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3. Modulation of the photobehavior of gefitinib and its phenolic metabolites by human transport proteins.

Author

Tamarit, Lorena, El Ouardi, Meryem, Lence, Emilio, Andreu, Inmaculada, González-Bello, Concepcion, Miranda, Miguel A., and Vayá, Ignacio

Subjects
CARRIER proteins, PROTEIN transport, FLUORESCENCE yield, METABOLITES, AMINO acid residues, ALBUMINS
Abstract

The photobiological damage that certain drugs or their metabolites can photosensitize in proteins is generally associated with the nature of the excited species that are generated upon interaction with UVA light. In this regard, the photoinduced damage of the anticancer drug gefitinib (GFT) and its two main photoactive metabolites GFT-M1 and GFT-M2 in cellular milieu was recently investigated. With this background, the photophysical properties of both the drug and its metabolites have now been studied in the presence of the two main transport proteins of human plasma, i.e., serum albumin (HSA) and α1-acid glycoprotein (HAG) upon UVA light excitation. In general, the observed photobehavior was strongly affected by the confined environment provided by the protein. Thus, GFT-M1 (which exhibits the highest phototoxicity) showed the highest fluorescence yield arising from long-lived HSA-bound phenolate-like excited species. Conversely, locally excited (LE) states were formed within HAG, resulting in lower fluorescence yields. The reserve was true for GFT-M2, which despite being also a phenol, led mainly to formation of LE states within HSA, and phenolate-like species (with a minor contribution of LE) inside HAG. Finally, the parent drug GFT, which is known to form LE states within HSA, exhibited a parallel behavior in the two proteins. In addition, determination of the association constants by both absorption and emission spectroscopy revealed that the two metabolites bind stronger to HSA than the parent drug, whereas smaller differences were observed for HAG. This was further confirmed by studying the competing interactions between GFT or its metabolites with the two proteins using fluorescence measurements. These above experimental findings were satisfactorily correlated with the results obtained by means of molecular dynamics (MD) simulations, which revealed the high affinity binding sites, the strength of interactions and the involved amino acid residues. In general, the differences observed in the photobehavior of the drug and its two photoactive metabolites in protein media are consistent with their relative photosensitizing potentials. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Phytochemicals Involved in Mitigating Silent Toxicity Induced by Heavy Metals.

Author

Ceramella, Jessica, De Maio, Azzurra Chiara, Basile, Giovanna, Facente, Anastasia, Scali, Elisabetta, Andreu, Inmaculada, Sinicropi, Maria Stefania, Iacopetta, Domenico, and Catalano, Alessia

Subjects
HEAVY metal toxicology, POISONS, HEAVY metals, CHELATION therapy, ATOMIC mass, CHELATING agents, PLANT extracts
Abstract

Heavy metals (HMs) are natural elements present in the Earth's crust, characterised by a high atomic mass and a density more than five times higher than water. Despite their origin from natural sources, extensive usage and processing of raw materials and their presence as silent poisons in our daily products and diets have drastically altered their biochemical balance, making them a threat to the environment and human health. Particularly, the food chain polluted with toxic metals represents a crucial route of human exposure. Therefore, the impact of HMs on human health has become a matter of concern because of the severe chronic effects induced by their excessive levels in the human body. Chelation therapy is an approved valid treatment for HM poisoning; however, despite the efficacy demonstrated by chelating agents, various dramatic side effects may occur. Numerous data demonstrate that dietary components and phytoantioxidants play a significant role in preventing or reducing the damage induced by HMs. This review summarises the role of various phytochemicals, plant and herbal extracts or probiotics in promoting human health by mitigating the toxic effects of different HMs. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Singlet oxygen and radical-mediated mechanisms in the oxidative cellular damage photosensitized by the protease inhibitor simeprevir

Author

Ministerio de Ciencia e Innovación (España), García-Laínez, Guillermo, El Ouardi, Meryem, Moreno, Alejandro, Lence, Emilio, González-Bello, Concepción, Miranda, M. A., Andreu, Inmaculada, Ministerio de Ciencia e Innovación (España), García-Laínez, Guillermo, El Ouardi, Meryem, Moreno, Alejandro, Lence, Emilio, González-Bello, Concepción, Miranda, M. A., and Andreu, Inmaculada

Abstract

Hepatitis C, a liver inflammation caused by the hepatitis C virus (HCV), is treated with antiviral drugs. In this context, simeprevir (SIM) is an NS3/4A protease inhibitor used in HCV genotypes 1 and 4. It is orally administered and achieves high virological cure rates. Among adverse reactions associated with SIM treatment, photosensitivity reactions have been reported. In the present work, it is clearly shown that SIM is markedly phototoxic, according to the in vitro NRU assay using BALB/c 3T3 mouse fibroblast. This result sheds light on the nature of the photosensitivity reactions induced by SIM in HCV patients, suggesting that porphyrin elevation in patients treated with SIM may not be the only mechanism responsible for SIM-associated photosensitivity. Moreover, lipid photoperoxidation and protein photooxidation assays, using human skin fibroblasts (FSK) and human serum albumin (HSA), respectively, reveal the capability of this drug to promote photodamage to cellular membranes. Also, DNA photo lesions induced by SIM are noticed through comet assay in FSK cells. Photochemical and photobiological studies on the mechanism of SIM-mediated photodamage to biomolecules indicate that the key transient species generated upon SIM irradiation is the triplet excited state. This species is efficiently quenched by oxygen giving rise to singlet oxygen, which is responsible for the oxidation of lipids and DNA (Type II mechanism). In the presence of HSA, the photobehavior is dominated by binding to site 3 of the protein, to give a stable SIM@HSA complex. Inside the complex, quenching of the triplet excited state is less efficient, which results in a longer triplet lifetime and in a decreased singlet oxygen formation. Hence, SIM-mediated photooxidation of the protein is better explained through a radical (Type I) mechanism.

Published
2023

7. Cellular photo(geno)toxicity of gefitinib after biotransformation

Author

Ministerio de Ciencia e Innovación (España), El Ouardi, Meryem, Tamarit, Lorena, Vayá, Ignacio, Miranda, M. A., Andreu, Inmaculada, Ministerio de Ciencia e Innovación (España), El Ouardi, Meryem, Tamarit, Lorena, Vayá, Ignacio, Miranda, M. A., and Andreu, Inmaculada

Abstract

Gefitinib (GFT) is a selective epidermal growth factor receptor (EGFR) inhibitor clinically used for the treatment of patients with non-small cell lung cancer. Bioactivation by mainly Phase I hepatic metabolism leads to chemically reactive metabolites such as O-Demethyl gefitinib (DMT-GFT), 4-Defluoro-4-hydroxy gefitinib (DF-GFT), and O-Demorpholinopropyl gefitinib (DMOR-GFT), which display an enhanced UV-light absorption. In this context, the aim of the present study is to investigate the capability of gefitinib metabolites to induce photosensitivity disorders and to elucidate the involved mechanisms. According to the neutral red uptake (NRU) phototoxicity test, only DF-GFT metabolite can be considered non-phototoxic to cells with a photoirritation factor (PIF) close to 1. Moreover, DMOR-GFT is markedly more phototoxic than the parent drug (PIF = 48), whereas DMT-GFT is much less phototoxic (PIF = 7). Using the thiobarbituric acid reactive substances (TBARS) method as an indicator of lipid photoperoxidation, only DMOR-GFT has demonstrated the ability to photosensitize this process, resulting in a significant amount of TBARS (similar to ketoprofen, which was used as the positive control). Protein photooxidation monitored by 2,4-dinitrophenylhydrazine (DNPH) derivatization method is mainly mediated by GFT and, to a lesser extent, by DMOR-GFT; in contrast, protein oxidation associated with DMT-GFT is nearly negligible. Interestingly, the damage to cellular DNA as revealed by the comet assay, indicates that DMT-GFT has the highest photogenotoxic potential; moreover, the DNA damage induced by this metabolite is hardly repaired by the cells after a time recovery of 18 h. This could ultimately result in mutagenic and carcinogenic effects. These results could aid oncologists when prescribing TKIs to cancer patients and, thus, establish the conditions of use and recommend photoprotection guidelines.

Published
2023

9. Drugs for COVID-19: An Update

Author

Ceramella, Jessica, primary, Iacopetta, Domenico, additional, Sinicropi, Maria Stefania, additional, Andreu, Inmaculada, additional, Mariconda, Annaluisa, additional, Saturnino, Carmela, additional, Giuzio, Federica, additional, Longo, Pasquale, additional, Aquaro, Stefano, additional, and Catalano, Alessia, additional

Published
2022
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11. Switching from ultrafast electron transfer to proton transfer in excited drug-protein complexes upon biotransformation

Author

Ministerio de Ciencia e Innovación (España), Tamarit, Lorena, El Ouardi, Meryem, Lence, Emilio, Andreu, Inmaculada, González-Bello, Concepción, Vayá, Ignacio, Miranda, M. A., Ministerio de Ciencia e Innovación (España), Tamarit, Lorena, El Ouardi, Meryem, Lence, Emilio, Andreu, Inmaculada, González-Bello, Concepción, Vayá, Ignacio, and Miranda, M. A.

Abstract

Photosensitization by drugs is directly related with the excited species and the photoinduced processes arising from interaction with UVA light. In this context, the ability of gefitinib (GFT), a tyrosine kinase inhibitor (TKI) used for the treatment of a variety of cancers, to induce phototoxicity and photooxidation of proteins has recently been demonstrated. In principle, photodamage can be generated not only by a given drug but also by its photoactive metabolites that maintain the relevant chromophore. In the present work, a complete study of O-desmorpholinopropyl gefitinib (GFT-MB) has been performed by means of fluorescence and ultrafast transient absorption spectroscopies, in addition to molecular dynamics (MD) simulations. The photobehavior of the GFT-MB metabolite in solution is similar to that of GFT. However, when the drug or its metabolite are in a constrained environment, i.e. within a protein, their behavior and the photoinduced processes that arise from their interaction with UVA light are completely different. For GFT in complex with human serum albumin (HSA), locally excited (LE) singlet states are mainly formed; these species undergo photoinduced electron transfer with Tyr and Trp. By contrast, since GFT-MB is a phenol, excited state proton transfer (ESPT) to form phenolate-like excited species might become an alternative deactivation pathway. As a matter of fact, the protein-bound metabolite exhibits higher fluorescence yields and longer emission wavelengths and lifetimes than GFT@HSA. Ultrafast transient absorption measurements support direct ESPT deprotonation of LE states (rather than ICT), to form phenolate-like species. This is explained by MD simulations, which reveal a close interaction between the phenolic OH group of GFT-MB and Val116 within site 3 (subdomain IB) of HSA. The reported findings are relevant to understand the photosensitizing properties of TKIs and the role of biotransformation in this type of adverse side effects.

