Leukotriene D4
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Leukotriene D4
Leukotriene D4 (LTD4) is one of the leukotrienes. Its main function in the body is to induce the contraction of smooth muscle, resulting in bronchoconstriction and vasoconstriction. It also increases vascular permeability. LTD4 is released by basophils. Other leukotrienes that function in a similar manner are leukotrienes C4 and E4. Pharmacological agents that inhibit the function of these leukotrienes are leukotriene receptor antagonists (e.g., zafirlukast, montelukast Montelukast, sold under the brand name Singulair among others, is a medication used in the maintenance treatment of asthma. It is generally less preferred for this use than inhaled corticosteroids. It is not useful for acute asthma attacks. Ot ...) and are useful for asthmatic individuals. References Eicosanoids {{biochemistry-stub ...
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Leukotrienes
Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase. Leukotrienes use lipid signaling to convey information to either the cell producing them (autocrine signaling) or neighboring cells (paracrine signaling) in order to regulate immune responses. The production of leukotrienes is usually accompanied by the production of histamine and prostaglandins, which also act as inflammatory mediators. One of their roles (specifically, leukotriene D4) is to trigger contractions in the smooth muscles lining the bronchioles; their overproduction is a major cause of inflammation in asthma and allergic rhinitis. Leukotriene antagonists are used to treat these disorders by inhibiting the production or activity of leukotrienes. History and name The name ''leukotriene'', introduced by Swedish biochemist Bengt Samuelss ...
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Muscle Contraction
Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such as when holding something heavy in the same position. The termination of muscle contraction is followed by muscle relaxation, which is a return of the muscle fibers to their low tension-generating state. For the contractions to happen, the muscle cells must rely on the interaction of two types of filaments which are the thin and thick filaments. Thin filaments are two strands of actin coiled around each, and thick filaments consist of mostly elongated proteins called myosin. Together, these two filaments form myofibrils which are important organelles in the skeletal muscle system. Muscle contraction can also be described based on two variables: length and tension. A muscle contraction is described as isometric if the muscle tension changes ...
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Bronchoconstriction
Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath. Causes The condition has a number of causes, the most common being emphysema as well as asthma. Exercise and allergies can bring on the symptoms in an otherwise asymptomatic individual. Emphysema With emphysema the shortness of breath due to effective bronchoconstriction from excessive very thick mucus blockage (it is so thick that great difficulty is encountered in expelling it resulting in near exhaustion at times) can bring on panic attacks unless the individual expects this and has effectively learned pursed lip breathing to more quickly transfer oxygen to the blood via the damaged alveoli resulting from the disease. The most common cause of emphysema is smoking and smoking cessation is mandatory if this incurable disease is to be treated. Prevention of bronchoconstriction by this pathway is vita ...
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Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in controlling hemorrhage and reducing acute blood loss. When blood vessels constrict, the flow of blood is restricted or decreased, thus retaining body heat or increasing vascular resistance. This makes the skin turn paler because less blood reaches the surface, reducing the radiation of heat. On a larger level, vasoconstriction is one mechanism by which the body regulates and maintains mean arterial pressure. Medications causing vasoconstriction, also known as vasoconstrictors, are one type of medicine used to raise blood pressure. Generalized vasoconstriction usually results in an increase in systemic blood pressure, but it may also occur in specific tissues, causing a localized reduction in bl ...
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Vascular Permeability
Vascular permeability, often in the form of capillary permeability or microvascular permeability, characterizes the capacity of a blood vessel wall to allow for the flow of small molecules (drugs, nutrients, water, ions) or even whole cells (lymphocytes on their way to the site of inflammation) in and out of the vessel. Blood vessel walls are lined by a single layer of endothelial cells. The gaps between endothelial cells (cell junctions) are strictly regulated depending on the type and physiological state of the tissue. There are several techniques to measure vascular permeability to certain molecules. For instance, the cannulation of a single microvessel with a micropipette, the microvessel is perfused with a certain pressure, occluded downstream and then the velocity of some cells will be related to the permeability.Michel, C. C., Mason, J. C., Curry, F. E. & Tooke, J. E. Development of Landis Technique for Measuring Filtration Coefficient of Individual Capillaries in Frog M ...
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Basophil
Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. However, they are the largest type of granulocyte. They are responsible for inflammatory reactions during immune response, as well as in the formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis and hay fever. They also produce compounds that coordinate immune responses, including histamine and serotonin that induce inflammation, heparin that prevents blood clotting, although there are less than that found in mast cell granules. Mast cells were once thought to be basophils that migrated from blood into their resident tissues (connective tissue), but they are now known to be different types of cells. Basophils were discovered in 1879 by German physician Paul Ehrlich, who one year earlier had found a cell type present in tissues that he termed ''mastzellen'' (now mast cells). Ehrl ...
