foreign substances through a process called phagocytosis. They are also involved in the release of inflammatory mediators, which can contribute to tissue damage in some cases. Neutrophils are characterized by the presence of granules in their cytoplasm, which contain enzymes and other proteins that help them carry out their immune functions.

Lipoxygenase inhibitors are a class of compounds that block the activity of lipoxygenase enzymes. These enzymes are involved in the metabolism of arachidonic acid and other polyunsaturated fatty acids, leading to the production of leukotrienes and other inflammatory mediators. By inhibiting lipoxygenase, these compounds can help reduce inflammation and may have potential therapeutic applications in the treatment of various diseases, including asthma, atherosclerosis, and cancer. Some examples of lipoxygenase inhibitors include nordihydroguaiaretic acid (NDGA), zileuton, and baicalein.

Hydroxyeicosatetraenoic acids (HETEs) are a type of metabolite produced by the oxidation of arachidonic acid, a polyunsaturated fatty acid that is found in the membranes of cells in the human body. This oxidation process is catalyzed by enzymes called lipoxygenases (LOXs) and cytochrome P450 monooxygenases (CYP450).

HETEs are biologically active compounds that play a role in various physiological and pathophysiological processes, including inflammation, immune response, and cancer. They can act as signaling molecules, modulating the activity of various cell types, such as leukocytes, endothelial cells, and smooth muscle cells.

There are several different types of HETEs, depending on the position of the hydroxyl group (-OH) attached to the arachidonic acid molecule. For example, 5-HETE, 12-HETE, and 15-HETE are produced by 5-LOX, 12-LOX, and 15-LOX, respectively, while CYP450 can produce 20-HETE.

It's worth noting that HETEs have been implicated in various diseases, such as atherosclerosis, hypertension, and cancer, making them potential targets for therapeutic intervention. However, further research is needed to fully understand their roles and develop effective treatments.

Epoxide hydrolases are a group of enzymes that catalyze the hydrolysis of epoxides, which are molecules containing a three-membered ring consisting of two carbon atoms and one oxygen atom. This reaction results in the formation of diols, which are molecules containing two hydroxyl groups (-OH).

Epoxide hydrolases play an important role in the detoxification of xenobiotics (foreign substances) and the metabolism of endogenous compounds. They help to convert toxic epoxides into less harmful products, which can then be excreted from the body.

There are two main types of epoxide hydrolases: microsomal epoxide hydrolase (mEH) and soluble epoxide hydrolase (sEH). mEH is primarily responsible for metabolizing xenobiotics, while sEH plays a role in the metabolism of endogenous compounds such as arachidonic acid.

Impaired function or inhibition of epoxide hydrolases has been linked to various diseases, including cancer, cardiovascular disease, and neurological disorders. Therefore, these enzymes are considered important targets for the development of drugs and therapies aimed at treating these conditions.

5-Lipoxygenase-activating proteins (FLAPs) are a type of enzyme found in the cell membrane that play a crucial role in the biosynthesis of leukotrienes, which are lipid mediators involved in inflammation and immune responses. FLAPs activate 5-lipoxygenase, an enzyme that catalyzes the conversion of arachidonic acid to leukotriene A4, a precursor for other leukotrienes.

FLAP inhibitors are a class of drugs that block the activity of FLAPs and have been investigated as potential treatments for inflammatory diseases such as asthma, rheumatoid arthritis, and atherosclerosis. By inhibiting FLAP, these drugs can reduce the production of leukotrienes and other pro-inflammatory mediators, thereby alleviating the symptoms of inflammation and potentially slowing down the progression of related diseases.

N-Formylmethionine Leucyl-Phenylalanine (fMLP) is not a medical condition, but rather a synthetic peptide that is often used in laboratory settings for research purposes. It is a formylated methionine residue linked to a leucine and phenylalanine tripeptide.

fMLP is a potent chemoattractant for certain types of white blood cells, including neutrophils and monocytes. When these cells encounter fMLP, they are stimulated to migrate towards the source of the peptide and release various inflammatory mediators. As such, fMLP is often used in studies of inflammation, immune cell function, and signal transduction pathways.

It's important to note that while fMLP has important research applications, it is not a substance that would be encountered or used in clinical medicine.

Arachidonic acids are a type of polyunsaturated fatty acid that is primarily found in the phospholipids of cell membranes. They contain 20 carbon atoms and four double bonds (20:4n-6), with the first double bond located at the sixth carbon atom from the methyl end.

Arachidonic acids are derived from linoleic acid, an essential fatty acid that cannot be synthesized by the human body and must be obtained through dietary sources such as meat, fish, and eggs. Once ingested, linoleic acid is converted to arachidonic acid in a series of enzymatic reactions.

Arachidonic acids play an important role in various physiological processes, including inflammation, immune response, and cell signaling. They serve as precursors for the synthesis of eicosanoids, which are signaling molecules that include prostaglandins, thromboxanes, and leukotrienes. These eicosanoids have diverse biological activities, such as modulating blood flow, platelet aggregation, and pain perception, among others.

However, excessive production of arachidonic acid-derived eicosanoids has been implicated in various pathological conditions, including inflammation, atherosclerosis, and cancer. Therefore, the regulation of arachidonic acid metabolism is an important area of research for the development of new therapeutic strategies.

15-Oxoprostaglandin 13-Reductase is an enzyme that catalyzes the reduction of 15-keto prostaglandins to 13,14-dihydro-15-keto prostaglandins. This enzyme plays a role in the metabolism and deactivation of prostaglandins, which are hormone-like substances that are involved in various physiological processes such as inflammation, blood flow regulation, and labor induction. The reduction of 15-keto prostaglandins to 13,14-dihydro-15-keto prostaglandins by 15-Oxoprostaglandin 13-Reductase results in the loss of biological activity of these prostaglandins.

Eicosanoids are a group of signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid and other polyunsaturated fatty acids with 20 carbon atoms. They include prostaglandins, thromboxanes, leukotrienes, and lipoxins, which are involved in a wide range of physiological and pathophysiological processes, such as inflammation, immune response, blood clotting, and smooth muscle contraction. Eicosanoids act as local hormones or autacoids, affecting the function of cells near where they are produced. They are synthesized by various cell types, including immune cells, endothelial cells, and neurons, in response to different stimuli, such as injury, infection, or stress. The balance between different eicosanoids can have significant effects on health and disease.

Arachidonic acid is a type of polyunsaturated fatty acid that is found naturally in the body and in certain foods. It is an essential fatty acid, meaning that it cannot be produced by the human body and must be obtained through the diet. Arachidonic acid is a key component of cell membranes and plays a role in various physiological processes, including inflammation and blood clotting.

In the body, arachidonic acid is released from cell membranes in response to various stimuli, such as injury or infection. Once released, it can be converted into a variety of bioactive compounds, including prostaglandins, thromboxanes, and leukotrienes, which mediate various physiological responses, including inflammation, pain, fever, and blood clotting.

Arachidonic acid is found in high concentrations in animal products such as meat, poultry, fish, and eggs, as well as in some plant sources such as certain nuts and seeds. It is also available as a dietary supplement. However, it is important to note that excessive intake of arachidonic acid can contribute to the development of inflammation and other health problems, so it is recommended to consume this fatty acid in moderation as part of a balanced diet.

Calcimycin is a ionophore compound that is produced by the bacterium Streptomyces chartreusensis. It is also known as Calcineurin A inhibitor because it can bind to and inhibit the activity of calcineurin, a protein phosphatase. In medical research, calcimycin is often used to study calcium signaling in cells.
It has been also used in laboratory studies for its antiproliferative and pro-apoptotic effects on certain types of cancer cells. However, it is not approved for use as a drug in humans.

Lipoxygenase is an enzyme that catalyzes the dioxygenation of polyunsaturated fatty acids containing a cis,cis-1,4-pentadiene structure, forming hydroperoxides. This reaction is important in the biosynthesis of leukotrienes and lipoxins, which are involved in various inflammatory responses and immune functions. There are several isoforms of lipoxygenase found in different tissues and organisms, including arachidonate 5-lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase.

Arachidonate lipoxygenases (ALOXs or ALOXE's) are a group of enzymes that catalyze the dioxygenation of polyunsaturated fatty acids, such as arachidonic acid, to form hydroperoxides. These enzymes play a crucial role in the biosynthesis of various eicosanoids, which are signaling molecules involved in inflammation, immunity, and other physiological processes.

There are several isoforms of ALOXs, including 5-lipoxygenase (5-LOX), 12-lipoxygenase (12-LOX), and 15-lipoxygenase (15-LOX), which differ in their substrate specificity and the position of the hydroperoxide group they introduce into the fatty acid. These enzymes are widely distributed in various tissues, including the lungs, liver, and brain, and have been implicated in a variety of diseases, such as cancer, cardiovascular disease, and neurodegenerative disorders.

Inhibition of ALOXs has been explored as a potential therapeutic strategy for the treatment of these diseases, although the development of selective and safe inhibitors has proven to be challenging.

Platelet-activating factor (PAF) is a potent phospholipid mediator that plays a significant role in various inflammatory and immune responses. It is a powerful lipid signaling molecule released mainly by activated platelets, neutrophils, monocytes, endothelial cells, and other cell types during inflammation or injury.

PAF has a molecular structure consisting of an alkyl chain linked to a glycerol moiety, a phosphate group, and an sn-2 acetyl group. This unique structure allows PAF to bind to its specific G protein-coupled receptor (PAF-R) on the surface of target cells, triggering various intracellular signaling cascades that result in cell activation, degranulation, and aggregation.

The primary functions of PAF include:

1. Platelet activation and aggregation: PAF stimulates platelets to aggregate, release their granules, and activate the coagulation cascade, which can lead to thrombus formation.
2. Neutrophil and monocyte activation: PAF activates these immune cells, leading to increased adhesion, degranulation, and production of reactive oxygen species (ROS) and pro-inflammatory cytokines.
3. Vasodilation and increased vascular permeability: PAF can cause vasodilation by acting on endothelial cells, leading to an increase in blood flow and facilitating the extravasation of immune cells into inflamed tissues.
4. Bronchoconstriction: In the respiratory system, PAF can induce bronchoconstriction and recruitment of inflammatory cells, contributing to asthma symptoms.
5. Neurotransmission modulation: PAF has been implicated in neuroinflammation and may play a role in neuronal excitability, synaptic plasticity, and cognitive functions.

Dysregulated PAF signaling has been associated with several pathological conditions, including atherosclerosis, sepsis, acute respiratory distress syndrome (ARDS), ischemia-reperfusion injury, and neuroinflammatory disorders. Therefore, targeting the PAF pathway may provide therapeutic benefits in these diseases.

Lipoxins are a group of naturally occurring, short-lived signaling molecules called eicosanoids that are derived from arachidonic acid, a type of omega-6 fatty acid. They were first discovered in the 1980s and are produced by cells involved in the inflammatory response, such as white blood cells (leukocytes).

Lipoxins have potent anti-inflammatory effects and play a crucial role in regulating and resolving the inflammatory response. They work by modulating the activity of various immune cells, including neutrophils, monocytes, and lymphocytes, and promoting the resolution of inflammation through the activation of anti-inflammatory pathways.

Lipoxins have been shown to have potential therapeutic applications in a variety of inflammatory diseases, such as asthma, arthritis, and inflammatory bowel disease. However, further research is needed to fully understand their mechanisms of action and therapeutic potential.

Chemotaxis, Leukocyte is the movement of leukocytes (white blood cells) towards a higher concentration of a particular chemical substance, known as a chemotactic factor. This process plays a crucial role in the immune system's response to infection and injury.

When there is an infection or tissue damage, certain cells release chemotactic factors, which are small molecules or proteins that can attract leukocytes to the site of inflammation. Leukocytes have receptors on their surface that can detect these chemotactic factors and move towards them through a process called chemotaxis.