Published
2022

15. Photoprocesses of the tyrosine kinase inhibitor gefitinib: From femtoseconds to microseconds and from solution to cells

Author

Ministerio de Ciencia, Innovación y Universidades (España), Generalitat Valenciana, Tamarit, Lorena, El Ouardi, Meryem, Andreu, Inmaculada, Vayá, Ignacio, Miranda, M. A., Ministerio de Ciencia, Innovación y Universidades (España), Generalitat Valenciana, Tamarit, Lorena, El Ouardi, Meryem, Andreu, Inmaculada, Vayá, Ignacio, and Miranda, M. A.

Abstract

Gefitinib (GFT) is a tyrosine kinase inhibitor currently used for the treatment of metastatic non-small cell lung cancer. Although it has been suggested that GFT can be phototoxic, there are no systematic studies on this issue. Here, the photosensitizing potential of GFT has been assessed by means of NRU assays and protein photooxidation. In addition, a thorough photophysical study is presented based on ultrafast transient absorption spectroscopy, fluorescence and laser flash photolysis. Transient species generated after excitation of GFT have been characterized in solution and in biological environments (i.e.HSA and HaCaT cells) to gain insight into the mechanisms involved in photodamage. The photobehavior of GFT was strongly medium-dependent. Excitation of the drug resulted in the formation of locally excited (LE) singlet states (GFT*), which were found to be the main emissive species in non-polar solvents and also within HSA and HaCaT cells. By contrast, in polar solvents, LE states rapidly evolved (∼1 ps) towards the formation of longer-lived intramolecular charge transfer (ICT) states. The triplet excited state of GFT (GFT*) can be formed through intersystem crossing fromGFT* in non-polar solvents and from ICT states in the polar ones, or in the particular case of ethanol, by photosensitization using 2-methoxyacetophenone as an energy donor. In the HSA environment,GFT* was hardly detected due to quenching of its LEGFT* precursor by Trp through an electron transfer process. Accordingly, HSA photooxidation by GFT was demonstrated using the protein carbonylation method. In summary, a good correlation is established between the photophysical behavior and the photobiological properties of GFT, which provides a mechanistic basis for the observed phototoxicity.

Published
2021

18. Photomutagenicity of chlorpromazine and its N-demethylated metabolites assessed by NGS

Author

Generalitat Valenciana, Agúndez, José Augusto G., García-Martín, Elena, García-Laínez, Guillermo, Miranda, M. A., Andreu, Inmaculada, Generalitat Valenciana, Agúndez, José Augusto G., García-Martín, Elena, García-Laínez, Guillermo, Miranda, M. A., and Andreu, Inmaculada

Abstract

The human genome is constantly attacked by endogenous and exogenous agents (ultraviolet light, xenobiotics, reactive oxygen species), which can induce chemical transformations leading to DNA lesions. To combat DNA damage, cells have developed several repair mechanisms; however, if the repair is defective, DNA lesions lead to permanent mutations. Single-cell gel electrophoresis (COMET assay) is a sensitive and well-established technique for quantifying DNA damage in individual cells. Nevertheless, this tool lacks relationship with mutagenesis. Therefore, to identify errors that give rise to mutations it would be convenient to test an alternative known procedure, such as next generation sequencing (NGS). Thus, the present work aims to evaluate the photomutagenicity of neuroleptic drug chlorpromazine (CPZ), and its N-demethylated metabolites using COMET assay and to test NGS as an alternative method to assess photomutagenesis. In this context, upon exposure to UVA radiation, COMET assay reveals CPZ-photosensitized DNA damage partially repaired by cells. Conversely with this result, metabolites demethylchlorpromazine (DMCPZ) and didemethylchlorpromazine (DDMCPZ) promote extensive DNA-photodamage, hardly repaired under the same conditions. Parallel assessment of mutagenesis by NGS is consistent with these results with minor discrepancies for DDMCPZ. To our knowledge, this is the first example demonstrating the utility of NGS for evaluating drug-induced photomutagenicity.

Published
2020

23. Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton

Author

Generalitat Valenciana, Palumbo, Fabrizio, Andreu, Inmaculada, Brunetti, M., Schmallegger, M., Gescheidt, G., Neshchadin, D., Miranda, M. A., Generalitat Valenciana, Palumbo, Fabrizio, Andreu, Inmaculada, Brunetti, M., Schmallegger, M., Gescheidt, G., Neshchadin, D., and Miranda, M. A.

Abstract

Cholesterol (Ch) is an integral part of cell membrane, where it is prone to oxidation. In humans, oxidation of Ch is commonly linked to various pathologies like Alzheimer's disease, atherosclerosis, and even cancer, which proceed via mechanisms involving enzymatic and free radical pathways. The latter begin with hydrogen abstraction (HA) from Ch by a reactive free radical. It has been established that the most efficient HA from Ch occurs at C7, although HA from C4 by peroxyl radicals has recently been observed. Conversely, HA from Ch positions other than the thermodynamically preferred C7 or C4 has never been reported. We have designed a Ch derivative where a benzophenone moiety is linked to C7 by a covalent bond. This mirrors a specific orientation of Ch within a confined environment. Product analysis and time-resolved spectroscopic studies reveal an unprecedented HA from C15, which is a thermodynamically unfavorable position. This indicates that a specific topology of reactants is crucial for the reactivity of Ch. The relative orientation of the reactants can also be relevant in biological membranes, where Ch, polyunsaturated fatty acids, and numerous oxidizing species are confined in highly restricted and anisotropic environments.

Published
2019

24. Photosafety of the antidiabetic drug sitagliptin

Author

Dubón, A., Morera, I., García-Laínez, Guillermo, Sahuquillo, A., Rodríguez, M., Miranda, M. A., Andreu, Inmaculada, Dubón, A., Morera, I., García-Laínez, Guillermo, Sahuquillo, A., Rodríguez, M., Miranda, M. A., and Andreu, Inmaculada

Abstract

descripción no proporcionada por scopus

Published
2019

25. Chemical tuning for potential antitumor fluoroquinolones

Author

Anaya-Gonzalez, Cristina, Soldevila, Sonia, García-Laínez, Guillermo, Boscá, Francisco, Andreu, Inmaculada, Anaya-Gonzalez, Cristina, Soldevila, Sonia, García-Laínez, Guillermo, Boscá, Francisco, and Andreu, Inmaculada

Abstract

Phototoxic effects of 6,8 dihalogenated quinolones confers to this type of molecules a potential property as photochemotherapeutic agents. Two photodehalogenation processes seem to be involved in the remarkable photoinduced cellular damage. In this context, a new 6,8 dihalogenated quinolone 1 (1-methyl-6,8-difluoro-4-oxo-7-aminodimethyl-1,4-dihydroquinoline-3-carboxylic acid) was synthetized looking for improving the phototoxic properties of fluoroquinolones (FQ) and to determine the role of the photodegradation pathways in the FQ phototoxicity. With this purpose, fluorescence emissions, laser flash photolysis experiments and photodegradation studies were performed with compound 1 using 1-ethyl-6,8-difluoro-4-oxo-7-aminodimethyl-1,4-dihidroquinoline-3-carboxylic acid (2) and lomefloxacin (LFX) as reference compounds. The shortening of alkyl chain of the N(1) of the quinolone ring revealed a lifetime increase of the reactive aryl cation generated from photolysis of the three FQ and a significant reduction of the FQ photodegradation quantum yield. The fact that these differences were smaller when the same study was done using a hydrogen donor solvent (ethanol-aqueous buffer, 50/50 v/v) evidenced the highest ability of the reactive intermediate arising from 1 to produce intermolecular alkylations. These results were correlated with in vitro 3T3 NRU phototoxicity test. Thus, when Photo-Irritation-Factor (PIF) was determined for 1, 2 and LFX using cytotoxicity profiles of BALB/c 3T3 fibroblasts treated with each compound in the presence and absence of UVA light, a PIF more higher than 30 was obtained for 1 while the values for 2 and LFX were only higher than 8 and 10, respectively. Thereby, the present study illustrates an approach to modulate the photosensitizing properties of FQ with the purpose to improve the chemotherapeutic properties of antitumor quinolones. Moreover, the results obtained in this study also evidence that the key pathway responsible for the phototox

Published
2019

26. Update on Quinolone Allergy

Author

Doña I, Moreno, E, Perez-Sanchez, N, ANDREU, INMACULADA, HERNANDEZ, MARÍA DOLORES, and Torres, MJ

Subjects
Quinolone, Skin test, Basophil activation test, Maculopapular exanthema, Drug provocation test, Anaphylaxis
Abstract

Purpose of Review Quinolones are a group of synthetic antibiotics widely use as first-line treatment for many infections. There has been an increase in the incidence of hypersensitivity reactions to quinolones in recent years, likely due to increased prescription. The purpose of this review is to summarize the clinical pictures, the methods used for diagnosing and the management of allergic reactions to quinolones. Recent Findings Allergic reactions to quinolones can be immediate or delayed, being anaphylaxis and maculopapular exanthema respectively the most frequent clinical entities. A precise diagnosis is particularly difficult since clinical history is often unreliable, skin tests can induce false-positive results, and commercial in vitro test are not well validated. Therefore, drug provocation testing is considered the gold standard to establish diagnosis, which is not a risk-free procedure. Cross-reactivity between quinolones is difficult to predict due to the small number of patients included in the few published studies. Moreover, hypersensitivity to quinolones has also been associated with beta-lactam and neuromuscular blocking agent allergies, although further studies are needed to understand the underlying mechanisms. Avoidance of the culprit quinolone is indicated in patients with a diagnosis of hypersensitivity to these drugs. When quinolone treatment is the only therapeutic option available, desensitization is necessary. Summary This review summarizes the complex diagnostic approach and management of allergic reactions to quinolones.

