Resistance to apoptosis in complicated Crohn's disease: Relevance in ileal fibrosis.

BACKGROUND AND AIMS: The stiffening of the extracellular matrix, and changes in its cellular and molecular composition, have been reported in the pathogenesis of fibrosis. We analyze the mechanisms that perpetuate ileal fibrosis in surgical resections of complicated Crohn's disease patients. METHODS: Ileal resections were obtained from affected and non-affected tissue of stenotic or penetrating Crohn's disease behavior. Ilea from non-IBD patients were used as control tissue. All samples underwent RNA sequencing. Human small intestinal fibroblasts were treated for 48 h with IL-1ß, TFGß1, PDGFB or TNF-α. Resistance to apoptosis was analysed by RT-PCR, western blot and immunohistochemistry in ileal tissue and by RT-PCR and FACS in cultured cells. RESULTS: Growth factor-driven signaling pathways and increased RAS GTPase activity were up-regulated in affected ilea in which we found expression of both the antiapoptotic molecule MCL1 and the transcription factor ETS1 in submucosal fibroblasts, and a senescence-associated secretory phenotype. In cultured intestinal fibroblasts, PDGFB induced an ETS1-mediated resistance to apoptosis that was associated with the induction of both of TGFB1 and IL1B, a cytokine that replicated the expression of SASP detected in ileal tissue. ETS1 drove fibroblast polarization between inflammatory and fibrogenic phenotypes in IL1ß-treated cells. CONCLUSIONS: Our data show resistance to apoptosis in complicated ileal CD, and demonstrate that PDGFB induce an ETS1-mediated resistance to apoptosis associated with an inflammatory and fibrogenic pattern of expression in intestinal fibroblasts. Results point to PDGFRB, IL1R1 or MCL1 as potential targets against ileal fibrosis.

Síndrome de realimentación en niña con parálisis cerebral / Refeeding syndrome in a girl with cerebral palsy

El síndrome de realimentación es una complicacióngrave y potencialmente mortal asociada a la terapianutricional por vía oral, enteral o parenteral. Afecta apacientes con desnutrición severa o en riesgo de desnutrición, como aquellos con parálisis cerebral infantil. Presentamos el caso de una paciente de ocho añoscon parálisis cerebral que ingresó por hipoglucemiasevera y que, tras iniciar la alimentación enteral porsonda nasogástrica, desarrolló un síndrome de realimentación. En niños con parálisis cerebral es fundamental valorar la presencia de factores de riesgo paradesarrollar un síndrome de realimentación, iniciar laalimentación de manera progresiva y monitorizar losiones séricos.(AU)

Refeeding syndrome is a serious and life-threateningcomplication associated with oral, enteral and parenteral nutritional therapy. It appears in severely malnourished patients or in those at risk of malnutrition,such as persons with cerebral palsy. We present the case of an 8-year-old girl with cerebral palsy who was admitted with severe hypoglycemia.After starting enteral nutrition by nasogastric tube, shedeveloped refeeding syndrome. In children with cere-bral palsy, it is essential to assess the presence of riskfactors for refeeding syndrome before starting any nutritional support, and then start feeding progressivelyand monitor serum electrolytes.(AU)

[Refeeding syndrome in a girl with cerebral palsy].

Refeeding syndrome is a serious and life-threatening complication associated with oral, enteral and parenteral nutritional therapy. It appears in severely malnourished patients or in those at risk of malnutrition, such as persons with cerebral palsy. We present the case of an 8-year-old girl with cerebral palsy who was admitted with severe hypoglycemia. After starting enteral nutrition by nasogastric tube, she developed refeeding syndrome. In children with cerebral palsy, it is essential to assess the presence of risk factors for refeeding syndrome before starting any nutritional support, and then start feeding progressively and monitor serum electrolytes.

M1 Macrophages Activate Notch Signalling in Epithelial Cells: Relevance in Crohn's Disease.

