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Drug hypersensitivity

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https://www.readbyqxmd.com/read/28634159/a-role-for-the-nonsense-mediated-mrna-decay-pathway-in-maintaining-genome-stability-in-caenorhabditis-elegans
#1
Víctor González-Huici, Bin Wang, Anton Gartner
Ionizing radiation (IR) is commonly used in cancer therapy and is a main source of DNA double-strand-breaks (DSBs), one of the most toxic forms of DNA damage. We have used Caenorhabditis elegans as an invertebrate model to identify novel factors required for repair of DNA damage inflicted by IR. We have performed an unbiased genetic screen, finding that smg-1 mutations confer strong hypersensitivity to IR. SMG-1 is a phosphoinositide-3 kinase (PI3K) kinase involved in mediating nonsense-mediated mRNA decay (NMD) of transcripts containing premature stop codons and related to the ATM and ATR kinases which are at the apex of DNA damage signalling pathways...
June 20, 2017: Genetics
https://www.readbyqxmd.com/read/28632196/drug-hypersensitivity-and-desensitizations-mechanisms-and-new-approaches
#2
REVIEW
Leticia de Las Vecillas Sánchez, Leila A Alenazy, Marlene Garcia-Neuer, Mariana C Castells
Drug hypersensitivity reactions (HSRs) are increasing in the 21st Century with the ever expanding availability of new therapeutic agents. Patients with cancer, chronic inflammatory diseases, cystic fibrosis, or diabetes can become allergic to their first line therapy after repeated exposures or through cross reactivity with environmental allergens. Avoidance of the offending allergenic drug may impact disease management, quality of life, and life expectancy. Precision medicine provides new tools for the understanding and management of hypersensitivity reactions (HSRs), as well as a personalized treatment approach for IgE (Immunoglobuline E) and non-IgE mediated HSRs with drug desensitization (DS)...
June 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28628008/basophil-histamine-release-to-amoxicilloyl-poly-l-lysine-compared-to-amoxicillin-in-patients-with-ige-mediated-allergic-reactions-to-amoxicillin
#3
F Arribas, S Falkencrone, J Sola, M P Gomez-Serranillos, J J Laguna, M I Montañez, T D Fernandez, D Rodríguez, F Pineda, P Stahl Skov, C Mayorga, M J Torres
BACKGROUND: Amoxicillin (AX) is the betalactam most often involved in IgE-mediated reactions and the diagnosis is mainly based on skin testing (ST) although without optimal sensitivity. We have produced a newly AX derivative, amoxicilloyl-poly-L-lysine (APL), and have analysed its IgE recognition by passive histamine release test (pHRT). METHODS: Patients (N=19) with confirmed AX allergy and with specific IgE positive to AX and controls (N=10) with good tolerance to AX were included...
June 19, 2017: Journal of Investigational Allergology & Clinical Immunology
https://www.readbyqxmd.com/read/28624430/comparative-assessment-of-immune-complex-mediated-hypersensitivity-reactions-with-biotherapeutics-in-the-nonhuman-primate-critical-parameters-safety-assessment-and-lessons-for-future-studies
#4
Sven Kronenberg, Elisabeth Husar, Christine Schubert, Christian Freichel, Thomas Emrich, Martin Lechmann, Anna Maria Giusti, Franziska Regenass
With the emergence of novel biotherapeutic formats and immunostimulatory biotherapeutics in cancer immunotherapy, an understanding of immune-complex (IC) mediated hypersensitivity reactions in toxicology studies - and their differentiation from pharmacology - remains key to the preclinical evaluation of these drugs. In this review we provide an in-depth evaluation and comparison of case examples where IC-mediated hypersensitivity reactions were observed in cynomolgus monkeys. We provide details of the parameters evaluated in each study to substantiate and guide the interpretation of these findings...