Published
2017

27. 7th drug hypersensitivity meeting: part one

Author

Carr, Daniel F., Chung, Wen-Hung, Jenkiins, Rosalind E., Chaponda, Mas, Nwikue, Gospel, Cornejo Castro, Elena M., Antoine, Daniel J., Pirmohamed, Munir, Wuillemin, Natascha, Dina, Dolores, Eriksson, Klara K., Yerly, Daniel, Pavlos, Rebecca, Mckinnin, Elizabeth, Ostrov, David, Peters, Bjoern, Buus, Soren, Koelle, David, Chopra, Abha, Rive, Craig, Redwood, Alec, Restrepo, Susana, Bracey, Austin, Yuan, Jing, Gaudieri, Silvana, Carrington, Mary, Haas, David, Mallal, Simon, Phillips, Elizabeth, De Boer, Douwe, Menheere, Paul, Nieuwhof, Chris, Bons, Judith, Jonsson, Friederike, De Chaisemartin, Luc, Granger, Vanessa, Gillis, Caitlin, Gouel, Aurelie, Neukirch, Catherine, Dib, Fadia, Nicaise, Pascale Roland, Longrois, Dan, Tubach, Florence, Martin, Sylvie, Bruhns, Pierre, Chen, Kai-Lung, Liao, Shu-Ling, Sheen, Yi-Shuan, Cho, Yung-Tsu, Yang, Che-Wen, Liau, Jau-Yu, Chu, Chia-Yu, Aguiar, Rita, Lopes, Anabela, Fernandes, Natália, Viegas, Leonor, Pereira-Barbosa, M. A., Bünter, Antonia, Gupta, Nisha, Petkovic, Tatjana Pecaric, Wirth, Nicole, Pichler, Werner J., Hausmann, Oliver, Yazicioglu, Mehtap, Ozdemir, Pinar G., Ciplak, Gokce, Kaya, Ozkan, Cooke, Peter John, Mota, Inês, Gaspar, Ângela, Benito-Garcia, Filipe, Chambel, Marta, Morais-Almeida, Mário, Marques, Luis, Alcoceba, Eva, Lara, Silvia, Carneiro-Leão, Leonor, Botelho, Carmen, Dias-Castro, Eunice, Cernadas, Josefina R., Nicholls, Katherine, Lay, William, Smith, Olivia, Collins, Christine, Unglik, Gary, Spriggs, Kymble, Auyeung, Priscilla, McComish, Jeremy, Douglass, Jo A., Peter, Jonny G., Potter, Paul, Carolino, Fabrícia, De Castro, Eunice Dias, Moreira, Ana Sofia, Abreu, Carmo, Gomes, Eva, Cardoso, Bárbara Kong, Tomaz, Elza, Correia, Sara, Inácio, Filipe, Arnold, Annabelle, Bear, Natasha, Rueter, Kristina, Gong, Grace, O’Sullivan, Michael, Muthusamy, Saravanan, Noble, Valerie, Lucas, Michaela, Buterleviciute, Neringa, Rudzeviciene, Odilija, May, Sara, Pongdee, Thanai, Park, Miguel, Griguola, Linas, Vinikovas, Arturas, Kašinskaite, Simona, Kvedariene, Violeta, Aktas, Ayse, Rahman, Suheyla, Elbi, Huseyin, Ozyurt, Beyhan Cengiz, Cavkaytar, Ozlem, Karaatmaca, Betul, Cetinkaya, Pinar Gur, Esenboga, Saliha, Sahiner, Umit M., Sekerel, Bulent E., Soyer, Ozge, Zubrinich, Celia, Tong, Bianca, Patel, Mittal, Giles, Michelle, O’Hehir, Robyn, Puy, Robert, Amaral, Luís, Demir, Semra, Gelincik, Asli, Olgac, Muge, Caskun, Raif, Unal, Derya, Colakoglu, Bahauddin, Buyukozturk, Suna, Matute, Olga Vega, Bernad, Amalia, Gastaminza, Gabriel, Madamba, Roselle, Lacasa, Carlos, Goikoetxea, M. J., D’Amelio, Carmen, Rifón, Jose, Martínez, Nicolas, Ferrer, Marta, Ribeiro, Carmelita, Faria, Emília, Frutuoso, Cristina, Barros, Anabela, Lebre, Rosário, Pego, Alice, Bom, Ana Todo, Ensina, Luis Felipe, Aranda, Carolina, Nunes, Ines Camelo, Martins, Ana Maria, Solé, Dirceu, Bavbek, Sevim, Kendirlinan, Resat, Çerçi, Pamir, Tutluer, Seda, Soyyigit, Sadan, Sözener, Zeynep Çelebi, Aydin, Ömür, Gümüsburun, Reyhan, Almeida, Marta, Sai, Kimie, Imatoh, Takuya, Nakamura, Ryosuke, Fukazawa, Chisato, Hinomura, Yasushi, Saito, Yoshiro, Sousa-Pinto, Bernardo, Correia, Cláudia, Gomes, Lídia, Gil-Mata, Sara, Araújo, Luís, Delgado, Luís, Okamoto-Uchida, Yoshimi, Kajinami, Koji, Matsunaga, Kayoko, Aihara, Michiko, Wang, Chuang-Wei, Su, Shih-Chi, Hung, Shuen-Iu, Ho, Hsin-Chun, Yang, Chih-Hsun, Paulmann, Maren, Dunant, Ariane, Mockenhaupt, Maja, Sekula, Peggy, Schumacher, Martin, Kardaun, Sylvia, Naldi, Luigi, Bellón, Teresa, Creamer, Daniel, Haddad, Cynthia, Sassolas, Bruno, Lebrun-Vignes, Bénédicte, Valeyrie-Allanore, Laurence, Roujeau, Jean-Claude, Kremmler, Carmen, Dodiuk-Gad, Roni P., Olteanu, Cristina, Feinstein, Anthony, Hashimoto, Rena, Alhusayen, Raed, Whyte-Croasdaile, Sonia, Finkelstein, Yaron, Burnett, Marjorie, Sade, Shachar, Cartotto, Robert, Jeschke, Marc, Shear, Neil H., Takamura, Naoko, Yamane, Yumiko, Matsukura, Setsuko, Nakamura, Kazuko, Watanabe, Yuko, Yamaguchi, Yukie, Kambara, Takeshi, Ikezawa, Zenro, Chew, Hall, Knezevic, Brittany, Ionmhain, Una Nic, Barraclough, Allison, Anstey, Matthew, Usui, Toru, Meng, Xiaoli, Farrell, John, Whitaker, Paul, Watson, John, French, Neil, Park, Kevin, Naisbitt, Dean, Neves, Ana Castro, Cadinha, Susana, Moreira, Ana, Da Silva, J. P. Moreira, Drvar, Daniela Ledic, Gulin, Sandra Jerkovic, Hadzavdic, Suzana Ljubojevic, Ceovic, Romana, De Francisco, Ana Montoro, De Vicente Jiménez, Talía, Luque, Amelia García, David, Natalia Rosado, Galván, José Mª Mateos, Darlenski, Razvigor, Gulin, Dario, Sikic, Jozica, Habek, Jasna Cerkez, Galic, Edvard, Specht, Philip, Staab, Doris, Mayer, Beate, Roehmel, Jobst, Solovan, Caius, Chiriac, Anca, Djurinec, Paola, Kostovic, Kresimir, Bradamante, Mirna, Almeida, Jose Pedro, Caiado, Joana, Pedro, Elisa, Da Silva, Pedro Canas, Barbosa, Manuel Pereira, Bogas, Gador, Blanca-López, Natalia, Pérez-Alzate, Diana, Doña, Inmaculada, Agúndez, José Augusto, García-Martín, Elena, Cornejo-García, José Antonio, Mayorga, Cristobalina, Torres, María José, Canto, Maria Gabriela, Blanca, Miguel, Aksakal, Sengül, Sin, Aytül Zerrin, Koç, Zeynep Peker, Günsen, Fatma Düsünür, Ardeniz, Ömür, Gökmen, Emine Nihal Mete, Gülbahar, Okan, Kokuludag, Ali, Pérez-Sánchez, Natalia, Salas, María, Salas, Maria, Gomez, Francisca, Barrionuevo, Esther, Andreu, Inmaculada, Miranda, Miguel Ángel, Didžiokaite, Gabija, Gaidej, Olesia, Garcimartin, Maria Isabel, Somoza, Maria Luisa, Bojas, Gador, Cornejo-Garcia, Jose Antonio, Perez, Francisco Javier Ruano, Miranda, Miguel Angel, Jerschow, Elina, Pelletier, Teresa, Ren, Zhen, Hudes, Golda, Sanak, Marek, Morales, Esperanza, Schuster, Victor, Spivack, Simon D, Rosenstreich, David, Erzen, Renato, Silar, Mira, Bajrovic, Nissera, Rijavec, Matija, Zidarn, Mihaela, Korosec, Peter, Castro, Eunice, Al-Ahmad, Mona, Rodriguez, Tito, Azevedo, João Pedro, Tavares, Beatriz, Regateiro, Frederico, Todo-Bom, Ana, Miranda, Pablo Andrés, De La Cruz Hoyos, Bautista, Abuzeid, Waleed, Akbar, Nadeem, Gibber, Marc, Fried, Marvin, Han, Weiguo, Keskin, Taha, Tamayev, Robert, Spivack, Simon D., Boni, Elisa, Russello, Marina, Mauro, Marina, Neto, Marta Ferreira, Brosseron, Lise, Malheiro, Daniela, Barreira, Patrícia, Sprigg, Dustin, Trevenen, Michelle, Seet, Jason, Trubiano, Jason, Smith, William, Jeelall, Yogesh, Vale, Sandra, Loh, Richard, Mclean-Tooke, Andrew, Müller, Sabine, Amstutz, Ursula, Jörg, Lukas, Yawalkar, Nikhil, Krähenbühl, Stephan, Leblanc, Ana, Ribeiro, Laura, Vega, Arantza, Rivas, Raquel Gutierrez, Alonso, Ana, Beitia, Juan Maria, Mateo, Belén, Cárdenas, Remedios, Garcia-Dominguez, Juan Jesus, Strautins, Kaija, James, Ian, Neves, Ana, Do Céu Machado, Maria, Dalgiç, Ceyda Tunakan, Bulut, Gökten, Ardeniz, Fatma Ömür, Hsu, Shao-Hsuan, Ye, Young-Min, Hur, Gyu-Young, Park, Hae-Sim, Kim, Seung-Hyun, Ali, Syed, Hollingsworth, Peter N., Mclean-Tooke, Andrew P. C., Chadly, Zohra, Fredj, Nadia Ben, Aouam, Karim, Romdhane, Haifa Ben, Boughattas, Naceur A., Chaabane, Amel, Salazar, Marina Lluncor, Pola, Beatriz, Fiandor, Ana, Ramírez, Elena, Ortega, Javier Domínguez, Quirce, Santiago, Cabañas, Rosario, Baynova, Krasimira, Labella, Marina, Prados, Manuel, Ramonaite, Agne, Bajoriuniene, Ieva, Sitkauskiene, Brigita, Sakalauskas, Raimundas, Kwon, Jae-Woo, Park, Shinyoung, Silva, Diana, Leão, Leonor Carneiro, Garcimartin, Maria, De La Torre, Maria Vazquez, Pérez, Francisco Javier Ruano, Haroun, Elisa, Diez, Gabriela Canto, Ónodi-Nagy, Katinka, Kinyó, Ágnes, Kemény, Lajos, Bata-Csörgo, Zsuzsanna, Pita, Joana Sofia, Fernandes, Rosa Anita, Moura, Ana, Sousa, Nuno, Loureiro, Carlos, Pfützner, Wolfgang, Marrouche, Nadine, Grattan, Clive, Chen, Yu-En, Chen, Chun-Bing, Hsiao, Yu-Ping, and Ruano, Francisco Javier

