Alterations in the small intestinal wall and motor function after repeated cisplatin in rat.

BACKGROUND: Gastrointestinal adverse effects occurring during cancer chemotherapy are well known and feared; those persisting once treatment has finished are relatively unknown. We characterized the alterations occurring in the rat small intestine, after repeated treatment with cisplatin. METHODS: Male Wistar rats received saline or cisplatin (2 mg kg-1  week-1 , for 5 weeks, ip). Gastric motor function was studied non-invasively throughout treatment (W1-W5) and 1 week after treatment finalization (W6). During W6, upper gastrointestinal motility was also invasively studied and small intestinal samples were collected for histopathological and molecular studies. Structural alterations in the small intestinal wall, mucosa, submucosa, muscle layers, and lymphocytic nodules were histologically studied. Periodic acid-Schiff staining and immunohistochemistry for Ki-67, chromogranin A, and neuronal-specific enolase were used to detect secretory, proliferating, endocrine and neural cells, respectively. The expression of different markers in the tunica muscularis was analyzed by RT/qPCR. KEY RESULTS: Repeated cisplatin induced motility alterations during and after treatment. After treatment (W6), the small intestinal wall showed histopathological alterations in most parameters measured, including a reduction in the thickness of circular and longitudinal muscle layers. Expression of c-KIT (for interstitial cells of Cajal), nNOS (for inhibitory motor neurons), pChAT, and cChAT (for excitatory motor neurons) increased significantly (although both ChATs to a lesser extent). CONCLUSIONS & INFERENCES: Repeated cisplatin induces relatively long-lasting gut dysmotility in rat associated with important histopathological and molecular alterations in the small intestinal wall. In cancer survivors, the possible chemotherapy-induced histopathological, molecular, and functional intestinal sequelae should be evaluated.

Estudio RN4CAST en Murcia: características organizacionales de los hospitales y perfiles enfermeros / RN4CAST Study in Murcia: Hospital organizational characteristics and nursing staff profiles

Objetivo. Conocer los perfiles de las enfermeras de los hospitales públicos de Murcia y su percepción sobre el entorno laboral, la calidad de los cuidados y su nivel de burnout (réplica metodológica proyecto RN4CAST). Material y métodos. Estudio descriptivo y transversal realizado en 8 hospitales de Murcia. Se recogieron datos entre 2009 y 2010 a 687 enfermeras (estratificando por tipo de unidades) mediante cuestionario autocumplimentado de 149 ítems con variables sociodemográficas, del trabajo, de la percepción del ambiente laboral (PES-NWI), del burnout (Maslach Burnout Inventory), de la calidad y de la seguridad del paciente. Análisis: pruebas no paramétricas para 2 muestras o k muestras según la comparación. Resultados. Se recogieron 495 encuestas (72%). El 80,4% eran mujeres con una edad media de 34,1 (DE = 7,1) años y de 9,4 (DE = 7,4) años trabajados. El 25,7% ha realizado durante los últimos 24 meses más de 300 h de formación. La ratio paciente/enfermera fue de 11,7 (DE = 3,6) con variabilidad entre hospitales. Dos hospitales tenían un clima desfavorable y 3 hospitales tuvieron clima favorable (los hospitales grandes obtuvieron peores valoraciones); se observó una baja intención de abandonar el trabajo (16,8%). Con respecto al burnout en agotamiento emocional se alcanzó una puntuación de 18,4; en despersonalización de 7,5 y en realización personal de 28,8. La percepción sobre la calidad presentó diferencias entre centros y la de los efectos adversos fue más favorable en los hospitales pequeños. Conclusiones. Los profesionales estudiados estaban satisfechos, pero habría que potenciar los factores que generan bienestar y minimizar los puntos débiles detectados en el análisis del clima laboral (AU)

Objective: To determine the profile of nurses in public hospitals in Murcia and to assess how they perceive their work environment, the quality of care and their level of burnout (the RN4CAST project repetition). Material and methods: A cross-sectional descriptive study was carried out in 8 hospitals in Murcia. Data were collected between 2009 and 2010 from 687 nurses (stratified by the type of unit) using a self-completed questionnaire with 149 items covering variables related to sociodemographics; work; perception of the work place (PES-NWI); burnout (Maslach Burnout Inventory); and the quality of patient care, and patient safety. Analysis: Non parametric tests, for two samples or k samples according to the comparison. Results: A total of 495 questionnaires were collected (72%). Most respondents were female (80.4%) having a mean age of 34.1 (SD = 7.1) years, and they had been working for 9.4 (SD = 7.4) years. Just over one-quarter (25.7%) had carried out more than 300 hours of training in the previous 24 months. The patient/nurse ratio was 11.7 (SD = 3.6), varying between hospitals. The nurses reported 25% of hospitals as having an unfavorable work environment, whereas 37.5% had favorable ones; large hospitals were less highly valued. Few respondents intended to give up their jobs (16.8%). Burnout levels revealed emotional exhaustion in 18.4% of respondents; depersonalization in 7.5%, and personal fulfillment in 28.8%. Perception of quality varied between centers and the perception of adverse effects was more favorable in small hospitals. Conclusions: Our professionals were generally satisfied, but given the unfavorable work environment, measures should be adopted for improving well-being and reducing weaknesses (AU)

[RN4CAST Study in Murcia: Hospital organizational characteristics and nursing staff profiles]. / Estudio RN4CAST en Murcia: características organizacionales de los hospitales y perfiles enfermeros.