BACKGROUND: The Notch signalling pathway plays an essential role in mucosal regeneration, which constitutes a key goal of Crohn's disease (CD) treatment. Macrophages coordinate tissue repair and several phenotypes have been reported which differ in the expression of surface proteins, cytokines and hypoxia-inducible factors (HIFs). We analysed the role of HIFs in the expression of Notch ligands in macrophages and the relevance of this pathway in mucosal regeneration. METHODS: Human monocytes and U937-derived macrophages were polarized towards the M1 and M2 phenotypes and the expression levels of HIF-1α, HIF-2α, Jagged 1 (Jag1) and delta-like 4 (Dll4) were evaluated. The effects of macrophages on the expression of hairy and enhancer of split-1 (HES1, the main target of Notch signalling) and intestinal alkaline phosphatase (IAP, enterocyte marker) in epithelial cells in co-culture were also analysed. Phenotype macrophage markers and Notch signalling were evaluated in the mucosa of CD patients. RESULTS: M1 macrophages were associated with HIF-1-dependent induction of Jag1 and Dll4, which increased HES1 protein levels and IAP activity in co-cultured epithelial cells. In the mucosa of CD patients a high percentage of M1 macrophages expressed both HIF-1α and Jag1 while M2 macrophages mainly expressed HIF-2α and we detected a good correlation between the ratio of M1/M2 macrophages and both HES1 and IAP protein levels. CONCLUSION: M1, but not M2, macrophages are associated with HIF-1-dependent induction of Notch ligands and activation of epithelial Notch signalling pathway. In the mucosa of chronic CD patients, the prevalence of M2 macrophages is associated with diminution of Notch signalling and impaired enterocyte differentiation.

The activation of Wnt signaling by a STAT6-dependent macrophage phenotype promotes mucosal repair in murine IBD.

The complete repair of the mucosa constitutes a key goal in inflammatory bowel disease (IBD) treatment. The Wnt signaling pathway mediates mucosal repair and M2 macrophages that coordinate efficient healing have been related to Wnt ligand expression. Signal transducer and activator of transcription 6 (STAT6) mediates M2 polarization in vitro and we hypothesize that a STAT6-dependent macrophage phenotype mediates mucosal repair in acute murine colitis by activating the Wnt signaling pathway. Our results reveal an impaired mucosal expression of M2 macrophage-associated genes and delayed wound healing in STAT6(-/-) mice treated with 2,4,6-trinitrobenzenesulfonic acid (TNBS). These mice also exhibited decreased mucosal expression of Wnt2b, Wnt7b, and Wnt10a, diminished protein levels of nuclear ß-catenin that is mainly located in crypts adjacent to damage, and reduced mRNA expression of two Wnt/ß-catenin target molecules Lgr5 and c-Myc when compared with wild-type (WT) mice. Murine peritoneal macrophages treated with interleukin-4 (IL-4) and polarized toward an M2a phenotype overexpressed Wnt2b, Wnt7b, and Wnt10a in a STAT6-dependent manner. Administration of a Wnt agonist as well as transfer of properly polarized M2a macrophages to STAT6(-/-) mice activated the Wnt signaling pathway in the damaged mucosa and accelerated wound healing. Our results demonstrate that a STAT6-dependent macrophage phenotype promotes mucosal repair in TNBS-treated mice through activation of the Wnt signaling pathway.

Hypoxic macrophages impair autophagy in epithelial cells through Wnt1: relevance in IBD.