Once they reach the site of inflammation, leukocytes can help eliminate pathogens or damaged cells by phagocytosis (engulfing and destroying) or releasing toxic substances that kill the invading microorganisms. Chemotaxis is an essential part of the immune system's defense mechanisms and helps to maintain tissue homeostasis and prevent the spread of infection.

Zymosan is a type of substance that is derived from the cell walls of yeast and some types of fungi. It's often used in laboratory research as an agent to stimulate inflammation, because it can activate certain immune cells (such as neutrophils) and cause them to release pro-inflammatory chemicals.

In medical terms, Zymosan is sometimes used as a tool for studying the immune system and inflammation in experimental settings. It's important to note that Zymosan itself is not a medical condition or disease, but rather a research reagent with potential applications in understanding human health and disease.

Glycols are a type of organic compound that contain two hydroxyl (OH) groups attached to adjacent carbon atoms. They are colorless, odorless, and have a sweet taste. The most common glycols are ethylene glycol and propylene glycol. Ethylene glycol is widely used as an automotive antifreeze and in the manufacture of polyester fibers and resins, while propylene glycol is used as a food additive, in pharmaceuticals, and as a solvent in various industries. Glycols are also used as a coolant, humectant, and in the production of unsaturated polyester resins. Exposure to high levels of glycols can cause irritation to the eyes, skin, and respiratory tract, and ingestion can be harmful or fatal.

Chemotactic factors are substances that attract or repel cells, particularly immune cells, by stimulating directional movement in response to a chemical gradient. These factors play a crucial role in the body's immune response and inflammation process. They include:

1. Chemokines: A family of small signaling proteins that direct the migration of immune cells to sites of infection or tissue damage.
2. Cytokines: A broad category of signaling molecules that mediate and regulate immunity, inflammation, and hematopoiesis. Some cytokines can also act as chemotactic factors.
3. Complement components: Cleavage products of the complement system can attract immune cells to the site of infection or tissue injury.
4. Growth factors: Certain growth factors, like colony-stimulating factors (CSFs), can stimulate the migration and proliferation of specific cell types.
5. Lipid mediators: Products derived from arachidonic acid metabolism, such as leukotrienes and prostaglandins, can also act as chemotactic factors.
6. Formyl peptides: Bacterial-derived formylated peptides can attract and activate neutrophils during an infection.
7. Extracellular matrix (ECM) components: Fragments of ECM proteins, like collagen and fibronectin, can serve as chemotactic factors for immune cells.

These factors help orchestrate the immune response by guiding the movement of immune cells to specific locations in the body where they are needed.

Quinolines are a class of organic compounds that consist of a bicyclic structure made up of a benzene ring fused to a piperidine ring. They have a wide range of applications, but they are perhaps best known for their use in the synthesis of various medications, including antibiotics and antimalarial drugs.

Quinolone antibiotics, such as ciprofloxacin and levofloxacin, work by inhibiting the bacterial enzymes involved in DNA replication and repair. They are commonly used to treat a variety of bacterial infections, including urinary tract infections, pneumonia, and skin infections.

Quinoline-based antimalarial drugs, such as chloroquine and hydroxychloroquine, work by inhibiting the parasite's ability to digest hemoglobin in the red blood cells. They are commonly used to prevent and treat malaria.

It is important to note that quinolines have been associated with serious side effects, including tendinitis and tendon rupture, nerve damage, and abnormal heart rhythms. As with any medication, it is important to use quinolines only under the supervision of a healthcare provider, and to follow their instructions carefully.

High-performance liquid chromatography (HPLC) is a type of chromatography that separates and analyzes compounds based on their interactions with a stationary phase and a mobile phase under high pressure. The mobile phase, which can be a gas or liquid, carries the sample mixture through a column containing the stationary phase.

In HPLC, the mobile phase is a liquid, and it is pumped through the column at high pressures (up to several hundred atmospheres) to achieve faster separation times and better resolution than other types of liquid chromatography. The stationary phase can be a solid or a liquid supported on a solid, and it interacts differently with each component in the sample mixture, causing them to separate as they travel through the column.

HPLC is widely used in analytical chemistry, pharmaceuticals, biotechnology, and other fields to separate, identify, and quantify compounds present in complex mixtures. It can be used to analyze a wide range of substances, including drugs, hormones, vitamins, pigments, flavors, and pollutants. HPLC is also used in the preparation of pure samples for further study or use.

Phenylpropionates are a group of organic compounds that contain a phenyl group and a propionate group. In the context of pharmaceuticals, phenylpropionates often refer to a specific type of esterified hormone, such as testosterone phenylpropionate or nandrolone phenylpropionate. These esters are used in some forms of anabolic-androgenic steroids and are created by attaching a phenylpropionate group to the parent hormone molecule. This modification allows for a slower release and longer duration of action when administered intramuscularly.

It is important to note that these substances have medical uses, but they also carry risks and potential side effects, especially when used inappropriately or without medical supervision. They are controlled substances in many countries due to their potential for misuse and abuse.

Dinoprostone is a prostaglandin E2 analog used in medical practice for the induction of labor and ripening of the cervix in pregnant women. It is available in various forms, including vaginal suppositories, gel, and tablets. Dinoprostone works by stimulating the contraction of uterine muscles and promoting cervical dilation, which helps in facilitating a successful delivery.

It's important to note that dinoprostone should only be administered under the supervision of a healthcare professional, as its use is associated with certain risks and side effects, including uterine hyperstimulation, fetal distress, and maternal infection. The dosage and duration of treatment are carefully monitored to minimize these risks and ensure the safety of both the mother and the baby.

Eosinophils are a type of white blood cell that play an important role in the body's immune response. They are produced in the bone marrow and released into the bloodstream, where they can travel to different tissues and organs throughout the body. Eosinophils are characterized by their granules, which contain various proteins and enzymes that are toxic to parasites and can contribute to inflammation.

Eosinophils are typically associated with allergic reactions, asthma, and other inflammatory conditions. They can also be involved in the body's response to certain infections, particularly those caused by parasites such as worms. In some cases, elevated levels of eosinophils in the blood or tissues (a condition called eosinophilia) can indicate an underlying medical condition, such as a parasitic infection, autoimmune disorder, or cancer.

Eosinophils are named for their staining properties - they readily take up eosin dye, which is why they appear pink or red under the microscope. They make up only about 1-6% of circulating white blood cells in healthy individuals, but their numbers can increase significantly in response to certain triggers.

Masoprocol is not a medication that has an established or widely accepted medical definition in the field of pharmacology or clinical medicine. It may refer to a chemical compound with the name 5-n-butyl-2-benzoxazolinone, which has been studied for its potential anti-cancer properties. However, it is not currently approved by regulatory agencies such as the U.S. Food and Drug Administration (FDA) for use in medical treatments.

Therefore, it's important to consult with healthcare professionals or reliable medical sources for information regarding medications and their uses, rather than relying on unverified or obscure sources.

Fatty alcohols, also known as long-chain alcohols or long-chain fatty alcohols, are a type of fatty compound that contains a hydroxyl group (-OH) and a long alkyl chain. They are typically derived from natural sources such as plant and animal fats and oils, and can also be synthetically produced.

Fatty alcohols can vary in chain length, typically containing between 8 and 30 carbon atoms. They are commonly used in a variety of industrial and consumer products, including detergents, emulsifiers, lubricants, and personal care products. In the medical field, fatty alcohols may be used as ingredients in certain medications or topical treatments.

12-Hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) is a type of fatty acid that is produced in the body as a result of the metabolism of arachidonic acid, which is an omega-6 fatty acid that is found in the membranes of cells throughout the body.

12-HETE is synthesized by the enzyme 12-lipoxygenase (12-LOX), which adds a hydroxyl group (-OH) to the twelfth carbon atom of arachidonic acid. This lipid mediator plays a role in various physiological and pathophysiological processes, including inflammation, immune response, and cancer development.

Increased levels of 12-HETE have been found in several diseases, such as atherosclerosis, asthma, and cancer, suggesting that it may contribute to the development and progression of these conditions. However, further research is needed to fully understand the role of 12-HETE in human health and disease.

Complement C5a is a protein fragment that is generated during the activation of the complement system, which is a part of the immune system. The complement system helps to eliminate pathogens and damaged cells from the body by tagging them for destruction and attracting immune cells to the site of infection or injury.

C5a is formed when the fifth component of the complement system (C5) is cleaved into two smaller fragments, C5a and C5b, during the complement activation cascade. C5a is a potent pro-inflammatory mediator that can attract and activate various immune cells, such as neutrophils, monocytes, and eosinophils, to the site of infection or injury. It can also increase vascular permeability, promote the release of histamine, and induce the production of reactive oxygen species, all of which contribute to the inflammatory response.

However, excessive or uncontrolled activation of the complement system and generation of C5a can lead to tissue damage and inflammation, contributing to the pathogenesis of various diseases, such as sepsis, acute respiratory distress syndrome (ARDS), and autoimmune disorders. Therefore, targeting C5a or its receptors has been explored as a potential therapeutic strategy for these conditions.

Thromboxane B2 (TXB2) is a stable metabolite of thromboxane A2 (TXA2), which is a potent vasoconstrictor and platelet aggregator synthesized by activated platelets. TXA2 has a very short half-life, quickly undergoing spontaneous conversion to the more stable TXB2.

TXB2 itself does not have significant biological activity but serves as a marker for TXA2 production in various physiological and pathophysiological conditions, such as thrombosis, inflammation, and atherosclerosis. It can be measured in blood or other bodily fluids to assess platelet activation and the status of hemostatic and inflammatory processes.

Carboxylic acids are organic compounds that contain a carboxyl group, which is a functional group made up of a carbon atom doubly bonded to an oxygen atom and single bonded to a hydroxyl group. The general formula for a carboxylic acid is R-COOH, where R represents the rest of the molecule.

Carboxylic acids can be found in various natural sources such as in fruits, vegetables, and animal products. Some common examples of carboxylic acids include formic acid (HCOOH), acetic acid (CH3COOH), propionic acid (C2H5COOH), and butyric acid (C3H7COOH).

Carboxylic acids have a variety of uses in industry, including as food additives, pharmaceuticals, and industrial chemicals. They are also important intermediates in the synthesis of other organic compounds. In the body, carboxylic acids play important roles in metabolism and energy production.

Pleurisy is a medical condition characterized by inflammation of the pleura, which are the thin membranes that surround the lungs and line the inside of the chest cavity. The pleura normally produce a small amount of lubricating fluid that allows for smooth movement of the lungs during breathing. However, when they become inflamed (a condition known as pleuritis), this can cause pain and difficulty breathing.

The symptoms of pleurisy may include sharp chest pain that worsens with deep breathing or coughing, shortness of breath, cough, fever, and muscle aches. The pain may be localized to one area of the chest or may radiate to other areas such as the shoulders or back.

Pleurisy can have many different causes, including bacterial or viral infections, autoimmune disorders, pulmonary embolism (a blood clot that travels to the lungs), and certain medications or chemicals. Treatment typically involves addressing the underlying cause of the inflammation, as well as managing symptoms such as pain and breathing difficulties with medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) or opioids. In some cases, more invasive treatments such as thoracentesis (removal of fluid from the chest cavity) may be necessary.

Eicosanoic acids are a type of fatty acid that contains 20 carbon atoms. They can be further classified into subgroups based on the presence and location of double bonds in their chemical structure. The most well-known eicosanoic acids include arachidonic acid (an omega-6 fatty acid with four double bonds), eicosapentaenoic acid (an omega-3 fatty acid with five double bonds), and docosahexaenoic acid (an omega-3 fatty acid with six double bonds). These fatty acids play important roles in various physiological processes, including inflammation, blood clotting, and cell signaling. They can be found in a variety of foods, such as fish, nuts, and seeds, and are also available as dietary supplements.

