Proteomics in drug hypersensitivity

21 p.-4 fig.-1 tab.Drug hypersensitivity reactions result from the activation of the immune system by drugs or their metabolites. The clinical presentations of drug hypersensitivity can range from relatively mild local manifestations to severe systemic syndromes that can be life-threatening. As in other allergic reactions, the causes are multifactorial as genetic, metabolic and concomitant factors may influence the occurrence of drug hypersensitivity. Formation of drug protein adducts is considered a key step in drug adverse reactions, and in particular in the immunological recognition in drug hypersensitivity reactions. Nevertheless, non-covalent interactions of drugs with receptors in immune cells or with MHC clefts and/or exposed peptides can also play an important role. In recent years, development of proteomic approaches has allowed the identification and characterization of the protein targets for modification by drugs in vivo and in vitro, the nature of peptides exposed on MHC molecules, the changes in protein levels induced by drug treatment, and the concomitant modifications induced by danger signals, thus providing insight into context factors. Nevertheless, given the complexity and multifactorial nature of drug hypersensitivity reactions, understanding the underlying mechanisms also requires the integration of knowledge from genomic, metabolomic and clinical studies.This work has been supported by grants SAF2012-36519 and SAF2015-68590R from MINECO/FEDER and RETIC RD12/0013/0008 from ISCIII to D.P.-S., and by RETIC RD12/0013/0001 and CP15/00103 from ISCIII, and PI-0699-2011 and PI-0179-2014 from Junta de Andalucía to M.I.M.Peer reviewe

A message emerging from development: the repression of mitochondrial β-F1-ATPase expression in cancer

The original publication is available at www.springerlink.com http://dx.doi.org/10.1007/s10863-007-9087-9Mitochondrial research has experienced a considerable boost during the last decade because organelle malfunctioning is in the genesis and/or progression of a vast array of human pathologies including cancer. The renaissance of mitochondria in the cancer field has been promoted by two main facts: (1) the molecular and functional integration of mitochondrial bioenergetics with the execution of cell death and (2) the implementation of 18FDG-PET for imaging and staging of tumors in clinical practice. The latter, represents the bed-side translational development of the metabolic hallmark that describes the bioenergetic phenotype of most cancer cells as originally predicted at the beginning of previous century by Otto Warburg. In this minireview we will briefly summarize how the study of energy metabolism during liver development forced our encounter with Warburg’s postulates and prompted us to study the mechanisms that regulate the biogenesis of mitochondria in the cancer cellThis review article was written while the research activity in the authors’ laboratory was supported by grants from the Ministerio de Sanidad (PI041255), Educación y Ciencia (SAF2005-4001) and Fundación Mutua Madrileña. The CBMSO is the recipient of an institutional grant from Fundación Ramón ArecesPeer reviewe

Characterization and expression of a Pinus radiata putative ortholog to the Arabidopsis SHORT-ROOT gene

We characterized a Pinus radiata D. Don putative ortholog to the Arabidopsis thaliana (L.) Heynh. SHORT-ROOT gene (AtSHR) and analyzed its expression in different organs during vegetative development and in response to exogenous auxin during adventitious rooting. The predicted protein sequence contained domains characteristic of the GRAS protein family and showed a strong similarity to the SHORT-ROOT (SHR) proteins. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and in situ hybridization showed that the gene is predominantly expressed in roots, root primordia and in the cambial region of hypocotyl cuttings. Increased mRNA levels were observed, independently of the presence or absence of exogenous auxin, in the cambial region and rooting competent cells of hypocotyl cuttings within the first 24 h of adventitious rooting, before the activation of cell divisions and the organization of the adventitious root meristem. The expression pattern in organs and during adventitious rooting was similar to that of a Pinus radiata SCARECROW-LIKE (PrSCL1) gene, except that PrSCL1 is induced in response to exogenous auxin. Results suggest that the Pinus radiata SHORT-ROOT (PrSHR) gene has a role in root meristem formation and maintenance and in the cambial region of hypocotyl cuttings.Spanish Ministry of Education and Science (AGL2002-04225-CO2-01 AGR/FOR and AGL2005-07228-CO2-02 AGR/FOR to C.S. and AGL2002-04225-CO2-02 AGR/FOR and AGL2005-07228-CO2-01 AGR/FOR to C.D.-S.) Partially supported by Xunta de Galicia (PGIDIT06PXIB400003PR to C.S.) University of Alcala (UAHCG2006-028 to C.D.-S.).Peer reviewe

