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Immunologically Mediated Diseases and Allergic Reactions
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Kim A. Campbell, Caroline C. Whitacre
The second class of mediators released by activated mast cells are the newly formed mediators. Generation of lipid mediators begins with the activation of the enzyme phospholipase A2, which catalyzes the release of arachidonic acid from the membrane phospholipids. Arachidonic acid is then sequentially metabolized by the enzymes in one of two separate pathways: the cyclooxygenase pathway that produces the prostaglandins or the 5-lipoxygenase pathway that forms the leukotrienes. During allergic reactions, prostaglandin D2 induces vasodilation and bronchoconstriction. The leukotrienes C4, D4, and E4, previously referred to as slow-reacting substance of anaphylaxis, mediate prolonged bronchoconstriction, vasopermeability, and mucus secretion. Another derivative of phospholipid is platelet activating factor, which aggregates platelets, leading to microthrombi. Platelet activating factor also causes severe bronchoconstriction, increases vasopermeability, and augments chemotaxis of neutrophils. Whereas mast cells have been shown to produce prostaglandin D2, the leukotrienes, and PAF, basophils apparently synthesize only the leukotrienes (See chapter 4).
Patient assessment
Published in Michael Parker, Charlie James, Fundamentals for Cosmetic Practice, 2022
Despite being blocked, sebaceous glands continue to produce sebum, despite it having no clear route of drainage. This may be an occult process, with the pilosebaceous unit slowly increasing in size within the dermis, unbeknownst to the patient. This process is further compounded by the effects of bacteria, such as Propionibacterium acnes, which feed off the oily sebum and as a by-product of this produces the pro-inflammatory protein complex NF-ΚB and the production of leukotrienes through the activation of the enzyme 5-lipoxygenase. The inflamma-tory response to P. acnes results in the formation of pustules as immune cells are drawn to the infected pilosebaceous units to try and destroy the bacterial infection. These pustules appear as small white pockets of fluid which commonly have a surrounding erythematous reaction, forming the characteristic lesions seen in acne. Should the pressure within an infected pilosebaceous gland become too great, then these lesions may spontaneously erupt with the infection draining spontaneously. Sadly, for the patient, the localised pockets of inflammation caused by P. acnes can be quite severe when infections track deeper into the dermis. These deeper infections are not only more difficult to treat but are also likely to result in permanent scarring.
Immunomodulating Agents in Gastrointestinal Disease
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Samir A. Shah, Athos Bousvaros, A. Christopher Stevens
Zileuton is a new drug that has been studied in the treatment of asthma. It acts to inhibit 5-lipoxygenase, thus preventing leukotriene synthesis. Findings of recent studies in patients with UC are conflicting. One study found a 25% remission rate with Zileuton 600 mg four times a day compared with only 7% for placebo [244], However, another study found Zileuton slightly more effective than placebo but not as effective as 5-ASA in maintenance of remission in patients with ulcerative colitis [245]. Further evaluation of this agent is needed before any conclusions can be drawn.
Cannabis as a potential compound against various malignancies, legal aspects, advancement by exploiting nanotechnology and clinical trials
Published in Journal of Drug Targeting, 2022
Nazeer Hasan, Mohammad Imran, Afsana Sheikh, Suma Saad, Gaurav Chaudhary, Gaurav Kumar Jain, Prashant Kesharwani, Farhan J. Ahmad
Additionally, the inhibition of various pathways promotes the downregulation of cancerous cells mediated by cannabidiol. Scott et al. explained that U87MG and T98G cells after treatment with cannabidiol (20 µM) reduced p42/44 MAPKs and pAKT levels, which further declined in a combined treatment with γ-irradiation [135]. Cannabidiol also downregulates the phosphorylation of p42/44 MAPKs and AKT1/2 (pAKT) responsible for activating the PI3K/AKT pathway without altering total individual p42/44 MAPK and AKT level [133,136,137]. Such an effect of cannabidiol is upregulation of PTEN and downregulation of AKT in glioma cells, causing autophagy and cell lysis. PI3K, on the other hand, also plays a significant role in the activation of TRPV2, an important target of cannabidiol. Also, a combination of cannabidiol and THC in poly-ε-caprolactone microparticle showed the antitumor advance effect on glioma cells than its local treatment in solution form [133]. Massi et al. investigated the effect of cannabidiol on 5-lipoxygenase, COX-2, and endocannabinoid systems. An in vivo study revealed a decrease in the level of 5-lipoxygenase but did not affect COX-2. Cannabinoid also showed enhancement in the level of fatty acid amide hydrolase (FAAH), an important anandamide-degrading enzyme indicating inhibition of release of inflammatory substances mediated by direct attenuation of the endocannabinoid system [73,138].
Nanosized silver, but not titanium dioxide or zinc oxide, enhances oxidative stress and inflammatory response by inducing 5-HETE activation in THP-1 cells
Published in Nanotoxicology, 2020
Wing-Lam Poon, Jetty Chung-Yung Lee, Kin Sum Leung, Harri Alenius, Hani El-Nezami, Piia Karisola
Gene expression of several enzymes involved in oxidation of PUFA were also found to be disrupted by n-Ag in the microarray analyses especially at 24 h. Phospholipase A2 isozymes are responsible for the hydrolytic release of sn-2 fatty acid (including AA) from membrane phospholipids and some of them were upregulated (PLA2G4C) by n/b-ZnO and especially by n-Ag, when compared to unexposed controls (Figure 4(A)). ALOX5 (arachidonate 5-Lipoxygenase, also known as 5-LOX, Figure 4(B)), which catalyzes the conversion of AA to 5-HpETE (the precursor of 5-HETE), and its activating protein, ALOX5AP (arachidonate 5-lipoxygenase-activating protein, also known as FLAP, Figure 4(C)) were down-regulated, whereas expression of the COX-2 gene (called also PTGS2) was found to be increased exclusively by n-Ag (Figure 4(D)).
Investigational drugs in phase II clinical trials for acute coronary syndromes
Published in Expert Opinion on Investigational Drugs, 2020
Amit Rout, Ajaypaul Sukhi, Rahul Chaudhary, Kevin P Bliden, Udaya S Tantry, Paul A Gurbel
Leukotrienes are mainly derived from arachidonic acid via the 5- lipoxygenase (5-LO) pathway in leukocytes. 5-LO, along with 5-lipooxygenase activating protein (FLAP), initially leads to the formation of precursor leukotriene A4. Leukotriene B4 (LTB4) is a potent leukocyte activator and chemokine. The cysteinyl leukotrienes (LTC4, LTD4, and LTE4) are potent vasoactive and inflammatory mediators [5,6]. Coronary artery disease (CAD) is an atheroinflammatory condition involving endothelial dysfunction, infiltration of inflammatory cells, and platelets into the arterial vessel wall, smooth muscle proliferation, and atherogenesis. 5-LO pathway mediators and products are increasingly expressed in the unstable atherosclerotic lesions and play a significant role in inflammation and progression of CAD and ACS [5,6].