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Telomerase activity in colorectal cancer,prognostic factor and implications in the microsatellite instability pathway

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World Journal of Gastroenterology 2007年第28期13卷 3868-3872页

作者： M Vidaurreta ML Maestro S Rafael S Veganzones MT Sanz-Casla J Cerdán M Arroyo servicio de Análisis Clínicos Hospital Clínico San CarlosMadrid 28040Spain servicio de Análisis Clínicos Hospital Clínico San CarlosMadrid 28040Spain Servicio de Cirugía General ⅢHospital Clínico San CarlosMadrid 28040Spain

AIM： To determine whether the telomerase activity is related to the Microsatellite instability （MSI） genetic pathway and whether it means a difference in the survival.METHODS： The population consisted of 97 colorectal cancer patients. MSI determination was performed in accordance with the NCI criteria using PCR and Genescan. Telomerase activity was determined by the TRAP-assay, an ELISA procedure based on the amplification of telomeric repeat sequences.RESULTS： 6.2% showed high MSI （MSI-H）, 10.3% showed low MSI （MSI-L） and 83.5% did not show this alteration （MSS）. Positive telomerase activity was detected in 92.8% of the patients. 83.3% of MSI-H tumors showed positive telomerase against 93.8% of MSS tumors. In the overall survival analysis the absence of telomerase activity conferred a better prognosis.CONCLUSION： Previous works have shown that tumors which develop via the MSI pathway present a better prognosis. No link between telomerase activity and MSl status is observed, although sample sizes are small. Patients with telomerase negative tumors had better overall survival than patients with telomerase positive tumors.

关键词： Microsatellite instability Telomerase Colorectal cancer Prognosis

Luminal oxidants selectively modulate electrogenic ion transport in rat colon

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World Journal of Gastroenterology 2006年第34期12卷 5523-5527页

作者： Julio M Mayol Yolanda Adame-Navarrete Pilar Alarma-Estrany Elena Molina-Roldan Fernando Huete-Toral Jesus A Fernandez-Represa servicio de Cirugia I Hospital Clinico San Carlos Universidad Complutense De Madrid Madrid 28040 Spain

AIM： To investigate the effects of luminal exposure to H2O2 and two related thiol oxidizing agents on basal and stimulated chloride secretion in native colon using electrophysiological and pharmacological approaches. METHODS： Unstripped rat distal colon segments were mounted in Ussing chambers. Potential difference, calculated resistance and short-circuit current across unstripped colon segments were monitored with a dual voltage/current clamp. Paracellular permeability was assessed by measuring the mucosa-to-serosa flux of a fluorescent probe （FITC）. RESULTS： Luminal exposure to hydrogen peroxide transitorily stimulated chloride secretion without altering barrier function. This stimulatory effect could be blocked by basolateral atropine but not indomethacin. The cysteine and methionine oxidizing compounds, phenylarsine oxide and chloramine T respectively, mimicked the effect of H2O2, except for a drop in transcolonic resistance after 30 min. In contrast to the observed stimulatory effect on basal secretion, cAMP-stimulated electrogenic ion transport was blunted by luminal H2O2. However, the Ca^2＋- activated response remained unchanged. CONCLUSION： H2O2 may be an important selective modulator of intestinal ion and water secretion in certain pathologic conditions such as inflammation or ischemiareperfusion by multiple mechanisms.

关键词： Chloride secretion Ion transport Rat distal colon Hydrogen peroxide Acetylcholine Atropine

Estrogen rapid effects:a window of opportunity for the aging brain?

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Neural Regeneration Research 2022年第8期17卷 1629-1632页

作者： Ivanny Marchant Jana Stojanova Lilian Acevedo Pablo Olivero Laboratorio de Modelamiento en Medicina Escuela de MedicinaUniversidad de ValparaísoViña del MarChile Interdisciplinary Centre for Health Studies(CIESAL) Universidad de ValparaísoViña del MarChile servicio de neurología hospital carlos van buren ValparaísoChile Laboratorio de Estructura y Función Celular Escuela de MedicinaFacultad de MedicinaUniversidad de ValparaísoValparaísoChile Centro Interoperativo en Ciencias Odontológicas y Médicas Universidad de ValparaísoValparaísoChile

Estrogen produces several beneficial effects in healthy neurological tissues and exhibits cardioprotective *** therapy has been widely used to treat menopausal estrogen deficiency for more than 80 *** high initial expectations of cardioprotective effects,there has been substantial distrust following important randomized clinical trials,such as the Women’s Health ***,the timing of treatment in relation to the onset of menopause came under consideration and led to the proposal of the timing hypothesis,that early initial treatment is important,and benefits are lost as the timing since menopause becomes *** analyses of the Women’s Health Initiative data,together with more recent data from randomized and observational trials,consistently show reductions in coronary heart disease and mortality in younger menopausal *** cognitive function,the timing hypothesis is consistent with observations from basic and animal *** is some clinical evidence to support the benefits of hormonal therapy in this context,though skepticism remains due to the paucity of clinical trials of substantial length in younger menopausal *** is likely that the effects of estrogens on cognitive performance are due to rapid mechanisms,including mechanisms that influence Ca2+homeostasis dynamics,provide protection in a hostile environment and reduce inflammatory signals from neural *** the future,inflammatory profiles accounting for early signs of pathological inflammation might help identify the‘window of opportunity’to use estrogen therapy for successful cognitive protection.

