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Chronic Urticaria Due to Allergy to Wheat Alpha-Amylase Inhibitor Proteins

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Case Reports in clinical Medicine 2016年第4期5卷 130-133页

作者： Nagore Arruti Oyarzabal Olga Villarreal Balza de Vallejo Nagore Bernedo Belar Maria Teresa Audicana Berasategui Natividad Longo Areso Borja Bartolomé servicio de Alergia e inmunología clínica Hospital Universitario Araba Vitoria-Gasteiz Spain Bial-Aristegui Laboratories Bilbao Spain

Chronic spontaneous urticaria (CSU) is defined as the spontaneous appearance of wheals, angioedema, or both, for at least 6 weeks, due to known or unknown causes [1]. In some patients who present a CSU with daily or almost daily symptoms a type I allergy could be the underlying cause. We present one adult patient with chronic urticaria who was finally diagnosed as a non-occupational case of IgE-mediated wheat allergy manifested following exposure by 3 different routes: inhalation (rhinitis and bronchial asthma), dermal absorption (contact urticaria) and ingestion (systemic chronic urticaria). We were able to detect the culprit proteins by immunoblotting. Serum IgE binds mainly to alpha-amylase/trypsin inhibitors and, to a lesser extent, to other proteins associated with food allergy to grains (e.g. beta-glucanase, serpin, peroxidase). In our opinion, skin prick tests with a food standard battery could help in the etiological diagnosis of chronic urticaria. The identification of responsible allergens could be difficult because only a few complex in vitro techniques allow detecting the allergy to several proteins.

关键词： Alpha-Amylase Inhibitor Wheat Chronic Urticaria Allergy

Current status of the genetic susceptibility in attenuated adenomatous polyposis

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World Journal of Gastrointestinal Oncology 2019年第12期11卷 1101-1114页

作者： Víctor Lorca Pilar Garre Laboratorio de Oncología Molecular Grupo de Investigación Clínica y Traslacional en OncologíaHospital Clínico San CarlosMadrid 28040Spain Laboratorio de Oncología Molecular Servicio de OncologíaHospital Clínico San CarlosMadrid 28040Spain

Adenomatous polyposis(AP)is classified according to cumulative adenoma number in classical AP(CAP)and attenuated AP(AAP).Genetic susceptibility is the major risk factor in CAP due to mutations in the known high predisposition genes APC and MUTYH.However,the contribution of genetic susceptibility to AAP is lower and less understood.New predisposition genes have been recently proposed,and some of them have been validated,but their scarcity hinders accurate risk estimations and prevalence calculations.AAP is a heterogeneous condition in terms of severity,clinical features and heritability.Therefore,clinicians do not have strong discriminating criteria for the recommendation of the genetic study of known predisposition genes,and the detection rate is low.Elucidation and knowledge of new AAP high predisposition genes are of great importance to offer accurate genetic counseling to the patient and family members.This review aims to update the genetic knowledge of AAP,and to expound the difficulties involved in the genetic analysis of a highly heterogeneous condition such as AAP.

关键词： Attenuated adenomatous polyposis Genetic susceptibility High predisposition gene Genetic heterogeneity Colorectal cancer

Preclinical models of idiosyncratic drug-induced liver injury(iDILI):Moving towards prediction

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3685-3726页

作者： Antonio Segovia-Zafra Daniel E.Di Zeo-Sanchez Carlos Lopez-Gomez Zeus Perez-Valdes Eduardo Garcıa-Fuentes Raul J.Andrade M.Isabel Lucena Marina Villanueva-Paz Unidad de Gestio´n clı´nica de Gastroenterologı´a Servicio de Farmacologıa ClınicaInstituto de Investigacio´n Biomedica de Malaga-IBIMAHospital Universitario Virgen de la VictoriaUniversidad de MalagaMalaga 29071Spain Centro de Investigacion Biomedica en Red en el Area Tematica de Enfermedades Hepaticas y Digestivas(CIBERehd) Madrid 28029Spain Platform ISCIII de Ensayos clınicos UICEC-IBIMAMalaga 29071Spain Unidad de Gestion clınica de Aparato Digestivo Instituto de Investigacion Biomedica de Malaga(IBIMA)Hospital Universitario Virgen de la VictoriaMalaga 29010Spai

Idiosyncratic drug-induced liver injury(iDILI) encompasses the unexpected harms that prescription and non-prescription drugs,herbal and dietary supplements can cause to the liver.iDILI remains a major public health problem and a major cause of drug attrition.Given the lack of biomarkers for iDILI prediction,diagnosis and prognosis,searching new models to predict and study mechanisms of iDILI is necessary.One of the major limitations of iDILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant iDILI.Thus,major advances in the understanding of iDILI susceptibility and pathogenesis have come from the study of well-phenotyped iDILI patients.However,there are many gaps for explaining all the complexity of iDILI susceptibility and mechanisms.Therefore,there is a need to optimize preclinical human in vitro models to reduce the risk of iDILI during drug development.Here,the current experimental models and the future directions in iDILI modelling are thoroughly discussed,focusing on the human cellular models available to study the pathophysiological mechanisms of the disease and the most used in vivo animal iDILI models.We also comment about in silico approaches and the increasing relevance of patient-derived cellular models.