Benzopyrans are a class of chemical compounds that contain a benzene ring fused to a pyran ring. They are also known as chromenes. Benzopyrans can be found in various natural sources, including plants and fungi, and have been studied for their potential biological activities. Some benzopyrans have been found to have anti-inflammatory, antioxidant, and anticancer properties. However, some benzopyrans can also be toxic or have other adverse health effects, so it is important to study their properties and potential uses carefully.

Eicosapentaenoic acid (EPA) is a type of omega-3 fatty acid that is found in fish and some algae. It is a 20-carbon long polyunsaturated fatty acid with five double bonds, and has the chemical formula C20:5 n-3. EPA is an essential fatty acid, meaning that it cannot be produced by the human body and must be obtained through the diet.

EPA is a precursor to a group of hormone-like substances called eicosanoids, which include prostaglandins, thromboxanes, and leukotrienes. These compounds play important roles in regulating various physiological processes, such as inflammation, blood clotting, and immune function.

EPA has been studied for its potential health benefits, including reducing inflammation, lowering the risk of heart disease, and improving symptoms of depression. It is often taken as a dietary supplement in the form of fish oil or algal oil. However, it is important to note that while some studies have suggested potential health benefits of EPA, more research is needed to confirm these effects and establish recommended dosages.

I must clarify that the term "Guinea Pigs" is not typically used in medical definitions. However, in colloquial or informal language, it may refer to people who are used as the first to try out a new medical treatment or drug. This is known as being a "test subject" or "in a clinical trial."

In the field of scientific research, particularly in studies involving animals, guinea pigs are small rodents that are often used as experimental subjects due to their size, cost-effectiveness, and ease of handling. They are not actually pigs from Guinea, despite their name's origins being unclear. However, they do not exactly fit the description of being used in human medical experiments.

Complement C5a, des-Arginine is a derivative of the complement component C5a. The complement system is a group of proteins that are part of the body's immune defense against foreign invaders such as bacteria and viruses. When activated, the complement system can help to eliminate pathogens by attracting immune cells to the site of infection, promoting inflammation, and directly killing the pathogen.

C5a is a small protein that is generated when the complement component C5 is cleaved during the activation of the complement system. C5a is a potent anaphylatoxin, which means it can cause the release of histamine from mast cells and basophils, leading to increased vascular permeability, smooth muscle contraction, and recruitment of immune cells to the site of infection.

Des-Arginine refers to the removal of an arginine residue from the C-terminus of C5a. This modified form of C5a is known as C5a-desArg and has reduced pro-inflammatory activity compared to intact C5a. However, it can still contribute to the regulation of the immune response by interacting with specific receptors on immune cells.

In summary, Complement C5a, des-Arginine is a derivative of the complement component C5a that has reduced pro-inflammatory activity due to the removal of an arginine residue from its C-terminus.

Acetates, in a medical context, most commonly refer to compounds that contain the acetate group, which is an functional group consisting of a carbon atom bonded to two hydrogen atoms and an oxygen atom (-COO-). An example of an acetate is sodium acetate (CH3COONa), which is a salt formed from acetic acid (CH3COOH) and is often used as a buffering agent in medical solutions.

Acetates can also refer to a group of medications that contain acetate as an active ingredient, such as magnesium acetate, which is used as a laxative, or calcium acetate, which is used to treat high levels of phosphate in the blood.

In addition, acetates can also refer to a process called acetylation, which is the addition of an acetyl group (-COCH3) to a molecule. This process can be important in the metabolism and regulation of various substances within the body.

Leukocytes, also known as white blood cells (WBCs), are a crucial component of the human immune system. They are responsible for protecting the body against infections and foreign substances. Leukocytes are produced in the bone marrow and circulate throughout the body in the bloodstream and lymphatic system.

There are several types of leukocytes, including:

1. Neutrophils - These are the most abundant type of leukocyte and are primarily responsible for fighting bacterial infections. They contain enzymes that can destroy bacteria.
2. Lymphocytes - These are responsible for producing antibodies and destroying virus-infected cells, as well as cancer cells. There are two main types of lymphocytes: B-lymphocytes and T-lymphocytes.
3. Monocytes - These are the largest type of leukocyte and help to break down and remove dead or damaged tissues, as well as microorganisms.
4. Eosinophils - These play a role in fighting parasitic infections and are also involved in allergic reactions and inflammation.
5. Basophils - These release histamine and other chemicals that cause inflammation in response to allergens or irritants.

An abnormal increase or decrease in the number of leukocytes can indicate an underlying medical condition, such as an infection, inflammation, or a blood disorder.

Phospholipases A are a group of enzymes that hydrolyze phospholipids into fatty acids and lysophospholipids by cleaving the ester bond at the sn-1 or sn-2 position of the glycerol backbone. There are three main types of Phospholipases A:

* Phospholipase A1 (PLA1): This enzyme specifically hydrolyzes the ester bond at the sn-1 position, releasing a free fatty acid and a lysophospholipid.
* Phospholipase A2 (PLA2): This enzyme specifically hydrolyzes the ester bond at the sn-2 position, releasing a free fatty acid (often arachidonic acid, which is a precursor for eicosanoids) and a lysophospholipid.
* Phospholipase A/B (PLA/B): This enzyme has both PLA1 and PLA2 activity and can hydrolyze the ester bond at either the sn-1 or sn-2 position.

Phospholipases A play important roles in various biological processes, including cell signaling, membrane remodeling, and host defense. They are also involved in several diseases, such as atherosclerosis, neurodegenerative disorders, and cancer.

N-Formylmethionine (fMet) is not a medical term per se, but rather a biochemical term. It is the formylated derivative of methionine, which is one of the twenty standard amino acids, and it plays a crucial role in the initiation of protein synthesis in prokaryotes and organelles of eukaryotic cells, such as mitochondria and chloroplasts.

In the context of medical research or clinical laboratory reports, you might encounter fMet in relation to bacterial infections, proteomics, or mitochondrial function. For example, formylated methionine residues on bacterial peptides can stimulate immune responses and are recognized by specific receptors on human immune cells, which can have implications for understanding infectious diseases and inflammation.

To provide a concise definition:
N-Formylmethionine (fMet) is the formylated derivative of methionine, primarily known for its role as the initiator amino acid in protein synthesis in prokaryotes and certain organelles of eukaryotic cells.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Asthma is a chronic respiratory disease characterized by inflammation and narrowing of the airways, leading to symptoms such as wheezing, coughing, shortness of breath, and chest tightness. The airway obstruction in asthma is usually reversible, either spontaneously or with treatment.

The underlying cause of asthma involves a combination of genetic and environmental factors that result in hypersensitivity of the airways to certain triggers, such as allergens, irritants, viruses, exercise, and emotional stress. When these triggers are encountered, the airways constrict due to smooth muscle spasm, swell due to inflammation, and produce excess mucus, leading to the characteristic symptoms of asthma.

Asthma is typically managed with a combination of medications that include bronchodilators to relax the airway muscles, corticosteroids to reduce inflammation, and leukotriene modifiers or mast cell stabilizers to prevent allergic reactions. Avoiding triggers and monitoring symptoms are also important components of asthma management.

There are several types of asthma, including allergic asthma, non-allergic asthma, exercise-induced asthma, occupational asthma, and nocturnal asthma, each with its own set of triggers and treatment approaches. Proper diagnosis and management of asthma can help prevent exacerbations, improve quality of life, and reduce the risk of long-term complications.

Complement C5 is a protein that plays a crucial role in the complement system, which is a part of the immune system that helps to eliminate pathogens and damaged cells from the body. The complement system is a complex series of biochemical reactions that help to identify and destroy foreign substances, such as bacteria and viruses.

Complement C5 is one of several proteins in the complement system that are activated in a cascading manner in response to an activating event, such as the binding of an antibody to a pathogen. Once activated, Complement C5 can be cleaved into two smaller proteins, C5a and C5b.

C5a is a powerful anaphylatoxin, which means it can cause the release of histamine from mast cells and basophils, leading to inflammation and increased vascular permeability. It also acts as a chemoattractant, drawing immune cells to the site of infection or injury.

C5b, on the other hand, plays a role in the formation of the membrane attack complex (MAC), which is a protein structure that can punch holes in the membranes of pathogens, leading to their lysis and destruction.

Overall, Complement C5 is an important component of the immune system's response to infection and injury, helping to eliminate pathogens and damaged cells from the body.

Mast cells are a type of white blood cell that are found in connective tissues throughout the body, including the skin, respiratory tract, and gastrointestinal tract. They play an important role in the immune system and help to defend the body against pathogens by releasing chemicals such as histamine, heparin, and leukotrienes, which help to attract other immune cells to the site of infection or injury. Mast cells also play a role in allergic reactions, as they release histamine and other chemicals in response to exposure to an allergen, leading to symptoms such as itching, swelling, and redness. They are derived from hematopoietic stem cells in the bone marrow and mature in the tissues where they reside.

Formyl peptide receptors (FPRs) are a type of G protein-coupled receptors that play a crucial role in the innate immune system. They are expressed on various cells including neutrophils, monocytes, and macrophages. FPRs recognize and respond to formylated peptides derived from bacteria, mitochondria, and host proteins during cell damage or stress. Activation of FPRs triggers a variety of cellular responses, such as chemotaxis, phagocytosis, and release of inflammatory mediators, which help to eliminate invading pathogens and promote tissue repair. There are three subtypes of human FPRs (FPR1, FPR2, and FPR3) that have distinct ligand specificities and functions in the immune response.

Phospholipase A2 (PLA2) is a type of enzyme that catalyzes the hydrolysis of the sn-2 ester bond in glycerophospholipids, releasing free fatty acids, such as arachidonic acid, and lysophospholipids. These products are important precursors for the biosynthesis of various signaling molecules, including eicosanoids, platelet-activating factor (PAF), and lipoxins, which play crucial roles in inflammation, immunity, and other cellular processes.

Phospholipases A2 are classified into several groups based on their structure, mechanism of action, and cellular localization. The secreted PLA2s (sPLA2s) are found in extracellular fluids and are characterized by a low molecular weight, while the calcium-dependent cytosolic PLA2s (cPLA2s) are larger proteins that reside within cells.

Abnormal regulation or activity of Phospholipase A2 has been implicated in various pathological conditions, such as inflammation, neurodegenerative diseases, and cancer. Therefore, understanding the biology and function of these enzymes is essential for developing novel therapeutic strategies to target these disorders.

Ionophores are compounds that have the ability to form complexes with ions and facilitate their transportation across biological membranes. They can be either organic or inorganic molecules, and they play important roles in various physiological processes, including ion homeostasis, signal transduction, and antibiotic activity. In medicine and research, ionophores are used as tools to study ion transport, modulate cellular functions, and as therapeutic agents, especially in the treatment of bacterial and fungal infections.

An "injection, intradermal" refers to a type of injection where a small quantity of a substance is introduced into the layer of skin between the epidermis and dermis, using a thin gauge needle. This technique is often used for diagnostic or research purposes, such as conducting allergy tests or administering immunizations in a way that stimulates a strong immune response. The injection site typically produces a small, raised bump (wheal) that disappears within a few hours. It's important to note that intradermal injections should be performed by trained medical professionals to minimize the risk of complications.

Anti-asthmatic agents are a class of medications used to prevent or alleviate the symptoms of asthma, such as wheezing, shortness of breath, and coughing. These medications work by reducing inflammation, relaxing muscles in the airways, and preventing allergic reactions that can trigger an asthma attack.

There are several types of anti-asthmatic agents, including:

1. Bronchodilators: These medications relax the muscles around the airways, making it easier to breathe. They can be short-acting or long-acting, depending on how long they work.
2. Inhaled corticosteroids: These medications reduce inflammation in the airways and help prevent asthma symptoms from occurring.
3. Leukotriene modifiers: These medications block the action of leukotrienes, chemicals that contribute to inflammation and narrowing of the airways.
4. Combination therapies: Some anti-asthmatic agents combine different types of medications, such as a bronchodilator and an inhaled corticosteroid, into one inhaler.
5. Biologics: These are newer types of anti-asthmatic agents that target specific molecules involved in the inflammatory response in asthma. They are usually given by injection.

