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Postoperative Crohn’s disease recurrence: A practical approach

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World Journal of Gastroenterology 2008年第36期14卷 5540-5548页

作者： Pilar nos Eugeni Domènech centro de investigación biomédica en Red de enfermedades Hepáticas y Digestivas (Ciberehd) Spain

Crohn's disease is a chronic inflammatory condition that may involve any segment of the gastrointestinal tract. Although several drugs have proven efficacy in inducing and maintaining disease in remission, resectional surgery remains as a cornerstone in the management of the disease, mainly for the treatment of its stenosing and penetrating complications. However, the occurrence of new mucosal (endoscopic) lesions in the neoterminal ileum early after surgery is almost constant, it is followed in the mid-term by clinical symptoms and, in a proportion of patients, repeated intestinal resections are required. Pathogenesis of postoperative recurrence (POR) is not fully understood, but luminal factors (commensal microbes, dietary antigens) seem to play an important role, and environmental and genetic factors may also have a relevant influence. Many studies tried to identify clinical predictors for POR with heterogeneous results, and only smoking has repeatedly been associated with a higher risk of POR. Ileocolonoscopy remains as the gold standard for the assessment of appearance and severity of POR, although the real usefulness of the available endoscopic score needs to be revisited and alternative techniques are emerging. Several drugs have been evaluated to prevent POR with limited success. Smoking cessation seems to be one of the more beneficial therapeutic measures. Aminosalicylates have only proved to be of marginal benefit, and they are only used in low-risk patients. nitroimidazolic antibiotics, although efficient, are associated with a high rate of intolerance and might induce irreversible side effects when used for a long-term. Thiopurines are not widely used after ileocecal resection, maybe because some concerns in giving immunomodulators in asymptomatic patients still remain. In the era of biological agents and genetic testing, a well-established preventive strategy for POR is still lacking, and larger studies to identify good clinical, serological, and geneti

关键词： Crohn's disease Postoperative recurrence Smoking Aminosalicylates nitroimidazolic antibiotics Thiopurines

Melatonin modifies SOX2^+ cell proliferation in dentate gyrus and modulates SIRT1 and MECP2 in long-term sleep deprivation

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neural Regeneration Research 2019年第10期14卷 1787-1795页

作者： Alan Hinojosa-Godínez Luis F. Jave-Suarez Mario Flores-Soto Alma Y. Gálvez-Contreras Sonia Luquín Edith Oregon-Romero Oscar González-Pérez Rocio E. González-Castaneda Laboratorio de Microscopía de Alta Resolución Departamento de NeurocienciasCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajaraMéxico Laboratorio de neurociencias Facultad de PsicologíaUniversidad de ColimaColimaMéxico División de Inmunología Centro de Investigación Biomédica de OccidenteInstituto Mexicano del Seguro SocialGuadalajaraMéxico División de neurociencias Centro de Investigación Biomédica de OccidenteInstituto Mexicano del Seguro SocialGuadalajaraMéxico Instituto de investigación en ciencias biomédicas (IICB) Departamento de Biología Molecular y GenómicaCentro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajaraMéxico Unidad de Atención en neurociencias Departamento de Neurociencias. Centro Universitario de Ciencias de la SaludUniversidad de GuadalajaraGuadalajaraMéxico

Melatonin is a pleiotropic molecule that,after a short-term sleep deprivation,promotes the proliferation of neural stem cells in the adult ***,this effect has not been observed in long-term sleep *** precise mechanism exerted by melatonin on the modulation of neural stem cells is not entirely elucidated,but evidence indicates that epigenetic regulators may be involved in this *** this study,we investigated the effect of melatonin treatment during a 96-hour sleep deprivation and analyzed the expression of epigenetic modulators predicted by computational text mining and keyword *** results showed that the administration of melatonin under sleep-deprived conditions increased the MECP2 expression and reduced the SIRT1 expression in the dentate *** observed that let-7 b,mir-132,and mir-124 were highly expressed in the dentate gyrus after melatonin administration,but they were not modified by sleep *** addition,we found more Sox2^+/5-bromo-2’-deoxyuridine(BrdU)^+cells in the subgranular zone of the sleep-deprived group treated with melatonin than in the untreated *** findings may support the notion that melatonin modifies the expression of epigenetic mediators that,in turn,regulate the proliferation of neural progenitor cells in the adult dentate gyrus under long-term sleep-deprived *** procedures performed in this study were approved by the Animal Ethics Committee of the University of Guadalajara,Mexico(approval ***-16610)on January 2,2016.