June 14, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28622334/sterol-14%C3%AE-demethylase-mutation-leads-to-amphotericin-b-resistance-in-leishmania-mexicana
#5
Roy Mwenechanya, Julie Kovářová, Nicholas J Dickens, Mudaliar Manikhandan, Pawel Herzyk, Isabel M Vincent, Stefan K Weidt, Karl E Burgess, Richard J S Burchmore, Andrew W Pountain, Terry K Smith, Darren J Creek, Dong-Hyun Kim, Galina I Lepesheva, Michael P Barrett
Amphotericin B has emerged as the therapy of choice for use against the leishmaniases. Administration of the drug in its liposomal formulation as a single injection is being promoted in a campaign to bring the leishmaniases under control. Understanding the risks and mechanisms of resistance is therefore of great importance. Here we select amphotericin B-resistant Leishmania mexicana parasites with relative ease. Metabolomic analysis demonstrated that ergosterol, the sterol known to bind the drug, is prevalent in wild-type cells, but diminished in the resistant line, where alternative sterols become prevalent...
June 16, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28622171/reactions-to-cytostatic-agents-in-children
#6
Josefina R Cernadas
PURPOSE OF REVIEW: The current review will focus on drug hypersensitivity reactions to chemotherapy specifically to those drugs most used in children. We know that potentially all chemotherapeutic agents can cause infusion reactions, generally defined as adverse drug reactions. Of these, some are Type A, defined as expected and described in the characteristics of the drug and others, and Type B, defined as unexpected reactions which cannot be explained by the known toxicity profile of the drug...
June 14, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28611928/a-case-of-granuloma-annulare-associated-with-secukinumab-use
#7
Lauren Bonomo, Sara Ghoneim, Jacob Levitt
Granuloma annulare (GA) is a benign inflammatory dermatosis characterized clinically by dermal papules and annular plaques. The pathogenesis of GA is not well understood, although it is thought to result from a delayed-type hypersensitivity reaction in which inflammatory cells elicit connective tissue degradation. This condition has been seen following the use of several drugs, including tumor necrosis factor-alpha (TNF-α) inhibitors, which paradoxically have also been reported to treat GA. We report the case of a patient who developed GA in association with secukinumab, an interleukin-17A antagonist, and discuss its implications for our understanding of the pathogenesis of GA...
2017: Case Reports in Dermatological Medicine
https://www.readbyqxmd.com/read/28611278/lysine-methylation-of-fen1-by-set7-is-essential-for-its-cellular-response-to-replicative-stress
#8
Palaniraja Thandapani, Anthony M Couturier, Zhenbao Yu, Xing Li, Jean-François Couture, Shawn Li, Jean-Yves Masson, Stéphane Richard
The DNA damage response (DDR) is central to the cell survival and it requires post-translational modifications, in part, to sense the damage, amplify the signaling response and recruit and regulate DNA repair enzymes. Lysine methylation of histones such as H4K20 and non-histone proteins including p53 has been shown to be essential for the mounting of the DDR. It is well-known that the lysine methyltransferase SET7 regulates the DDR, as cells lacking this enzyme are hypersensitive to chemotherapeutic drugs. To define addition substrates of SET7 involved in the DDR, we screened a peptide array encompassing potential lysine methylation sites from >100 key DDR proteins and identified peptides from 58 proteins to be lysine methylated defining a methylation consensus sequence of [S>K-2; S>R-1; K0] consistent with previous findings...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28603631/hepatic-expression-profiles-in-retroviral-infection-relevance-to-drug-hypersensitivity-risk
#9
Yat Yee Wong, Brian Johnson, Thomas C Friedrich, Lauren A Trepanier
HIV-infected patients show a markedly increased risk of delayed hypersensitivity (HS) reactions to potentiated sulfonamide antibiotics (trimethoprim/sulfamethoxazole or TMP/SMX). Some studies have suggested altered SMX biotransformation in HIV infection, but hepatic biotransformation pathways have not been evaluated directly. Systemic lupus erythematosus (SLE) is another chronic inflammatory disease with a higher incidence of sulfonamide HS, but it is unclear whether retroviral infection and SLE share risk factors for drug HS...