A defective induction of epithelial autophagy may have a role in the pathogenesis of inflammatory bowel diseases. This process is regulated mainly by extracellular factors such as nutrients and growth factors and is highly induced by diverse situations of stress. We hypothesized that epithelial autophagy is regulated by the immune response that in turn is modulated by local hypoxia and inflammatory signals present in the inflamed mucosa. Our results reveal that HIF-1α and Wnt1 were co-localized with CD68 in cells of the mucosa of IBD patients. We have observed increased protein levels of ß-catenin, phosphorylated mTOR, and p62 and decreased expression of LC3II in colonic epithelial crypts from damaged mucosa in which ß-catenin positively correlated with phosphorylated mTOR and negatively correlated with autophagic protein markers. In cultured macrophages, HIF-1 mediated the increase in Wnt1 expression induced by hypoxia, which enhanced protein levels of ß-catenin, activated mTOR, and decreased autophagy in epithelial cells in co-culture. Our results demonstrate a HIF-1-dependent induction of Wnt1 in hypoxic macrophages that undermines autophagy in epithelial cells and suggest a role for Wnt signaling and mTOR pathways in the impaired epithelial autophagy observed in the mucosa of IBD patients.

Soporte nutricional en el lactante y niño menor de 3 años / Nutritional support in the infant and child under 3 years of age

La alimentación y nutrición en los primeros años de la vida presentan aspectos particulares respecto a otras edades; algunos dependen de las habilidades y posibles enfermedades del niño y otros, de los conocimientos y de la interacción de los padres con sus hijos en el momento de la alimentación. La falta de apetito, el rechazo del alimento o la excesiva duración de las comidas, y la afectación ponderal son consultas habituales en estas edades. La valoración médica en estos casos debe partir de una historia clínica general, una valoración dietético-alimentaria y un examen físico, valorando la necesidad de exámenes complementarios posteriormente. Deberá detectarse déficit de ingesta de alimentos, enfermedad orgánica, problemas en la interacción cuidador-niño y problemas de crecimiento o malnutrición. Los pilares que constituyen la base del tratamiento de estos problemas son el soporte nutricional, el tratamiento de los trastornos de la alimentación y el tratamiento de las deficiencias nutricionales específicas. El soporte nutricional se inicia con una correcta evaluación clí- nica y consistirá en mejoras en el rendimiento de la ingesta oral, para evaluar la indicación de alimentación enteral mediante sonda nasogástrica o gastrostomía con dietoterápicos en forma de módulos o dietas enterales completas. El tratamiento de los trastornos de la alimentación se inicia valorando y fomentando los conocimientos de alimentación y nutrición en los cuidadores, instruyéndoles en las situaciones de conflicto. A pesar de ello, el tratamiento en ocasiones deberá ser multidisciplinario (AU)

Diet and nutrition early in life have particular aspects regarding other ages, some depend on infant, their skills and possible diseases, and other on parents, nutritional knowledge and interaction with their infant at feeding. Lack of appetite, food refusal, excessive duration of meals, and poor weight are common queries involvement in these ages. Medical assessment in these cases must start from a clinical history, a dietary assessment and physical examination considering the need for additional tests. Poor food intake, physical illness, problems in caregiver-child interaction and growth problems or malnutrition must be identified. The basis of the treatment of these problems are nutritional support, treatment of eating disorders and treatment of specific nutritional deficiencies. Nutritional support begins with a clinical assessment and will consist of improvements of oral intake, evaluating the indication for enteral feeding via nasogastric or gastrostomy and using nutritional supplements or complete enteral diets. The treatment of eating disorders starts valuing the knowledge about food and nutrition in caregivers, encouraging and instructing them in conflict situations. However, sometimes multidisciplinary approach will be necessary (AU)

Nitric oxide induces HIF-1α stabilization and expression of intestinal trefoil factor in the damaged rat jejunum and modulates ulcer healing.