It's important to note that different people with asthma may require different medications or combinations of medications to manage their symptoms effectively. Therefore, it is essential to work closely with a healthcare provider to determine the best treatment plan for each individual.

Neutrophil infiltration is a pathological process characterized by the accumulation of neutrophils, a type of white blood cell, in tissue. It is a common feature of inflammation and occurs in response to infection, injury, or other stimuli that trigger an immune response. Neutrophils are attracted to the site of tissue damage by chemical signals called chemokines, which are released by damaged cells and activated immune cells. Once they reach the site of inflammation, neutrophils help to clear away damaged tissue and microorganisms through a process called phagocytosis. However, excessive or prolonged neutrophil infiltration can also contribute to tissue damage and may be associated with various disease states, including cancer, autoimmune disorders, and ischemia-reperfusion injury.

Calcium is an essential mineral that is vital for various physiological processes in the human body. The medical definition of calcium is as follows:

Calcium (Ca2+) is a crucial cation and the most abundant mineral in the human body, with approximately 99% of it found in bones and teeth. It plays a vital role in maintaining structural integrity, nerve impulse transmission, muscle contraction, hormonal secretion, blood coagulation, and enzyme activation.

Calcium homeostasis is tightly regulated through the interplay of several hormones, including parathyroid hormone (PTH), calcitonin, and vitamin D. Dietary calcium intake, absorption, and excretion are also critical factors in maintaining optimal calcium levels in the body.

Hypocalcemia refers to low serum calcium levels, while hypercalcemia indicates high serum calcium levels. Both conditions can have detrimental effects on various organ systems and require medical intervention to correct.

Neutrophil activation refers to the process by which neutrophils, a type of white blood cell, become activated in response to a signal or stimulus, such as an infection or inflammation. This activation triggers a series of responses within the neutrophil that enable it to carry out its immune functions, including:

1. Degranulation: The release of granules containing enzymes and other proteins that can destroy microbes.
2. Phagocytosis: The engulfment and destruction of microbes through the use of reactive oxygen species (ROS) and other toxic substances.
3. Formation of neutrophil extracellular traps (NETs): A process in which neutrophils release DNA and proteins to trap and kill microbes outside the cell.
4. Release of cytokines and chemokines: Signaling molecules that recruit other immune cells to the site of infection or inflammation.

Neutrophil activation is a critical component of the innate immune response, but excessive or uncontrolled activation can contribute to tissue damage and chronic inflammation.

A lung is a pair of spongy, elastic organs in the chest that work together to enable breathing. They are responsible for taking in oxygen and expelling carbon dioxide through the process of respiration. The left lung has two lobes, while the right lung has three lobes. The lungs are protected by the ribcage and are covered by a double-layered membrane called the pleura. The trachea divides into two bronchi, which further divide into smaller bronchioles, leading to millions of tiny air sacs called alveoli, where the exchange of gases occurs.

Chemotactic factors are substances that attract and guide cells, particularly immune cells, to specific locations in the body. Eosinophils are a type of white blood cell that play a role in the immune response, particularly against parasites and in allergic reactions. Therefore, chemotactic factors for eosinophils are substances that attract eosinophils to specific sites in the body.

These factors can be produced by various cells, including mast cells, basophils, and T-lymphocytes, in response to an infection or inflammation. They work by binding to receptors on the surface of eosinophils and activating signaling pathways that cause the eosinophils to migrate towards the source of the chemotactic factor.

Examples of chemotactic factors for eosinophils include:

1. Eotaxins: These are a group of chemokines (a type of signaling protein) that specifically attract eosinophils. They are produced by various cells, including endothelial cells, epithelial cells, and immune cells.
2. Leukotrienes: These are lipid mediators produced by mast cells and basophils in response to an allergic reaction or infection. They can attract eosinophils to the site of inflammation.
3. Platelet-activating factor (PAF): This is a lipid mediator produced by various cells, including endothelial cells and immune cells. It can attract eosinophils and activate them, leading to degranulation and release of their contents.
4. Complement components: The complement system is a group of proteins that play a role in the immune response. Some complement components, such as C3a and C5a, can act as chemotactic factors for eosinophils.

Overall, chemotactic factors for eosinophils play an important role in the immune response by recruiting these cells to sites of infection or inflammation. However, excessive activation of eosinophils and production of chemotactic factors can contribute to the development of various diseases, such as asthma and allergies.

Inflammation is a complex biological response of tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is characterized by the following signs: rubor (redness), tumor (swelling), calor (heat), dolor (pain), and functio laesa (loss of function). The process involves the activation of the immune system, recruitment of white blood cells, and release of inflammatory mediators, which contribute to the elimination of the injurious stimuli and initiation of the healing process. However, uncontrolled or chronic inflammation can also lead to tissue damage and diseases.

Unsaturated fatty acids are a type of fatty acid that contain one or more double bonds in their carbon chain. These double bonds can be either cis or trans configurations, although the cis configuration is more common in nature. The presence of these double bonds makes unsaturated fatty acids more liquid at room temperature and less prone to spoilage than saturated fatty acids, which do not have any double bonds.

Unsaturated fatty acids can be further classified into two main categories: monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs). MUFAs contain one double bond in their carbon chain, while PUFAs contain two or more.

Examples of unsaturated fatty acids include oleic acid (a MUFA found in olive oil), linoleic acid (a PUFA found in vegetable oils), and alpha-linolenic acid (an omega-3 PUFA found in flaxseed and fish). Unsaturated fatty acids are essential nutrients for the human body, as they play important roles in various physiological processes such as membrane structure, inflammation, and blood clotting. It is recommended to consume a balanced diet that includes both MUFAs and PUFAs to maintain good health.

Indole is not strictly a medical term, but it is a chemical compound that can be found in the human body and has relevance to medical and biological research. Indoles are organic compounds that contain a bicyclic structure consisting of a six-membered benzene ring fused to a five-membered pyrrole ring.

In the context of medicine, indoles are particularly relevant due to their presence in certain hormones and other biologically active molecules. For example, the neurotransmitter serotonin contains an indole ring, as does the hormone melatonin. Indoles can also be found in various plant-based foods, such as cruciferous vegetables (e.g., broccoli, kale), and have been studied for their potential health benefits.

Some indoles, like indole-3-carbinol and diindolylmethane, are found in these vegetables and can have anti-cancer properties by modulating estrogen metabolism, reducing inflammation, and promoting cell death (apoptosis) in cancer cells. However, it is essential to note that further research is needed to fully understand the potential health benefits and risks associated with indoles.

Pruritus is a medical term derived from Latin, in which "prurire" means "to itch." It refers to an unpleasant sensation on the skin that provokes the desire or reflex to scratch. This can be caused by various factors, such as skin conditions (e.g., dryness, eczema, psoriasis), systemic diseases (e.g., liver disease, kidney failure), nerve disorders, psychological conditions, or reactions to certain medications.

Pruritus can significantly affect a person's quality of life, leading to sleep disturbances, anxiety, and depression. Proper identification and management of the underlying cause are essential for effective treatment.

Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) that is commonly used to reduce pain, inflammation, and fever. It works by inhibiting the activity of certain enzymes in the body, including cyclooxygenase (COX), which plays a role in producing prostaglandins, chemicals involved in the inflammatory response.

Indomethacin is available in various forms, such as capsules, suppositories, and injectable solutions, and is used to treat a wide range of conditions, including rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout, and bursitis. It may also be used to relieve pain and reduce fever in other conditions, such as dental procedures or after surgery.

Like all NSAIDs, indomethacin can have side effects, including stomach ulcers, bleeding, and kidney damage, especially when taken at high doses or for long periods of time. It may also increase the risk of heart attack and stroke. Therefore, it is important to use indomethacin only as directed by a healthcare provider and to report any unusual symptoms or side effects promptly.

Histamine release is the process by which mast cells and basophils (types of white blood cells) release histamine, a type of chemical messenger or mediator, into the surrounding tissue fluid in response to an antigen-antibody reaction. This process is a key part of the body's immune response to foreign substances, such as allergens, and helps to initiate local inflammation, increase blood flow, and recruit other immune cells to the site of the reaction.

Histamine release can also occur in response to certain medications, physical trauma, or other stimuli. When histamine is released in large amounts, it can cause symptoms such as itching, sneezing, runny nose, watery eyes, and hives. In severe cases, it can lead to anaphylaxis, a life-threatening allergic reaction that requires immediate medical attention.

Autacoids are endogenous substances that are released by various cells in the body and have a localized, hormone-like effect on nearby tissues. They include chemicals such as histamine, serotonin (5-HT), prostaglandins, leukotrienes, and bradykinin. Autacoids are involved in various physiological processes, including inflammation, pain perception, smooth muscle contraction, and blood vessel dilation or constriction. They often act as mediators of the immune response and can contribute to the symptoms of allergies, asthma, and other medical conditions.

Cyclooxygenase (COX) inhibitors are a class of drugs that work by blocking the activity of cyclooxygenase enzymes, which are involved in the production of prostaglandins. Prostaglandins are hormone-like substances that play a role in inflammation, pain, and fever.

There are two main types of COX enzymes: COX-1 and COX-2. COX-1 is produced continuously in various tissues throughout the body and helps maintain the normal function of the stomach and kidneys, among other things. COX-2, on the other hand, is produced in response to inflammation and is involved in the production of prostaglandins that contribute to pain, fever, and inflammation.

COX inhibitors can be non-selective, meaning they block both COX-1 and COX-2, or selective, meaning they primarily block COX-2. Non-selective COX inhibitors include drugs such as aspirin, ibuprofen, and naproxen, while selective COX inhibitors are often referred to as coxibs and include celecoxib (Celebrex) and rofecoxib (Vioxx).

COX inhibitors are commonly used to treat pain, inflammation, and fever. However, long-term use of non-selective COX inhibitors can increase the risk of gastrointestinal side effects such as ulcers and bleeding, while selective COX inhibitors may be associated with an increased risk of cardiovascular events such as heart attack and stroke. It is important to talk to a healthcare provider about the potential risks and benefits of COX inhibitors before using them.

Basophils are a type of white blood cell that are part of the immune system. They are granulocytes, which means they contain granules filled with chemicals that can be released in response to an infection or inflammation. Basophils are relatively rare, making up less than 1% of all white blood cells.

When basophils become activated, they release histamine and other chemical mediators that can contribute to allergic reactions, such as itching, swelling, and redness. They also play a role in inflammation, helping to recruit other immune cells to the site of an infection or injury.

Basophils can be identified under a microscope based on their characteristic staining properties. They are typically smaller than other granulocytes, such as neutrophils and eosinophils, and have a multi-lobed nucleus with dark purple-staining granules in the cytoplasm.

While basophils play an important role in the immune response, abnormal levels of basophils can be associated with various medical conditions, such as allergies, infections, and certain types of leukemia.

Superoxides are partially reduced derivatives of oxygen that contain one extra electron, giving them an overall charge of -1. They are highly reactive and unstable, with the most common superoxide being the hydroxyl radical (•OH-) and the superoxide anion (O2-). Superoxides are produced naturally in the body during metabolic processes, particularly within the mitochondria during cellular respiration. They play a role in various physiological processes, but when produced in excess or not properly neutralized, they can contribute to oxidative stress and damage to cells and tissues, potentially leading to the development of various diseases such as cancer, atherosclerosis, and neurodegenerative disorders.

Eicosanoid receptors are a type of cell surface receptor that bind and respond to signaling molecules called eicosanoids. These receptors play a crucial role in various physiological processes, including inflammation, immune response, blood clotting, and the regulation of blood pressure and flow.

Eicosanoids are derived from the metabolism of arachidonic acid and other polyunsaturated fatty acids with 20 carbon atoms (hence "eicosa" in eicosanoid). They include prostaglandins, thromboxanes, leukotrienes, and lipoxins.