Eleven-year descriptive analysis of closed court verdicts on medical errors in Spain and Massachusetts

To evaluate and compare the characteristics of court verdicts on medical errors allegedly harming patients in Spain and Massachusetts from 2002 to 2012. We reviewed 1041 closed court verdicts obtained from data on litigation in the Thomson Reuters Aranzadi Westlaw databases in Spain (Europe), and 370 closed court verdicts obtained from the Controlled Risk and Risk Management Foundation of Harvard Medical Institutions (CRICO/RMF) in Massachusetts (USA). We included closed court verdicts on medical errors. The definition of medical errors was based on that of the Institute of Medicine (USA). We excluded any agreements between parties before a judgement. Medical errors were involved in 25.9% of court verdicts in Spain and in 74% of those in Massachusetts. The most frequent cause of medical errors was a diagnosis-related problem (25.1%; 95% CI 20.7% to 31.1% in Spain; 35%; 95% CI 29.4% to 40.7% in Massachusetts). The proportion of medical errors classified as high severity was 34% higher in Spain than in Massachusetts (p=0.001). The most frequent factors contributing to medical errors in Spain were surgical and medical treatment (p=0.001). In Spain, 98.5% of medical errors resulted in compensation awards compared with only 6.9% in Massachusetts. This study reveals wide differences in litigation rates and the award of indemnity payments in Spain and Massachusetts; however, common features of both locations are the high rates of diagnosis-related problems and the long time interval until resolution

Cu(II) 4-phenoxybenzoate dimers and monomer coordinated by pyridines: synthesis and crystal structures

The complexes [Cu(PhOBz)2(dPy)]2 (PhOBz = 4-phenoxybenzoate; dPy = pyridine (1), 3-phenylpyridine (2), 4-benzylpyridine (3) and 4-phenylpyridine (4) and the complex [Cu(PhOBz)2(4-Phpy)2(H2O)] (5) were prepared and fully characterized. X-ray crystal structures of the five complexes have been determined. Complexes 1-4 consist of binuclear units where both Cu(II) are linked by four syn-syn carboxylate bridges, showing a paddle-wheel unit. The compound 5 is mononuclear and the metal center is coordinated to two PhOBz in monodentate form, two 4-Phpy ligands and one H2O molecule with slightly distorted square pyramidal geometry. Finally, the magnetic properties of compounds 3 and 5 have also been studied, confirming the different strength interactions between Cu(II) cations

El análisis proteómico del interactoma intracelular revela que las tetraspaninas modulan el repertorio de proteínas que forman parte de los exosomas de linfocitos T humanos

Comunicaciones a congreso

Real-World Safety and Effectiveness Evidence of a Microcrystalline Tyrosine-Associated Mite Allergoid in Children and Adolescents with Allergic Rhinitis