June 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28603499/campania-preventability-assessment-committee-italy-a-focus-on-the-preventability-of-non-steroidal-anti-inflammatory-drugs-adverse-drug-reactions
#10
Maurizio Sessa, Liberata Sportiello, Annamaria Mascolo, Cristina Scavone, Silvia Gallipoli, Gabriella di Mauro, Daniela Cimmaruta, Concetta Rafaniello, Annalisa Capuano
Purpose: This study aims to investigate preventability criteria of adverse drug reactions (ADRs) involving non-steroidal anti-inflammatory drugs (NSAIDs) by analyzing individual case safety reports (ICSRs) sent through Campania region (Italy) spontaneous reporting system from July 2012 to October 2016. Methods: For all the ICSRs that reported NSAIDs as suspected drug, a trained multidisciplinary team of Campania Pharmacovigilance Regional Centre composed of clinical pharmacologists and pharmacists with pluriannual experience in Pharmacovigilance assessed preventability by using the P-method...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28603455/tetramethylpyrazine-attenuates-periorbital-allodynia-and-neuroinflammation-in-a-model-of-traumatic-brain-injury
#11
Zhijing Wang, Qi Wang, Cuijie Wang, Xiuzhen Xu, Hongmei Yu
BACKGROUND: Traumatic brain injury (TBI) is a public health issue. As the major complaint in 51% of TBI patients, chronic pain is an important aspect in TBI treatment. Tetramethylpyrazine (TMP) is an important compound in Ligustrazine, an analgesic drug in traditional Chinese medicine, but its potential in relieving pain symptom in TBI has not been tested. We established a TBI mouse model with controlled cortical impact (CCI), and measured periorbital hypersensitivity with von Frey monofilaments...
2017: Journal of Inflammation
https://www.readbyqxmd.com/read/28602129/from-the-children-s-oncology-group-evidence-based-recommendations-for-peg-asparaginase-nurse-monitoring-hypersensitivity-reaction-management-and-patient-family-education
#12
Deborah Woods, Kari Winchester, Alison Towerman, Katie Gettinger, Christina Carey, Karen Timmermann, Rachel Langley, Emily Browne
PEG-aspariginase is a backbone chemotherapy agent in pediatric acute lymphoblastic leukemia and in some non-Hodgkin lymphoma therapies. Nurses lack standardized guidelines for monitoring patients receiving PEG-asparaginase and for educating patients/families about hypersensitivity reaction risks. An electronic search of 6 databases using publication years 2000-2015 and multiple professional organizations and clinical resources was conducted. Evidence sources were reviewed for topic applicability. Each of the final 23 sources was appraised by 2 team members...
June 1, 2017: Journal of Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses
https://www.readbyqxmd.com/read/28602024/self-diagnosed-drug-allergies-the-belief-of-patients
#13
Arnaud Jannic, Amandine Servy, Xavier Chevalier, Audrey Colin, Olivier Chosidow, Saskia Ingen-Housz-Oro, Pierre Wolkenstein
The term of "drug allergy" (DA) may include true hypersensitivity or non-allergic reactions. The rate of self-reporting DA ranges from 4.7% to 11% regardless of age. When patients report a DA, the medical team often decides a full and definitive elimination of the incriminated drug from future therapy, which deeply affects medical care. This article is protected by copyright. All rights reserved.
June 11, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28601883/skin-homing-il-13-producing-t-cells-expand-in-the-circulation-of-patients-with-drug-rash-with-eosinophilia-and-systemic-symptoms
#14
Yuichi Teraki, Tomoo Fukuda
BACKGROUND: Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome, is characterized by severe drug-induced reactions with extensive cutaneous lesions and visceral involvement. Although T cell-mediated hypersensitivity reactions to drugs may be involved in the pathogenesis of DRESS, there is limited data regarding the T-cell phenotypes responsible for the pathogenesis of DRESS. OBJECTIVE AND METHODS: Using flow cytometry, we investigated the cytokine profiles and cutaneous lymphocyte antigen (CLA) expression in circulating T cells in patients with DRESS...