Eicosanoid receptors are found on various cell types throughout the body, including immune cells, endothelial cells, smooth muscle cells, and neurons. When an eicosanoid binds to its specific receptor, it triggers a cascade of intracellular signaling events that ultimately lead to changes in gene expression, cell behavior, or both.

There are several families of eicosanoid receptors, including prostaglandin receptors, thromboxane receptors, leukotriene receptors, and lipoxin receptors. Each family contains multiple subtypes with distinct pharmacological properties and physiological functions.

Understanding the role of eicosanoid receptors in health and disease has important implications for drug development and the treatment of various medical conditions, such as inflammation, pain, asthma, cardiovascular diseases, and cancer.

Prostaglandin E (PGE) is a type of prostaglandin, which is a group of lipid compounds that are synthesized in the body from fatty acids and have diverse hormone-like effects. Prostaglandins are not actually hormones, but are similar to them in that they act as chemical messengers that have specific effects on certain cells.

Prostaglandin E is one of the most abundant prostaglandins in the body and has a variety of physiological functions. It is involved in the regulation of inflammation, pain perception, fever, and smooth muscle contraction. Prostaglandin E also plays a role in the regulation of blood flow, platelet aggregation, and gastric acid secretion.

Prostaglandin E is synthesized from arachidonic acid, which is released from cell membranes by the action of enzymes called phospholipases. Once formed, prostaglandin E binds to specific receptors on the surface of cells, leading to a variety of intracellular signaling events that ultimately result in changes in cell behavior.

Prostaglandin E is used medically in the treatment of several conditions, including dysmenorrhea (painful menstruation), postpartum hemorrhage, and patent ductus arteriosus (a congenital heart defect). It is also used as a diagnostic tool in the evaluation of kidney function.

Histamine is defined as a biogenic amine that is widely distributed throughout the body and is involved in various physiological functions. It is derived primarily from the amino acid histidine by the action of histidine decarboxylase. Histamine is stored in granules (along with heparin and proteases) within mast cells and basophils, and is released upon stimulation or degranulation of these cells.

Once released into the tissues and circulation, histamine exerts a wide range of pharmacological actions through its interaction with four types of G protein-coupled receptors (H1, H2, H3, and H4 receptors). Histamine's effects are diverse and include modulation of immune responses, contraction and relaxation of smooth muscle, increased vascular permeability, stimulation of gastric acid secretion, and regulation of neurotransmission.

Histamine is also a potent mediator of allergic reactions and inflammation, causing symptoms such as itching, sneezing, runny nose, and wheezing. Antihistamines are commonly used to block the actions of histamine at H1 receptors, providing relief from these symptoms.

8,11,14-Eicosatrienoic acid is a type of fatty acid that contains 20 carbon atoms and three double bonds. The locations of these double bonds are at the 8th, 11th, and 14th carbon atoms, hence the name of the fatty acid. It is an omega-3 fatty acid, which means that the first double bond is located between the third and fourth carbon atoms from the methyl end of the molecule.

This particular fatty acid is not considered to be essential for human health, as it can be synthesized in the body from other fatty acids. It is a component of certain types of lipids found in animal tissues, including beef and lamb. It has been studied for its potential role in various physiological processes, such as inflammation and immune function, but its specific functions and effects on human health are not well understood.

Chemotaxis is a term used in biology and medicine to describe the movement of an organism or cell towards or away from a chemical stimulus. This process plays a crucial role in various biological phenomena, including immune responses, wound healing, and the development and progression of diseases such as cancer.

In chemotaxis, cells can detect and respond to changes in the concentration of specific chemicals, known as chemoattractants or chemorepellents, in their environment. These chemicals bind to receptors on the cell surface, triggering a series of intracellular signaling events that ultimately lead to changes in the cytoskeleton and directed movement of the cell towards or away from the chemical gradient.

For example, during an immune response, white blood cells called neutrophils use chemotaxis to migrate towards sites of infection or inflammation, where they can attack and destroy invading pathogens. Similarly, cancer cells can use chemotaxis to migrate towards blood vessels and metastasize to other parts of the body.

Understanding chemotaxis is important for developing new therapies and treatments for a variety of diseases, including cancer, infectious diseases, and inflammatory disorders.

Lipoxins are a group of anti-inflammatory mediators that play a role in the resolution of inflammation. They are produced from arachidonic acid, a type of omega-6 fatty acid, through the action of lipoxygenase enzymes. There are several types of lipoxin receptors (ALX/FPR2 and GPR31) that have been identified, which belong to the family of G protein-coupled receptors. These receptors are expressed in various tissues, including the cardiovascular, respiratory, and gastrointestinal systems. Activation of lipoxin receptors leads to a variety of cellular responses, such as inhibition of inflammatory cytokine production, reduction of oxidative stress, and promotion of tissue repair. Dysregulation of the lipoxin signaling pathway has been implicated in several diseases, including asthma, atherosclerosis, and cancer.

Group IV Phospholipases A2 (PLA2) are a subclass of the PLA2 family, which are enzymes that hydrolyze the sn-2 acyl bond of glycerophospholipids to release free fatty acids and lysophospholipids. Specifically, Group IV PLA2s are calcium-dependent enzymes that are primarily located in the cytoplasm of cells and are involved in various cellular processes such as membrane remodeling, signal transduction, and inflammation.

Group IV PLA2s can be further divided into several subgroups, including Group IVA (also known as cPLA2s) and Group IVB (also known as iPLA2s). These enzymes have distinct structural features and play different roles in cellular physiology. For example, cPLA2s are involved in the production of eicosanoids, which are signaling molecules that mediate inflammation and other responses to injury or infection. On the other hand, iPLA2s are involved in maintaining membrane homeostasis and regulating cellular energy metabolism.

Abnormal regulation of Group IV PLA2 activity has been implicated in various pathological conditions, including cancer, neurodegenerative diseases, and cardiovascular disease. Therefore, understanding the function and regulation of these enzymes is an important area of research with potential therapeutic implications.

5,8,11,14-Eicosatetraynoic acid (ETYA) is a polyunsaturated fatty acid that contains four double bonds in its chemical structure. It is a non-methylene interrupted fatty acid, which means that the double bonds are separated by three methylene bridges. ETYA is not a naturally occurring fatty acid and is typically synthesized in the laboratory for research purposes.

ETYA has been used as a tool to study the biochemical mechanisms of inflammation and cancer. It can inhibit the activity of enzymes called lipoxygenases and cyclooxygenases, which are involved in the production of inflammatory mediators such as prostaglandins and leukotrienes. ETYA can also induce the formation of reactive oxygen species, which can contribute to cell damage and death.

While ETYA has been used in research to better understand the biochemical pathways involved in inflammation and cancer, it is not used as a therapeutic agent in clinical medicine due to its potential toxicity and lack of specificity for targeting disease processes.

Inflammation mediators are substances that are released by the body in response to injury or infection, which contribute to the inflammatory response. These mediators include various chemical factors such as cytokines, chemokines, prostaglandins, leukotrienes, and histamine, among others. They play a crucial role in regulating the inflammatory process by attracting immune cells to the site of injury or infection, increasing blood flow to the area, and promoting the repair and healing of damaged tissues. However, an overactive or chronic inflammatory response can also contribute to the development of various diseases and conditions, such as autoimmune disorders, cardiovascular disease, and cancer.

Exudates and transudates are two types of bodily fluids that can accumulate in various body cavities or tissues as a result of injury, inflammation, or other medical conditions. Here are the medical definitions:

1. Exudates: These are fluids that accumulate due to an active inflammatory process. Exudates contain high levels of protein, white blood cells (such as neutrophils and macrophages), and sometimes other cells like red blood cells or cellular debris. They can be yellow, green, or brown in color and may have a foul odor due to the presence of dead cells and bacteria. Exudates are often seen in conditions such as abscesses, pneumonia, pleurisy, or wound infections.

Examples of exudative fluids include pus, purulent discharge, or inflammatory effusions.

2. Transudates: These are fluids that accumulate due to increased hydrostatic pressure or decreased oncotic pressure within the blood vessels. Transudates contain low levels of protein and cells compared to exudates. They are typically clear and pale yellow in color, with no odor. Transudates can be found in conditions such as congestive heart failure, liver cirrhosis, or nephrotic syndrome.

Examples of transudative fluids include ascites, pleural effusions, or pericardial effusions.

It is essential to differentiate between exudates and transudates because their underlying causes and treatment approaches may differ significantly. Medical professionals often use various tests, such as fluid analysis, to determine whether a fluid sample is an exudate or transudate.

Interleukin-8 (IL-8) is a type of cytokine, which is a small signaling protein involved in immune response and inflammation. IL-8 is also known as neutrophil chemotactic factor or NCF because it attracts neutrophils, a type of white blood cell, to the site of infection or injury.

IL-8 is produced by various cells including macrophages, epithelial cells, and endothelial cells in response to bacterial or inflammatory stimuli. It acts by binding to specific receptors called CXCR1 and CXCR2 on the surface of neutrophils, which triggers a series of intracellular signaling events leading to neutrophil activation, migration, and degranulation.

IL-8 plays an important role in the recruitment of neutrophils to the site of infection or tissue damage, where they can phagocytose and destroy invading microorganisms. However, excessive or prolonged production of IL-8 has been implicated in various inflammatory diseases such as chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, and cancer.

Alveolar macrophages are a type of macrophage (a large phagocytic cell) that are found in the alveoli of the lungs. They play a crucial role in the immune defense system of the lungs by engulfing and destroying any foreign particles, such as dust, microorganisms, and pathogens, that enter the lungs through the process of inhalation. Alveolar macrophages also produce cytokines, which are signaling molecules that help to coordinate the immune response. They are important for maintaining the health and function of the lungs by removing debris and preventing infection.

Cell aggregation is the process by which individual cells come together and adhere to each other to form a group or cluster. This phenomenon can occur naturally during embryonic development, tissue repair, and wound healing, as well as in the formation of multicellular organisms such as slime molds. In some cases, cell aggregation may also be induced in the laboratory setting through the use of various techniques, including the use of cell culture surfaces that promote cell-to-cell adhesion or the addition of factors that stimulate the expression of adhesion molecules on the cell surface.

Cell aggregation can be influenced by a variety of factors, including the type and properties of the cells involved, as well as environmental conditions such as pH, temperature, and nutrient availability. The ability of cells to aggregate is often mediated by the presence of adhesion molecules on the cell surface, such as cadherins, integrins, and immunoglobulin-like cell adhesion molecules (Ig-CAMs). These molecules interact with each other and with extracellular matrix components to promote cell-to-cell adhesion and maintain the stability of the aggregate.

In some contexts, abnormal or excessive cell aggregation can contribute to the development of diseases such as cancer, fibrosis, and inflammatory disorders. For example, the aggregation of cancer cells can facilitate their invasion and metastasis, while the accumulation of fibrotic cells in tissues can lead to organ dysfunction and failure. Understanding the mechanisms that regulate cell aggregation is therefore an important area of research with potential implications for the development of new therapies and treatments for a variety of diseases.