BACKGROUND: The induction of intestinal trefoil factor (ITF) has been reported to depend on hypoxia-inducible factor-1 (HIF-1). Nitric oxide modulates HIF-1 activity. The present study aims to analyze the role of nitric oxide in jejunum damage induced by indomethacin and its ability to modulate epithelial function through the expression of ITF. METHODS: Rats received indomethacin (7.5 mg/kg, s.c., twice), and a time course analysis of damage was performed (24-96 h after the first administration). In these animals, the role of nitric oxide was analyzed by using 1400W, a selective iNOS activity inhibitor (5 mg/kg, i.p./day), on: (1) intestinal damage, (2) ulcer healing, (3) the presence of nitrated proteins in the jejunum and (4) the protein expression of inducible nitric oxide synthase (iNOS), HIF-1α and ITF. RESULTS: Indomethacin induced damage in the jejunum that was apparent at 24 h and peaked at 48-72 h. An increase in iNOS, HIF-1α, ITF and nitrated proteins was observed in the injured jejunum. Immunoprecipitation of HIF-1α allowed determination of the nitration/nitrosylation of this protein by using nitrotyrosine and nitrocysteine antibodies. Blockade of iNOS activity did not significantly modify damage or iNOS expression, but did significantly impede ITF induction, HIF-1α stabilization and HIF-1α detection with antibodies against nitrated proteins. In parallel to these results, pre-treatment with 1400W delayed the healing of the ulcer provoked by indomethacin. CONCLUSIONS: These results suggest that iNOS-derived NO is involved in HIF-1α stabilization, probably through S-nitrosylation, and ITF expression in goblet cells of the damaged jejunum of indomethacin-treated rats and mediates ulcer healing.

Nitric oxide, derived from inducible nitric oxide synthase, decreases hypoxia inducible factor-1alpha in macrophages during aspirin-induced mesenteric inflammation.

BACKGROUND AND PURPOSE: Nitric oxide (NO) modulates expression of hypoxia inducible factor-1 (HIF-1), a transcription factor regulating function of myeloid cells. Here, we have assessed the role played by NO, formed by inducible NOS (iNOS), in the inflammation induced by aspirin in the gut, by modulating HIF-1 activity. EXPERIMENTAL APPROACH: The role of iNOS-derived NO on leucocyte-endothelial interactions induced by aspirin was evaluated by intravital microscopy in mesenteric venules of rats pretreated with selective iNOS inhibitors, 1400W or l-N6-(1-iminoethyl)-lysine. NO was localized by fluorescence microscopy, using DAF-FM. iNOS, HIF-1alpha and CD36 were localized by immunohistochemistry. KEY RESULTS: Leucocyte-endothelial interactions increased at 6 h and returned to normal levels 24 h after aspirin administration. Numbers of migrated leucocytes were similar between 6 and 24 h after aspirin. iNOS expression and iNOS-derived NO synthesis were observed in leucocytes of the mesentery of aspirin-treated rats. Blockade of iNOS activity in aspirin-treated rats: (i) did not modify leucocyte infiltration at 6 h, but reduced the number of polymorphonuclear leucocyte and increased that of macrophages at 24 h; (ii) increased HIF-1alpha immunostaining in macrophages of the mesentery; and (iii) prevented the decrease in CD36 immunostaining induced by aspirin in these cells. CONCLUSIONS AND IMPLICATIONS: NO, associated with acute gut inflammation induced by aspirin, diminished HIF-1alpha stabilization in macrophages. Early inhibition of iNOS-derived NO synthesis, by increasing the activity of HIF-1 in these cells, may accelerate the clearance of leucocytes.

Induction of trefoil factor (TFF)1, TFF2 and TFF3 by hypoxia is mediated by hypoxia inducible factor-1: implications for gastric mucosal healing.