关键词： aging cardiovascular prevention cognitive function estrogen hormone treatment inflammaging rapid effects timing hypothesis TRPV1 window of opportunity

A functional variant in the CD209 promoter is associated with DQ2-negative celiac disease in the Spanish population

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World Journal of Gastroenterology 2006年第27期12卷 4397-4400页

作者： C Nú■ez B Rueda A Martínez C Maluenda I Polanco MA López-Nevot E Ortega E Sierra E Gómez de la Concha E Urcelay J Martín servicio de Inmunología Clínica Hospital Clínico San CarlosMadridSpain Instituto de Parasitología y Biomedicina "López Neyra" CSICGranadaSpain servicio de Pediatría Hospital Clínico San CarlosMadrid Spain servicio de Gastroenterología y Nutrición Pediátrica Hospital La PazMadridSpain servicio de Inmunología Hospital Virgen de las NievesGranadaSpain servicio de Pediatría Hospital Virgen de las NievesGranadaSpain Centro de Investigaciones Biológicas CISCMadridSpain

AIM： To address the role of CD209 in celiac disease （CD） patients. Non-human leukocyte antigen （HLA） genetic factors in CD predisposition are poorly understood, and environmental factors like infectious pathogens may play a role. CD209 is a dendritic and macrophage surface molecule involved in pathogen recognition and immune activation. Recently, a functional variant in the promoter of the CD209 gene （-336A/G） has been shown to affect the transcriptional CD209 activity in vitro and it has been associated with a higher susceptibility to/or severity of infection. METHODS： The study population was composed of two case-control cohorts of 103 and 386 CD patients and 312 y 419 healthy controls as well as a panel of 257 celiac families. Genotyping for the -336A/G CD209 promoter polymorphism was performed using a TaqMan 5＇ allelic discrimination assay. HLA-DQ was determined by hybridization with allele specific probes. RESULTS： Initially, the case-control and familial studies did not find any association of the -336 A/G CD209 genetic variant with CD susceptibility. However, the stratification by HLA-DQ2 did reveal a significant association of CD209 promoter polymorphism in the HLA-DQ2 （-） group （carrier A vs GG in DQ2 （-） vs DQ2 （＋） patients （P = 0.026, OR = 3.71）. CONCLUSION： The -336G CD209 allele seems to be involved in CD susceptibility in HLA-DQ2 （-） patients. Our results might suggest a possible role of pathogens in the onset of a minor group of CD patients.

关键词： CD209 HLA-DQ2 Celiac disease Single nucleotide polymorphism Susceptibility

Inflammatory bowel disease and celiac disease:Overlaps and differences

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World Journal of Gastroenterology 2014年第17期20卷 4846-4856页

作者： Virginia Pascual Romina Dieli-Crimi Natalia López-Palacios Andrés Bodas Luz María Medrano Concepción Nú?ez UGC de Inmunología Hospital Clínico San CarlosInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)28040 MadridSpain servicio de Digestivo Hospital Clínico San CarlosInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)28040 MadridSpain servicio de Pediatría Hospital Clínico San CarlosInstituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC)28040 MadridSpain

Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn’s disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults.

关键词： Disease susceptibility Gene-environment interaction Immune system Inflammation Microbiota Inflammatory bowel disease

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 *** this scenario,health interventions are ne-cessary to improve prognosis and quality of life of elderly with cardiovascular risk factors and cardiovascular ***,the number of elderly patients included in clinical trials is low,thus current clinical practice guidelines do not include specific *** 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 ***,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

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 *** 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 ***-life studies in the elderly population are *** 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 *** 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 *** 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 *** these,107 were treated with sacubitril-valsartan and 92 with *** 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

Differential response of injured and healthy retinas to syngeneic and allogeneic transplantation of a clonal cell line of immortalized olfactory ensheathing glia:a double-edged sword

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Neural Regeneration Research 2025年第8期20卷 2395-2407页