关键词： sleep-deprivation melatonin microRnA neurogenesis Sirtuin 1 SIRT1 methyl-CpG-binding protein 2 MECP2 epigenetic text-mining mir-9 let-7b

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Common misconceptions about 5-aminosalicylates and thiopurines in inflammatory bowel disease

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World Journal of Gastroenterology 2011年第30期17卷 3467-3478页

作者： Javier P Gisbert María Chaparro Fernando Gomollón Gastroenterology Unit Hospital Universitario de La PrincesaInstituto de Investigación SanitariaPrincesa(IP)and Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas28006 MadridSpain Gastroenterology Unit Hospital Clínico Universitario and Centro de Investigación Biomédica en Redde Enfermedades Hepáticasy DigestivasIACS50009 ZaragozaSpain

Misconceptions are common in the care of patients with inflammatory bowel disease(IBD).In this paper,we state the most commonly found misconceptions in clinical practice and deal with the use of 5-aminosalicylates and thiopurines,to review the related scientificevidence,and make appropriate *** of errors needs knowledge to avoid making such errors through ***,the amount of knowledge is increasing so quickly that one new danger is an overabundance of *** is a model of a very complex disease and our goal with this review is to summarize the key evidence for the most common daily clinical *** regard to the use of 5-aminosalicylates,the best practice may to be consider abandoning the use of these drugs in patients withsmall bowel Crohn's *** combined approach with oral plus topical 5-aminosalicylates should be the first-line therapy in patients with active ulcerative colitis;once-daily treatment should be offered as a first choice regimen due to its better compliance and higher *** regard to thiopurines,they seem to be as effective in ulcerative colitis as in Crohn's *** of thiopurines is a form of *** should probably be continued indefinitely because their withdrawal is associated with a high risk of *** is a safe alternative in patients with digestive intolerance or hepatotoxicity due to ***,thiopurine methyltransferase(TPMT)screening cannot substitute for regular monitoring because the majority of cases of myelotoxicity are not TPMT-related.

关键词： Crohn' s disease Ulcerative colitis Inflam-matory bowel disease Aminosalicylates Steroids Azathioprine Mercaptopurine Misconceptions

ApoB-100, ApoE and CYP7A1 gene polymorphisms in Mexican patients with cholesterol gallstone disease

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World Journal of Gastroenterology 2010年第37期16卷 4685-4690页

作者： Sánchez-Cuén Jaime Aguilar-Medina Maribel Arámbula-Meraz Eliakym Romero-navarro José Granados Julio Sicairos-Medina Laura Ramos-Payán Rosalío División de Gastroenterología Hospital Regional ISSSTE Facultad de ciencias Químico Biológicas Doctorado en Biotecnología y Maestría en Ciencias Biomédicas Universidad Autónoma de Sinaloa División de Inmunogenética Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

AIM: To determine the possible association of the ApoB100 (Xba Ⅰ ), ApoE (Hha Ⅰ ) and CYP7A1 (Bsa Ⅰ ) gene polymorphisms, with the development of cholesterol gallstone disease (GD) in a Mexican population. METHODS: The polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by ethnicity, age and sex: patients with GD (n = 101) and stone-free control subjects (n = 101). RESULTS: Allelic frequencies in patients and controls were: 34.16% vs 41.58% (P = 0.124) for X+of ApoB-100; 4.46% vs 5.94% (P = 0.501) for E2, 85.64% vs 78.22% (P = 0.052) for E3, 9.90% vs 15.84% (P = 0.075) for E4 of ApoE; and 25.74% vs 27.72% (P = 0.653) for C of CYP7A1. Differences in genotypic frequencies between the studied groups were not significant (P nCLUSIOn: These results demonstrated that no association exists between the studied polymorphisms and cholelithiasis in this high prevalent population.

关键词： Apolipoprotein CYP7A1 Gallstones Mexicans Polymorphisms

Precision medicine in pantothenate kinase-associated neurodegeneration

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neural Regeneration Research 2019年第7期14卷 1177-1185页

作者： Mónica álvarez-Córdoba Marina Villanueva-Paz Irene Villalón-García Suleva Povea-Cabello Juan M.Suárez-Rivero Marta Talaverón-Rey Javier Abril-Jaramillo Ana Belén Vintimilla-Tosi José A.Sánchez-Alcázar centro Andaluz de Biología del desarrollo(CABD-CSIC-Universidad Pablo de Olavide) and Centro de Investigación Biomédica en Red:Enfermedades RarasInstituto de Salud Carlos Ⅲ centro de neurología Avanzada centro Civet

neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas,mainly the basal *** predominant clinical symptoms include spasticity,progressive dystonia,Parkinson's disease-like symptoms,neuropsychiatric alterations,and retinal *** the neurodegeneration with brain iron accumulation disorders,the most frequent subtype is pantothenate kinase-associated neurodegeneration(PKAn) caused by defects in the gene encoding the enzyme pantothenate kinase 2(PAnK2)which catalyzed the first reaction of the coenzyme A biosynthesis *** there is no effective treatment to prevent the inexorable course of these *** aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in ***,we have described that dermal fibroblasts obtained from PKAn patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules,mitochondrial dysfunction and a pronounced increase of markers of oxidative *** addition,PKAn fibroblasts showed a morphological senescence-like ***,pantothenate supplementation,the substrate of the PAnK2 enzyme,corrected all pathophysiological alterations in responder PKAn fibroblasts with low/residual PAnK2 enzyme ***,pantothenate treatment had no favourable effect on PKAn fibroblasts harbouring mutations associated with the expression of a truncated/incomplete *** correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAn *** observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PAnK2 in s

关键词： neurodegeneration with brain iron accumulation pantothenate kinase-associated neurodegeneration pantothenate kinase 2 pantothenate induced neurons precision medicine induced neuron fibroblast

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Historical fluxes of metal and metalloids in an aquatic ecosystem affected by land-use change and mining activities in northwestern Mexico

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International Journal of Sediment Research 2023年第5期38卷 724-738页

作者： Ochoa-Contreras Roberto Jara-Marini Martín enrique Ruiz-Fernández Ana Carolina Sanchez-Cabeza Joan Albert Meza-Figueroa Diana Pérez-Bernal Libia Hascibe Posgrado en ciencias Centro de Investigación en Alimentación y Desarrollo Unidad Hermosillo 2. Centro de Investigación en Alimentación y Desarrollo Unidad Hermosillo Unidad Acad emica Mazatlán Instituto de Ciencias del Mar y Limnología Universidad Nacional Autónoma de M exico departamento de Geología División de Ciencias Exactas y Naturales Universidad de Sonora Rosales y Encinas

Freshwater reservoirs are essential owing because of their ecological, economic, and social *** are particularly vulnerable to contamination, as of metal and metalloids, derived from anthropogenic activities like mining. The temporal variations in trace element concentrations(arsenic(As),mercury(Hg), chromium(Cr), copper(Cu), nickel(ni), lead(Pb), and zinc(Zn)), enrichment, fluxes, and possible sources were evaluated by studying two sediment cores from the La Angostura(AnG) Reservoir(northwest Mexico), using210Pb geochronology. The enrichment factors showed from null to minor enrichment for most elements, but moderate to severe enrichment of mercury(Hg). Most trace element concentrations had a detrital origin, and notable Hg concentration increases since the past decade were associated with severe drought periods, likely resulting from wildfires. The observed sediment concentrations of As and Hg can cause adverse effects on biota in the ecosystem since they are above the probable effect level(PEL). development of strategies for metal attenuation in this reservoir is recommended and metals should be controlled until specific ecotoxicological studies are performed.

关键词： Aquatic ecosystems ~(210)Pb geochronology Mining activities Metals Metalloids enrichment factors

Immunotherapy and immunoescape in colorectal cancer

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World Journal of Gastroenterology 2007年第44期13卷 5822-5831页

作者： Guillermo Mazzolini Oihana Murillo Catalina Atorrasagasti Juan Dubrot Iigo Tirapu Miguel Rizzo Ainhoa Arina Carlos Alfaro Arantza Azpilicueta Carmen Berasain José L Perez-Gracia Alvaro Gonzalez Ignacio Melero Liver Unit Facultad de Ciencias Biomédicas Universidad Austral Presidente Perón 1500 (1635) Derqui-Pilar Buenos Aires Argentina centro de investigación Médica Aplicada and Clínica Universitaria Universidad de Navarra Pamplona Spain

Immunotherapy encompasses a variety of interventions and techniques with the common goal of eliciting tumor cell destructive immune responses. Colorectal carcinoma often presents as metastatic disease that impedes curative surgery. novel strategies such as active immunization with dendritic cells (DCs), gene transfer of cytokines into tumor cells or administration of immunostimulatory monoclonal antibodies (such as anti-CD137 or anti-CTLA-4) have been assessed in preclinical studies and are at an early clinical development stage. Importantly, there is accumulating evidence that chemotherapy and immunotherapy can be combined in the treatment of some cases with colorectal cancer, with synergistic potentiation as a result of antigens cross-presented by dendritic cells and/or elimination of competitor or suppressive T lymphocyte populations (regulatory T-cells). However, genetic and epigenetic unstable carcinoma cells frequently evolve mechanisms of immunoevasion that are the result of either loss of antigen presentation, or an active expression of immunosuppressive substances. Some of these actively immunosuppressive mechanisms are inducible by cytokines that signify the arrival of an effector immune response. For example, induction of 2, 3 indoleamine dioxygenase (IDO) by IFnγ in colorectal carcinoma cells. Combinational and balanced strategies fostering antigen presentation, T-cell costimulation and interference with immune regulatory mechanisms will probably take the stage in translational research in the treatment of colorectal carcinoma.