BACKGROUND AND PURPOSE: Mucosal microcirculation is compromised during gastric damage induced by non-steroidal anti-inflammatory drugs, such as aspirin. Consequently, oxygen supply to epithelial cells is decreased. The trefoil factor (TFF) peptides are involved in mechanisms of defence and repair in the gastrointestinal tract but their regulation at sites of gastric injury is unknown. EXPERIMENTAL APPROACH: Hypoxia and expression of TFF genes and peptides were measured in the damaged stomach of aspirin-treated rats. In a human gastric cell line (AGS cells), the effects of hypoxia and of hypoxia inducible factor (HIF)-1 (through transient transfection of HIF-1alpha siRNA or over-expression of HIF-1alpha) on TFF gene expression were evaluated. KEY RESULTS: Hypoxyprobe immunostaining, up-regulation of TFF2 (1.9-fold) and TFF3 (1.8-fold) and a non-significant increase of TFF1 (1.5-fold) mRNA were observed in the damaged stomach of aspirin-treated rats, compared with control animals. Hypoxia (3% O(2), 16 h) induced mRNA for TFF1 (5.8-fold), TTF2 (9.1-fold) and TFF3 (9.3-fold) in AGS cells, an effect mediated by HIF-1, as transient transfection of HIF-1alpha siRNA reduced the effects of hypoxia. Over-expression of HIF-1alpha by transfection in non-hypoxic epithelial cells produced a similar pattern of TFF induction to that observed with hypoxia and transactivated a TFF1 reporter construct. CONCLUSIONS AND IMPLICATIONS: Hypoxia inducible factor-1 mediated the induction of TFF gene expression by hypoxia in gastric epithelial cells. Low oxygen levels and up-regulation of TFF gene expression in the damaged stomach of aspirin-treated rats suggest that hypoxia induced expression of TFF genes at sites of gastric injury.

Consideraciones anestésicas y uso de la máscara laríngea proseal en un paciente afecto de miotonía distrófica de steinert / The Proseal laryngeal mask during anesthesia in a patient with Steinert myotonic dystrophy

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[Childhood cancer in the Autonomous Community of Cantabria in Spain (1995-2000)]. / Cáncer infantil en la comunidad de Cantabria (1995-2000).

BACKGROUND: Since 1980, the epidemiology of childhood cancer in Spain has been registered through the National Registry of Childhood Cancer. However, this registry does not include patients from Autonomous Community of Cantabria because there is no reporting clinical center. The absence of data on childhood cancer in this region justifies this study. OBJECTIVES: To analyze the clinical presentation, diagnostic delay and incidence of childhood cancer in Cantabria. METHODS: We performed a retrospective analysis of 89 children (aged 0-15 years) diagnosed with cancer in Cantabria from 1995-2000. RESULTS: The annual incidence of childhood cancer in the region was 198.1 cases per million inhabitants with a predominance of males (53.9 %) and children aged less than 5 years (46.1 %). The most frequent cancers were leukemia (32.6 %) and brain tumors (23.6 %). The most frequent signs and symptoms were fever (29.2 %) and decreased appetite or fatigue (19.1 %). The mean delay in diagnosis for all tumors was 5.99 weeks and delays were longest for brain tumors. There was a direct statistical relationship between non-specific clinical presentation and diagnostic delay. A total of 20.2 % of all patients received treatment outside Cantabria. CONCLUSIONS: The incidence of all childhood cancers and especially that of neuroblastoma was higher in Cantabria than in other areas of Spain. In general, the major difficulties in the diagnosis of childhood cancer are its low incidence and non-specific presenting symptoms. Specialized pediatric oncology units near to patients' homes should be created to avoid problems due to treatment outside the area of residence.

Cáncer infantil en la comunidad de Cantabria (1995-2000) / Childhood cancer in the autonomous community of Cantabria in Spain (1995-2000)