... (LTB4) is a leukotriene involved in inflammation. It has been shown to promote insulin resistance in obese mice ... Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It is produced from leukocytes in response to inflammatory ... A study at the University of California, San Diego School of Medicine has shown that leukotriene B4 promotes insulin resistance ... It is synthesized by leukotriene-A4 hydrolase from leukotriene A4. ...
The leukotriene B4 receptors (BLTRs) include the following two receptors: Leukotriene B4 receptor 1 (BLTR1) Leukotriene B4 ... receptor 2 (BLTR2) Eicosanoid receptor Leukotriene receptor v t e (Articles with short description, Short description matches ...
Other names in common use include leukotriene-B4 20-hydroxylase, leucotriene-B4 omega-hydroxylase, LTB4 20-hydroxylase, and ... In enzymology, a leukotriene-B4 20-monooxygenase (EC 1.14.13.30) is an enzyme that catalyzes the chemical reaction (6Z,8E,10E, ... Soberman RJ, Harper TW, Murphy RC, Austen KF (1985). "Identification and functional characterization of leukotriene B4 20- ... Shak S, Goldstein IM (1985). "Leukotriene B4 omega-hydroxylase in human polymorphonuclear leukocytes. Partial purification and ...
... is a protein that in humans is encoded by the LTB4R gene. Eicosanoid receptor Etalocib, an antagonist ... "Entrez Gene: LTB4R leukotriene B4 receptor". Raport CJ, Schweickart VL, Chantry D, et al. (1996). "New members of the chemokine ... LTB4R+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH) Receptors,+Leukotriene+B4 at the ... 2003). "Leukotriene B4 receptor antagonist LY293111 inhibits proliferation and induces apoptosis in human pancreatic cancer ...
Discovered several years after the leukotriene B4 receptor 1 (BLT1), BLT2 receptor binds leukotriene B4 (LTB4) with far lower ... "Novel involvement of leukotriene B4 receptor 2 through ERK activation by PP2A down-regulation in leukotriene B4-induced keratin ... "Entrez Gene: LTB4R2 leukotriene B4 receptor 2". Wang S, Gustafson E, Pang L, Qiao X, Behan J, Maguire M, Bayne M, Laz T (Dec ... Leukotriene B4 receptor 2, also known as BLT2, BLT2 receptor, and BLTR2, is an Integral membrane protein that is encoded by the ...
internet checked April 24, 2012[full citation needed] Crooks, S.W; Stockley, R.A (1998). "Leukotriene B4". The International ... Leukotriene antagonists are used to treat these disorders by inhibiting the production or activity of leukotrienes. The name ... Leukotrienes are involved in asthmatic and allergic reactions and act to sustain inflammatory reactions. Several leukotriene ... Leukotrienes also have a powerful effect in bronchoconstriction and increase vascular permeability. Leukotrienes contribute to ...
... leukotriene B4, leukotriene C4, leukotriene D4, leukotriene E4, lipoxin A4, and lipoxin B4. It and other members of the 5-(S)- ... Leukotriene A4 may then be further metabolized either to leukotriene B4 by leukotriene A4 hydrolase or to leukotriene C4 by ... Finally, leukotriene C4 may be metabolized to leukotriene D4 and then to leukotriene E4. The relative amounts of these ... Since a previously discovered arachidonic acid metabolite made by neutrophils, leukotriene B4 (LTB4), also stimulates human ...
... carcinoma Esophageal cancer Pancreatic cancer Colon cancer Leukotriene B4 receptor 2 Leukotriene B4 receptor 1 Leukotriene B4 ... Leukotriene B4 (i.e. LTB4) is an arachidonic acid metabolite made by the 5-lipoxygenase enzyme pathway. It activates cells ... BLT2, also called leukotriene B4 receptor 2, is closely associated with 12-HHT in stimulation of metastasis (malignant behavior ... Hicks, A; Monkarsh, S. P.; Hoffman, A. F.; Goodnow Jr, R (2007). "Leukotriene B4 receptor antagonists as therapeutics for ...
... (LTA4) is a leukotriene, and is the precursor for the productions of LTB4 (leukotriene B4) and LTC4 (leukotriene ... Abu, J. I.; Konje, J. C. (March 2000). "Leukotrienes in gynaecology: the hypothetical value of anti-leukotriene therapy in ... Abu, J. I.; Konje, J. C. (March 2000). "Leukotrienes in gynaecology: the hypothetical value of anti-leukotriene therapy in ... "Blocking Macrophage Leukotriene B4 Prevents Endothelial Injury and Reverses Pulmonary Hypertension". Science Translational ...
"Leukotriene B4 antagonism ameliorates experimental lymphedema". Science Translational Medicine. 9 (389): eaal3920. doi:10.1126/ ... Muskardin, D.T.; Voelkel, N.F.; Fitzpatrick, F.A. (1994). "Modulation of pulmonary leukotriene formation and perfusion pressure ... It is an inhibitor of arginyl aminopeptidase (aminopeptidase B), leukotriene A4 hydrolase (a zinc metalloprotease that displays ... leukotriene D4 hydrolase). It is being studied for use in the treatment of acute myelocytic leukemia and lymphedema. It is ...
Leukotriene B4 is a pro-inflammatory eicosanoid with strong chemoattractant properties. It can be rapidly produced by activated ... CYP4F2 then coverts 20-hydroxyleukotriene B4 to 20-oxoleukotriene B4 and then to 20-carboxyleukotrene B4. It is α-, β-, and ω- ... The enzyme starts the process of inactivating and degrading leukotriene B4, a potent mediator of inflammation. This gene is ... CYP4F2 starts the process of inactivating and degrading leukotriene B4, by converting it to its ω-hydroxylated metabolite 20- ...
Yokomizo T (February 2015). "Two distinct leukotriene B4 receptors, BLT1 and BLT2". Journal of Biochemistry. 157 (2): 65-71. ... an agonist of Leukotriene B4 receptors (i.e. BLT2 receptors) and mediator of certain BLT2 receptor actions. The enzyme plays a ... 10E-trienoic acid is a natural ligand for leukotriene B4 receptor 2". The Journal of Experimental Medicine. 205 (4): 759-766. ...
Leukotrienes: BLT1 (Leukotriene B4 receptor) - LTB4R; BLT1 is the primary receptor for leukotriene B4. Relative potencies in ... BLT2 (Leukotriene B4 receptor 2) - LTB4R2; the receptor for 12-Hydroxyheptadecatrienoic acid, leukotriene B4, and certain other ... CysLT1 (Cysteinyl leukotriene receptor 1) - CYSLTR1;CYSLTR1 is the receptor for Leukotriene C4 and Leukotriene D4; in binds and ... GPR17 - GPR17; while one study reported that leukotriene C4, leukotriene D4, and leukotriene E4 bind to and activate GPR17 with ...
Gelfand EW (October 2017). "Importance of the leukotriene B4-BLT1 and LTB4-BLT2 pathways in asthma". Seminars in Immunology. 33 ... Yokomizo T (February 2015). "Two distinct leukotriene B4 receptors, BLT1 and BLT2". Journal of Biochemistry. 157 (2): 65-71. ... which like the receptors for leukotriene B4, is a G protein-coupled receptor. Aside from the skin, neutrophils are the body's ... Their most prominent member with chemotactic factor activity is leukotriene B4, which elicits adhesion, chemotaxis, and ...
Yokomizo, T. (2014). "Two distinct leukotriene B4 receptors, BLT1 and BLT2". Journal of Biochemistry. 157 (2): 65-71. doi: ...
Kikuta Y, Kato M, Yamashita Y, Miyauchi Y, Tanaka K, Kamada N, Kusunose M (March 1998). "Human leukotriene B4 omega-hydroxylase ... cDNA cloning and expression of leukotriene B4 omega-hydroxylase". The Journal of Biological Chemistry. 268 (13): 9376-80. doi: ... March 2006). "Cytochrome P-450 4F18 is the leukotriene B4 omega-1/omega-2 hydroxylase in mouse polymorphonuclear leukocytes: ... The hydroxylation-induced inactivation of the mediators of inflammation, perhaps particularly of leukotriene B4, may underlie ...
An antioxidant-type inhibitor of leukotriene B4 formation". Planta Medica. 60 (5): 410-3. doi:10.1055/s-2006-959520. PMID ...
In contrast, PPARα is activated by leukotriene B4. Certain members of the 15-hydroxyeicosatetraenoic acid family of arachidonic ...
A new role for leukotriene B4 12-hydroxydehydrogenase/15-oxoprostaglandin 13-reductase". J. Biol. Chem. 276 (44): 40803-10. doi ...
Kumar KCS, Müller K (April 2000). "Depsides as non-redox inhibitors of leukotriene B4 biosynthesis and HaCaT cell growth, 2. ... 1. Inhibitory action against leukotriene B4 biosynthesis by a non-redox mechanism". J. Nat. Prod. 62 (6): 817-20. doi:10.1021/ ... As inhibitors of prostaglandin synthesis and leukotriene B4 biosynthesis, some depsides have in vitro anti-inflammatory ...
... activates the Leukotriene B4 receptor, Leukotriene B4 receptor 2 (BLT2) but not its Leukotriene B4 receptor 1 (BLT1). This ... GPR31 and the Leukotriene B4 receptor 2; 12S-HETE also acts as a receptor antagonist by binding to but not stimulating the ... HETE bind to and activate the Leukotriene B4 receptor 2, activate the Peroxisome proliferator-activated receptor gamma, and at ... "Hydroxyeicosanoids bind to and activate the low affinity leukotriene B4 receptor, BLT2". The Journal of Biological Chemistry. ...
15-leukotrienes B4) and to two isomeric erythro-14,15-dihydroxy-5-cis-8,10,12-eicosatetraenoic acids (14,15-leukotrienes B4). ... 15(S)-HpETE and 15(S)-HETE bind to and activate the G protein-coupled receptor, leukotriene B4 receptor 2, i.e. BLT2. This ... Eoxin A4, eoxin C4, eoxin D4, and eoxin E4 are analogs of leukotriene A4, C4, leukotriene D4, and E4. Formation of the ... "Hydroxyeicosanoids bind to and activate the low affinity leukotriene B4 receptor, BLT2". Journal of Biological Chemistry. 276 ( ...
"An enzyme that inactivates the inflammatory mediator leukotriene b4 restricts mycobacterial infection". PLOS ONE. 8 (7): e67828 ... "Leukotriene A4 Hydrolase Genotype and HIV Infection Influence Intracerebral Inflammation and Survival From Tuberculous ...
Leukotriene B4, vis., Leukotriene B4 receptor 2 (BLT2), but not its Leukotriene B4 receptor 1, mediates responses to 12(S)-HETE ... "Antiinflammatory effects of second-generation leukotriene B4 receptor antagonist, SC-53228: Impact upon leukotriene B4- and 12( ... Kim, G. Y.; Lee, J. W.; Cho, S. H.; Seo, J. M.; Kim, J. H. (2009). "Role of the low-affinity leukotriene B4 receptor BLT2 in ... Based on the effects of LTB4 receptor antagonists, for example, leukotriene B4 receptor 2 mediates: the rise in cytosolic Ca2+ ...
Prostaglandin E2 and inflammatory exudate are also reduced and leukotriene B4 is inhibited. Carprofen can also be given orally ...
It acts as a leukotriene B4 receptor antagonist and a PPARγ agonist. Clinical trials were conducted measuring efficacy for ... Adrian, T. E.; Hennig, R; Friess, H; Ding, X (2008). "The Role of PPARgamma Receptors and Leukotriene B(4) Receptors in ... Leukotriene antagonists, Salicylic acids, Phenol ethers, Fluoroarenes, Abandoned drugs, Biphenyls, All stub articles, ...
"Purification and characterization of recombinant human neutrophil leukotriene B4 omega-hydroxylase (cytochrome P450 4F3)". ...
"Purification and characterization of recombinant human neutrophil leukotriene B4 omega-hydroxylase (cytochrome P450 4F3)". ...
Studies have shown that it does not inhibit 5-lipoxygenase and leukotriene B4, as originally claimed. It is therefore not ... "Benoxaprofen does not inhibit formation of leukotriene B4 in a model of acute inflammation". Biochemical Pharmacology. 33 (18 ...
It also inhibits the release of leukotriene B4 from monocytes after stimulation with bacterial lipopolysaccharides. It blocks ...
Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It has been shown to promote insulin resistance in obese mice ... Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. It is produced from leukocytes in response to inflammatory ... A study at the University of California, San Diego School of Medicine has shown that leukotriene B4 promotes insulin resistance ... It is synthesized by leukotriene-A4 hydrolase from leukotriene A4. ...
