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NSAIDs-hypersensitivity often induces a blended reaction pattern involving multiple organs

Inmaculada Doña, Esther Barrionuevo, María Salas, José Julio Laguna, José Agúndez, Elena García-Martín, Gádor Bogas, James Richard Perkins, José Antonio Cornejo-García, María José Torres
2018 Scientific Reports  
Non-steroidal anti-inflammatory drugs (NSAIDs)-induced hypersensitivity reactions are classified by the European Network on Drug Allergy (ENDA) as either cross-reactive or selective. The former is the most frequent type and includes patients with exclusively respiratory symptoms (NSAIDsexacerbated respiratory disease, NERD) or exclusively cutaneous symptoms: NSAIDs-induced urticaria/ angioedema (NIUA); and NSAIDs-exacerbated cutaneous disease (NECD). However, although not reflected in the
more » ... t classification scheme (ENDA), in clinical practice a combination of both skin and respiratory symptoms or even other organs such as gastrointestinal tract symptoms (mixed or blended reactions) is frequently observed. This entity has not been sufficiently characterised. Our aim was to clinically characterize blended reactions to NSAIDs, comparing their clinical features with NERD and NIUA. We evaluated patients with symptoms suggestive of hypersensitivity to NSAIDs who attended the Allergy Unit of the Regional University Hospital of Malaga (Malaga, Spain) between 2008 and 2015. We included 880 patients confirmed as cross-reactive based on clinical history, positive nasal provocation test with lysine acetylsalicylate (NPT-LASA), and/or positive drug provocation test (DPT) with acetylsalicylic acid (ASA), who were classified as blended (261; 29.6%), NERD (108; 12.3%) or NIUA (511; 58.1%). We compared symptoms, drugs, underlying diseases and diagnostic methods within and between groups. Among blended patients the most common sub-group comprised those developing urticaria/angioedema plus rhinitis/asthma (n = 138), who had a higher percentage of underlying rhinitis (p < 0.0001) and asthma (p < 0.0001) than NIUA patients, showing similarities to NERD. These differences were not found in the sub-group of blended patients who developed such respiratory symptoms as glottis oedema; these were more similar to NIUA. The percentage of positive NPT-LASA was similar for blended (77%) and NERD groups (78.7%). We conclude that blended reactions are hypersensitivity reactions to NSAIDs affecting at least two organs. In addition to classical skin and respiratory involvement, in our population a number of patients also develop gastrointestinal symptoms. Given the high rate of positive responses to NPT-LASA in NERD as well as blended reactions, we suggest that all patients reporting respiratory symptoms, regardless of whether they have other associated symptoms, should be initially evaluated using NPT-LASA, which poses less risk than DPT. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most frequent triggers of drug hypersensitivity reactions (DHRs) 1-4 . Several classifications have been proposed 5-8 , including a recently published and heavily cited publication from the European Network on Drug Allergy (ENDA) group from the European Academy of Allergy and Clinical Immunology (EAACI) 9 . They classify hypersensitivity reactions to NSAIDs according to the clinical symptoms induced, the number of NSAIDs involved, and the presence or absence of underlying Published: xx xx xxxx OPEN
doi:10.1038/s41598-018-34668-1 pmid:30420763 pmcid:PMC6232098 fatcat:czbv2ocbbzfjtnglaclgl3xl3q