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Leukotriene C4
Leukotriene C4 (LTC4) is a leukotriene. LTC4 has been extensively studied in the context of allergy and asthma. In cells of myeloid origin such as mast cells, its biosynthesis is orchestrated by translocation to the nuclear envelope along with co-localization of cytosolic phospholipase A2 (cPLA2), Arachidonate 5-lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and LTC4 synthase (LTC4S), which couples glutathione to an LTA4 intermediate. The MRP1 transporter then secretes cytosolic LTC4 and cell surface proteases further metabolize it by sequential cleavage of the γ-glutamyl and glycine residues off its glutathione segment, generating the more stable products LTD4 and LTE4. All three leukotrienes then bind at different affinities to two G-protein coupled receptors: CYSLTR1 and CYSLTR2, triggering pulmonary vasoconstriction and bronchoconstriction. In cells of non-haematopoietic lineage, endoplasmic reticulum (ER) stress and chemotherapy induce LTC4 biosynthesi ...
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Leukotriene E4
Leukotriene E4 (LTE4) is a cysteinyl leukotriene involved in inflammation. It is known to be produced by several types of white blood cells, including eosinophils, mast cells, tissue macrophages, and basophils, and recently was also found to be produced by platelets adhering to neutrophils. It is formed from the sequential conversion of LTC4 to LTD4 and then to LTE4, which is the final and most stable cysteinyl leukotriene. Compared to the short half lives of LTC4 and LTD4, LTE4 is relatively stable and accumulates in breath condensation, in plasma, and in urine, making it the dominant cysteinyl leukotriene detected in biologic fluids. Therefore, measurements of LTE4, especially in the urine, are commonly monitored in clinical research studies. Increased production and excretion of LTE4 has been linked to several respiratory diseases, and urinary LTE4 levels are increased during severe asthma attacks and are especially high in people with aspirin-induced asthma Aspirin exacerba ...
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Antileukotriene
An antileukotriene, also known as leukotriene modifier and leukotriene receptor antagonist, is a medication which functions as a leukotriene-related enzyme inhibitor (arachidonate 5-lipoxygenase) or leukotriene receptor antagonist (cysteinyl leukotriene receptors) and consequently opposes the function of these inflammatory mediators; leukotrienes are produced by the immune system and serve to promote bronchoconstriction, inflammation, Vascular permeability, microvascular permeability, and mucus secretion in asthma and COPD. Leukotriene receptor antagonists are sometimes colloquially referred to as ''leukasts''. Leukotriene receptor antagonists, such as montelukast, zafirlukast, and pranlukast, and 5-lipoxygenase inhibitors, like zileuton and ''Hypericum perforatum'', can be used to treat these diseases. They are less effective than corticosteroids for treating asthma, but more effective for treating certain mast cell disorders. Approaches There are two main approaches to block the ...
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Zafirlukast
Zafirlukast is an orally administered leukotriene receptor antagonist (LTRA) used for the chronic treatment of asthma. While zafirlukast is generally well tolerated, headache and stomach upset often occur. Some rare side effects can occur, which can be life-threatening, such as liver failure. Churg-Strauss syndrome has been associated with zafirlukast, but the relationship isn't thought to be causative in nature. Overdoses of zafirlukast tend to be self-limiting. Zafirlukast, like other LTRAs, works by inhibiting the immune system. Through its action on inflammatory cells in the lungs, zafirlukast reduces the production of inflammatory mediators that are implicated in the pathogenesis of asthma. Zafirlukast is extensively hepatically metabolized by an enzyme called CYP2C9. Zafirlukast inhibits the action of CYP3A4, leading to drug–drug interactions with other drugs that are metabolized by CYP3A4. Genetic differences in LTC4 synthase and CYP2C9 may predict how a person reacts t ...
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Montelukast
Montelukast, sold under the brand name Singulair among others, is a medication used in the maintenance treatment of asthma. It is generally less preferred for this use than inhaled corticosteroids. It is not useful for acute asthma attacks. Other uses include allergic rhinitis and hives of long duration. For allergic rhinitis it is a second-line treatment. Common side effects include abdominal pain, cough, and headache. Severe side effects may include allergic reactions, such as anaphylaxis and eosinophilia. Use in pregnancy appears to be safe. Montelukast is in the leukotriene receptor antagonist family of medications. It works by blocking the action of leukotriene D4 in the lungs resulting in decreased inflammation and relaxation of smooth muscle. Montelukast was approved for medical use in the United States in 1998. It is available as a generic medication. In 2020, it was the fourteenth most commonly prescribed medication in the United States, with more than 31million pr ...
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Asthma
Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, coughing, chest tightness, and shortness of breath. These may occur a few times a day or a few times per week. Depending on the person, asthma symptoms may become worse at night or with exercise. Asthma is thought to be caused by a combination of genetic and environmental factors. Environmental factors include exposure to air pollution and allergens. Other potential triggers include medications such as aspirin and beta blockers. Diagnosis is usually based on the pattern of symptoms, response to therapy over time, and spirometry lung function testing. Asthma is classified according to the frequency of symptoms, forced expiratory volume in one second (FEV1), and peak expiratory flow rate. It may also be classified as atopic or non-atopic, ...
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