[Diagnostic protocol for chronic manifestations of COVID-19]. / Protocolo diagnóstico de las manifestaciones crónicas de la COVID-19.

Many people who have had COVID-19 continue to have symptoms weeks and months after recovering from the acute disease. They present with a highly heterogeneous set of manifestations whose pathophysiology is unknown. There is no uniform nomenclature or agreed-upon diagnostic criteria. One of the main risk factors for its onset is having required intensive care unit admission. The most common manifestations are fatigue and respiratory symptoms, of note among which is dyspnea. The diagnostic approach is focused on ruling out other possible causes that could be responsible for said manifestations. Therefore, a comprehensive evaluation of the patient is conducted followed by a later approach aimed at the nonspecific symptoms.

Síndrome de Kounis tras la administración de Cefditorén / Kounis syndrome after Cefditorén administration

El síndrome de Kounis fue definido, por primera vez, en 1991, como la aparición simultánea de episodios coronarios agudos y reacciones alérgicas anafilácticas o anafilactoides. Los agentes etiológicos asociados a su aparición son múltiples y los más frecuentes son los fármacos, en especial, los antibióticos. Su diagnóstico es eminentemente clínico, no existe ninguna prueba patognomónica. No hay consenso ni guías de práctica clínica específicas; se recomienda el tratamiento específico para el síndrome coronario agudo enfocado en tratar el vasoespasmo y la anafilaxia, con el agravante de que puede haber contraindicaciones cuando se usan conjuntamente y que dichos fármacos antianginosos pueden desencadenar el cuadro. Se presenta un caso clínico de síndrome de Kounis asociado a cefditorén, el primero descrito en la literatura(AU)

Kounis syndrome was first described in 1991 as the simultaneous occurrence of acute coronary events and allergic anaphylactic or anaphylactoid reactions. Multiple etiologic agents are associated with this syndrome, the most common are drugs, especially antibiotics. Diagnosis is eminently clinical, there are not pathognomonic tests. Consensus and specific clinical practice guidelines are lacking; specific acute coronary syndrome treatment is recommended focusing on vasospasm and anaphylaxis, with the aggravating circumstance that contraindications can be present when used together and such antianginal drugs may trigger the condition. We present a case of Kounis syndrome associated with cefditoren, the first reported in the literature.(AU)

Ecocardiografía funcional en cuidados intensivos neonatales: experiencia en una unidad española a lo largo de un año / Functional echocardiography in neonatal intensive care: 1 year experience in a unit in Spain

INTRODUCCIÓN: Numerosas publicaciones destacan la utilidad de la ecocardiografía funcional (EcoFn) en neonatología. No existen datos sobre su uso en unidades españolas. OBJETIVO: Evaluar la frecuencia de uso, pacientes, indicaciones, mediciones y repercusión sobre el tratamiento de la EcoFn en un año en una unidad de cuidados intensivos neonatales (UCIN) española. MÉTODOS: Estudio descriptivo retrospectivo en pacientes ingresados en UCIN en un año. VARIABLES: edad gestacional, peso, diagnóstico principal, días de vida en el momento del estudio, indicación, parámetros medidos y modificaciones del tratamiento. RESULTADOS: Se realizaron 168 ecografías en 50 pacientes, con una media ± desviación estándar de 3,4 ± 2,83 por paciente. Las indicaciones más frecuentes fueron la valoración del ductus (58,3%) seguida de la inestabilidad hemodinámica (22,2%). El resultado de la ecografía modificó el tratamiento en 62 casos (36,9%). En un 17,4% se inició tratamiento con ibuprofeno y en un 1,2% de los casos se adelantó el fin de este. En un 10,8% de los casos, la ecografía modificó el soporte hemodinámico. Los parámetros principales valorados fueron: valoración de presencia/repercusión del ductus 100%; función miocárdica: fracción de eyección/acortamiento 23,8%, gasto ventrículo del izquierdo 24,4%, gasto del ventrículo derecho 21,4%; flujo sistémico 42,3%; signos de hipertensión pulmonar 7,7%. CONCLUSIONES: La EcoFn es utilizada frecuentemente en UCIN y en muchos casos guía el tratamiento de los pacientes. La valoración del ductus y de la inestabilidad hemodinámica son las indicaciones más frecuentes. Queda por determinar si el uso de la EcoFn modifica la evolución de los pacientes de UCIN