关键词： Drug-induced liver injury Preclinical models Mechanisms Oxidative stress Mitochondrial damage Immune response Personalized medicine

Cardiovascular prevention in elderly patients

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Journal of Geriatric Cardiology 2022年第5期19卷 377-392页

作者： clara Bonanad Rosa Fernández-Olmo Sergio García-Blas Jose Antonio Alarcon Pablo Díez-Villanueva Carmen Rus Mansilla Héctor García-Pardo Pablo Toledo Ana Ayesta Eva Pereira Antoni Carol Almudena Castro-Conde Carmen de Pablo-Zarzoso Manuel Martínez-Sellés Vicente Arrarte Raquel Campuzano Albert Ariza-Solé servicio de Cardiología Hospital Clínico Universitario de ValenciaValenciaSpain Instituto de Investigación Sanitaria INclIVA ValenciaSpain servicio Cardiología Hospital Universitario de Jaén Spain servicio Cardiología Hospital de Donosti Spain servicio de Cardiología Hospital Universitario La Princesa de MadridSpain servicio de Cardiología Hospital Alto Gudalquivir de AndújarJaénSpain servicio de Cardiología Hospital Rio Hortega de ValladolidSpain servicio Cardiología Hospital clínico San Cecilio de Granada Spain servicio de Cardiología Hospital Universitario Central de AsturiasSpain servicio de Cardiologia Hospital de LugoSpain servicio de Cardiología Hospital Moisés Broggi de BarcelonaSpain servicio de Cardiología Hospital Universitario de la Paz de Madrid Spain servicio de Cardiología Hospital Ramón y Cajal de MadridSpain department of Cardiology.Hospital Universitario Gregorio Marañón CIBERCV.Universidad EuropeaUniversidad Compluten servicio de Cardiología del Hospital General de Alicante Spain servicio de Cardiología Hospital Universitario Fundación de Alcorcón de MadridSpain servicio de Cardiología Hospital Bellvitge de BarcelonaBioheartGrup de Malalties CardiovascularsInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatBarcelonaSpain

In recent decades,life expectancy has been increasing significantly.In this scenario,health interventions are ne-cessary to improve prognosis and quality of life of elderly with cardiovascular risk factors and cardiovascular disease.However,the number of elderly patients included in clinical trials is low,thus current clinical practice guidelines do not include specific re-commendations.This document aims to review prevention recommendations focused in patients≥75 years with high or very high cardiovascular risk,regarding objectives,medical treatment options and also including physical exercise and their inclusion in cardiac rehabilitation programs.Also,we will show why geriatric syndromes such as frailty,dependence,cognitive impair-ment,and nutritional status,as well as comorbidities,ought to be considered in this population regarding their important pro-gnostic impact.

关键词： prevention patients cardiovascular

Therapeutic alternatives for the treatment of type 1 hepatorenal syndrome: A delphi technique-based consensus

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World Journal of Hepatology 2016年第25期8卷 1075-1086页

作者： Juan P Arab Juan C claro Juan P Arancibia Jorge Contreras Fernando Gomez Cristian Munoz Leyla Nazal Eric Roessler Rodrigo Wolff Marco Arrese Carlos Benítez departamento de Gastroenterología Escuela de Medicina Pontificia Universidad Católica de Chile departamento de Medicina Interna and Programa de Salud Basada en la Evidencia Escuela de Medicina Pontificia Universidad Católica de Chile Sección de Gastroenterología Departamento de Medicina Hospital Clínico Universidad de Chile and Clínica Santa María Unidad de Gastroenterología Universidad del Desarrollo Clínica Alemana servicio de Gastroentero-logía Unidad de Trasplante Hepático Hospital del Salvador Facultad de Medicina Universidad de Chile and Unidad de Gastroenterología Clínica Alemana de Santiago Clínica Indisa clínica Las Condes y servicio de Gastroenterología Hospital Fuerza Aérea de Chile departamento de Nefrología Facultad de Medicina Pontificia Universidad Católica de Chile