Antecedentes: Desde el año 1980, el Registro Nacional de Tumores Infantiles recoge los datos estadísticos del cáncer infantil en España. Este registro no recoge los pacientes de la Comunidad de Cantabria debido a la ausencia de un centro informante y ello justifica la realización del presente trabajo. Objetivos Analizar la incidencia, demora diagnóstica y aspectos clínicos del cáncer infantil en Cantabria. Métodos Estudio retrospectivo mediante la revisión de historias clínicas de 89 pacientes menores de 15 años con cáncer, diagnosticados en Cantabria durante los años 1995-2000.Resultados La incidencia anual de cáncer infantil en Cantabria fue 198,1 casos por millón de habitantes, predominando en varones (53,9 per cent) y menores de 5 años (46,1 per cent). El tumor más frecuente fue la leucemia (32,6 per cent), seguido de los tumores cerebrales (23,6 per cent). Los síntomas de presentación más frecuentes fueron fiebre-febrícula (29,2 per cent) y astenia-anorexia (19,1 per cent). La demora diagnóstica media fue de 5,99 semanas, presentando la mayor demora los tumores cerebrales. Se observa una relación estadística directa entre la demora diagnóstica y la inespecificidad de los síntomas de presentación. El 20,2 per cent de los pacientes fueron seguidos fuera de Cantabria. Conclusiones En Cantabria, la incidencia global de cáncer infantil y, en concreto, de neuroblastomas resultó alta comparada con nuestro entorno. En general, las principales dificultades diagnósticas del cáncer infantil son su baja frecuencia y la inespecificidad de su clínica inicial. Se debe fomentar la creación de unidades de seguimiento del paciente oncológico infantil cercanos a sus lugares de residencia y evitar los trastornos derivados de su desplazamiento (AU)

Modulation of colony stimulating factor release and apoptosis in human colon cancer cells by anticancer drugs.

Modulation of the immune response against tumour cells is emerging as a valuable approach for cancer treatment. Some experimental studies have shown that secretion of colony stimulating factors by cancer cells reduces their tumorigenicity and increases their immunogenicity probably by promoting the cytolitic and antigen presenting activities of leukocytes. We have observed that human colon cancer cells (HT-29) are able to secrete granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor when stimulated with cytokines (IL-1beta and TNF-alpha). In this study we assessed, for the first time, the effects of several anticancer drugs on colony stimulating factor release or apoptosis in HT-29 cells. Cytokine-induced release of granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor was significantly increased by cisplatin and 6-mercaptopurine. Taxol only increased macrophage-colony stimulating factor release while reduced that of granulocyte-colony stimulating factor. No changes in colony stimulating factor secretion were observed after treatment with methotrexate. Only cisplatin and taxol induced apoptosis in these cells. Secretion of colony stimulating factors by colon cancer cells may contribute to the immune host response against them. Anticancer drugs such as cisplatin and 6-mercaptopurine increase colony stimulating factor secretion by cytokine stimulated cancer cells probably through mechanisms different to those leading to cell apoptosis, an effect that may contribute to their anti-neoplasic action.

Relationship between endogenous colony stimulating factors and apoptosis in human colon cancer cells: role of cyclo-oxygenase inhibitors.

1. Nonsteroidal anti-inflammatory drug (NSAID) usage is associated with gastrointestinal inflammatory damage and aggravation of gut inflammatory conditions. NSAIDs also exert a preventive effect against colon cancer that seems to be due to increased colon cell apoptosis. NSAIDs have been shown to modulate the release of colony stimulating factors (CSFs) in some cells. In the present study we analysed the effect of these drugs on secretion of CSFs and apoptosis in human colon epithelial cells (HT-29). 2. HT-29 cells secreted bioactive levels of GM-CSF, G-CSF and M-CSF when stimulated with IL-1ss and TNF-alpha, and diclofenac (10(-7)-10(-4) M), indomethacin (10(-7)-10(-4) M) and sodium salicylate (10(-5)-10(-2) M) induced concentration-dependent increases in GM-CSF secretion. 3. Reduced secretion of G-CSF and M-CSF and increased cell apoptosis were observed with the highest concentrations of these non-selective NSAIDs. 4. No changes in any CSF release or HT-29 cell apoptosis were detected in the presence of the COX-2 selective inhibitor DFP (10(-7)-10(-4) M). 5. Neither the exogenous addition of CSFs nor the blockade of secreted CSFs modified apoptosis in HT-29 cells stimulated with cytokines and/or NSAIDs. 6. These results suggest that colon epithelial cells can contribute to local inflammatory responses by releasing CSFs and thus extend the life span of local leukocytes. Modulation of CSF levels by non-selective NSAIDs may be involved in the pro-inflammatory effects of these agents in the gut.