INTRODUCTION: Several publications highlight the usefulness of functional echocardiography (FnECHO) in neonatal intensive care. Data is lacking on its use in units neonatal in Spain. OBJECTIVES: To evaluate frequency of use, patient characteristics, indications, measurements, and impact on patient management of FnECHO in a neonatal intensive care unit (NICU) in Spain over a 1 year period. METHODS: A retrospective study conducted in NICU patients during 1 year. VARIABLES: gestational age, birthweight, admission criteria, days of life at examination, indication for FnECHO, parameters assessed, and treatment modifications. RESULTS: 168 echocardiographic studies were performed in 50 patients (mean 3,4. SD 2,83). The most frequent indication was patent ductus (PDA) assessment (58.3%), followed by hemodynamic instability (22.2%). The results of FnECHO modified treatment in 62 cases (36.9%). In 17.4% of them treatment with ibuprofen was initiated, and in 1.2% it was discontinued. In 10.8% of the cases, the results of FnECHO modified hemodynamic support. Echocardiographic evaluation included: assessment of presence/hemodynamic significance of PDA (100%); myocardiac function: ejection fraction/shortening fraction (EF/SF) 23.8%, left ventricular output 24.4%, right ventricular output 21.4%, systemic blood flow 42.3%; and signs of pulmonary hypertension 7.7%. CONCLUSIONS: FnECHO is frequently used in the NICU, and in many cases it guides treatment. PDA assessment and hemodynamic instability are the most frequent indications. It still needs to be elucidated if the use of FnECHO modifies patient outcomes

[Functional echocardiography in neonatal intensive care: 1 year experience in a unit in Spain]. / Ecocardiografía funcional en cuidados intensivos neonatales: experiencia en una unidad española a lo largo de un año.

INTRODUCTION: Several publications highlight the usefulness of functional echocardiography (FnECHO) in neonatal intensive care. Data is lacking on its use in units neonatal in Spain. OBJECTIVES: To evaluate frequency of use, patient characteristics, indications, measurements, and impact on patient management of FnECHO in a neonatal intensive care unit (NICU) in Spain over a 1 year period. METHODS: A retrospective study conducted in NICU patients during 1 year. VARIABLES: gestational age, birthweight, admission criteria, days of life at examination, indication for FnECHO, parameters assessed, and treatment modifications. RESULTS: 168 echocardiographic studies were performed in 50 patients (mean 3,4. SD 2,83). The most frequent indication was patent ductus (PDA) assessment (58.3%), followed by hemodynamic instability (22.2%). The results of FnECHO modified treatment in 62 cases (36.9%). In 17.4% of them treatment with ibuprofen was initiated, and in 1.2% it was discontinued. In 10.8% of the cases, the results of FnECHO modified hemodynamic support. Echocardiographic evaluation included: assessment of presence/hemodynamic significance of PDA (100%); myocardiac function: ejection fraction/shortening fraction (EF/SF) 23.8%, left ventricular output 24.4%, right ventricular output 21.4%, systemic blood flow 42.3%; and signs of pulmonary hypertension 7.7%. CONCLUSIONS: FnECHO is frequently used in the NICU, and in many cases it guides treatment. PDA assessment and hemodynamic instability are the most frequent indications. It still needs to be elucidated if the use of FnECHO modifies patient outcomes.

Incidence of hand-foot syndrome with capecitabine in combination with chemotherapy as first-linetreatment in patients with advanced and/or metastatic gastric cancer suitable for treatment with a fluoropyrimidine-based regimen

INTRODUCTION: Hand-foot syndrome (HFS) is a limiting toxicity of capecitabine, which is not life-threatening but could compromise capecitabine efficacy. MATERIALS AND METHODS: This phase II, multicenter, non-controlled study assessed the safety, particularly grade three HFS incidence, and efficacy of four capecitabine-based chemotherapy regimens [cisplatin/capecitabine (CX), epirubicin/cisplatin/capecitabine (ECX), epirubicin/oxaliplatin/capecitabine (EOX) and docetaxel/cisplatin/capecitabine (DCX)] as first-line treatment for advanced and/or metastatic gastric cancer. RESULTS: One hundred and eight patients were assigned to one of the four treatment groups, according to investigator's criteria, and grouped together for both safety and efficacy primary analyses. HFS was reported in 31 patients (19.6%) and its first presentation occurred at a median of 72 days (range 19-209 days). Grade 3 HFS developed in 6.3, 5.2, 3.7 and 2.4%, of patients receiving ECX, DCX, EOX or CX chemotherapy regimen, respectively. Capecitabine dose reduction/discontinuation due to HFS was required in 5.7% of patients (9/158). The most common (> 10%) grade 3-4 treatment-related AEs were neutropenia (15.2%), asthenia (12.0%) and diarrhoea (11.4%). CONCLUSIONS: A moderate incidence of HFS was reported in patients treated with capecitabine, which generally presented late and required dose reduction in < 1/3 of patients. The results suggest that capecitabine may be useful in combination with standard fluorouracil-based regimens in patients with advanced and/or metastatic gastric cancer with favourable safety profile (AU)

Lynch syndrome diagnostics: decision-making process for germ-line testing.