AIM To propose several alternatives treatment of type 1 hepatorenal syndrome(HRS-1) what is the most severe expression of circulatory dysfunction on patients with portal hypertension.METHODS A group of eleven gastroenterologists and nephrologists performed a structured analysis of available literature.Each expert was designated to review and answer a question.They generated draft statements for evaluation by all the experts.Additional input was obtained from medical community.In order to reach consensus,a modified three-round delphi technique method was used.According to United States Preventive Services Task Force criteria,the quality of the evidence and level of recommendation supporting each statement was graded.RESULTS Nine questions were formulated.The available evidence was evaluated considering its quality,number of patients included in the studies and the consistency of its results.The generated questions were answered by the expert panel with a high level of agreement.Thus,a therapeutic algorithm was generated.The role of terlipressin and norepinephrine was confirmed as the pharmacologic treatment of choice.On the other hand the use of the combination of octreotide,midodrine and albumin without vasoconstrictors was discouraged.The role of several other options was also evaluated and the available evidence was explored and discussed.Liver transplantation is considered the definitive treatment for HRS-1.The present consensus is an important effort that intends to organize the available strategies based on the available evidence in the literature,the quality of the evidence and the benefits,adverse effects and availability of the therapeutic tools described.CONclUSION Based on the available evidence the expert panel was able to discriminate the most appropriate therapeutic alternatives for the treatment of HRS-1.

关键词： Hepatorenal syndrome delphi Consensus Evidence-based medicine Treatment

Effectiveness of sacubitril-varsartan versus angiotensin converting enzyme inhibitors in patients hospitalized for acute heart failure:a retrospective cohort study of the RICA registry

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Journal of Geriatric Cardiology 2022年第11期19卷 802-810页

作者： Llanos Soler-Rangel Manuel Méndez-Bailón JoséPérez-Silvestre JoséMaría Fernández-Rodríguez Beatriz Cuesta García Adrián Argüelles-Curto Álvaro González-Franco Alicia Conde-Martel Sara Carrascosa-García Marta Sánchez-Marteles JoséManuel Cerqueiro-González Noel Lorenzo-Villalba Manuel Montero-Pérez-Barquero Llanos Soler-Rangel Servicio de Medicina InternaHospital Universitario Infanta SofíaFIIB HUIS HHENMadridSpain servicio de Medicina Interna Hospital Clínico San CarlosInstituto de Investigación San Carlos(IdISSC)Spain servicio de Medicina Interna Consorcio Hospital General Universitario de ValenciaSpain servicio de Medicina Interna Hospital Carmen y Severo OchoaCangas del NarceaAsturiasSpain servicio de Medicina Interna Hospital Universitario Central de AsturiasOviedoSpain servicio de Medicina Interna Hospital Universitario de Gran Canaria Dr NegrínSpain servicio de Medicina Interna Hospital Clínico Universitario Lozano Blesa de ZaragozaZaragozaSpain Hospital Universitario Lucus Augusti de Lugo LugoSpain Service de Médecine Interne Diabète et Maladies MétaboliquesHôpitaux Universitaires de StrasbourgFrance servicio de Medicina Interna IMIBIC/Hospital Universitario Reina SofíaCórdobaSpain

BACKGROUND Sacubitril-valsartan has been shown to reduce hospitalizations and mortality in patients with heart failure(HF)and reduced ejection fraction.The PIONEER-HF trial demonstrated that initiation of the drug during acute HF hospitalization reduced NT-proBNP levels and a post-hoc analysis of the trial found a reduction in HF hospitalizations and deaths.Real-life studies in the elderly population are scarce.The aim of our study was to assess the effectiveness of sacubitril-valsartan versus angiotensin converting enzyme inhibitors(ACEI)in elderly patients who initiate this treatment during hospitalization for acute HF.METHODS We conducted a retrospective cohort study using the Spanish acute heart failure registry(RICA)comparing rehospitalizations and deaths at 3 months and 1 year among patients aged 70 years or older who had initiated treatment with sacubitrilvalsartan during hospitalization for acute HF versus those treated with ACEI.RESULTS One hundred and ninety-nine patients hospitalized between October 2016 and November 2020 were included,with a median age of 82 years and high rate of comorbidity.Of these,107 were treated with sacubitril-valsartan and 92 with ACEI.The adjusted OR for readmission for HF at 3 months was 0.906(95%CI:0.241-3.404)and for the combined variable readmission for HF or death at 3 months was 0.696(95%CI:0.224-2.167).The adjusted OR for HF readmission at one year was 0.696(95%CI:0.224-2.167).and for the combined variable HF readmission or death at one year 0.724(95%CI:0.325-1.612).CONclUSION Treatment with sacubitril-valsartan initiated early in hospitalization for HF in elderly patients with high comorbidity was associated with a trend towards a reduction in readmissions and death due to HF compared to treatment with ACEI,which did not reach statistical significance either at 3 months or 1 year of follow-up.