June 10, 2017: Dermatology: International Journal for Clinical and Investigative Dermatology
https://www.readbyqxmd.com/read/28601750/sex-specific-effects-of-intranasal-oxytocin-on-thermal-pain-perception-a-randomised-double-blind-placebo-controlled-cross-over-study
#15
Lincoln M Tracy, Izelle Labuschagne, Nellie Georgiou-Karistianis, Stephen J Gibson, Melita J Giummarra
Chronic neck and shoulder pain (CNSP) is a common musculoskeletal disorder in adults, which is linked to hypersensitivity to noxious stimuli. The hormone oxytocin has been implicated as a potential therapeutic for the management of chronic pain disorders, and has been suggested to have sex-specific effects on the salience of threatening stimuli. This study investigated the influence of intranasal oxytocin on the perception of noxious thermal stimuli. Participants were 24 individuals with CNSP lasting >12months (eight women), and 24 age- and sex-matched healthy, pain-free controls...
June 3, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28598865/drug-allergy-hypersensitivity-in-adults-and-children
#16
Bernard Yu-Hor Thong, Miguel Blanca
No abstract text is available yet for this article.
June 8, 2017: Current Opinion in Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28598363/drug-reaction-with-eosinophilia-and-systemic-symptoms-dress-an-interplay-among-drugs-viruses-and-immune-system
#17
REVIEW
Yung-Tsu Cho, Che-Wen Yang, Chia-Yu Chu
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe multiorgan hypersensitivity reaction mostly caused by a limited number of eliciting drugs in patients with a genetic predisposition. Patients with DRESS syndrome present with characteristic but variable clinical and pathological features. Reactivation of human herpesviruses (HHV), especially HHV-6, is the hallmark of the disease. Anti-viral immune responses intertwined with drug hypersensitivity make the disease more complicated and protracted...
June 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28598197/hypersensitivity-pneumonitis-perspectives-in-diagnosis-and-management
#18
Martina Vasakova, Ferran Morell, Simon Walsh, Kevin Leslie, Ganesh Raghu
Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease caused by recurrent exposure to one or more offending inducers in genetically susceptible individuals. It mimics other acute and chronic pulmonary diseases and is often misdiagnosed as idiopathic pulmonary fibrosis (IPF) or another idiopathic interstitial pneumonia if the history of exposure to the inducer is not elicited. We propose a new classification of HP based not only on clinical data but also radiologic and histopathologic findings which might have potential to serve as predictors of disease behaviour and therefore guide management...
June 9, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28593995/codon-bias-imposes-a-targetable-limitation-on-kras-driven-therapeutic-resistance
#19
Moiez Ali, Erin Kaltenbrun, Grace R Anderson, Sarah Jo Stephens, Sabrina Arena, Alberto Bardelli, Christopher M Counter, Kris C Wood
KRAS mutations drive resistance to targeted therapies, including EGFR inhibitors in colorectal cancer (CRC). Through genetic screens, we unexpectedly find that mutant HRAS, which is rarely found in CRC, is a stronger driver of resistance than mutant KRAS. This difference is ascribed to common codon bias in HRAS, which leads to much higher protein expression, and implies that the inherent poor expression of KRAS due to rare codons must be surmounted during drug resistance. In agreement, we demonstrate that primary resistance to cetuximab is dependent upon both KRAS mutational status and protein expression level, and acquired resistance is often associated with KRAS(Q61) mutations that function even when protein expression is low...
June 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/28590439/reclassifying-anaphylaxis-to-neuromuscular-blocking-agents-based-on-the-presumed-patho-mechanism-ige-mediated-pharmacological-adverse-reaction-or-innate-hypersensitivity
#20
REVIEW
David Spoerl, Haig Nigolian, Christoph Czarnetzki, Thomas Harr
Approximately 60% of perioperative anaphylactic reactions are thought to be immunoglobulin IgE mediated, whereas 40% are thought to be non-IgE mediated hypersensitivity reactions (both considered non-dose-related type B adverse drug reactions). In both cases, symptoms are elicited by mast cell degranulation. Also, pharmacological reactions to drugs (type A, dose-related) may sometimes mimic symptoms triggered by mast cell degranulation. In case of hypotension, bronchospasm, or urticarial rash due to mast cell degranulation, identification of the responsible mechanism is complicated...
June 7, 2017: International Journal of Molecular Sciences
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