Specific inhibition of leukotriene B4-induced neutrophil activation by LY223982.. W T Jackson, R J Boyd, L L Froelich, B E ... Specific inhibition of leukotriene B4-induced neutrophil activation by LY223982.. W T Jackson, R J Boyd, L L Froelich, B E ... Specific inhibition of leukotriene B4-induced neutrophil activation by LY223982.. W T Jackson, R J Boyd, L L Froelich, B E ... Specific inhibition of leukotriene B4-induced neutrophil activation by LY223982. Message Subject (Your Name) has forwarded a ...
Leukotriene B4 induces formation of inositol phosphates in rat peritoneal polymorphonuclear leukocytes.. S Mong, G Chi-Rosso, J ... Leukotriene B4 induces formation of inositol phosphates in rat peritoneal polymorphonuclear leukocytes.. S Mong, G Chi-Rosso, J ... Leukotriene B4 induces formation of inositol phosphates in rat peritoneal polymorphonuclear leukocytes.. S Mong, G Chi-Rosso, J ... Leukotriene B4 (LTB4) induced rapid breakdown of prelabeled inositol phospholipids in rat peritoneal polymorphonuclear ...
In vitro inhibitory activity against human neutrophil leukotriene B4 (LTB4) induced Chemotaxis. ...
LifeSpan has used multiple antibodies to study the localization profile of the Leukotriene B4 Receptor / BLT1 protein across an ...
HTLV-1-induced leukotriene B4 secretion promotes the recruitment of target cells. *Florent Percher1,3, ... Percher, F., Jeannin, P., Gessain, A. et al. HTLV-1-induced leukotriene B4 secretion promotes the recruitment of target cells. ... HTLV-1-induced leukotriene B4 secretion promotes the recruitment of target cells ... could secrete higher levels of leukotriene B4 (LTB4), a potent chemoattractant, than cells from healthy donors. We proposed ...
... the key enzyme in leukotriene biosynthesis, which may account for their anti-inflammatory effec … ... Leukotriene B4 / metabolism * Lipoxygenase Inhibitors* * Neutrophils / drug effects * Neutrophils / enzymology * Plant Extracts ... and plasma leukotriene B(4) of frankincense-treated healthy volunteers was determined. Factors influencing 5-LO activity (i.e ... oral administration of frankincense extracts to human healthy volunteers failed to suppress leukotriene B(4) plasma levels. Our ...
... and leukotriene B4 (LTB4), which represent the cyclooxygenase and 5-lipoxygenase pathways, were determined in 21 pairs of ...
19] and leukotriene B4. [20] Tissue dysfunction is thought to be due to lipid storage in membranes. [16] FALDH is a component ... Defective metabolism of leukotriene B4 in the Sjogren-Larsson syndrome. J Neurol Sci. 2001 Jan 15. 183(1):61-7. [QxMD MEDLINE ... Patients with severe pruritus may benefit from treatment with zileuton, which blocks the synthesis of leukotriene B4, a ... Patients with Sjögren-Larsson syndrome accumulate leukotriene B4 and its omega-hydroxy metabolite, which are probably ...
The leukotriene B4 receptors BLT1. and BLT2 form an antagonistic sensitizing system in peripheral sensory neurons. J Biol Chem ... Leukotriene B4 mediatesinflammation via. TRPV1 in duct obstruction-induced pancreatitis in rats. Pancreas. 2011; 40(5):708-14. ... Leukotriene B4 is a proinflammatory lipid-mediator whose role in peripheral nociceptive sensitization is to date not well ... Accordingly, Leukotriene B4 -induced thermal hyperalgesia was mediated through BLT1 and TRPV1 as shown using the respective ...
LTB4: Leukotriene B-4. N-CoR: Nuclear receptor corepessor. NSAID: Non steroidal anti inflammatory. NCoA-1: Nuclear receptor ...
Leukotrienes (LTs) are lipid mediators derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. Cysteinyl (cys) ... Islam SA, Thomas SY, Hess C, et al.: The leukotriene B4 lipid chemoattractant receptor BLT1 defines antigen-primed T cells in ... Tager AM, Bromley SK, Medoff BD, et al.: Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Nat Immunol ... Weller CL, Collington SJ, Brown JK, et al.: Leukotriene B4, an activation product of mast cells, is a chemoattractant for their ...
Structure, properties, spectra, suppliers and links for: (5R,6E,8E,10Z,12S,14Z)-5,12-Dihydroxy-6,8,10,14-icosatetraenoic acid.
Leukotriene synthesis was further enhanced by glucocorticoids and remained elevated at 3-5 months, but had returned to baseline ... Leukotriene B4 strongly increases monocyte chemoattractant protein-1 in human monocytes. Arterioscler Thromb. Vasc. Biol. 24, ... Pernet, E., Downey, J., Vinh, D. C., Powell, W. S. & Divangahi, M. Leukotriene B4-type I interferon axis regulates macrophage- ... Monocyte chemoattractant protein-1/CC chemokine ligand 2 controls microtubule-driven biogenesis and leukotriene B4-synthesizing ...
Leukotriene B4 receptor locus gene characterisation and association studies in asthma. BMC medical genetics. 13(1), 110 (In ... Human bronchial epithelial cells express an active and inducible biosynthetic pathway for leukotrienes B4 and C4. Clinical and ... The cysteinyl-leukotriene type 1 receptor polymorphism 927T/C is associated with atopy severity but not with asthma. Clinical ... Leukotriene pathway genetics and pharmacogenetics in allergy. Allergy. 64(6), 823-39 ...
12-oxo-leukotriene B4. This is an initial and key step of metabolic inactivation of leukotriene B4. ... Has no activity towards PGE1, PGE2 and PGE2-alpha (By similarity). Catalyzes the conversion of leukotriene B4 into its ...
leukotriene B4 receptor. ISO. CTD Direct Evidence: marker/mechanism. CTD. PMID:30818366. NCBI chr15:29,263,199...29,265,716 ...
The effect of atorvastatin on formation of leukotriene B4 in patients with coronary artery disease. Korsgaard, A. M., Lysgaard ...
nuclear-neutrophil biosynthesis of leukotriene B4. Am J Clin. Nutr. 1992;55:39-45. ...
Leukotriene B4 10. Cyclooxygenase 2 (Cyclooxygenase-2) Related Therapies and Procedures. 1. Oral Administration ...
2014). Reduced 15-lipoxygenase 2 and lipoxin A4/leukotriene B4 ratio in children with cystic fibrosis. Eur. Respir. J. 44, 394- ... Konstan, M. W., Walenga, R. W., Hilliard, K. A., and Hilliard, J. B. (1993). Leukotriene B4 markedly elevated in the epithelial ... Papayianni, A., Serhan, C. N., and Brady, H. R. (1996). Lipoxin A4 and B4 inhibit leukotriene-stimulated interactions of human ... Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. J. Immunol. 178, 3912 ...
Hofer M, Rechsteiner T, Becher G, et al. Leukotriene B4 in exhaled breath condensate of patients after lung transplantation. ... Only exhaled carbonyl sulphide as a marker of acute rejection 137 and leukotriene B4 as a marker of infection 138 have been ...
PPARγ is activated by PGJ2 (a prostaglandin). In contrast, PPARα is activated by leukotriene B4." - from Wikipedia (PPAR) --Y ... Leukotriene B4 does not look too promising (http://www.ncbi.nlm.nih.gov/pubmed/8975956) --Y ...
Mita H, Turikisawa N, Yamada T, Taniguchi M. Quantification of leukotriene B4 glucuronide in human urine. Prostaglandins Other ... Increased urinary leukotriene E4 concentration in patients with eosinophilic pneumonia. E. Ono, M. Taniguchi, H. Mita, N. ... Increased urinary leukotriene E4 concentration in patients with eosinophilic pneumonia. E. Ono, M. Taniguchi, H. Mita, N. ... Increased urinary leukotriene E4 concentration in patients with eosinophilic pneumonia. E. Ono, M. Taniguchi, H. Mita, N. ...
19] and leukotriene B4. [20] Tissue dysfunction is thought to be due to lipid storage in membranes. [16] FALDH is a component ... Defective metabolism of leukotriene B4 in the Sjogren-Larsson syndrome. J Neurol Sci. 2001 Jan 15. 183(1):61-7. [QxMD MEDLINE ... Patients with severe pruritus may benefit from treatment with zileuton, which blocks the synthesis of leukotriene B4, a ... Patients with Sjögren-Larsson syndrome accumulate leukotriene B4 and its omega-hydroxy metabolite, which are probably ...
Leukotrienes, such as leukotriene B4, are critical mediators of asthma. Further studies into lipid mediators and their ... Class 2 lipid mediators are eicosanoids, such as prostaglandins and leukotrienes, that are produced from arachidonic acid via ...
Leukotriene b4 12-hydroxydehydrogenase/prostaglandin 15-keto reductase [110405] (1 species). *. Species Guinea pig (Cavia ...
Metabolism of leukotriene B4 by cultured human keratinocytes. Formation of glutathione conjugates and dihydro metabolites. ... Metabolism of leukotriene B4 by cultured human keratinocytes. Formation of glutathione conjugates and dihydro metabolites.. Six ... previously unidentified leukotriene (LT) B4 metabolites formed during incubation of LTB4 with human keratinocytes in primary ...
Leukotriene B4 amplifies eosinophil accumulation in response to nematodes. The Journal of experimental medicine Patnode, M. L ... Surprisingly, collective migration toward worms requires paracrine leukotriene B4 signaling between eosinophils. In contrast, ... Our findings establish that nematode-derived signals can directly induce leukotriene production by eosinophils and that ... However, mice deficient in leukotriene signaling show markedly attenuated eosinophil accumulation after injection of C. elegans ...
CTX-4430 works by inhibiting Leukotriene A4 Hydrolase (LTA4H), the major rate-limiting step in Leukotriene B4 (LTB4) production ... which blocks the pro-inflammatory enzyme Leukotriene A4 Hydrolase (LTA4H). ...
  • Leukotriene B4 (LTB4) is a leukotriene involved in inflammation. (wikipedia.org)
  • Leukotriene B4 (LTB4) induced rapid breakdown of prelabeled inositol phospholipids in rat peritoneal polymorphonuclear leukocytes (PMNs). (aspetjournals.org)
  • showed that PBMCs from HTLV-1 infected individuals (HTLV-1 asymptomatic carrier and HAM/TSP patients) could secrete higher levels of leukotriene B4 (LTB4), a potent chemoattractant, than cells from healthy donors. (biomedcentral.com)
  • Blocking LTB4 secretion (with diverse specific inhibitors of the leukotriene pathway) prevented the recruitment of potential target cells, as well as the formation of cell-to-cell contacts. (biomedcentral.com)
  • In conclusion, HTLV-1 diverts the leukotriene pathway and LTB4-mediated chemotaxis facilitates viral propagation. (biomedcentral.com)
  • The levels of prostaglandin E2 (PGE2), PGF2 alpha, PGI2, thromboxane A2 (TXA2), and leukotriene B4 (LTB4), which represent the cyclooxygenase and 5-lipoxygenase pathways, were determined in 21 pairs of surgically excised human colon cancer and histologically normal mucosa samples 5 to 10 cm away from the tumor. (nih.gov)
  • CTX-4430 works by inhibiting Leukotriene A4 Hydrolase (LTA4H), the major rate-limiting step in Leukotriene B4 (LTB4) production. (benzinga.com)
  • It acts by targeting complement C5 and leukotriene B4 (LTB4). (pharmaceutical-technology.com)
  • CYP4F3A, which encodes the leukotriene B4 (LTB4) omega-hydroxylase, is important for inactivation of LTB4 in neutrophils. (cdc.gov)
  • The potential of Akari's investigational nomacopan, a novel bispecific inhibitor of both complement C5 and leukotriene B4 (LTB4), as a potential treatment for HSCT-TMA also will be discussed. (texomashomepage.com)
  • Akari's lead asset, investigational nomacopan, is a bispecific recombinant inhibitor of complement C5 activation and leukotriene B4 (LTB4) activity. (texomashomepage.com)
  • Dose-dependent reduction of leukotriene B4 (LTB4): DG051 was shown to reduce LTB4 production in a dose-dependent manner, with a peak reduction of more than 70% versus baseline after 7 days of treatment. (decode.com)