关键词： patients initiated admission

A review of Helicobacter pylori diagnosis, treatment, and methods to detect eradication

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World Journal of Gastroenterology 2014年第6期20卷 1438-1449页

作者： Elvira Garza-González Guillermo Ignacio Perez-Perez Héctor Jesús Maldonado-Garza Francisco Javier Bosques-Padilla servicio de Gastroenterología y departamento de Patología clínica Hospital Universitario "Dr. José Eleuterio González" Universidad Autónoma de Nuevo León departments of Medicine and Microbiology New York University School of Medicine

Helicobacter pylori(H. pylori) affects nearly half of the world's population and, thus, is one of the most frequent and persistent bacterial infections worldwide. H. pylori is associated with peptic ulcer disease, gastric ulcers, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Various diagnostic methods exist to detect infection, and the choice of one method or another depends on several factors, such as accessibility, advantages and disadvantages of each method, cost, and the age of patients. Once H. pylori infection is diagnosed, the clinician decides whether treatment is necessity, according to the patient's clinical condition. Typically, eradication of H. pylori is recommended for treatment and prevention of the infection. Cure rates with the standard triple therapy are acceptable, and effective quadruple therapies, sequential therapies, and concomitant therapies have been introduced as key alternatives to treat H. pylori infection. In this work, we review the main diagnostic methods used to identify H. pylori infection and to confirm eradication of infection. In addition, key factors related to treatment are reviewed.

关键词： Diagnosis Helicobacter pylori Treatment Hybrid the

Bone marrow-derived mononuclear stem cells in the treatment of retinal degenerations

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Neural Regeneration Research 2022年第9期17卷 1937-1944页

作者： Diego García-Ayuso Johnny Di Pierdomenico David García-Bernal Manuel Vidal-Sanz María P.Villegas-Pérez departamento de Oftalmología Facultad de MedicinaUniversidad de MurciaCampus de Ciencias de la saludMurciaSpain Instituto Murciano de Investigación Biosanitaria Hospital Virgen de la Arrixaca(IMIB-Virgen de la Arrixaca) MurciaSpain servicio de Hematología Hospital Clínico Universitario Virgen de la ArrixacaMurciaSpain

Retinal degenerative diseases affecting the outer retina in its many forms(inherited,acquired or induced)are characterized by photoreceptor loss,and represent currently a leading cause of irreversible vision loss in the world.At present,there are very few treatments capable of preventing,recovering or reversing photoreceptor degeneration or the secondary retinal remodeling,which follows photoreceptor loss and can also cause the death of other retinal cells.Thus,these diseases are nowadays one of the greatest challenges in the field of ophthalmological research.Bone marrow derived-mononuclear stem cell transplantation has shown promising results for the treatment of photoreceptor degenerations.These cells may have the potential to slow down photoreceptor loss,and therefore should be applied in the early stages of photoreceptor degenerations.Furthermore,because of their possible paracrine effects,they may have a wide range of clinical applications,since they can potentially impact on several retinal cell types at once and photoreceptor degenerations can involve different cells and/or begin in one cell type and then affect adjacent cells.The intraocular injection of bone marrow derived-mononuclear stem cells also enhances the outcomes of other treatments aimed to protect photoreceptors.Therefore,it is likely that future investigations may combine bone marrow derived-mononuclear stem cell therapy with other systemic or intraocular treatments to obtain greater therapeutic effects in degenerative retinal diseases.

关键词： age-related macular degeneration bone marrow stem cells intravitreal injection macroglia microglia photoreceptor degeneration retinal ganglion cells retinitis pigmentosa subretinal injection transplant

Reversal of Cancer by Dual Strategy?

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Journal of Cancer Therapy 2013年第2期4卷 518-520页

作者： Mario Gosalvez Laboratorio y servicio de Bioquímica Experimental Clínica and Hospital Universitario Puerta de Hierro Madrid Spain.

I present herewith a concise historic account of our development of the new technique for cancer therapy: Reversal of Cancer by Dual Strategy. This new method is based on the possible correction of the mitochondrial filamentation defect of tumors plus minor cytotoxicity addressed to the anoxic and fagocitic tumor’s redoubts, using the administration of the anticancer agents with a chrono-therapeutic emphasis on the patient’s mobility. Such methods probably will reach patients in the near future with the collaboration of private clinical trials mainly at least in the USA, Europe and Japan. Only the more essential references of this effort are provided.

关键词： Cancer Reversal Mitochondrial Filamentation Personal Mobility Chronotherapy Mitochondrial Glycolysis Respiration Anoxic and Fagocitic Tumoral Redoubts