Subjects
Pulmonary and Respiratory Medicine, Drug, Allergy, business.industry, media_common.quotation_subject, Immunology, medicine.disease, Meeting Abstracts, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Drug Hypersensitivity Syndrome, 030220 oncology & carcinogenesis, Immunology and Allergy, Medicine, business, media_common
Abstract

Table of contents Oral Abstracts O1 Functionally distinct HMGB1 isoforms correlate with physiological processes in drug-induced SJS/TEN Daniel F. Carr, Wen-Hung Chung, Rosalind E. Jenkiins, Mas Chaponda, Gospel Nwikue, Elena M. Cornejo Castro, Daniel J. Antoine, Munir Pirmohamed O2 Hypersensitivity reactions to beta-lactams, does the t cell recognition pattern influence the clinical picture? Natascha Wuillemin, Dolores Dina, Klara K. Eriksson, Daniel Yerly O3 Specific binding characteristics of HLA alleles associated with nevirapine hypersensitivity Rebecca Pavlos, Elizabeth Mckinnin, David Ostrov, Bjoern Peters, Soren Buus, David Koelle, Abha Chopra, Craig Rive, Alec Redwood, Susana Restrepo, Austin Bracey, Jing Yuan, Silvana Gaudieri, Mary Carrington, David Haas, Simon Mallal, Elizabeth Phillips O4 Do we need to measure total ige for the interpretation of analytical results of ImmunoCAP dnd 3gAllergy specific IgE? Douwe De Boer, Paul Menheere, Chris Nieuwhof, Judith Bons O5 Neutrophil activation in systemic anaphylaxis: results from the multicentric NASA study Friederike Jonsson, Luc De Chaisemartin, Vanessa Granger, Caitlin Gillis, Aurelie Gouel, Catherine Neukirch, Fadia Dib, Pascale Roland Nicaise, Dan Longrois, Florence Tubach, Sylvie Martin, Pierre Bruhns, NASA Study Group O6 Purpuric drug eruptions due to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for non-small-cell lung cancer (NSCLC): a clinic-pathological study of 32 cases Kai-Lung Chen, Shu-Ling Liao, Yi-Shuan Sheen, Yung-Tsu Cho, Che-Wen Yang, Jau-Yu Liau, Chia-Yu Chu Poster presentations: Poster Walk 1—Anaphylaxis (P01–P09) P1 Anaphylactic reactions during anaesthesia and the perioperative period Rita Aguiar, Anabela Lopes, Natália Fernandes, Leonor Viegas, M. A. Pereira-Barbosa P2 Anaphylaxis to chlorhexidine: is there a cross-reactivity to alexidine? Antonia Bünter, Nisha Gupta, Tatjana Pecaric Petkovic, Nicole Wirth, Werner J. Pichler, Oliver Hausmann P3 Cefotaxime-induced severe anaphylaxis in a neonate Mehtap Yazicioglu, Pinar G. Ozdemir, Gokce Ciplak, Ozkan Kaya P4 Clinical features and diagnosis of anaphylaxis resulting from exposure to chlorhexidine Peter John Cooke P5 Drug-induced anaphylaxis: five-year single-center survey Inês Mota, Ângela Gaspar, Filipe Benito-Garcia, Marta Chambel, Mário Morais-Almeida P6 Intraoperative severe anaphylactic reaction due to patent blue v dye Luis Marques, Eva Alcoceba, Silvia Lara P7 Kounis syndrome in the setting of anaphylaxis to diclofenac Leonor Carneiro-Leão, Carmen Botelho, Eunice Dias-Castro, Josefina Cernadas P8 Perioperative anaphylaxis audit: Royal Melbourne Hospital Katherine Nicholls, William Lay, Olivia Smith, Christine Collins, Gary Unglik, Kymble Spriggs, Priscilla Auyeung, Jeremy McComish, Jo A. Douglass P9 Recurrent peri-operative anaphylaxis: a perfect storm Jonny G. Peter, Paul Potter Poster Walk 2: DH regions and patient groups (P10–P19) P10 A rare presentation of amoxicillin allergy in a young child Fabrícia Carolino, Eunice Dias De Castro, Josefina R. Cernadas P11 Adverse drug reactions in children: antibiotics or virus? Ana Sofia Moreira, Carmo Abreu, Eva Gomes P12 Allergic reactions in invasive medical procedures Bárbara Kong Cardoso, Elza Tomaz, Sara Correia, Filipe Inácio P13 Antibiotic allergy in children: room for improvement Annabelle Arnold, Natasha Bear, Kristina Rueter, Grace Gong, Michael O’Sullivan, Saravanan Muthusamy, Valerie Noble, Michaela Lucas P14 Drug hypersensitivity reactions in children and results of diagnostic evaluation Neringa Buterleviciute, Odilija Rudzeviciene P15 Nonimmediate cutaneous drug reactions in children: are skin tests required? Ana Sofia Moreira, Carmo Abreu, Eva Gomes P16 Pediatric patients with a history of penicillin allergy and a positive penicillin skin test may not be at an increased risk for multiple drug allergies Sara May, Thanai Pongdee, Miguel Park P17 Proved hypersensitivity to drugs according data of Vilnius University Hospital Santariskiu Klinikos Linas Griguola, Arturas Vinikovas, Simona Kašinskaite, Violeta Kvedariene P18 Self-reported prevalence of drug hypersensitivity reactions among students in Celal Bayar University, Turkey Ayse Aktas, Suheyla Rahman, Huseyin Elbi, Beyhan Cengiz Ozyurt P19 Severe drug hypersensitivity reactions in pediatric age Ozlem Cavkaytar, Betul Karaatmaca, Pinar Gur Cetinkaya, Saliha Esenboga, Umit M. Sahiner, Bulent E. Sekerel, Ozge Soyer Poster Walk 3: Desensitisation (P20–P28) P20 A protocol for desensitisation to valaciclovir Celia Zubrinich, Bianca Tong, Mittal Patel, Michelle Giles, Robyn O’Hehir, Robert Puy P21 A rare case of desensitization to modafinil Josefina Cernadas, Luís Amaral, Fabrícia Carolino P22 A sixteen-day desensitization protocol in delayed type hypersensitivity reactions to oral drugs Semra Demir, Asli Gelincik, Muge Olgac, Raif Caskun, Derya Unal, Bahauddin Colakoglu, Suna Buyukozturk P23 Desensitization to intravenous etoposide using a 12 and a 13-step protocol. Two cases report Olga Vega Matute, Amalia Bernad, Gabriel Gastaminza, Roselle Madamba, Carlos Lacasa, M. J. Goikoetxea, Carmen D’Amelio, Jose Rifón, Nicolas Martínez, Marta Ferrer P24 Drug desensitisation in oncology: the experience of an immunoallergology department for 5 years Carmelita Ribeiro, Emília Faria, Cristina Frutuoso, Anabela Barros, Rosário Lebre, Alice Pego, Ana Todo Bom P25 Filgrastim anaphylaxis: a successful desensitization protocol Luis Amaral, Josefina Cernadas P26 Galsulfase hypersensitivity and desensitization of a mucopolysaccharidosis VI patient Luis Felipe Ensina, Carolina Aranda, Ines Camelo Nunes, Ana Maria Martins, Dirceu Solé P27 Rapid drug desensitization with biologicals: one-center experience with four biologicals Sevim Bavbek, Resat Kendirlinan, Pamir Çerçi, Seda Tutluer, Sadan Soyyigit, Zeynep Çelebi Sözener, Ömür Aydin, Reyhan Gümüsburun P28 Successful desensitization to a high dose of methotrexate in a delayed type hypersensitivity reaction Josefina Cernadas, Leonor Carneiro-Leão, Fabrícia Carolino, Marta Almeida Poster Walk 4: SJS (P29–P38) P29 Assessment of impact of infection on drug-induced severe cutaneous adverse reactions and rhabdomyolysis using the Japanese adverse drug event report database Kimie Sai, Takuya Imatoh, Ryosuke Nakamura, Chisato Fukazawa, Yasushi Hinomura, Yoshiro Saito P30 Characterization of erythema multiforme and severe cutaneous adverse reactions hospitalizations Bernardo Sousa-Pinto, Cláudia Correia, Lídia Gomes, Sara Gil-Mata, Luís Araújo, Luís Delgado P31 Effects of infection on incidence/severity of SJS/TEN and myopathy in Japanese cases analyzed by voluntary case reports Ryosuke Nakamura, Kimie Sai, Takuya Imatoh, Yoshimi Okamoto-Uchida, Koji Kajinami, Kayoko Matsunaga, Michiko Aihara, Yoshiro Saito P32 Efficacy of tumor necrosis factor—a antagonists in Stevens–Johnson syndrome and toxic epidermal necrolysis: a randomized controlled trial and immunosuppressive effects evaluation Chuang-Wei Wang, Shih-Chi Su, Shuen-Iu Hung, Hsin-Chun Ho, Chih-Hsun Yang, Wen-Hung Chung P33 Evolution of drug causality in Stevens–Johnson syndrome and toxic epidermal necrolysis in Europe: analysis of 10 years RegiSCAR-Study Maren Paulmann, Ariane Dunant, Maja Mockenhaupt, Peggy Sekula, Martin Schumacher, Sylvia Kardaun, Luigi Naldi, Teresa Bellón, Daniel Creamer, Cynthia Haddad, Bruno Sassolas, Bénédicte Lebrun-Vignes, Laurence Valeyrie-Allanore, Jean-Claude Roujeau P34 Long-term sequelae in patients with Stevens–Johnson syndrome and toxic epidermal necrolysis: a 5-year analysis Maren Paulmann, Carmen Kremmler, Peggy Sekula, Laurence Valeyrie-Allanore, Luigi Naldi, Sylvia Kardaun, Maja Mockenhaupt P35 Major emotional complications and decreased health related quality of life among survivors of Stevens–Johnson syndrome and toxic epidermal necrolysis Roni P. Dodiuk-Gad, Cristina Olteanu, Anthony Feinstein, Rena Hashimoto, Raed Alhusayen, Sonia Whyte-Croasdaile, Yaron Finkelstein, Marjorie Burnett, Shachar Sade, Robert Cartotto, Marc Jeschke, Neil H. Shear P36 Retrospective analysis of Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients: treatment and outcome Naoko Takamura, Yumiko Yamane, Setsuko Matsukura, Kazuko Nakamura, Yuko Watanabe, Yukie Yamaguchi, Takeshi Kambara, Zenro Ikezawa, Michiko Aihara P37 Severe physical complications among survivors of Stevens–Johnson syndrome and toxic epidermal necrolysis Roni P. Dodiuk-Gad, Cristina Olteanu, Rena Hashimoto, Hall Chew, Raed Alhusayen, Sonia Whyte-Croasdaile, Yaron Finkelstein, Marjorie Burnett, Shachar Sade, Robert Cartotto, Marc Jeschke, Neil H. Shear P38 Stevens–Johnson syndrome/toxic epidermal necrolysis combined with haemophagocytic lymphohistiocytosis: a case report Brittany Knezevic, Una Nic Ionmhain, Allison Barraclough, Michaela Lucas, Matthew Anstey Poster Walk 5: Other organs/unexpected immune reactions (P39–P47) P39 A case report of patient with anti-tuberculosis drug-related severe liver failure Toru Usui, Xiaoli Meng, John Farrell, Paul Whitaker, John Watson, Neil French, Kevin Park, Dean Naisbitt P40 Acute interstitial nephritis induced by ibuprofen Ana Castro Neves, Susana Cadinha, Ana Moreira, J. P. Moreira Da Silva P41 Cetuximab induced acneiform rash—two case reports Daniela Ledic Drvar, Sandra Jerkovic Gulin, Suzana Ljubojevic Hadzavdic, Romana Ceovic P42 Enteropathy associated with losartan Ana Montoro De Francisco, Talía De Vicente Jiménez, Amelia García Luque, Natalia Rosado David, José Mª Mateos Galván P43 