关键词： Colorectal carcinoma Immunotherapy Gene therapy interleukin-12 dendritic cells CD137 indoleamine 2, 3 dioxygenase

Malignant colorectal polyps

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World Journal of Gastroenterology 2010年第25期16卷 3103-3111页

作者： Luis Bujanda Angel Cosme Ines Gil Juan I Arenas-Mirave department of Gastroenterology Donostia Hospital Uni-versity of Basque Country Centro de Investigación Biomédica en Enfermedades Hepáticas y Digestivas 20010 San Sebastián Guipúzcoa Spain University of Basque Country Centro de Investigación Biomédica en Enfermedades Hepáticas y Digestivas 20010 San Sebastián Guipúzcoa Spain

nowadays, the number of cases in which malignant colorectal polyps are removed is increasing due to colorectal cancer screening programmes. Cancerous polyps are classified into non-invasive high grade neoplasia (nHGn), when the cancer has not reached the muscularis mucosa, and malignant polyps, classed as T1, when they have invaded the submucosa. nHGn is considered cured with polypectomy, while the prognosis for malignant polyps depends on various morphological and histological factors. The prognostic factors include, sessile or pedunculated morphology of the polyp, whether partial or en bloc resection is carried out, the degree of differentiation of the carcinoma, vascular or lymphatic involvement, and whether the polypectomy resection margin is tumor free. A malignant polyp at T1 is considered cured with polypectomy ifit is a pedunculated polyp (Ip of the Paris classification), it has been completely resected, it is not poorly differentiated, the resection edge is not affected by the tumor and there is no vascular or lymphatic involvement. The sessile malignant polyp (Is of the Paris classification) at T1 is considered not cured with polypectomy. Only in some cases (e.g. older people with high surgical risk) local excision(polypectomy or endoscopic submucosal dissection or conventional endoscopic mucosal resection) is considered the definitive treatment.

关键词： Favourable histology Follow-up Malignant polyps non-invasive high grade neoplasia Treatment

Effectiveness of infliximab after adalimumab failure in Crohn's disease

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World Journal of Gastroenterology 2012年第37期18卷 5219-5224页

作者： María Chaparro Montserrat Andreu Manuel Barreiro-de Acosta Esther García-Planella Elena Ricart Eugeni Domènech María Esteve Olga Merino Pilar nos Mireia Pealva Javier P Gisbert department of Gastroenterology Hospital Universitario de La PrincesaInstituto de Investigación Princesa(IP)and Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas(CIBEREHD)28006 MadridSpain Americio 17 portal E 2℃28021 Madrid department of Gastroenterology Hospital del Mar department of Gastroenterology Hospital Clínico Universitario de Santiago department of Gastroenterology Hospital Santa Creui Sant Pau department of Gastroenterology Hospital ClínicBarcelonaand Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas department of Gastroenterology Hospital Germans Triasi Pujol and Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas(CIBEREHD) department of Gastroenterology Hospital Mutua de Terrassa department of Gastroenterology Hospital de Cruces department of Gastroenterology Hospital Universitario La Fe and Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas(CIBEREHD) department of Gastroenterology Hospital de Bellvitge department of Gastroenterology Hospital Universitario de La PrincesaInstituto de Investigación Princesa(IP)and Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas(CIBEREHD)

AIM:To evaluate the effectiveness of infliximab as a second-line therapy in Crohn's disease patients after adalimumab failure. METHODS:A historical cohort study in a community-based gastroenterology practice evaluated Crohn's disease patients treated with infliximab (induction plus maintenance) after adalimumab failure. Patients were identified using a large Spanish database (enEIDA). RESULTS:We included 15 Crohn's disease patients who received infliximab after adalimumab failure. Five patients discontinued adalimumab due to loss of response, 3 due to adverse events and 7 due to partial response. After infliximab therapy was started, all patients who had interrupted adalimumab due to loss of efficacy regained response. All patients who discontinued adalimumab due to adverse events responded to infliximab and maintained this response; one of these patients had an uneventful course on infliximab, but 2 developed adverse events. none of the 7 patients who interrupted adalimumab due to partial response reached remission with infliximab. COnCLUSIOn:Switching from adalimumab to infliximab may be useful in patients who develop adverse effects or loss of response, however, the benefit of infliximab in primary nonresponders was not established.

关键词： Adalimumab Biologics Crohn's disease In-fliximab Switch