OBJECTIVE: To determine the profile of nurses in public hospitals in Murcia and to assess how they perceive their work environment, the quality of care and their level of burnout (the RN4CAST project repetition). MATERIAL AND METHODS: A cross-sectional descriptive study was carried out in 8 hospitals in Murcia. Data were collected between 2009 and 2010 from 687 nurses (stratified by the type of unit) using a self-completed questionnaire with 149 items covering variables related to sociodemographics; work; perception of the work place (PES-NWI); burnout (Maslach Burnout Inventory); and the quality of patient care, and patient safety. ANALYSIS: Non parametric tests, for two samples or k samples according to the comparison. RESULTS: A total of 495 questionnaires were collected (72%). Most respondents were female (80.4%) having a mean age of 34.1 (SD=7.1) years, and they had been working for 9.4 (SD=7.4) years. Just over one-quarter (25.7%) had carried out more than 300 hours of training in the previous 24 months. The patient/nurse ratio was 11.7 (SD=3.6), varying between hospitals. The nurses reported 25% of hospitals as having an unfavorable work environment, whereas 37.5% had favorable ones; large hospitals were less highly valued. Few respondents intended to give up their jobs (16.8%). Burnout levels revealed emotional exhaustion in 18.4% of respondents; depersonalization in 7.5%, and personal fulfillment in 28.8%. Perception of quality varied between centers and the perception of adverse effects was more favorable in small hospitals. CONCLUSIONS: Our professionals were generally satisfied, but given the unfavorable work environment, measures should be adopted for improving well-being and reducing weaknesses.

WNT/beta-catenin increases the production of incretins by entero-endocrine cells.

AIMS/HYPOTHESIS: Glucose-dependent insulinotropic peptide (GIP) plays a pivotal role in the regulation of glucose homeostasis. Rates of diet-induced obesity, insulin resistance and type 2 diabetes are decreased when GIP signalling is disturbed in mice, suggesting that GIP plays a role in the onset of type 2 diabetes. WNT signalling is linked to type 2 diabetes and induces synthesis of the other incretin, glucagon-like peptide 1 (GLP-1). GLP-1 analogues improve treatment of type 2 diabetes patients in whom GLP-1 signalling is intact and have captured clinical attention. GIP levels are altered at the onset of type 2 diabetes and later on, while GIP signalling is impaired. Thus, GIP is not a candidate for treatment but might be an important target from a prevention perspective. Hypothesising that hypersecretion of GIP links altered WNT signalling to the onset of type 2 diabetes, we sought to determine whether WNT signalling induces GIP production by entero-endocrine cells. METHODS: RT-PCR and chromatin immunoprecipitation (ChIP) were used to study Gip gene induction. Gip promoter elements mediating WNT/lithium induction were identified (electrophoretic mobility shift assay, co-transfection of deletion mutants, ChIP). RESULTS: Lithium or WNT/beta-catenin signalling enhanced GIP production by entero-endocrine cells through a conserved site in the proximal Gip promoter. Lithium favours lymphoid enhancer factor-1/beta-catenin binding to Gip promoter and diminishes ChIP through T cell factor-4 and histone deacetylase 1. CONCLUSIONS/INTERPRETATION: Lithium and WNT are incretin inducers in general. This work provides a novel link between WNT signalling, obesity and diabetes.

La enfermería en salud pública: el caso de la Influenza / The public health nursing: the case of influenza

Ante un brote de una enfermedad infecto-contagiosa, el estudio de contactos limita la transmisión de esta. El objetivo de este trabajo fue identificar a los contactos de los posibles casos de influenza en trabajadores de la UNAM para establecer una comunicación y proporcionar educación para la salud sobre medidas higiénicas. Material y métodos: Se elaboró un cuestionario, se estableció contacto con los casos por vía telefónica y se llevó a cabo una visita domiciliaria. Se llevó a cabo un análisis descriptivo de los datos y una descripción de las experiencias y percepciones durante las visitas. Resultados: Se identificó que la mayoría de los contactos eran familiares directos de los casos, que no contaban con un esquema de vacunación completo, ni contra la influenza y la frecuencia de síntomas varió de 1 hasta 4. Comentarios finales: Ante una situación de este tipo (la Pandemia del Virus de la Influenza Humana A (H1N1)) el papel de la enfermera en salud pública es de suma importancia no solo en la búsqueda de los casos y sus contactos, sino también en la orientación y educación de la población en relación a las medidas preventivas.