Rinitis al·lèrgica; Infants i adolescents; Tirosina microcristal·linaRinitis alérgica; Niños y adolescentes; Tirosina microcristalinaAllerghic rhinitis; Children and adolescents; Microcrystalline tyrosineEvidence regarding allergen immunotherapy (AIT) in pediatric population is scarce. We have assessed safety and effectiveness of subcutaneous AIT with a microcrystalline tyrosine (MCT)-associated mite allergoid, Acarovac Plus®, in children and adolescents with allergic rhinitis (AR), with and without asthma, in the real-world setting. This was a retrospective, multicenter study including children and adolescents aged 5 years to 17 years with AR, with and without asthma, and sensitized to mites, receiving AIT with Acarovac Plus® during ≥6 months. Primary and secondary objectives were safety and effectiveness, respectively. Effectiveness variables were assessed during 12 months before and after AIT and included unscheduled visits to the healthcare center and emergency room admissions, rhinitis and asthma symptoms according to ARIA and GEMA classifications, respectively, medication use, and patients’ and physicians’ disease perception graded on a visual analog scale (VAS). All 79 patients included had a mean (SD) age of 12.7 (3.3) years. Two patients experienced systemic adverse reactions (none severe). Unscheduled visits to the healthcare center and emergency room admissions decreased (mean (SD) 3.02 [2.48] and 0.63 [1.35] vs. 1.08 [1.38] and 0.09 [0.38], before and after treatment, p < 0.001 and p = 0.001, respectively). After AIT, rhinitis and asthma classification changed (p < 0.0001 for all classifications), showing improvements in symptoms and a significant decrease in rhinitis and use of medication for asthma and VAS scores grading patients’ and physicians’ disease perception (p < 0.001). In conclusion, these results show that AIT with an MCT-associated mite allergoid appears safe and effective in children and adolescents with AR treated in the real-world setting.This study was supported by Allergy Therapeutics Ibérica

Theoretical analysis of acoustic stop bands in two-dimensional periodic scattering arrays

This paper presents a theoretical analysis of the recently reported observation of acoustic stop bands in two-dimensional scattering arrays (Robertson and Rudy, J. Acoust. Soc. Am. {\bf 104}, 694, 1998). A self-consistent wave scattering theory, incorporating all orders of multiple scattering, is used to obtain the wave transmission. The band structures for the regular arrays of cylinders are computed using the plane wave expansion method. The theoretical results compare favorably with the experimental data.Comment: 18 pages, 4 page

Acoustic Attenuation by Two-dimensional Arrays of Rigid Cylinders

In this Letter, we present a theoretical analysis of the acoustic transmission through two-dimensional arrays of straight rigid cylinders placed parallelly in the air. Both periodic and completely random arrangements of the cylinders are considered. The results for the sound attenuation through the periodic arrays are shown to be in a remarkable agreement with the reported experimental data. As the arrangement of the cylinders is randomized, the transmission is significantly reduced for a wider range of frequencies. For the periodic arrays, the acoustic band structures are computed by the plane-wave expansion method and are also shown to agree with previous results.Comment: 4 pages, 3 figure

Comparative efficacy between atorvastatin and rosuvastatin in the prevention of cardiovascular disease recurrence

Background: There is no randomized clinical trials with recurrence of atherosclerotic cardiovascular disease (ASCVD) as a major outcome with rosuvastatin. In order to analyze potential differences in the clinical response to atorvastatin and rosuvastatin in secondary ASCVD prevention, we have analyzed the clinical evolution of those subjects of the Dyslipemia Registry of the Spanish Society of Arteriosclerosis (SEA) who at the time of inclusion in the Registry had already suffered an ASCVD. Methods: This observational, retrospective, multicenter, national study was designed to determine potential differences between the use of atorvastatin and rosuvastatin in the ASCVD recurrence. Three different follow-up start-times were performed: time of inclusion in the registry; time of first event if this occurred after 2005, and time of first event without date restriction. Results: Baseline characteristics were similar between treatment groups. Among atorvastatin or rosuvastatin users, 89 recurrences of ASCVD were recorded (21.9%), of which 85.4% were coronary. At the inclusion of the subject in the registry, 345 participants had not suffered a recurrence yet. These 345 subjects accumulated 1050 person-years in a mean follow-up of 3 years. Event rates were 2.73 (95% CI: 1.63, 4.25) cases/100 person-years and 2.34 (95% CI: 1.17, 4.10) cases/100 person-years in the atorvastatin and rosuvastatin groups, respectively. There were no statistically significant differences between the two groups independently of the follow-up start-time. Conclusions: This study does not find differences between high doses of rosuvastatin and atorvastatin in the recurrence of ASCVD, and supports their use as clinically equivalent in secondary prevention of ASCVD