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Biomarkers in Drug Hypersensitivity

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889452262 Year: Pages: 104 DOI: 10.3389/978-2-88945-226-2 Language: English
Publisher: Frontiers Media SA
Subject: Therapeutics --- Science (General)
Added to DOAB on : 2017-10-13 14:57:01
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Abstract

Biomarkers, especially those based on pharmacogenomics testing, have proved to be extremely useful for type A adverse drug reactions. Clinical practice guidelines based on biomarker testing are presently being developed and updated for type A adverse drug reactions. In contrast, little attention has been paid to the potential use of biomarkers in type B adverse reactions, characterized by the occurrence of reactions not directly related to the pharmacological properties of the drug. Drug-induced hypersensitivity belongs to those type B reactions. Drug-induced hypersensitivity reactions involve complex mechanisms that include, among others, the metabolic activation and haptenization of drug metabolites. Hence, factors that influence the pharmacokinetics of drug and metabolites may contribute to the development of some drug-induced hypersensitivity reactions. This implies that processes such as ADME (absorption, distribution, metabolism and excretion) that are typically involved in type A adverse drug reactions, may have a role in hypersensitivity reactions too. In addition to metabolic activation, several signal transduction pathways participate and modulate the development and the clinical presentation of drug hypersensitivity. The diverse mechanisms underlying such drug-hypersensitivity reactions lead to four major groups of reactions according to the Gell and Coombs classification: immediate, cytotoxic, immune complex and delayed. The enormous complexity of drug-hypersensitivity reactions is a consequence of the variety of mechanisms involved, which may be related, among others, to drug metabolism, generation of antigenic signals, stimulation and maturation of dendritic cells, presentation of haptens and mechanisms of cytotoxicity. In addition, a plethora of possible clinical presentations exists, including urticaria, angioedema, anaphylaxis, cytopenias, nephritis, serum sickness, vasculitis, contact dermatitis, drug rash, eosinophilia and systemic symptoms, Stevens–Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis. The rapid progress in the field in recent years indicates that the combination of several disciplines is essential to understand the mechanisms involved in this particular, and not completely understood, type of adverse drug reactions. The objective of this Research Topic is to present insights obtained from both basic and clinical scientists, which may include studies related to the identification, validation, refinement and clinical implementation of biomarkers for drug-induced hypersensitivity. The Topic aims to include recent findings related, but not limited to, potential phenomic, genomic, proteomic, metabolomic and signal transduction biomarkers. These biomarkers could eventually be used in clinical practice and/or these might contribute, as a proof of concept, to our understanding of the complex events leading to drug hypersensitivity reactions. In addition the Topic will cover recent developments and methodological advances in the diagnosis, prevention and therapeutic management of drug-induced hypersensitivity.

Metal Metabolism in Animals

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ISBN: 9783038428435 9783038428442 Year: Pages: X, 356 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2018-04-20 14:25:48
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Through evolution of life, animals have adapted to the ubiquitous presence of metals in the biosphere. They utilize the more frequent ones as essential constituents of their biochemical machinery. In fact, about 40% of all proteins present in animal cells are so-called metalloproteins. On the other hand, animals have invented regulatory and detoxifying mechanisms to protect themselves from critical concentrations of both essential and non-essential metal concentrations. Metallomics is a modern approach applying cellular, biochemical, molecular and analytical methods to investigate the relationships of metals in their cellular context. The present edition contains a number of original articles and reviews dealing with various aspects of metallomics in animals, published as Special Issues of the International Journal of Molecular Sciences in 2016 and 2017. The book addresses subjects such as metal definition in biology, metabolism of metals in invertebrate and vertebrate animals, metal detoxification and regulation strategies, supplementation of essential trace elements, metal behavior in pregnancy and embryonic development, as well as metal toxicology and emerging medical implications.

TRP Channels in Health and Disease

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ISBN: 9783039210824 / 9783039210831 Year: Pages: 266 DOI: 10.3390/books978-3-03921-083-1 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2019-06-26 08:44:07
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Almost 25 years ago, the first mammalian transient receptor potential (TRP) channel was cloned and published. TRP channels now represent an extended family of 28 members fulfilling multiple roles in the living organism. Identified functions include control of body temperature, transmitter release, mineral homeostasis, chemical sensing, and survival mechanisms in a challenging environment. The TRP channel superfamily covers six families: TRPC with C for “canonical”, TRPA with A for “ankyrin”, TRPM with M for “melastatin”, TRPML with ML for “mucolipidin”, TRPP with P for “polycystin”, and TRPV with V for “vanilloid”. Over the last few years, new findings on TRP channels have confirmed their exceptional function as cellular sensors and effectors. This Special Book features a collection of 8 reviews and 7 original articles published in “Cells” summarizing the current state-of-the-art on TRP channel research, with a main focus on TRP channel activation, their physiological and pathophysiological function, and their roles as pharmacological targets for future therapeutic options.