Microcefalia, opacidad corneal bilateral y holoprosencefalia lobarcongénitas con desarrollo posterior de un rabdomio sarcoma en un paciente expuesto a radiación prenatal / Microcephaly, bilateral corneal opacity and congenital lobar holoprosencephaly with subsequent development of a rhabdomyosarcoma in a patient exposed to prenatal radiation

Introducción. La mayoría de las malformaciones congénitas de causa identificada se corresponden con causas genéticas, multifactoriales o secundarias a algún teratógeno. Muchas malformaciones congénitas tienen un origen desconocido, pero la asociación de diferentes malformaciones permite al menos definir el momento prenatal en que la noxa afectó el desarrollo embrionario o fetal. Caso clínico. Presentamos el caso de un recién nacido de una gestación de 40 semanas, con exposición prenatal a radiaciones ionizantes, hallazgos ecográficos prenatales de microcefalia y cariotipo normal. El neonato presenta opacidades corneales, microcefalia y malformación encefálica compleja. Las opacidades corneales, unidas al glaucoma congénito constituyen un síndrome de Peters que condiciona ceguera. El pacientes fue tratado con trabeculectomía y trasplante corneal bilateral. La microcefalia y la holoprosencefalia lobar con agenesia de cuerpo calloso determinaron un escaso desarrollo psicomotor, hipertonía y una epilepsia con registro electroencefalográfico de hemihipsarritmia, tratada sin éxito con valproato y vigabatrina. A los 21 meses el paciente desarrolla un rabdomiosarcoma embrionario de base de lengua, y fallece en el contexto de una infección sistémica tras la quimioterapia. Conclusiones. La asociación de malformaciones descrita no ha sido referida anteriormente en las bases de datos internacionales. Aunque la posible relación causal entre radioexposición prenatal y el cuadro clínico no puede demostrarse, la posibilidad teratogénica y carcinogénica de dicha exposición llevan a insistir en evitar que las mujeres gestantes o que desconocen su estado gestacional estén presentes en las salas de radiodiagnóstico (AU)

A cerebral nitrergic pathway modulates endotoxin-induced changes in gastric motility.

1. This study analyses the neural pathway involved in the modulation of gastric motor function by stress. 2. Systemic administration of low doses of endotoxin (40 microg kg(-1), i.v.) prevents the increase in gastric tone induced by 2-deoxy-D-glucose (200 mg kg(-1), i.v., 2-DG) in urethane-anaesthetized rats. 3. Functional inhibition of afferent neurones by systemic administration of capsaicin (20+30+50 mg kg(-1), i.m.) in adult rats prevented the inhibitory effects of endotoxin. 4. Pre-treatment with the nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), both i.v. (10 mg kg(-1)) and i.c. (200 microg rat(-1)), prevented the inhibitory effects of endotoxin on gastric tone induced by 2-DG. 5. Immunohistochemical studies show Fos expression in the dorsal vagal complex (DVC) of the brainstem of 2-DG-treated animals. Peripheral administration of endotoxin (40 microg kg(-1), i.p.) increased the number of Fos-immunoreactive cells induced by 2-DG, both in the nucleus tractus solitarii (NTS) and in the dorsal motor nucleus (DMN) of the DVC. Pre-treatment with L-NAME prevented the increase in Fos expression induced by endotoxin in both nuclei. 6. Endotoxin (40 microg kg(-1), i.p.) increased Ca(2+)-dependent nitric oxide synthase (cNOS) activity in the brainstem. Addition of 7-nitroindazole (600 microM, 7-NI) to the assay significantly inhibited the increase in cNOS activity caused by endotoxin. No change in NOS activity of any isoform was observed in the stomach of animals treated with endotoxin. 7. The present study suggests that inhibition of gastric motor function by low doses of endotoxin involves activation of capsaicin-sensitive afferent neurones and neuronal NOS in the brainstem.