作者： María Norte-Muñoz María Portela-Lomba Paloma Sobrado-Calvo Diana Simón Johnny Di Pierdomenico Alejandro Gallego-Ortega Mar Pérez JoséMCabrera-Maqueda Javier Sierra Manuel Vidal-Sanz María Teresa Moreno-Flores Marta Agudo-Barriuso Grupo de Investigación Oftalmología Experimental Departamento de OftalmologíaOptometríaOtorrinolaringología y Anatomía PatológicaFacultad de MedicinaUniversidad de MurciaInstituto Murciano de Investigación Biosanitaria(IMIB)Campus de Ciencias de la SaludMurciaSpain Experimental Sciences Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain Anatomy Histology and Neuroscience DepartmentMedicine FacultyUniversidad Autónoma de MadridMadridSpain Center of Neuroimmunology Service of NeurologyLaboratory of Advanced Imaging in Neuroimmunological DiseasesHospital Clínic of BarcelonaInstitut d’Investigacions Biomèdiques August Pi i Sunyer(IDIBAPS)and Universitat de BarcelonaBarcelonaSpain Medicine Faculty Universidad Francisco de VitoriaPozuelo de AlarcónMadridSpain

Olfactory ensheathing glia promote axonal regeneration in the mammalian central nervous system,including retinal ganglion cell axonal growth through the injured optic ***,it is unknown whether olfactory ensheathing glia also have neuroprotective *** ensheathing glia express brain-derived neurotrophic factor,one of the best neuroprotectants for axotomized retinal ganglion ***,we aimed to investigate the neuroprotective capacity of olfactory ensheating glia after optic nerve *** ensheathing glia cells from an established rat immortalized clonal cell line,TEG3,were intravitreally injected in intact and axotomized retinas in syngeneic and allogeneic mode with or without microglial inhibition or immunosuppressive *** and gene expression analyses were *** bulb-derived primary olfactory ensheathing glia and TEG3 express major histocompatibility complex classⅡ*** and syngenically transplanted TEG3 cells survived in the vitreous for up to 21 days,forming an *** axotomized retinas,only the allogeneic TEG3 transplant rescued retinal ganglion cells at 7 days but not at 21 *** these retinas,microglial anatomical activation was higher than after optic nerve crush *** intact retinas,both transplants activated microglial cells and caused retinal ganglion cell death at 21 days,a loss that was higher after allotransplantation,triggered by pyroptosis and partially rescued by microglial inhibition or ***,neuroprotection of axotomized retinal ganglion cells did not improve with these *** different neuroprotective properties,different toxic effects,and different responses to microglial inhibitory treatments of olfactory ensheathing glia in the retina depending on the type of transplant highlight the importance of thorough preclinical studies to explore these variables.

关键词： cell therapy immune recognition major histocompatibility complex class II(MHCII) neuroprotection olfactory ensheathing glia retinal ganglion cells

Gastrointestinal disorders associated with migraine: A comprehensive review

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World Journal of Gastroenterology 2016年第36期22卷 8149-8160页

作者： carlos R Cámara-Lemarroy Rene Rodriguez-Gutierrez Roberto Monreal-Robles Alejandro Marfil-Rivera servicio de neurología Hospital Universitario "Dr. José E. González" Universidad Autónoma de Nuevo León servicio de Endocrinología Hospital Universitario "Dr. José E. González" Universidad Autónoma de Nuevo León servicio de Gastroenterología Hospital Universitario "Dr. José E. González" Universidad Autónoma de Nuevo León

Migraine is a recurrent and commonly disabling primary headache disorder that affects over 17% of women and 5%-8% of men. Migraine susceptibility is multifactorial with genetic, hormonal and environmental factors all playing an important role. The physiopathology of migraine is complex and still not fully understood. Many different neuropeptides, neurotransmitters and brain pathways have been implicated. In connection with the myriad mechanisms and pathways implicated in migraine, a variety of multisystemic comorbidities(e.g., cardiovascular, psychiatric and other neurological conditions) have been found to be closely associated with migraine. Recent reports demonstrate an increased frequency of gastrointestinal(GI) disorders in patients with migraine compared with the general population. Helicobacter pylori infection, irritable bowel syndrome, gastroparesis, hepatobiliary disorders, celiac disease and alterations in the microbiota have been linked to the occurrence of migraine. Several mechanisms involving the gut-brain axis, such as a chronic inflammatory response with inflammatory and vasoactive mediators passing to the circulatory system, intestinal microbiota modulation of the enteric immunological milieu and dysfunction of the autonomic and enteric nervous system, have been postulated to explain these associations. However, the precise mechanisms and pathways related to the gut-brain axis in migraine need to be fully elucidated. In this review, we survey the available literature linking migraine with GI disorders. We discuss the possible physiopathological mechanisms, and clinical implications as well as several future areas of interest for research.

关键词： Migraine Headache Microbiota Review Gastrointestinal diseases