Metallo-Liposomes of Ruthenium Used as Promising Vectors of Genetic Material

José Antonio Lebrón, Francisco José Ostos, Manuel López-López, María Luisa Moyá, Carlos Sales, Encarnación García, Clara Beatriz García-Calderón, Margarita García-Calderón, María José Peña-Gómez, Iván V. Rosado, Fernando R. Balestra, Pablo Huertas (+1 others)
2020 Pharmaceutics  
Gene therapy is a therapeutic process consisting of the transport of genetic material into cells. The design and preparation of novel carriers to transport DNA is an important research line in the medical field. Hybrid compounds such as metallo-liposomes, containing a mixture of lipids, were prepared and characterized. Cationic metal lipids derived from the [Ru(bpy)3]2+ complex, RuC11C11 or RuC19C19, both with different hydrophobic/lipophilic ratios, were mixed with the phospholipid DOPE. A
more » ... tion between the size and the molar fraction α was found and a multidisciplinary study about the interaction between the metallo-liposomes and DNA was performed. The metallo-liposomes/DNA association was quantified and a relationship between Kapp and α was obtained. Techniques such as AFM, SEM, zeta potential, dynamic light scattering and agarose gel electrophoresis demonstrated the formation of lipoplexes and showed the structure of the liposomes. L/D values corresponding to the polynucleotide's condensation were estimated. In vitro assays proved the low cell toxicity of the metallo-liposomes, lower for normal cells than for cancer cell lines, and a good internalization into cells. The latter as well as the transfection measurements carried out with plasmid DNA pEGFP-C1 have demonstrated a good availability of the Ru(II)-based liposomes for being used as non-toxic nanovectors in gene therapy.
doi:10.3390/pharmaceutics12050482 pmid:32466339 pmcid:PMC7284339 fatcat:nyteoykwh5fzpetyzqjz6b23ha

Drug-Induced Anaphylaxis

Natalia Blanca-López, María del Carmen Plaza-Serón, José Antonio Cornejo-García, James Richard Perkins, Gabriela Canto, Miguel Blanca
2015 Current Treatment Options in Allergy  
doi:10.1007/s40521-015-0055-z fatcat:kjatzprmynhkblziqcp4qbkqny

Allergic Reactions to Metamizole: Immediate and Delayed Responses

Natalia Blanca-López, Natalia Pérez-Sánchez, José Augusto Agúndez, Elena García-Martin, María José Torres, José Antonio Cornejo-García, James R. Perkins, Miguel Angel Miranda, Inmaculada Andreu, Cristobalina Mayorga, Gabriela Canto, Miguel Blanca (+1 others)
2016 International Archives of Allergy and Immunology  
28% of the SNIUAA patients with negative skin tests. In 5.1% of the cases, DPT with metamizole was needed to establish the diagnosis. In 22.62% of the cases, diagnosis was established by consistent and unequivocal history of repeated allergic episodes in spite of a negative skin test and BAT. Conclusions: SNIUAA to metamizole is the most frequent type of selective NSAID hypersensitivity, with anaphylaxis being the most common clinical entity. It may occur within 1 h after drug intake. SNIDHR
more » ... urs in a very low percentage of cases. The low sensitivity of diagnostic tests may be due to incomplete characterization of the chemical structures of metamizole and its metabolites.
doi:10.1159/000444798 pmid:27224978 fatcat:xwv2s36rsvbofn3zkv4witkkcm

Aquacultural Homoeopathy: A Focus on Marine Species [chapter]

Mazón-Suástegui José Manuel, Tovar-Ramírez Dariel, Salas-Leiva Joan Sebastian, Arcos-Ortega Guadalupe Fabiola, García-Bernal Milagro, Avilés-Quevedo María Araceli, López-Carvallo Jesús Antonio, García-Corona José Luis, Ibarra-García Laura Elizabeth, Ortíz-Cornejo Nadia Livia, Teles Andressa, Rosero-García Antonia (+13 others)
2019 Aquaculture - Plants and Invertebrates  
The bacterial 16S rDNA was extracted according to Garcia-Bernal et al.  ...  The bacterial 16S rDNA was extracted according to Garcia-Bernal et al. [3] and amplified using Illumina MiSeq Platform (Illumina, San Diego, CA) in a certified Genomic Services Laboratory (  ... 
doi:10.5772/intechopen.78030 fatcat:wcqwh2iypfcv3h6lga2uge3mxm

Cationic Single-Chained Surfactants with a Functional Group at the End of the Hydrophobic Tail DNA Compacting Efficiency