Cancer risks and medical management of Lynch syndrome (LS) differ from other hereditary or familial clustering of colorectal cancer. Differential diagnosis has improved as a result of the growing clinical and molecular knowledge about LS. Appropriate application of these advances in several scenarios constitutes a decision-making process to further decide germ-line testing with accuracy and efficiency. However, an only molecular-screening algorithm, with a limited number of steps and choices, may be difficult to devise. How, when, where and at what expense to use the different diagnostic tools remain dynamic and changeable under different circumstances. From a clinical point of view, it is advisable to discuss conflicting aspects to guide LS diagnosis.

Lynch syndrome diagnostics: decision-making process for germ-line testing

Cancer risks and medical management of Lynch syndrome (LS) differ from other hereditary or familial clustering of colorectal cancer. Differential diagnosis has improved as a result of the growing clinical and molecular knowledge about LS. Appropriate application of these advances in several scenarios constitutes a decision-making process to further decide germ-line testing with accuracy and efficiency. However, an only molecular-screening algorithm, with a limited number of steps and choices, may be difficult to devise. How, when, where and at what expense to use the different diagnostic tools remain dynamic and changeable under different circumstances. From a clinical point of view, it is advisable to discuss conflicting aspects to guide LS diagnosis (AU)

Seguridad del paciente

La seguridad del paciente es un factor esencial de la calidad asistencial y desde la publicación del informe \"Errar es humano\" es objeto de atención general. Las estrategias de mejora han estimulado el desarrollo de modelos que permiten un mejor conocimiento de los efectos adversos ligados a la asistencia sanitaria. Los sistemas de comunicación de efectos adversos generan información que permitirá adoptar medidas que incrementen la calidad asistencial. Los efectos adversos más comunes son los relacionados con el uso de medicamentos y con frecuencia son evitables. Para disminuirlos, detectarlos y mitigarlos cuando se producen, se pueden emplear estrategias dirigidas a reducir la complejidad, optimizar la información y la automatización de procesos. Aunque el progreso sea lento los cambios se están acelerando especialmente en la implantación de sistemas de prescripción electrónica y difusión de prácticas seguras.

A quantitative real-time PCR method for in planta monitoring of Phytophthora infestans growth.

AIMS: To establish a reliable and rapid protocol to simultaneously obtain high quality DNA from an infected host plant and the infecting pathogen. To develop an accurate and sensitive low-cost assay for the quantification and in planta monitoring of Phytophthora infestans growth. METHODS AND RESULTS: In this study, we describe a SYBR Green-based quantitative real-time PCR (qPCR) method for the quantification of P. infestans. The method is based on a simultaneous plant-pathogen DNA purification followed by a qPCR in which the relative quantification of pathogen and plant DNA is performed. Besides assuring an accurate quantification, the use of a plant gene provides a reliable indicator of sample quality, allowing the exclusion of inappropriate samples. By applying this methodology, we were able to detect P. infestans in potato leaf and tuber tissue before the first symptoms of the disease were observed and to monitor the in planta growth of the pathogen for 6 days. CONCLUSIONS: This is a reliable low-cost assay that provides rapid, accurate and sensitive quantification of the late blight pathogen, allowing the in planta monitoring of P. infestans growth. SIGNIFICANCE AND IMPACT OF THE STUDY: The quantitative nature of the assay described in this study may be useful in plant breeding programmes and basic research. The method is appropriate for the comparison of cultivars with different, and even subtle, degrees of pathogen resistance and in the screening of new anti-oomycete compounds. The method can be easily adapted to tomato and the model plant Nicotiana benthamiana.