In the view of an infectious and contagious disease epidemic, the identification of the contacts limits its transmission. The objective of this work was to identify the contacts of the possible cases of UNAM workers in order to establish communication and provide health education about hygiene measures. Material and methods: A questionnaire was prepared, telephone contact was established with the cases, and a home visit was arranged. A descriptive analysis of the data was carried out, as well as, a description of the experiences and perception during the home visit. Results: Most identified contacts were relatives of the cases, which did not have a complete vaccine scheme, no even against influenza, and the frequency of symptoms varied between 1 a 4. Final comments: In a situation like this (A(H1N1) human influenza virus pandemic) the public health nurse roll is of great importance, not just in the identification of the cases and its contacts, but also in the orientation and education of the population in relation to preventive measures.

[Bilateral ureterohydronephrosis secondary to massive vesical hernia]. / Uropatía obstructiva bilateral secundaria a hernia vesical masiva.

Bladder hernia is not a rare pathological condition, with a frequency between 0,3 and 3%. Massive bladder hernia is less frequent an very rarely ureterohydronephrosis with this pathology. We will present a case a renal failure secondary to inguinoscrotal bladder hernia with bilateral obstructive uropathy and an analyzed the clinical presentation, the diagnosis and the treatment for those hernias.

Insulin regulation of malic enzyme gene expression in rat liver: evidence for nuclear proteins that bind to two putative insulin response elements.

Diabetes in rats is characterized by insulin deficiency accompanied by a decrease in lipogenic enzymes. The malic enzyme (ME) gene, which encodes an important lipogenic enzyme, was used to investigate insulin regulation of gene expression. ME mRNA levels were reduced by more than 90% in the liver of diabetic rats. The administration of insulin (3 U/15 days) to either control or diabetic rats increased ME mRNA by 2- to 10-fold, respectively. Since diabetes reduces circulating T3 and the levels of nuclear T3-receptors, the potential role of thyroid hormone on insulin regulation of ME gene expression was also evaluated in thyroidectomized-diabetic rats. In these animals the levels of ME mRNA were undetectable but were increased by insulin even in the absence of thyroid hormones. These in vivo effects of insulin and T3 were not additive. The transcription rate of the gene was also reduced in the diabetic liver and recovered after insulin therapy. By computer analyses we have identified two different putative insulin response elements (IREs) in the ME gene promoter, hereafter referred to as IRE-I (-683 to -692), which is similar to the phosphoenol pyruvate carboxy kinase promoter IRE and IRE-II (-161 to -170), which is similar to the glyceraldehyde phosphate dehydrogenase gene promoter IRE-A. Results from gel retardation assays suggest that a single nuclear protein binds to IRE-I whereas two different nuclear proteins bind to IRE-II. The protein/IRE-I complex increased in liver nuclear extracts from diabetic rats and decreased after insulin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of malic-enzyme-gene expression by cAMP and retinoic acid in differentiating brown adipocytes.

Brown adipose tissue (BAT) is composed of highly specialized cells, whose main function is to produce heat under adrenergic stimulation, uncoupling oxidative phosphorylation. For this function, lipogenesis must be accurately regulated. Malic enzyme has a central role in lipogenesis and is strongly expressed in brown adipocytes. In this work, we study the modulation by adrenergic stimuli, cAMP effectors and retinoic acid on the induction produced by insulin and 3,5,3'-triiodothyronine on malic-enzyme-gene expression. Primary cultures of differentiating brown adipocytes have been used. The results obtained demonstrate that physiological doses of norepinephrine do not modify malic-enzyme mRNA levels when acting alone, but considerably reduce the induction produced by insulin, 3,5,3'-triiodothyronine or both together. Other cAMP inducers such as glucagon, forskolin or 8-bromo-cAMP, greatly inhibit both, basal and 3,5,3'-triiodothyronine-induced malic-enzyme-gene gene expression. Retinoic acid abolishes basal and also inhibits 3,5,3'-triiodothyronine-induced malic-enzyme-gene expression.

Malic enzyme gene expression in differentiating brown adipocytes: regulation by insulin and triiodothyronine.

Primary cultures of brown adipocytes were used to investigate the regulation of malic enzyme (ME) gene expression by insulin and T3. No ME gene expression was detected in undifferentiated preadipocytes. The levels of ME mRNA increased slightly during cell differentiation. Physiological doses of insulin or T3 increased ME gene expression, which reached a maximum after 24 h, on whichever culture day they were added. The effects of insulin and T3 were at the transcriptional level, as measured by run-on assays. Both hormones also increased the stabilization of the transcripts and required ongoing protein synthesis to exert their effects. A comparison of the potencies of insulin and insulin-like growth factor-I and -II (IGF-I and -II) in this system indicated that induction by insulin is mediated via its own receptor. The effects of insulin and T3 were independent of the extracellular glucose concentration, but were additive to that of glucose. Moreover, insulin and T3 act additively to increase ME gene expression, suggesting that they interact either at the transcription level or that of mRNA stabilization.