José Antonio Lebrón, Pilar López-Cornejo, Elena García-Dionisio, Pablo Huertas, Margarita García-Calderón, María Luisa Moyá, Francisco José Ostos, Manuel López-López
2021 Pharmaceutics  
The interaction between calf-thymus DNA, ctDNA, and various single-chained surfactants with different functional groups at the end of hydrophobic tail was studied with the goal of investigating the influence of the functional group nature on surfactant DNA compacting efficiency. The surfactants investigated were dodecyltriethylammonium bromide (DTEABr), triethyl(1-phenoxydodecyl)ammonium bromide (12PhBr), triethyl(2-naphthoxydodecyl)ammonium bromide (12NBr) and
more » ... yl-1-undecanaminium bromide (11PyBr). Results made evident that the surfactants' tendencies to self-aggregation is the key factor determining their efficiency to compact the nucleic acid. Subsequently, DOPE/12NBr/pEGFP-C1 lipoplexes, with different cationic surfactant molar fractions (α) and mass ratios (L/D), were prepared and characterized. DOPE is a zwitterionic phospholipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, and the plasmid pEGFP-C1 carries a GFP coding sequence with the necessary regulatory elements for constitutive expression of the gene in human cells. 12NBr was chosen because it was the most efficient DNA compacting agent among the surfactants investigated. Finally, the cytotoxicity and transfection efficiency (TE) of DOPE/12NBr/pDNA lipoplexes, with different compositions, were investigated.
doi:10.3390/pharmaceutics13040589 pmid:33924284 pmcid:PMC8074900 fatcat:3d3wigzfynbszl7i4dzyaze764

Value-Creating Strategies in Dairy Farm Entrepreneurship: A Case Study in Northern Spain

Antonio Alvarez, Beatriz García-Cornejo, José A. Pérez-Méndez, David Roibás
2021 Animals  
This paper explores different value-creating strategies (VCS) used by dairy farmers engaged in on-farm diversification ventures. In order to explicitly identify the informal strategies followed by 49 farmers in their value-added ventures, we applied a theoretically informed business model framework combining three dimensions: value proposition linked to local food, customer engagement via quality schemes and shorter supply chains, and the key capabilities of the entrepreneur. Using cluster
more » ... sis, four different types of VCS were identified and labelled as 'Ecological', 'Single-product', 'Innovative', and 'Traditional'. Whilst we found that these strategies are influenced by contextual factors and the owner's entrepreneurial skills, in general, we did not observe significant differences in performance between them. The results suggest that farmers respond entrepreneurially to sectorial changes adopting those VCS that tend to align with their entrepreneurial capabilities and context, thus enabling them to succeed with any of the strategies pursued. Hence, our work contributes towards clarifying the relationship between VCS, entrepreneurial capabilities, and context. This is important for farmers and policymakers because it reveals the diversity of farm management and the resilience of farm systems. As a result, the potential challenges for Single-product VCS and Traditional VCS are discussed.
doi:10.3390/ani11051396 pmid:34068433 fatcat:r5wijabdfvf6plkfeusi6orvle

HAVCR1 Gene Haplotypes and Infection by Different Viral Hepatitis C Virus Genotypes

Cristina Abad-Molina, José-Raúl Garcia-Lozano, Marco-Antonio Montes-Cano, Almudena Torres-Cornejo, Fuensanta Torrecillas, José Aguilar-Reina, Manuel Romero-Gómez, Luis-Fernando López-Cortés, Antonio Núñez-Roldan, María-Francisca González-Escribano
2011 Clinical and Vaccine Immunology  
ABSTRACTThe hepatitis A virus cellular receptor 1 (HAVCR1) gene is highly polymorphic, and several variants have been associated with susceptibility to allergic and autoimmune diseases. The HAVCR1 gene region was identified as a candidate for hepatitis C virus (HCV) natural clearance in a genotyping study of selected immune response genes in both European-American and African-American populations. The aim of the present study was to explore the influence of HAVCR1 in the outcome of HCV
more » ... in the Spanish population. Three cohorts, consisting of 354 subjects with persistent HCV infection (285 with persistent HCV monoinfection and 69 with natural clearance), 182 coinfected HIV/HCV patients, and 320 controls, were included. Samples were genotyped in several polymorphic positions, insertion/deletion variants in exon 4 and tag single nucleotide polymorphisms (SNPs), in order to define previously described HAVCR1 haplotypes (haplotypes A to D). No statistically significant differences were observed with spontaneous resolution of infection or with viral clearance after treatment. Nevertheless, different rates of infection by viral genotypes (G's) were observed among the HAVCR1 haplotypes. Individuals bearing haplotype C had the highest viral G1 infection rate when compared to individuals bearing other haplotypes (75.82% versus 57.72%, respectively; correctedPvalue [Pc], 3.2 × 10−4; odds ratio [OR], 2.30; 95% confidence interval [CI], 1.51 to 3.47). Thus, HAVCR1 could be involved in susceptibility or resistance to infection by a particular HCV genotype.
doi:10.1128/cvi.05305-11 pmid:22190394 pmcid:PMC3272938 fatcat:5pgsef546vc53j3skaiw4o4ane