Granuloma annulare after therapy with canakinumab Razvigor Darlenski P44 Hypersensitivity eosinophilic myocarditis or acute coronary syndrome? Case report Dario Gulin, Jozica Sikic, Jasna Cerkez Habek, Sandra Jerkovic Gulin, Edvard Galic P45 Piperacillin-induced immune haemolytic anaemia: a severe and frequent complication of antibiotic treatment in patients with cystic fibrosis Philip Specht, Doris Staab, Beate Mayer, Jobst Roehmel P46 Progesterone triggered pemphigus foliaceus: case report Sandra Jerkovic Gulin, Caius Solovan, Anca Chiriac P47 Ramipril: triggered generalized pustular psoriasis Paola Djurinec, Kresimir Kostovic, Mirna Bradamante, Sandra Jerkovic Gulin, Romana Ceovic Poster Walk 6: NSAIDs (P48–P56) P48 Aspirin desensitization in cardiovascular disease—Portuguese experience Jose Pedro Almeida, Joana Caiado, Elisa Pedro, Pedro Canas Da Silva, Manuel Pereira Barbosa P49 Asthma and/or rhinitis to NSAIDs with good tolerance to ASA Gador Bogas, Natalia Blanca-López, Diana Pérez-Alzate, Inmaculada Doña, José Augusto Agúndez, Elena García-Martín, José Antonio Cornejo-García, Cristobalina Mayorga, María José Torres, Gabriela Canto, Miguel Blanca P50 Clinical characteristics of 196 patients with non-steroidal anti-inflammatory drug (NSAIDs) hypersensitivity Sengül Aksakal, Aytül Zerrin Sin, Zeynep Peker Koç, Fatma Düsünür Günsen, Ömür Ardeniz, Emine Nihal Mete Gökmen, Okan Gülbahar, Ali Kokuludag P51 Development of immediate hypersensitivity to several NSAIDs maintaining good tolerance to ASA Natalia Pérez-Sánchez, Natalia Blanca-López, Diana Pérez-Alzate, Gador Bogas, Inmaculada Doña, María Salas, María José Torres, Miguel Blanca, Gabriela Canto P52 Diagnosis of hypersensitivity reactions to paracetamol in a large series of cases Inmaculada Doña, Maria Salas, Francisca Gomez, Natalia Blanca-Lopez, Diana Perez-Alzate, Gador Bogas, Esther Barrionuevo, Maria Jose Torres, Inmaculada Andreu, Miguel Ángel Miranda, Gabriela Canto, Miguel Blanca P53 Hypersensitivity to paracetamol according to the new classification of hypersensitivity to NSAIDs Gabija Didžiokaite, Olesia Gaidej, Simona Kašinskaite, Violeta Kvedariene P54 Ibuprofen and other aryl propionic derivates can induce immediate selective hypersensitivity responses Diana Perez-Alzate, Natalia Blanca-López, Maria Isabel Garcimartin, Inmaculada Doña, Maria Luisa Somoza, Cristobalina Mayorga, Maria Jose Torres, Gador Bojas, Jose Antonio Cornejo-Garcia, Maria Gabriela Canto, Miguel Blanca P55 Subjects developing immediate responses to several NSAIDs can be selective with good tolerance to ASA Natalia Blanca-Lopez, Diana Pérez-Alzate, Francisco Javier Ruano Perez, Inmaculada Doña, Maria Luisa Somoza, Inmaculada Andreu, Miguel Angel Miranda, Cristobalina Mayorga, Maria Jose Torres, Jose Antonio Cornejo-Garcia, Miguel Blanca, Maria Gabriela Canto P56 Utility of low-dose oral aspirin challenges for diagnosis of aspirin exacerbated respiratory disease Elina Jerschow, Teresa Pelletier, Zhen Ren, Golda Hudes, Marek Sanak, Esperanza Morales, Victor Schuster, Simon D. Spivack, David Rosenstreich Poster Walk 7: NSAID 2 (P57–P65) P57 Alternate regulation of cyclooxygenase-2 (COX-2) MRNA expression may predispose patients to aspirin-induced exacerbations Renato Erzen, Mira Silar, Nissera Bajrovic, Matija Rijavec, Mihaela Zidarn, Peter Korosec P58 Anaphylaxis to diclofenac: what about the underlying mechanism? Leonor Carneiro-Leão, Fabrícia Carolino, Luís Amaral, Carmen Botelho, Eunice Dias-Castro, Josefina Cernadas P59 COX-2 inhibitors: are they always a safe alternative in hypersensitivity to nonsteroidal anti-inflammatory drugs? Luis Amaral, Fabricia Carolino, Eunice Castro, Josefina Cernadas P60 Management of patients with history of NSAIDs reactions prior to coronary angioplasty Mona Al-Ahmad, Tito Rodriguez P61 Oral drug challenge with non-steroidal anti-inflammatory drug under spirometric control: clinical series of 110 patients João Pedro Azevedo, Emília Faria, Beatriz Tavares, Frederico Regateiro, Ana Todo-Bom P62 Prevalence and incidence of analgesic hypersensitivity reactions in Colombia Pablo Andrés Miranda, Bautista De La Cruz Hoyos P63 Recent endoscopic sinus surgery lessens reactions during aspirin challenge in patients with aspirin exacerbated respiratory disease Teresa Pelletier, Waleed Abuzeid, Nadeem Akbar, Marc Gibber, Marvin Fried, Weiguo Han, Taha Keskin, Robert Tamayev, Golda Hudes, Simon D. Spivack, David Rosenstreich, Elina Jerschow P64 Safe use of imidazole salycilate in a case of multiple NSAIDs induced urticaria-angioedema Elisa Boni, Marina Russello, Marina Mauro P65 Selective hypersensitivity reactions to ibuprofen—seven years experience Marta Ferreira Neto Poster Walk 8: Epidemiological methods (P66–P72) P66 Allopurinol hypersensitivity: a 7-year review Lise Brosseron, Daniela Malheiro, Susana Cadinha, Patrícia Barreira, J. P. Moreira Da Silva P67 Antibiotic allergy labelling is associated with increased hospital readmission rates in Australia Brittany Knezevic, Dustin Sprigg, Michelle Trevenen, Jason Seet, Jason Trubiano, William Smith, Yogesh Jeelall, Sandra Vale, Richard Loh, Andrew Mclean-Tooke, Michaela Lucas P68 Experts’ opinions on severe cutaneous adverse drug reactions-report of a survey from the 9th international congress on cutaneous adverse drug reactions 2015 Roni P. Dodiuk-Gad, Cristina Olteanu, Wen-Hung Chung, Neil H. Shear P69 HLA-A*31-positive AGEP with carbamazepine use and other severe cutaneous adverse drug reactions (SCARs) detected by electronic medical records screening Sabine Müller, Ursula Amstutz, Lukas Jörg, Nikhil Yawalkar, Stephan Krähenbühl P70 Patients with suspected drug allergy: a specific psychological profile? Eunice Dias-Castro, Ana Leblanc, Laura Ribeiro, Josefina R. Cernadas P71 Use of an electronic device and a computerized mathematic algorithm to detect the allergic drug reactions through the analysis of heart rate variability Arantza Vega, Raquel Gutierrez Rivas, Ana Alonso, Juan Maria Beitia, Belén Mateo, Remedios Cárdenas, Juan Jesus Garcia-Dominguez P72 Variation in ERAP influences risk for HLA-B*57:01 positive abacavir hypersensitivity Rebecca Pavlos, Kaija Strautins, Ian James, Simon Mallal, Alec Redwood, Elizabeth Phillips Poster Walk 9: DRESS/AGEP (P73–P81) P73 A clinical case of DRESS syndrome in a child after administration of amoxicillin-clavulanic acid Rita Aguiar, Anabela Lopes, Ana Neves, Maria Do Céu Machado, M. A. Pereira-Barbosa P74 Acute generalized exanthematous pustulosis (AGEP) induced by mesalazine, reliable and oftenly used drug to treat inflammatory bowel disease Ceyda Tunakan Dalgiç, Emine Nihal Mete Gökmen, Fatma Düsünür Günsen, Gökten Bulut, Fatma Ömür Ardeniz, Okan Gülbahar, Ali Kokuludag, Aytül Zerrin Sin P75 Changes of blood plasmacytoid dendritic cells, myeloid dendritic cells, and basophils during the acute stage of drug reaction with eosinophilia and systemic symptoms (DRESS) and other drug eruptions Shao-Hsuan Hsu, Yung-Tsu Cho, Che-Wen Yang, Kai-Lung Chen, Chia-Yu Chu P76 Characterization of isoniazid/rifampicin-specific t-cell responses in patients with DRESS syndrome Young-Min Ye, Gyu-Young Hur, Hae-Sim Park, Seung-Hyun Kim P77 DRESS syndrome secondary to sulfasalazine with delayed TEN: a case presentation Syed Ali, Michaela Lucas, Peter N. Hollingsworth, Andrew P. C. Mclean-Tooke P78 Drug rash with eosinophilia and systemic symptoms (DRESS) features according to the culprit drug Zohra Chadly, Nadia Ben Fredj, Karim Aouam, Haifa Ben Romdhane, Naceur A. Boughattas, Amel Chaabane P79 Drug reaction with eosinophilia and systemic symptoms induced by allopurinol: not always easy to diagnose Marina Lluncor Salazar, Beatriz Pola, Ana Fiandor, Teresa Bellón, Elena Ramírez, Javier Domínguez Ortega, Santiago Quirce, Rosario Cabañas P80 Drug reaction with eosinophilia and systemic symptoms syndrome induced by two drugs simultaneously: a case report Krasimira Baynova, Marina Labella, Manuel Prados P81 The drug reaction with eosinophilia and systemic symptoms (DRESS) induced by the second-line antituberculosis drugs and Epstein–Barr virus infection Agne Ramonaite, Ieva Bajoriuniene, Brigita Sitkauskiene, Raimundas Sakalauskas Poster Walk 10: Miscellaneous drug hypersensitivity (P82–P91) P82 A case of cycloserine-induced lichenoid drug eruption confirmed with a lymphocatye transformation test Jae-Woo Kwon, Shinyoung Park P83 Allergic reaction to topical eye drops: 5 years’ retrospective study in a drug allergy unit Diana Silva, Leonor Carneiro Leão, Fabricia Carolino, Eunice Castro, Josefina Cernadas P84 Allergy to heparins Diana Perez-Alzate, Natalia Blanca-López, Maria Luisa Somoza Alvarez, Maria Garcimartin, Maria Vazquez De La Torre, Francisco Javier Ruano Pérez, Elisa Haroun, Gabriela Canto Diez P85 Allopurinol-induced adverse drug reactions Katinka Ónodi-Nagy, Ágnes Kinyó, Lajos Kemény, Zsuzsanna Bata-Csörgo P86 Analysis of a population with immediate hypersensitivity to corticosteroids: an 11 year review Joana Sofia Pita, Emília Faria, Rosa Anita Fernandes, Ana Moura, Nuno Sousa, Carmelita Ribeiro, Carlos Loureiro, Ana Todo Bom P87 Anaphylaxis against mivacurium in a 12-months old boy at first-time exposure Wolfgang Pfützner P88 Antihistamine-exacerbated chronic spontaneous urticaria: a paradox? Nadine Marrouche, Clive Grattan P89 Anti-osteoporotic agents-induced cutaneous adverse drug reactions in Asians Yu-En Chen, Chun-Bing Chen, Wen-Hung Chung, Yu-Ping Hsiao, Chia-Yu Chu P90 Diagnosis of allergic reactions to eye drops Maria Vazquez De La Torre, Natalia Blanca-Lopez, Diana Perez-Alzate, Maria Isabel Garcimartin, Francisco Javier Ruano, Maria Luisa Somoza, Elisa Haroun, Gabriela Canto P91 Diagnostic approach in suspected hypersensitivity reactions to corticosteroids Fabrícia Carolino, Eunice Dias De Castro, Josefina R. Cernadas