Keywords

ion channel --- TRPC --- small molecules --- calcium --- chemical probes --- TRPV1 --- TRPV2 --- TRPV3 --- TRPV4 --- mucosal epithelium --- ulcerative colitis --- inflammatory bowel disease --- TRPM4 channel --- cardiovascular system --- physiology --- pathophysiology --- TRPC6 --- elementary immunology --- inflammation --- calcium --- sodium --- neutrophils --- lymphocytes --- endothelium --- platelets --- human medulla oblongata --- cuneate nucleus --- dorsal column nuclei --- TRPV1 --- calcitonin gene-related peptide --- substance P --- TRP channels --- calcium signaling --- salivary glands --- xerostomia --- radiation --- inflammation --- transient receptor potential channels --- TRPC3 pharmacology --- channel structure --- lipid mediators --- photochromic ligands --- transient receptor potential --- TRPC3 --- mGluR1 --- GABAB --- EPSC --- Purkinje cell --- cerebellum --- toxicology --- TRP channels --- organ toxicity --- chemicals --- pollutants --- chemosensor --- TRPM7 --- kinase --- inflammation --- lymphocytes --- calcium signalling --- SMAD --- TH17 --- hypersensitivity --- regulatory T cells --- thrombosis --- graft versus host disease --- 2D gel electrophoresis --- AP18 --- HEK293 --- HSP70 --- MALDI-TOF MS(/MS) --- nanoHPLC-ESI MS/MS --- proteomics --- sulfur mustard --- TRPA1 --- TRPC channels --- diacylglycerol --- TRPC4 --- TRPC5 --- NHERF --- TRP channel --- TRPY1 --- Saccharomyces cerevisiae --- calcium --- manganese --- oxidative stress --- ion channels --- overproduction --- production platform --- protein purification --- Saccharomyces cerevisiae --- sensors --- transient receptor potential (TRP) channels --- yeast --- adipose tissue --- bioavailable --- menthol --- topical --- TRPM8 --- n/a

Amide Bond Activation

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ISBN: 9783039212033 / 9783039212040 Year: Pages: 466 DOI: 10.3390/books978-3-03921-204-0 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Chemistry (General)
Added to DOAB on : 2019-08-28 11:21:27
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The amide bond represents a privileged motif in chemistry. The recent years have witnessed an explosion of interest in the development of new chemical transformations of amides. These developments cover an impressive range of catalytic N–C bond activation in electrophilic, Lewis acid, radical, and nucleophilic reaction pathways, among other transformations. Equally relevant are structural and theoretical studies that provide the basis for chemoselective manipulation of amidic resonance. This monograph on amide bonds offers a broad survey of recent advances in activation of amides and addresses various approaches in the field.

Keywords

fumardiamide --- primaquine --- succindiamide --- Michael acceptor --- biofilm eradication --- antibacterial screening --- antiviral activity --- cytostatic activity --- N,N-dimethylformamide --- DMF --- N,N-dimethylacetamide --- DMAc --- amination --- amidation --- thioamidation --- formylation --- carbonylation --- cyanation --- insertion --- cyclization --- amide --- arynes --- insertion --- activation --- heterocycles --- organic synthesis --- multi-component coupling reaction --- aryl thioamides --- thiourea --- C-H/C-N activation --- C-S formation --- transition-metal-free --- rotational barrier energy --- amide bond --- nuclear magnetic resonance --- kinetic --- density functional theory --- non planar amide --- base-catalyed hydrolysis --- water solvation --- entropy --- transamidation --- amide --- amine --- catalyst --- catalysis --- acylative cross-coupling --- trialkylborane --- amide activation --- palladium --- N-heterocyclic carbene --- ruthenium (Ru) --- N-heterocyclic carbenes (NHCs) --- homogeneous catalysis --- in situ --- amide bonds --- synthesis --- density functional theory --- cis/trans isomerization --- secondary amides --- dipeptides --- steric effects --- tert-butyl --- additivity principle --- amino acid transporters --- amide bond --- gemcitabine prodrug --- metabolic stability --- pancreatic cancer cells --- pharmacokinetics --- peptide bond cleavage --- amide bond resonance --- twisted amides --- enzymes --- metal complexes --- catalysts --- amide C–N bond activation --- nickel catalysis --- amidation --- DFT study --- reaction thermodynamics --- amide resonance --- anomeric effect --- HERON reaction --- pyramidal amides --- physical organic chemistry --- reaction mechanism --- amide --- activation --- amidicity --- carbonylicity --- transamidation --- acyl transfer --- excited state --- Suzuki-Miyaura --- cross-coupling --- aryl esters --- C–O activation --- Pd-catalysis --- amides --- carbanions --- C–H acidity --- nitro-aci tautomerism --- molecular dynamics --- density-functional theory --- alkynes --- C–H bond cleavage --- C–N bond cleavage --- cyclopentadienyl complexes --- N-(1-naphthyl)acetamide --- rhodium --- [2+2+2] annulation --- amide bond --- sulfonamide bond --- alkynes --- addition reaction --- aminoacylation --- aminosulfonylation --- pre-catalysts --- palladium catalysis --- amide bond activation --- ester bond activation --- cross-coupling --- amide bond --- bridged lactams --- twisted amides --- amides --- Winkler-Dunitz parameters --- N–C activation --- hypersensitivity --- nitrogen heterocycles --- distortion --- bridged sultams --- amides --- C-N ? bond cleavage --- sodium --- crown ether --- amide hydrolysis --- model compound --- intramolecular catalysis --- twisted amide --- protease --- intein --- C-H functionalization --- directing groups --- amides --- transition metals --- catalysis

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