The profitability of value-added products in dairy farm diversification initiatives

Antonio Alvarez, Beatriz García-Cornejo, José A. Pérez-Méndez, David Roibás
2018 Spanish Journal of Agricultural Research  
A more open and competitive dairy market has encouraged certain dairy farms to adopt value-adding strategies in order to achieve a higher profitability, which may be important for farms' survival. This paper investigated the role of some product characteristics in the profitability of value-added products in these farms. For this purpose, we used a unique database of 265 different products commercialized by 49 Spanish dairy farms that offers information on nine attributes of each product. Using
more » ... hedonic models as a baseline, we examined the influence of these attributes on the margin per liter (ML) of the products. The results of the regression indicated that cheese and yogurt generated 0.688 and 1.518 € more of margin per liter than liquid milk. Similarly, we found a set of attributes that have a positive influence on ML, including possession of a certificate of protected designation of origin (PDO), the milk-type composition (proportion of sheep milk), a longer expiration period, and involvement in direct marketing strategies (DMS). However, other recognized attributes such as organic labeling, maturation period, size of the sales unit and returnable packaging did not have a significant influence on ML. Our findings also showed that firms producing more elaborated products as cheese and yogurt need a lower percentage of their production to cover the fixed costs associated to transformation and commercialization. Overall, our results revealed that the elaboration of value-added dairy products improves the profitability of dairy farms.
doi:10.5424/sjar/2018162-11813 fatcat:hsdzqtcaizb65j6lr3llghtnui

Metallo-Liposomes Derived from the [Ru(bpy)3]2+ Complex as Nanocarriers of Therapeutic Agents

Maria Luisa Moyá, Francisco José Ostos, Izamar Moreno, Diandra García, Paula Moreno-Gordillo, Ivan V. Rosado, Pilar López-Cornejo, José Antonio Lebrón, Manuel López-López
2021 Chemosensors  
The obtaining of nanocarriers of gene material and small drugs is still an interesting research line. Side-effects produced by the toxicity of several pharmaceutics, the high concentrations needed to get therapeutic effects, or their excessive use by patients have motivated the search for new nanostructures. For these reasons, cationic metallo-liposomes composed by phosphatidylcholine (PC), cholesterol (CHO) and RuC1C19 (a surfactant derived from the metallic complex [Ru(bpy)3]2+) were prepared
more » ... and characterized by using diverse techniques (zeta potential, dynamic light scattering and electronic transmission microscopy –TEM-). Unimodal or bimodal populations of spherical aggregates with small sizes were obtained depending on the composition of the liposomes. The presence of cholesterol favored the formation of small aggregates. ct-DNA was condensed in the presence of the liposomes investigated. In-vitro assays demonstrated the ability of these nanoaggregates to internalize into different cell lines. A positive gene transfection into human bone osteosarcoma epithelial cells (U2OS) was also observed. The RuC1C19 surfactant was used as sensor to quantify the binding of DNA to the liposomes. Doxorubicin was encapsulated into the metallo-liposomes, demonstrating their ability to be also used as nanocarriers of drugs. A relationship between then encapsulation percentage of the antibiotic and the composition of the aggregates has been established.
doi:10.3390/chemosensors9050090 doaj:b4b827e5bbda4f949b9c018372c12cff fatcat:rdcewtrfabaazjpjga6xipep5y

Variants of CEP68 Gene Are Associated with Acute Urticaria/Angioedema Induced by Multiple Non-Steroidal Anti-Inflammatory Drugs