Osteopetrosis del adulto. Conceptos actuales / Osteopetrosis of the adult. Current concepts

Se presentan cuatro casos de osteopetrosis del adulto, entidad poco frecuente, recogidos en nuestro hospital desde 1985 hasta 2005. Se revisa la patogenia y se actualizan conceptos y clasificación. Las manifestaciones clínicas se corresponden con otras publicaciones en las que la edad al diagnóstico es muy variable y el primer síntoma oscila desde dolor óseo a un hallazgo tras una fractura. Se revisan las mutaciones genéticas clásicas de todos los tipos, actualizando conceptos. Se introduce la propuesta de retirada de la osteopetrosis tipo I del adulto, ya que su patogenia parece un defecto intrínseco osteoblástico(AU)

We presents four cases of adult osteopetrosis, a very rare disease, compiled from our hospital from 1985 to 2005. Revising the pathogenesis and updating the current concept and classification. The clinical manifestations correspond with other publications where the age at diagnosis is highly variable and the first symptom oscillate from bone pain to a fracture. Presents the classic genetic mutations of all types updating concepts. Introducing the propose withdrawal of adult osteoporosis type I, because the pathogenesis seemed a intrinsic osteoblastic defect(AU)

[Introducing formative portfolio as a tool for Internal Medicine residents mentoring: review of a pilot project, 2005-2006]. / Introducción del portafolio formativo como instrumento de tutorización de residentes de Medicina Interna: revisión de una experiencia piloto, 2005-2006.

Recent educational projects in our country have been trying to introduce professional portfolios as assessment/learning tools on the undergraduate and specialized post-graduate education levels. The approval of a new formative program for the Internal Medicine specialty in an effort to adapt to the present health care needs offers an opportunity to apply these formative and evaluative methodologies in the learning process of future internists. During the 2005-2006 academic year, the Formative Work Group of the Spanish Internal Medicine Society (SEMI) developed a pilot study on portfolio application as a tool for formative assessment and mentoring. This article describes the project of designing, developing, applying and assessing an electronic portfolio for first year Internal Medicine residents. It presents an analysis of the SEMI Portfolio strengths and weaknesses and finally makes suggestions for future development.

Introducción del portafolio formativo como instrumento de tutorización de residentes de Medicina Interna: revisión de una experiencia piloto, 2005-2006 / Introducing formative portfolio as a tool for Internal Medicine residents mentoring: review of a pilot project, 2005-2006

Experiencias recientes en nuestro país tratan deintroducir los portafolios profesionales comoherramientas de evaluación-aprendizaje, tanto anivel de pregrado como en la formaciónespecializada de posgrado. La aprobación del nuevoprograma de la especialidad de Medicina Interna, enun esfuerzo de adaptación a las necesidades de laatención sanitaria actual, ofrece la oportunidad parala aplicación de estas metodologías docentes y deevaluación formativa del proceso de aprendizaje delos futuros internistas. Durante el curso 2005-2006,el Grupo de Formación de la Sociedad Española deMedicina Interna (SEMI) se propuso desarrollar unaexperiencia piloto demostrativa de la aplicación delportafolio como instrumento para la evaluaciónformativa y la tutorización. Este artículo describedicha experiencia de diseño, desarrollo,implantación y evaluación de un portafolio ensoporte electrónico para residentes de MedicinaInterna de primer año de la especialidad, realiza unanálisis de las fortalezas y las debilidades delPortafolio SEMI y, por último, proponerecomendaciones para su futuro desarrollo

Recent educational projects in our country havebeen trying to introduce professional portfolios asassessment/learning tools on the undergraduate andspecialized post-graduate education levels. Theapproval of a new formative program for theInternal Medicine specialty in an effort to adapt tothe present health care needs offers an opportunityto apply these formative and evaluativemethodologies in the learning process of futureinternists. During the 2005-2006 academic year, theFormative Work Group of the Spanish InternalMedicine Society (SEMI) developed a pilot study onportfolio application as a tool for formativeassessment and mentoring. This article describes theproject of designing, developing, applying andassessing an electronic portfolio for first yearInternal Medicine residents. It presents an analysisof the SEMI Portfolio strengths and weaknesses and finally makes suggestions for future development (AU)

Impact of erythropoietin on the reduction of blood transfusions and on survival of lung cancer patients receiving first-line chemotherapy.