Published
2016

28. Photosensitivity to triflusal: formation of a photoadduct with ubiquitin demonstrated by photophysical and proteomic techniques

Author

Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Nuin, Edurne, Pérez-Sala, Dolores, Lhiaubet-Vallet, Virginie, Andreu, Inmaculada, Miranda, Miguel A., Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Nuin, Edurne, Pérez-Sala, Dolores, Lhiaubet-Vallet, Virginie, Andreu, Inmaculada, and Miranda, Miguel A.

Abstract

Triflusal is a platelet aggregation inhibitor chemically related to acetylsalicylic acid, which is used for the prevention and/or treatment of vascular thromboembolisms, which acts as a prodrug. Actually, after oral administration it is absorbed primarily in the small intestine, binds to plasma proteins (99%) and is rapidly biotransformed in the liver into its deacetylated active metabolite 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). In healthy humans, the half-life of triflusal is ca. 0.5 h, whereas for HTB it is ca. 35 h. From a pharmacological point of view, it is interesting to note that HTB is itself highly active as a platelet anti-aggregant agent. Indeed, studies on the clinical profile of both drug and metabolite have shown no significant differences between them. It has been evidenced that HTB displays ability to induce photoallergy in humans. This phenomenon involves a cell-mediated immune response, which is initiated by covalent binding of a light-activated photosensitizer (or a species derived therefrom) to a protein. In this context, small proteins like ubiquitin could be appropriate models for investigating covalent binding by means of MS/MS and peptide fingerprint analysis. In previous work, it was shown that HTB forms covalent photoadducts with isolated lysine. Interestingly, ubiquitin contains seven lysine residues that could be modified by a similar reaction.With this background, the aim of the present work is to explore adduct formation between the triflusal metabolite and ubiquitin as model protein upon sunlight irradiation, combining proteomic and photophysical (fluorescence and laser flash photolysis) techniques. Photophysical and proteomic analysis demonstrates monoadduct formation as the major outcome of the reaction. Interestingly, addition can take place at any of the +-amino groups of the lysine residues of the protein and involves replacement of the trifluoromethyl moiety with a new amide function. This process can in principle occur w

