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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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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.

Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape

Authors: ---
ISBN: 9783038427971 9783038427988 Year: Pages: VIII, 302 DOI: 10.3390/books978-3-03842-798-8 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Therapeutics
Added to DOAB on : 2018-04-06 13:44:18
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Canadian Pharmaceutical Scientists have a rich history of ground-breaking research in pharmacokinetics and drug metabolism undertaken throughout its Pharmacy and Medical Schools and within the Pharmaceutical and biotechnology industry. The principle of drug Absorption, Distribution, Metabolism and Excretion (ADME) is the foundational basis of rationale drug-design, and pharmacotherapy. The study of ADME and its descriptive quantitative analysis is the basis of pharmacokinetics. Pharmacokinetics is fundamental in the development of a new chemical entity into a marketable product and is essential in understanding the bioavailability, bioequivalence and biosimilarities of drugs. Pharmacokinetics and drug development studies facilitate an understanding of organ-based functionality. Population pharmacokinetic variability and the modeling of drug concentrations has significant utility in translating individual response in a target patient population.This special issue serves to highlight and capture the contemporary progress and current landscape of pharmacokinetics and drug metabolism within the prevailing Canadian context. We invite articles on all aspects of Pharmacokinetics and Drug Metabolism studies highlighting the world-class research currently undertaken in Canada for this special issue.

Role of Protein-Protein Interactions in Metabolism: Genetics, Structure, Function

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453856 Year: Pages: 152 DOI: 10.3389/978-2-88945-385-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Therapeutics
Added to DOAB on : 2018-11-16 17:17:57
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Genetic variations may change the structure and function of individual proteins as well as affect their interactions with other proteins and thereby impact metabolic processes dependent on protein-protein interactions. For example, cytochrome P450 proteins, which metabolize a vast array of drugs, steroids and other xenobiotics, are dependent on interactions with redox and allosteric partner proteins for their localization, stability, (catalytic) function and metabolic diversity (reactions). Genetic variations may impact such interactions by changing the splicing and/or amino acid sequence which in turn may impact protein topology, localization, post translational modifications and three dimensional structure. More generally, research on single gene defects and their role in disease, as well as recent large scale sequencing studies suggest that a large number of genetic variations may contribute to disease not only by affecting gene function or expression but also by modulating complex protein interaction networks.The aim of this research topic is to bring together researchers working in the area of drug, steroid and xenobiotic metabolism who are studying protein-protein interactions, to describe their recent advances in the field. We are aiming for a comprehensive analysis of the subject from different approaches including genetics, proteomics, transcriptomics, structural biology, biochemistry and pharmacology. Of particular interest are papers dealing with translational research describing the role of novel genetic variations altering protein-protein interaction. Authors may submit original articles, reviews and opinion or hypothesis papers dealing with the role of protein-protein interactions in health and disease.

Role of Protein-Protein Interactions in Metabolism: Genetics, Structure, Function, 2nd Edition

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889454914 Year: Pages: 152 DOI: 10.3389/978-2-88945-491-4 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Therapeutics
Added to DOAB on : 2019-01-23 14:53:42
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Genetic variations may change the structure and function of individual proteins as well as affect their interactions with other proteins and thereby impact metabolic processes dependent on protein-protein interactions. For example, cytochrome P450 proteins, which metabolize a vast array of drugs, steroids and other xenobiotics, are dependent on interactions with redox and allosteric partner proteins for their localization, stability, (catalytic) function and metabolic diversity (reactions). Genetic variations may impact such interactions by changing the splicing and/or amino acid sequence which in turn may impact protein topology, localization, post translational modifications and three dimensional structure. More generally, research on single gene defects and their role in disease, as well as recent large scale sequencing studies suggest that a large number of genetic variations may contribute to disease not only by affecting gene function or expression but also by modulating complex protein interaction networks. The aim of this research topic is to bring together researchers working in the area of drug, steroid and xenobiotic metabolism who are studying protein-protein interactions, to describe their recent advances in the field. We are aiming for a comprehensive analysis of the subject from different approaches including genetics, proteomics, transcriptomics, structural biology, biochemistry and pharmacology. Of particular interest are papers dealing with translational research describing the role of novel genetic variations altering protein-protein interaction. Authors may submit original articles, reviews and opinion or hypothesis papers dealing with the role of protein-protein interactions in health and disease. Potential topics include, but are not limited to: • Role of protein-protein interactions in xenobiotic metabolism by cytochrome P450s and other drug metabolism enzymes.• Role of classical and novel interaction partners for cytochrome P450-dependent metabolism which may include interactions with redox partners, interactions with other P450 enzymes to form P450 dimers/multimers, P450-UGT interactions and proteins involved in posttranslational modification of P450s.• Effect of genetic variations (mutations and polymorphisms) on metabolism affected by protein-protein interactions. • Structural implications of mutations and polymorphisms on protein-protein interactions. • Functional characterization of protein-protein interactions.• Analysis of protein-protein interaction networks in health and disease.• Regulatory mechanisms governing metabolic processes based on protein-protein interactions.• Experimental approaches for identification of new protein-protein interactions including changes caused by mutations and polymorphisms.

Molecular Science for Drug Development and Biomedicine

ISBN: 9783906980836 9783906980843 Year: Pages: 356
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Added to DOAB on : 2015-10-22 06:15:53
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With the avalanche of biological sequences generated in the postgenomic age, molecular science is facing an unprecedented challenge, i.e., how to timely utilize the huge amount of data to benefit human beings. Stimulated by such a challenge, a rapid development has taken place in molecular science, particularly in the areas associated with drug development and biomedicine, both experimental and theoretical. The current thematic issue was launched with the focus on the topic of “Molecular Science for Drug Development and Biomedicine”, in hopes to further stimulate more useful techniques and findings from various approaches of molecular science for drug development and biomedicine.

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