José Antonio Cornejo-García, Carlos Flores, María C. Plaza-Serón, Marialbert Acosta-Herrera, Natalia Blanca-López, Inmaculada Doña, María J. Torres, Cristobalina Mayorga, Rosa M. Guéant-Rodríguez, Pedro Ayuso, Javier Fernández, José J. Laguna (+6 others)
2014 PLoS ONE  
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most consumed drugs worldwide because of their efficacy and utility in the treatment of pain and inflammatory diseases. However, they are also responsible for an important number of adverse effects including hypersensitivity reactions. The most important group of these reactions is triggered by nonimmunological, pharmacological mechanisms catalogued under the denomination of cross-intolerance (CRI), with acute urticaria/angioedema induced
more » ... multiple NSAIDs (MNSAID-UA) the most frequently associated clinical entity. A recent genome-wide association study identified the gene encoding the centrosomal protein of 68 KDa (CEP68) as the major locus associated with aspirin intolerance susceptibility in asthmatics. In this study, we aimed to assess the role of this locus in susceptibility to CRI to NSAIDs by examining 53 common gene variants in a total of 635 patients that were classified as MNSAID-UA (n = 399), airway exacerbations (n = 110) or blended pattern (n = 126), and 425 controls. We found in the MNSAID-UA group a number of variants (17) associated (lowest p-value = 1.13610 26 ), including the non-synonymous Gly74Ser variant (rs7572857) previously associated with aspirin intolerance susceptibility in asthmatics. Although not being significant in the context of multiple testing, eight of these variants were also associated with exacerbated respiratory disease or blended reactions. Our results suggest that CEP68 gene variants may play an important role in MNSAID-UA susceptibility and, despite the different regulatory mechanisms involved depending on the specific affected organ, in the development of hypersensitivity reactions to NSAIDs.
doi:10.1371/journal.pone.0090966 pmid:24618698 pmcid:PMC3949706 fatcat:77xcqt6qybgaldbp7zwtoxn2fe

Gene variants of IL13, IL4, and IL4RA are predictors of β-lactam allergy

Jean-Louis Guéant, Rosa-Maria Guéant-Rodriguez, Jose-Antonio Cornejo-Garcia, Marinella Viola, Miguel Blanca, Antonino Romano
2009 Journal of Allergy and Clinical Immunology  
We appreciate the comments of Guéant et al. 1 We agree our study supports the IL-4 pathway as playing a mechanistic role in beta-lactam allergy. 2 We thank you for drawing attention to your study that, like the one we referenced, found an association with an IL4R SNP while we did not. 3 We agree there may be several reasons why our relatively small study did not find an association, including small sample size and different allele frequencies of the controls between countries. Therefore,
more » ... nal research is needed before definitive conclusion can be made about the generalizability of Guéant et al.'s results to non-Italian populations. Our limited resources did not allow us to include IL13 polymorphisms and our emphasis was a little different: identifying clinical as well as genetic risk factors and examining the importance of genetic risk factors relative to those clinical risk factors. We agree it would be informative to study IL4 and IL13 gene pathway interactions. The products of these two genes, closely located on chromosome 5, both use the IL-4RA receptor. Thus, an interaction between IL4 or IL13 and the IL4Ra would support the role of IgE in drug allergy. Nonetheless, for genegene interaction studies a very large sample size is needed to obtain reliable results. We also call attention to the marginal association of a SNP from another gene: LACTB was marginally associated lending support to the other aspect of our theory that penicillin is multi-factorial with contributions from several genes, IL-4 pathway but also others, and the environment (exposure to antibiotic).
doi:10.1016/j.jaci.2008.10.058 pmid:19121856 pmcid:PMC2768426 fatcat:bflhbj3tybfnvkx4cqb4nqx6ci

Effect of homeopathic medicines on growth, survival and gastrointestinal microbiota of juvenile scallop Argopecten ventricosus