INTRODUCTION: Anaemia is a common problem in patients with cancer who receive chemotherapy and is normally associated with a negative impact on patients' quality of life (QOL), poor cancer control and diminished survival. In clinical trials, recombinant human erythropoietin has been shown to correct and prevent anaemia, decrease the need for blood transfusions and improve cancer patients' QOL. METHODS: A retrospective study followed lung cancer patients who received first-line chemotherapy in our hospital in 1998 and in 2005. The incidence of anaemia was analysed, as was the impact of incorporating erythropoietin into the treatment. RESULTS: The incidence of anaemia was 68% (69% of which reported asthenia) in 1998 vs. 54% (60% with asthenia) in 2005. The comparison of anaemia rates (1998 vs. 2005) were grade 1 (16% vs. 32%), grade 2 (36% vs. 16%), grade 3 (16% vs. 5%) and grade 4 (none). Treatment for anaemia included transfusion 52%, intravenous iron 5% and epoetin 4% in 1998. In 2005 anaemia was treated with transfusion 9%, intravenous iron 41%, and epoetin 49%. Median survival (1998 vs. 2005) was 242 days [95% confidence interval (CI) 217-329) vs. 356 days (95% CI 322-382). CONCLUSIONS: Erythropoietin is a valid alternative for cancer patients with anaemia undergoing chemotherapy. It can possibly avoid the need for transfusions without negatively impacting survival.

[Perception of clinical practice derived risks compared to adverse effects detected in an internal medicine service]. / Percepción de riesgos derivados de la práctica clínica frente a los efectos adversos detectados en un servicio de medicina interna.

BACKGROUND AND OBJECTIVE: To know how the health care workers perceive the risks derived from the care practice. To estimate the most frequent adverse effects (AE) and establish differences and similarities between the perception of risks and the AE produced. MATERIAL AND METHOD: A self-administered questionnaire was applied to all the workers of an Internal Medicine Department of a General University Hospital on perception of risks and safety of the patient. After, and by using the screening guide of the IDEA project, edition 1, the clinical histories of the patients selected were analyzed by medical residents of preventive Medicine and Internal Medicine. RESULTS: Questionnaire. Fifty questionnaires we sent with a 42% response rate. Risks prioritized by obtaining a lower mean score: there is not action plan against catastrophes (2.79/10) and lack of spaces to report (3/10); those having greater percentage of open questions: long maintenance of urinary probes (47.61%) and inadequate prescription of antibiotics (33.33%). Study of AE. Incidence of patients with AE: 25% (95% CI 11.06-38.9). Incidence of AE: 26.6% (95% CI 12.6-40.6). 41.6% of AE was related to medication, 25% to nosocomial infection, 16.66% to technical problems in procedures and 16.66% were related to nursing cares. CONCLUSIONS: The perception of the health care workers on health care practice derived risks is different from the adverse events that really appear. The professionals are concerned about the information to patients than about scientific and technical quality. The most frequent adverse events produced are those related with medication. The only common point is concern for nosocomial infection.

Impact of erythropoietin on the reduction of blood transfusions and on survival of lung cancer patients receiving first-line chemotherapy

INTRODUCTION: Anaemia is a common problem in patients with cancer who receive chemotherapy and is normally associated with a negative impact on patients' quality of life (QOL), poor cancer control and diminished survival. In clinical trials, recombinant human erythropoietin has been shown to correct and prevent anaemia, decrease the need for blood transfusions and improve cancer patients' QOL. METHODS: A retrospective study followed lung cancer patients who received first-line chemotherapy in our hospital in 1998 and in 2005. The incidence of anaemia was analysed, as was the impact of incorporating erythropoietin into the treatment. RESULTS: The incidence of anaemia was 68% (69% of which reported asthenia) in 1998 vs. 54% (60% with asthenia) in 2005. The comparison of anaemia rates (1998 vs. 2005) were grade 1 (16% vs. 32%), grade 2 (36% vs. 16%), grade 3 (16% vs. 5%) and grade 4 (none). Treatment for anaemia included transfusion 52%, intravenous iron 5% and epoetin 4% in 1998. In 2005 anaemia was treated with transfusion 9%, intravenous iron 41%, and epoetin 49%. Median survival (1998 vs. 2005) was 242 days [95% confidence interval (CI) 217-329) vs. 356 days (95% CI 322-382). CONCLUSIONS: Erythropoietin is a valid alternative for cancer patients with anaemia undergoing chemotherapy. It can possibly avoid the need for transfusions without negatively impacting survival (AU)

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Percepción de riesgos derivados de la práctica clínica frente a los efectos adversos detectados en un servicio de medicina interna / Perception of clinical practice derived risks compared to adverse effects detected in an internal medicine service