Published
2016

30. 7th Drug hypersensitivity meeting: part two

Author

Elera, Javier Dionicio, primary, Boteanu, Cosmin, additional, Blanco, Maria Aranzazu Jimenez, additional, Gonzalez-Mendiola, Rosario, additional, García, Irene Carrasco, additional, Alvarez, Antonio, additional, Martinez, Jose Julio Laguna, additional, Garrido, Jaume Martí, additional, Barona, Carla Torán, additional, Chorda, Carolina Perales, additional, Salgueiro, Ramón López, additional, Palacios, Miguel Díaz, additional, De Rojas, Dolores Hernández Fernández, additional, Acar, Emre Ali, additional, Aktas, Ayse, additional, Ermertcan, Aylin Türel, additional, Temiz, Peyker, additional, Lin, Chien-Yio, additional, Hui, Chung-Yee Rosaline, additional, Chang, Ya-Ching, additional, Yang, Chih-Hsun, additional, Chung, Wen-Hung, additional, Carolino, Fabrícia, additional, Silva, Diana, additional, De Castro, Eunice Dias, additional, Cernadas, Josefina R., additional, Ensina, Luis Felipe, additional, Aranda, Carolina, additional, Nunes, Ines Camelo, additional, Lacerda, Alex, additional, Martins, Ana Maria, additional, Goudouris, Ekaterini, additional, Ribeiro, Marcia, additional, Da Silva Franco, José Francisco, additional, Queiroz, Leandra, additional, Solé, Dirceu, additional, Dalgiç, Ceyda Tunakan, additional, Sin, Aytül Zerrin, additional, Günsen, Fatma Düsünür, additional, Bulut, Gökten, additional, Ardeniz, Fatma Ömür, additional, Gülbahar, Okan, additional, Gökmen, Emine Nihal Mete, additional, Kokuludag, Ali, additional, De Francisco, Ana M. Montoro, additional, De Vicente Jiménez, Talía Mª, additional, Mendoza Parra, Adriana M., additional, Burgos Pimentel, Angella M., additional, Luque, Amelia García, additional, Amaral, Luis, additional, Leão, Leonor Carneiro, additional, Pinto, Nicole, additional, Belo, Joana, additional, Marques, João, additional, Carreiro-Martins, Pedro, additional, Leiria-Pinto, Paula, additional, Chaabane, Amel, additional, Romdhane, Haifa Ben, additional, Fredj, Nadia Ben, additional, Chadly, Zohra, additional, Boughattas, Naceur A., additional, Aouam, Karim, additional, Uyttebroek, Astrid P., additional, Bridts, Chris H., additional, Romano, Antonino, additional, Ebo, Didier G., additional, Sabato, Vito, additional, Lopes, Anabela, additional, Cosme, Joana, additional, Aguiar, Rita, additional, Lourenço, Tatiana, additional, Paes, Maria-João, additional, Spínola-Santos, Amélia, additional, Pereira-Barbosa, Manuel, additional, Cruz, Cíntia Rito, additional, Dos Reis, Rute Pereira, additional, Tomaz, Elza, additional, Pires, Ana Paula, additional, Inácio, Filipe, additional, Benito-Garcia, Filipe, additional, Mota, Inês, additional, Correia, Magna, additional, Gaspar, Ângela, additional, Chambel, Marta, additional, Piedade, Susana, additional, Morais-Almeida, Mário, additional, Nakonechna, Alla, additional, Antipkin, Yurij, additional, Umanets, Tetiana, additional, Pineda, Fernando, additional, Arribas, Francisca, additional, Lapshyn, Volodymyr, additional, Miranda, Pablo Andrés, additional, De La Cruz Hoyos, Bautista, additional, Blanco, Aranzazu Jimenez, additional, Del Pozo, Marta, additional, Vultaggio, Alessandra, additional, Nencini, Francesca, additional, Pratesi, Sara, additional, Matucci, Andrea, additional, Maggi, Enrico, additional, Cegec, Ivana, additional, Nahal, Danica Juricic, additional, Turk, Viktorija Erdeljic, additional, Aumiler, Matea Radacic, additional, Ausperger, Ksenija Makar, additional, Kraljickovic, Iva, additional, Simic, Iveta, additional, Yamaguchi, Yukie, additional, Watanabe, Tomoya, additional, Satoh, Megumi, additional, Tanegashima, Tomohiko, additional, Oda, Kayoko, additional, Wada, Hidefumi, additional, Aihara, Michiko, additional, Lee, Jaechun Jason, additional, Choi, Jay Chol, additional, Lee, Hwa Young, additional, Fernandes, Rosa-Anita Rodrigues, additional, Faria, Emília, additional, Pita, Joana, additional, Sousa, Nuno, additional, Ribeiro, Carmelita, additional, Carrapatoso, Isabel, additional, Bom, Ana Todo, additional, Rodolfo, Ana, additional, Dias-Castro, Eunice, additional, Voronova, Marina, additional, Valle, Diana Kury, additional, Coronel, Verónica Pacheco, additional, Chordá, Carolina Perales, additional, Madamba, Roselle Catherine Yu, additional, Ferrer, Marta, additional, Goikoetxea, Maria Jose, additional, D’Amelio, Carmen, additional, Bernad, Amalia, additional, Vega, Olga, additional, Gastaminza, Gabriel, additional, Bibián, Beatriz Pola, additional, Salazar, Marina Lluncor, additional, Vilà-Nadal, Gemma, additional, Roman, Ana María Fiandor, additional, Ortega, Javier Dominguez, additional, Muñoz, Miguel Gonzalez, additional, Gancedo, Santiago Quirce, additional, Moreno, Maria Rosario Cabañas, additional, Hofmeier, Kathrin Scherer, additional, Barzylovych, Vladyslava, additional, Pola, Beatriz, additional, Lluncor, Marina, additional, Fiandor, Ana, additional, Bellón, Teresa, additional, Domínguez, Javier, additional, Quirce, Santiago, additional, Yang, Min-Suk, additional, Kim, Sun-Sin, additional, Kim, Sae-Hoon, additional, Kang, Hye-Ryun, additional, Park, Heung-Woo, additional, Cho, Sang-Heon, additional, Min, Kyung-Up, additional, Chang, Yoon-Seok, additional, Delahaye, Clémence, additional, Flabbee, Jenny, additional, Waton, Julie, additional, Bauvin, Olivia, additional, Barbaud, Annick, additional, Fadhel, Najah Ben, additional, Gulin, Sandra Jerkovic, additional, Chiriac, Anca, additional, Cardoso, Bárbara Kong, additional, Viseu, Regina, additional, Moreira, Ana, additional, Cadinha, Susana, additional, Neves, Ana Castro, additional, Barreira, Patrícia, additional, Malheiro, Daniela, additional, Da Silva, J. P. Moreira, additional, Jurakic-Toncic, Ružica, additional, Ljubojevic, Suzana, additional, Turcic, Petra, additional, Gilissen, Liesbeth, additional, Huygens, Sara, additional, Goossens, An, additional, Andreu, Inmaculada, additional, Romero, Alicia Martinez, additional, Cabezas, Pau Gomez, additional, Parejo, Pedro Ayuso, additional, Del Carmen Plaza-Serón, Maria, additional, Doña, Inmaculada, additional, Blanca-López, Natalia, additional, Flores, Carlos, additional, Galindo, María Luisa, additional, Molina, Ana, additional, Perkins, James Richard, additional, Cornejo-García, José Antonio, additional, García-Agúndez, José Augusto, additional, García-Martín, Elena, additional, Campo, Paloma, additional, Canto, María Gabriela, additional, Blanca, Miguel, additional, Guéant-Rodríguez, Rosa María, additional, Jurado-Escobar, Raquel, additional, Barrionuevo, Esther, additional, Salas, María, additional, Canto, Gabriela, additional, Guéant, Jean-Louis, additional, Usui, Toru, additional, Tailor, Arun, additional, Faulkner, Lee, additional, Farrell, John, additional, Alfirevic, Ana, additional, Kevin Park, B., additional, Naisbitt, Dean J., additional, Trelles, Oswaldo, additional, Guerrero, María Auxiliadora, additional, Upton, Alex, additional, Ueta, Mayumi, additional, Sawai, Hiromi, additional, Sotozono, Chie, additional, Tokunaga, Katushi, additional, Kinoshita, Shigeru, additional, Sukasem, Chonlaphat, additional, Satapornpong, Patompong, additional, Tempark, Therdpong, additional, Rerknimitr, Pawinee, additional, Pairayayutakul, Kulprapat, additional, Klaewsongkram, Jettanong, additional, Koomdee, N., additional, Jantararoungtong, T., additional, Santon, S., additional, Puangpetch, A., additional, Intusoma, U., additional, Tassaneeyakul, W., additional, Theeramoke, V., additional, Ramirez, Elena, additional, Borobia, Alberto Manuel, additional, Tong, Hoi, additional, Castañer, Jose Luis, additional, De Abajo, Francisco José, additional, Galvao, Violeta Régnier, additional, Pavlos, Rebecca, additional, Mckinnon, Elizabeth, additional, Williams, Kristina, additional, Beeghly-Fadiel, Alicia, additional, Redwood, Alec, additional, Phillips, Elizabeth, additional, Castells, Mariana, additional, Boni, Elisa, additional, Russello, Marina, additional, Mauro, Marina, additional, Ue, Kok Loong, additional, Rutkowski, Krzysztof, additional, Gomis, Victor Soriano, additional, Ferre, Jorge Frances, additional, Rodriguez, Angel Esteban, additional, Reig, Vicente Cantó, additional, Sanchez, Javier Fernandez, additional, Breynaert, Christine, additional, Van Hoeyveld, Erna, additional, Schrijvers, Rik, additional, Irigoyen, Raquel Fuentes, additional, Collado, Daniel, additional, Vida, Yolanda, additional, Najera, Francisco, additional, Perez-Inestrosa, Ezequiel, additional, Mesa-Antunez, Pablo, additional, Mayorga, Cristobalina, additional, Torres, María José, additional, Tannert, Line K., additional, Mortz, Charlotte G., additional, Skov, Per Stahl, additional, Bindslev-Jensen, Carsten, additional, Pfützner, Wolfgang, additional, Dörnbach, Hannah, additional, Visse, Johanna, additional, Rauber, Michele, additional, Möbs, Christian, additional, Elzagallaai, Abdelbaset A., additional, Chow, Lindsey, additional, Abuzgaia, Awatif M., additional, Rieder, Michael J., additional, Trubiano, Jason, additional, Woolnough, Emily, additional, Stautins, Kaija, additional, Cheng, Christina, additional, Kato, Kenichi, additional, Azukizawa, Hiroaki, additional, Hanafusa, Takaaki, additional, Katayama, Ichiro, additional, Fujiyama, Toshiharu, additional, Hashizume, Hideo, additional, Umayahara, Takatsune, additional, Ito, Taisuke, additional, Tokura, Yoshiki, additional, Silar, Mira, additional, Zidarn, Mihaela, additional, Rupnik, Helena, additional, Korosec, Peter, additional, Redwood, Alec James, additional, Strautins, Kaija, additional, White, Katie, additional, Chopra, Abha, additional, Konvinse, Katherine, additional, Leary, Shay, additional, Mallal, Simon, additional, Cabañas, Rosario, additional, Fiandor, Ana María, additional, Sullivan, Andrew, additional, Whitaker, Paul, additional, Peckham, Daniel, additional, Haw, Wei Yann, additional, Polak, Marta E., additional, Mcguire, Carolann, additional, Ardern-Jones, Michael R., additional, Aoyama, Yumi, additional, Shiohara, Tetsuo, additional, Correia, Sara, additional, Gelincik, Asli, additional, Demir, Semra, additional, Sen, Fatma, additional, Bozbey, Hamza Ugur, additional, Olgac, Muge, additional, Unal, Derya, additional, Coskun, Raif, additional, Colakoglu, Bahauddin, additional, Buyuozturk, Suna, additional, Çatin-Aktas, Esin, additional, Deniz, Gunnur, additional, Laguna, Jose Julio, additional, Dionicio, J., additional, Fernandez, Tahia, additional, Olazabal, I., additional, Ruiz, Maria Dolores, additional, Torres, Maria José, additional, Lafuente, Alberto, additional, Núñez, Jorge, additional, Fernández, Tahia Diana, additional, Palomares, Francisca, additional, Fernández, Rubén, additional, Sanchez, Maria Isabel, additional, Fernandez, Tahía, additional, Ruiz, Arturo, additional, Ariza, Adriana, additional, Alonso, Amalia Bernad, additional, Garófalo, Carmen D’Amelio, additional, Matute, Olga Vega, additional, Puga, Marta Ferrer, additional, Lapresa, María José Goikoetxea, additional, Lasarte, Gabriel Gastaminza, additional, Thinnes, Antonia, additional, Merk, Hans F., additional, Baron, Jens Malte, additional, Leverkus, Martin, additional, Balakirski, Galina, additional, Gibson, Andrew, additional, Ogese, Monday, additional, Al-Attar, Zaid, additional, Yaseen, Fiazia, additional, Meng, Xiaoli, additional, Jenkins, Rozalind, additional, Farrel, John, additional, Alhilali, Khetam, additional, Xue, Yanni, additional, Illing, Patricia, additional, Mifsud, Nicole, additional, Fettke, Heidi, additional, Lai, Jeffrey, additional, Ho, Rebecca, additional, Kwan, Patrick, additional, Purcell, Anthony, additional, Ogese, Monday O., additional, Betts, Catherine, additional, Thomson, Paul, additional, Alhaidari, Mohammad, additional, Berry, Neill, additional, O’Neill, Paul M., additional, Alzahrani, Abdulaziz, additional, Azoury, Marie Eliane, additional, Fili, Lucia, additional, Bechara, Rami, additional, Scornet, Noémie, additional, Nhim, Cathy, additional, Weaver, Richard, additional, Claude, Nancy, additional, Joseph, Delphine, additional, Maillere, Bernard, additional, Parronchi, Paola, additional, Pallardy, Marc, additional, Villani, Axel Patrice, additional, Rozières, Aurore, additional, Bensaïd, Benoît, additional, Tardieu, Mathilde, additional, Albert, Floriane, additional, Mutez, Virginie, additional, Baysal, Tugba, additional, Maryanski, Janet, additional, Nicolas, Jean-François, additional, Kanagawa, Osami, additional, Vocanson, Marc, additional, Hung, Shuen-Iu, additional, Harrison, Caroline J., additional, Jenkins, Rosalind E., additional, French, Neil S., additional, Montañez, Maria Isabel, additional, Fernandez, Tahia D., additional, Martin-Serrano, Angela, additional, Torres, Maria Jose, additional, Molina, Noemi, additional, Wood, Sally, additional, Pirmohamed, Munir, additional, Montañez, María Isabel, additional, Martín-Serrano, Ángela, additional, Pérez-Inestrosa, Ezequiel, additional, Pérez-Sala, Dolores, additional, Guzmán, Antonio E., additional, Ko, Tai-Ming, additional, Chen, Yuan-Tsong, additional, Wu, Jer-Yuarn, additional, Sánchez-Gómez, Francisco J., additional, González-Morena, Juan M., additional, Torres, María J., additional, Arreola, Alejandra Monroy, additional, Corona, Jesus Agustin Badillo, additional, Flores, Silvia Mendez, additional, Cherit, Judith Dominguez, additional, Figueroa, Noe Valentin Duran, additional, Flores, Jose Luis Castrejon, additional, Perkins, James, additional, Pérez-Alzate, Diana, additional, Bogas, Gador, additional, Torres, María J, additional, Marti, Luis Mario Tubella, additional, De La Losa, Fernando Pineda, additional, Poves, Francisca Arribas, additional, Lopez, Jaime Tubella, additional, and Santiago, Teodora Lopez, additional