José Manuel Mazón-Suástegui, Dariel Tovar-Ramírez, Nadia Livia Ortíz-Cornejo, Milagro García-Bernal, Jesús Antonio López-Carvallo, Joan Sebastian Salas-Leiva, Fernando Abasolo-Pacheco
2019 Revista MVZ Cordoba  
Ishii et al Delfino Barajas, Pablo Ormart, Julián Garzón, Guillermo García, Eulalia Meza. Diana Fischer editó el manuscrito en inglés. 4.  ... 
doi:10.21897/rmvz.1536 fatcat:i5xndpvhfzcxjlmr2dezzhojoa

Blood Flow-Restricted Training in Older Adults: A Narrative Review

Abel Plaza-Florido, Jairo H. Migueles, Antonio Piepoli, Pablo Molina-Garcia, Maria Rodriguez-Ayllon, Cristina Cadenas-Sanchez, Jose Mora-Gonzalez, Irene Esteban-Cornejo, Francisco B. Ortega
2019 Journal of Science in Sport and Exercise  
Low-intensity resistance training (LI-RT) combined with blood flow restriction (BFR) is an alternative to traditional moderate-high-intensity resistance training to increase strength and muscle mass. However, the evidence about the efficacy of this novel training method to increase strength and muscle mass in healthy and older adults with pathologies is limited. Furthermore, the possible risk and adverse effects with BFR training methodology in older adults should be considered. Objectives (1)
more » ... o summarize the current evidence on training with BFR strategies in older adults aiming to improve strength and to increase muscle mass; and (2) to provide recommendations for resistance and aerobic training with BFR in older adults based on the studies reviewed. Methods Studies that investigated the chronic responses to resistance training or aerobic training with BFR related to strength and muscle mass changes in older adults were identified. Two independent researchers conducted the search in PubMed, Web of Science, and Google Scholar databases from their inception up to November 1, 2018. Results Seventeen out of 35 studies, which performed resistance or aerobic training with BFR in older adults focused on strength and muscle mass outcomes, were included in this review. Studies performing resistance and aerobic training with BFR found better improvements in strength and higher increase in muscle mass compared to non-BFR groups that performed the same training protocol. High-intensity resistance training (HI-RT) without BFR provided greater improvements in strength and a similar increase in muscle mass compared to light-intensity resistance training (LI-RT) with BFR. Conclusions Current evidence suggests that LI-RT and/or aerobic training with BFR improves strength and increases muscle mass in older people. Light-intensity training without BFR would normally not obtain such benefits. Therefore, LI-RT and aerobic training with BFR is an alternative to traditional methods to improve strength and by way of an increase in muscle mass, which are important in the elderly who have progressive muscle atrophy and are at higher risk of falls.
doi:10.1007/s42978-019-00034-4 fatcat:sorseibgajboxiqnc22voelhzy

Multivalent Calixarene-Based Liposomes as Platforms for Gene and Drug Delivery

José Antonio Lebrón, Manuel López-López, Clara B. García-Calderón, Ivan V. Rosado, Fernando R. Balestra, Pablo Huertas, Roman V. Rodik, Vitaly I. Kalchenko, Eva Bernal, María Luisa Moyá, Pilar López-Cornejo, Francisco J. Ostos
2021 Pharmaceutics  
The formation of calixarene-based liposomes was investigated, and the characterization of these nanostructures was carried out using several techniques. Four amphiphilic calixarenes were used. The length of the hydrophobic chains attached to the lower rim as well as the nature of the polar group present in the upper rim of the calixarenes were varied. The lipid bilayer was formed with one calixarene and with the phospholipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, DOPE. The cytotoxicity
more » ... f the liposomes for various cell lines was also studied. From the results obtained, the liposomes formed with the least cytotoxic calixarene, (TEAC12)4, were used as nanocarriers of both nucleic acids and the antineoplastic drug doxorubicin, DOX. Results showed that (TEAC12)4/DOPE/p-EGFP-C1 lipoplexes, of a given composition, can transfect the genetic material, although the transfection efficiency substantially increases in the presence of an additional amount of DOPE as coadjuvant. On the other hand, the (TEAC12)4/DOPE liposomes present a high doxorubicin encapsulation efficiency, and a slow controlled release, which could diminish the side effects of the drug.
doi:10.3390/pharmaceutics13081250 pmid:34452211 pmcid:PMC8398082 fatcat:jtddsm6zefhyxlhoze6izxwx3y
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