Fundamento y objetivos. Conocer la percepción que los profesionales sanitarios tienen sobre los riesgos derivados de la práctica asistencial, estimar los efectos adversos (EA) más frecuentes, y establecer las diferencias y similitudes entre la percepción de riesgos y los EA producidos. Material y método. Se realizó una encuesta autoadministrada sobre percepción de riesgos y seguridad del paciente a todo el personal de un servicio de medicina interna de un hospital general universitario. Posteriormente, y a través de la guía de cribado del proyecto IDEA 1ª edición, se analizaron las historias clínicas de los pacientes seleccionados por médicos residentes de medicina preventiva y de medicina interna. Resultados. Encuesta. Se enviaron 50 cuestionarios y se obtuvo una tasa de respuesta del 42%. Los riesgos priorizados por obtener una puntuación media más baja fueron la no existencia de plan de actuación frente a catástrofes (2,79 sobre 10) y la falta de espacios para informar (3 sobre 10.); y por mayor porcentaje en las preguntas abiertas, el mantenimiento prolongado de sondajes urinarios, con un 47.61% y la prescripción inadecuada de antibióticos (33,33%). Estudio sobre efectos adversos. Incidencia acumulada (IA) de pacientes con EA: 25% (intervalo de confianza [IC] 95% 11,06-38,9); IA de EA: 26,6% (IC 95% 12,6-40,6). El 41,6% de los EA estuvieron relacionados con la medicación, un 25% con la infección nosocomial, y con problemas técnicos de procedimientos y con fallos en los cuidados del paciente un 16,66% cada uno. Conclusiones. La percepción de los profesionales sanitarios sobre los riesgos derivados de la práctica asistencial es diferente a los sucesos adversos que realmente se terminan materializando. Los profesionales están más preocupados por la información a los pacientes y por la calidad científico-técnica. Los sucesos adversos más frecuentes que se producen son los relacionados con la medicación. El único punto común es la preocupación por la infección nosocomial (AU)

Background and objective. To know how the health care workers perceive the risks derived from the care practice. To estimate the most frequent adverse effects (AE) and establish differences and similarities between the perception of risks and the AE produced. Material and method. A self-administered questionnaire was applied to all the workers of an Internal Medicine Department of a General University Hospital on perception of risks and safety of the patient. After, and by using the screening guide of the IDEA project, edition 1, the clinical histories of the patients selected were analyzed by medical residents of preventive Medicine and Internal Medicine. Results. Questionnaire. Fifty questionnaires we sent with a 42% response rate. Risks prioritized by obtaining a lower mean score: there is not action plan against catastrophes (2.79/10) and lack of spaces to report (3/10); those having greater percentage of open questions: long maintenance of urinary probes (47.61%) and inadequate prescription of antibiotics (33.33%). Study of AE. Incidence of patients with AE: 25% (95% CI 11.06-38.9). Incidence of AE: 26.6% (95% CI 12.6-40.6). 41.6% of AE was related to medication, 25% to nosocomial infection, 16.66% to technical problems in procedures and 16.66% were related to nursing cares. Conclusions. The perception of the health care workers on health care practice derived risks is different from the adverse events that really appear. The professionals are concerned about the information to patients than about scientific and technical quality. The most frequent adverse events produced are those related with medication. The only common point is concern for nosocomial infection (AU)

Upregulation of annexin A1 expression by butyrate in human colon adenocarcinoma cells: role of p53, NF-Y, and p38 mitogen-activated protein kinase.

Annexin A1 is a member of a phospholipid and calcium binding family of proteins; it is involved in anti-inflammation and in the regulation of differentiation, proliferation, and apoptosis. Here, we show the existence of a functional binding site for the tumor suppressor p53 near the proximal CCAAT box and the fact that the basal expression of annexin A1 in human colon adenocarcinoma cells is driven by p53 at the transcriptional level. Posttranscriptional mechanisms may also play an important role in maintaining constitutive annexin A1 expression. In addition, a p53/NF-Y complex is detected bound to the p53 binding site on its promoter. Butyrate is a natural product of fiber degradation in the colon and a key regulator of colonic epithelium homeostasis. We show that butyrate, a class I and II histone deacetylase inhibitor, induces transcriptional activation of annexin A1 expression correlated with differentiation. The effect of butyrate is mediated through a release of NF-Y from the proximal CCAAT box and an enhancement of p53 binding. The interaction of p53 with the promoter is dependent on p38 MAPK activity either in the absence or in the presence of butyrate. Further, activation of p38 MAPK by this agent is required to increase annexin A1 promoter activity and to increase protein expression.

Seguridad del paciente y gestión de riesgos. Réplica / No disponible

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