Published
2016
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34. Evaluation of immediate allergic reactions to dipyrone using dipyrone metabolites in basophil activation test

Author

Montanez, Maria Isabel, primary, Garcia‐Martin, Elena, additional, Ariza, Adriana, additional, Torres, Maria Jose, additional, Agundez, Jose AG, additional, Mayorga, Cristobalina, additional, Doña, Inmaculada, additional, Blanca‐Lopez, Natalia, additional, Zambonino, Maria A, additional, Andreu, Inmaculada, additional, and Blanca, Miguel, additional

Published
2014
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35. Synergistic Effect between Amoxicillin and TLR Ligands on Dendritic Cells from Amoxicillin-Delayed Allergic Patients

Author

Sanchez-Quintero, Maria J., primary, Torres, Maria J., additional, Blazquez, Ana B., additional, Gómez, Enrique, additional, Fernandez, Tahia D., additional, Doña, Inmaculada, additional, Ariza, Adriana, additional, Andreu, Inmaculada, additional, Melendez, Lidia, additional, Blanca, Miguel, additional, and Mayorga, Cristobalina, additional

Published
2013
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37. Photosensitivity to Triflusal:Formation of a Photoadduct with Ubiquitin Demonstrated by Photophysical and Proteomic Techniques.

Author

Nuin, Edurne, Pérez-Sala, Dolores, Lhiaubet-Vallet, Virginie, Andreu, Inmaculada, and Miranda, Miguel A.

Subjects
UBIQUITIN, PROTEOMICS, PHOTOSENSITIVITY
Abstract

Triflusal is a platelet aggregation inhibitor chemically related to acetylsalicylic acid, which is used for the prevention and/or treatment of vascular thromboembolisms, which acts as a prodrug. Actually, after oral administration it is absorbed primarily in the small intestine, binds to plasma proteins (99%) and is rapidly biotransformed in the liver into its deacetylated active metabolite 2-hydroxy-4-trifluoromethylbenzoic acid (HTB). In healthy humans, the half-life of triflusal is ca. 0.5 h, whereas for HTB it is ca. 35 h. From a pharmacological point of view, it is interesting to note that HTB is itself highly active as a platelet anti-aggregant agent. Indeed, studies on the clinical profile of both drug and metabolite have shown no significant differences between them. It has been evidenced that HTB displays ability to induce photoallergy in humans. This phenomenon involves a cell-mediated immune response, which is initiated by covalent binding of a light-activated photosensitizer (or a species derived therefrom) to a protein. In this context, small proteins like ubiquitin could be appropriate models for investigating covalent binding by means of MS/MS and peptide fingerprint analysis. In previous work, it was shown that HTB forms covalent photoadducts with isolated lysine. Interestingly, ubiquitin contains seven lysine residues that could be modified by a similar reaction.With this background, the aim of the present work is to explore adduct formation between the triflusal metabolite and ubiquitin as model protein upon sunlight irradiation, combining proteomic and photophysical (fluorescence and laser flash photolysis) techniques. Photophysical and proteomic analysis demonstrates monoadduct formation as the major outcome of the reaction. Interestingly, addition can take place at any of the +-amino groups of the lysine residues of the protein and involves replacement of the trifluoromethyl moiety with a new amide function. This process can in principle occur with other trifluoroaromatic compounds and may be responsible for the appearance of undesired photoallergic side effects. [ABSTRACT FROM AUTHOR]

Published
2016
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44. Triplet Excimers of Fluoroquinolonesin Aqueous Media.

Author

Cuquerella, M. Consuelo, Andreu, Inmaculada, Soldevila, Sonia, and Bosca, Francisco

Subjects
*EXCIMERS, *FLUOROQUINOLONES, *AQUEOUS solutions, *QUINOLONE antibacterial agents, *CARBOXYLIC acids, *CHEMICAL processes, *FLUORESCENCE
Abstract

Generation of triplet eximers of 6-fluoro-7-piperazinyl-quinolone-3-carboxylicacids (FQs) have been detected in aqueous media using laser flashphotolysis (LFP). These transient species (SS) are generated by self-quenchingreactions of FQ triplet excited states such as pefloxacin (PFX), norfloxacin(NFX), the N-acetylated form of NFX (ANFX), and itsmethyl ester (EANFX) with their ground states. In this context, self-quenchingrate constants in the range of (1–7) × 108M–1s–1were determined. The tripletexcimers show transient absorption spectra with λmaxca. 710 nm for SSNFX, 740 nm for SSPFX, and620 nm for SSANFXand EANFX, which are red-shifted with respect to their predecessors tripletexcited states. These excimers can be also observed in the presenceof phosphate buffer (PB). Experiments performed with NFX and ANFXat different PB concentrations showed that deprotonation processesare not involved in the generation of SS. The triplet multiplicityof the FQ excimers was confirmed by energy transfer reactions withnaproxen. The correlation between fluorescence, intersystem crossing,excimer and photodegradation quantum yields of (A)NFX indicated thatFQ self-quenching reactions are mainly a deactivation pathway. Onthe other hand, generation of FQ radical anions absorbing at λmaxca. 620 nm has been observed by an efficient electron transferreaction from Trp to NFX, PFX, and ANFX (rate constants ca. 1 ×109M–1s–1). [ABSTRACT FROM AUTHOR]

Published
2012
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45. Enhanced photosafety of cinacalcet upon complexation with serum albumin.

Author

Nuin E, Andreu I, Torres MJ, Jiménez MC, and Miranda MA

Subjects
Cinacalcet, Humans, Photolysis, Singlet Oxygen metabolism, Spectrophotometry, Ultraviolet, Naphthalenes chemistry, Serum Albumin chemistry
Abstract

Cinacalcet (CIN) is a calcimimetic drug, which contains a naphthalene chromophore and binds almost quantitatively to human serum albumin (HSA). In the present work, the excited states of CIN have been characterized in order to obtain relevant information about complexation of CIN with HSA. The fluorescence spectrum in acetonitrile, at λ(exc) = 290 nm, displayed two bands with maxima at 332 and 439 nm, assigned to the monomer and exciplex emission. Upon protonation of the amino group, the exciplex band disappeared, with a concomitant increase of the monomer emission intensity. Time-resolved fluorescence evidenced an intramolecular dynamic quenching, attributed to exciplex formation and/or photoinduced electron transfer, in agreement with the favorable thermodynamics predicted by the Rehm-Weller equations. Diffusion controlled dynamic quenching of CINH(+) fluorescence by oxygen was observed. The emission properties in PBS were similar to those obtained for CINH(+) in acetonitrile. Laser flash photolysis (LFP) of CIN and CINH(+) in acetonitrile/N(2), at λ(exc) = 308 nm, gave rise to the naphthalene-like triplet excited states, with maxima at 420 nm and lifetimes of 4 and 7 μs; they were efficiently quenched by oxygen. No significant singlet excited state interaction was observed in CINH(+)/HSA complexes, as revealed by the emission spectra, which were roughly explained taking into account the relative contributions of drug and protein in the absorption spectra. Upon LFP of the complexes, triplet excited states were generated; the decays monitored at 420 nm were satisfactorily fitted using a function containing two monoexponential terms, corresponding to a short-lived (τ(1) = 8 μs) and a long-lived (τ(2) = 37 μs) component. This indicates that the drug is incorporated into two different binding sites of HSA. Despite the long triplet lifetimes of the CINH(+)/HSA complexes, the rate constant of quenching by oxygen was found to be 2 orders of magnitude lower than that determined in acetonitrile, which can be attributed to the relative slower diffusion rates in this microheterogeneous system. Therefore, the protein microenvironment protects cinacalcet from attack by oxygen; this prevents the phototoxic effects caused by formation of singlet oxygen and results in an enhanced photosafety of the drug.

Published
2011
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