  • The at-risk versions of these genes confer increased risk of heart attack by increasing the production of the pro-inflammatory molecule leukotriene B4 (LTB4). (decode.com)
  • Leukotriene B4 (LTB4) stimulates the release of cytokines and mediators that participate in tissue inflammation and acts as a chemoattractant for neutrophils, eosinophils and monocytes at the inflammation site. (bioworld.com)
  • Furthermore, DS patients with PD presented high levels of 5-LO expression, suggesting the presence of leukotriene B4 (LTB4) in PD, thus demonstrating that the changes in NE function due to the elevation of inflammatory mediators contribute to PD. (bvsalud.org)
  • Patients with severe pruritus may benefit from treatment with zileuton, which blocks the synthesis of leukotriene B4, a compound that, along with its omega-hydroxy metabolite, probably gives rise to the itching. (medscape.com)
  • Patients with Sjögren-Larsson syndrome accumulate leukotriene B4 and its omega-hydroxy metabolite, which are probably responsible for the pruritus seen in this disease. (medscape.com)
  • Class 2 lipid mediators are eicosanoids, such as prostaglandins and leukotrienes, that are produced from arachidonic acid via cyclooxygenase (COX) and lipoxygenase (LOX) pathways. (rndsystems.com)
  • In general, the host response to bacterial stimuli leads to a cascade of inflammatory mediators such as cytokines (TNF-α), chemokines (IL-8) as well as prostaglandins and leukotrienes, which are metabolites from arachidonic acid. (bvsalud.org)
  • MDM from convalescent SARS-CoV-2-infected individuals showed a downregulation of pro-resolving factors and an increased production of pro-inflammatory eicosanoids, particularly 5-lipoxygenase-derived leukotrienes. (nature.com)
  • Eicosanoids are formed from arachidonic acid (AA) through different enzymatic pathways, including the cyclooxygenase (COX) pathway, synthesizing prostanoids and the 5-lipoxygenase (5-LOX) pathway, generating leukotrienes (LTs) 8 . (nature.com)
  • This phase can be measured in gingival crevicular fluid by a breakdown product of neutrophils, leukotriene B4. (rdhmag.com)
  • They play important roles in the pain pathway where in concert with proinflammatory factors such as leukotrienes they mediate sensitization and hyperalgesia. (researchgate.net)
  • Leukotrienes (LTs) are lipid mediators derived from the 5-lipoxygenase pathway of arachidonic acid metabolism. (springer.com)
  • LTA4H is encoded by one of the genes in the leukotriene pathway deCODE has linked to increased risk of heart attack. (decode.com)
  • It is synthesized by leukotriene-A4 hydrolase from leukotriene A4. (wikipedia.org)
  • Celtaxsys, Inc., a private biopharmaceutical company developing a new class of drugs to treat chronic inflammatory disorders, today announced the initiation of a first-in-human Phase 1 clinical study of CTX-4430, which blocks the pro-inflammatory enzyme Leukotriene A4 Hydrolase (LTA4H). (benzinga.com)
  • DG051 is a first-in-class, small-molecule inhibitor of leukotriene A4 hydrolase (LTA4H) discovered by deCODE's chemistry unit and being developed for the prevention of heart attack. (decode.com)
  • Leukotriene synthesis was further enhanced by glucocorticoids and remained elevated at 3-5 months, but had returned to baseline at 12 months post SARS-CoV-2 infection. (nature.com)
  • Resident and recruited macrophages in the lung produce high levels of cysteinyl LTs (cysLTs) and leukotriene B 4 (LTB 4 ), thereby promoting granulocyte infiltration, airway inflammation and tissue remodeling 8 . (nature.com)
  • Although eosinophils produce cysteinyl leukotrienes (CysLTs) in large quantities, information on the relationship between CysLTs and eosinophilic pneumonia (EP) is lacking. (ersjournals.com)
  • Leukotrienes, such as leukotriene B4, are critical mediators of asthma. (rndsystems.com)
  • Specific inhibition of leukotriene B4-induced neutrophil activation by LY223982. (aspetjournals.org)
  • Moreover, interference of boswellic acids with 5-LO in neutrophil incubations in the presence of albumin and in human whole blood was assessed, and plasma leukotriene B(4) of frankincense-treated healthy volunteers was determined. (nih.gov)
  • Such substances include eosinophil chemotactic factor of anaphylaxis, leukotriene B4, complement complex (C5-C6-C7), and histamine (over a narrow range of concentration). (msdmanuals.com)
  • Leukotriene B4 induces formation of inositol phosphates in rat peritoneal polymorphonuclear leukocytes. (aspetjournals.org)
  • LifeSpan has used multiple antibodies to study the localization profile of the Leukotriene B4 Receptor / BLT1 protein across an extensive panel of normal and diseased human tissue types. (kxcdn.com)
  • Methods A next-generation sequencing (NGS) panel was created for the human TRPV1 gene and in addition, for the leukotriene receptors BLT1 and BLT2 recently described to modulate TRPV1 mediated sensitisation processes rendering the coding genes LTB4R and LTB4R2 important co-players in pharmacogenetic approaches involving TRPV1. (researchgate.net)
  • It was shown that in vitro 11-keto-boswellic acids inhibit 5-lipoxygenase (5-LO, EC 1.13.11.34), the key enzyme in leukotriene biosynthesis, which may account for their anti-inflammatory effectiveness. (nih.gov)
  • The increased urinary concentrations of leukotriene and eosinophil-derived neurotoxin were associated with acute exacerbation in eosinophilic pneumonia patients. (ersjournals.com)
  • The essential components of eosinophil migration into the lung, such as leukotriene (LT)D 4 , LTB 4 and IL-5, are generally considered chemotactic factors. (ersjournals.com)
  • A study at the University of California, San Diego School of Medicine has shown that leukotriene B4 promotes insulin resistance in obese mice. (wikipedia.org)
  • The increased leukotriene concentration significantly correlated with diffusing capacity of the lung for carbon monoxide, suggesting that the monitoring of leukotriene concentration may aid in the management of eosinophilic pneumonia patients. (ersjournals.com)
  • Finally, single dose (800 mg) oral administration of frankincense extracts to human healthy volunteers failed to suppress leukotriene B(4) plasma levels. (nih.gov)
  • A simplification of this process is as follows: Cell injury results in the release of prostaglandins, leukotrienes, bradykinin, substance P, and other autacoids. (nationalacademies.org)
  • 3. Molecular cloning and functional characterization of murine cysteinyl-leukotriene 1 (CysLT(1)) receptors. (nih.gov)
  • 5. Characterization of mouse cysteinyl leukotriene receptors mCysLT1 and mCysLT2: differential pharmacological properties and tissue distribution. (nih.gov)
  • 12. Cysteinyl leukotriene receptors. (nih.gov)
  • 17. Functional recognition of a distinct receptor preferential for leukotriene E4 in mice lacking the cysteinyl leukotriene 1 and 2 receptors. (nih.gov)
  • Lipid chemoattractant receptors (PAF and leukotriene B4) were also desensitized by peptide chemoattractants but not vice versa. (duke.edu)
  • Cysteinyl leukotrienes are potent lipid mediators in inflammation, inducing smooth muscle contractions and increased capillary permeability. (enzolifesciences.com)
  • 16. Pharmacological characterization of the first potent and selective antagonist at the cysteinyl leukotriene 2 (CysLT(2)) receptor. (nih.gov)
  • While the precise mechanism underlying leukotriene B4's effects on liver macrophages has yet to be determined, these results are "important findings highlighting the value of a systems or biological approach to experimentation not possible with reductionist approaches," immunologist Kevin Tracey of the Feinstein Institutes for Medical Research who also did not participate in the research writes in an email to The Scientist . (the-scientist.com)
  • Specific inhibition of leukotriene B4-induced neutrophil activation by LY223982. (aspetjournals.org)
  • The cysteinyl leukotrienes (LTC 4 , LTD 4 , and LTE 4 ) are formed by addition of cysteine derivatives to LTA 4 . (enzolifesciences.com)
  • The conversion of LTA 4 to LTC 4 by the enzyme LTC 4 synthase limits the rate of cysteinyl leukotriene formation. (enzolifesciences.com)
  • Although eosinophils produce cysteinyl leukotrienes (CysLTs) in large quantities, information on the relationship between CysLTs and eosinophilic pneumonia (EP) is lacking. (ersjournals.com)
  • 1. The murine cysteinyl leukotriene 2 (CysLT2) receptor. (nih.gov)
  • 2. Identification in mice of two isoforms of the cysteinyl leukotriene 1 receptor that result from alternative splicing. (nih.gov)
  • 4. Characterization of the human cysteinyl leukotriene 2 receptor. (nih.gov)
  • 6. The molecular characterization and tissue distribution of the human cysteinyl leukotriene CysLT(2) receptor. (nih.gov)
  • 7. Molecular cloning and characterization of a second human cysteinyl leukotriene receptor: discovery of a subtype selective agonist. (nih.gov)
  • 9. Guinea pig cysteinyl leukotriene receptor 2 (gpCysLT2) mediates cell proliferation and intracellular calcium mobilization by LTC4 and LTD4. (nih.gov)
  • 10. Differential signaling of cysteinyl leukotrienes and a novel cysteinyl leukotriene receptor 2 (CysLT₂) agonist, N-methyl-leukotriene C₄, in calcium reporter and β arrestin assays. (nih.gov)
  • 11. IL-5 up-regulates cysteinyl leukotriene 1 receptor expression in HL-60 cells differentiated into eosinophils. (nih.gov)
  • 13. An alternative pathway for metabolism of leukotriene D(4): effects on contractions to cysteinyl-leukotrienes in the guinea-pig trachea. (nih.gov)
  • A study at the University of California, San Diego School of Medicine has shown that leukotriene B4 promotes insulin resistance in obese mice. (wikipedia.org)
  • This led to the identification of the lipid leukotriene B4-a known inflammatory molecule-as the likely spleen signal. (the-scientist.com)
  • Leukotriene B4 plays an important role in inflammatory conditions such as eczema, psoriasis, rheumatoid arthritis, and inflammatory bowel disease. (wrinkle-free-skin-tips.com)
  • The excessive amounts of n-6 fatty acids in our food have led to excessive production of inflammatory factors such as the arachidonic acid metabolites prostaglandin E2 and leukotriene B4. (ergo-log.com)
  • Dietary 0.5% EGCG also increased serum levels of leukotriene B4 and prostaglandin E2. (nih.gov)
  • The increased leukotriene concentration significantly correlated with diffusing capacity of the lung for carbon monoxide, suggesting that the monitoring of leukotriene concentration may aid in the management of eosinophilic pneumonia patients. (ersjournals.com)
  • The essential components of eosinophil migration into the lung, such as leukotriene (LT)D 4 , LTB 4 and IL-5, are generally considered chemotactic factors. (ersjournals.com)
  • Studies in a mouse model of GWI have also shown upregulation of several phospholipids that serve as reservoirs of arachidonic acid, a precursor of leukotrienes (LTs). (tamu.edu)
  • Leukotrienes are major products of 5-lipoxygenase metabolism of arachidonic acid. (enzolifesciences.com)
  • Brain-Specific Increase in Leukotriene Signaling Accompanies Chronic Neuroinflammation and Cognitive Impairment in a Model of Gulf War Illness. (tamu.edu)
  • And, when cultured liver cells were treated with the lipid, it induced TNF production in a dose-dependent manner, an effect that was blocked by leukotriene B4 inhibitors. (the-scientist.com)