Recurrent acute thermal lesion induces esophageal hyperproliferative premalignant lesions in mice esophagus.

Hot beverage consumption is a risk factor for esophageal squamous cell carcinoma, but the underlying mechanisms are still unknown. We developed an experimental mouse model to understand the mechanism of thermal lesion to esophageal carcinogenesis. Female BALB/c mice were treated by gavage with water at different temperatures three times a week and nitrosamines in the drinking water. Water at 70°C, but not at lower temperatures, initially induced an esophageal necrosis that healed and became resistant to necrosis after further administrations. However, when 70°C water was associated with N-nitrosodiethylamine at doses above 1 ppm, there was interference in epithelial regeneration, allowing recurrent thermal injury and inflammation. Recurrent thermal injury resulted in hyper proliferative premalignant lesions being induced earlier (at 4 weeks) and at a higher frequency (4-fold increase at 16 weeks) when compared to mice treated with NDEA only. Ki-67 immunostaining revealed that recurrent thermal injury induced basal cell proliferation resulting in the expansion of epithelial basal cells, confirmed by the increase in cytokeratin 14 positive cells with concomitant reduction of differentiated cytokeratin 5 positive cells. We conclude that recurrent thermal lesion may act as a tumor promoter though a strong proliferation stimulus of esophageal epithelial basal cells.

Neutrophil migration induced by IL-1beta depends upon LTB4 released by macrophages and upon TNF-alpha and IL-1beta released by mast cells.

In the present study, we investigate whether mast cells and macrophages are involved in the control of IL-1beta-induced neutrophil migration, as well as the participation of chemotactic mediators. IL-1beta induced a dose-dependent neutrophil migration to the peritoneal cavity of rats which depends on LTB(4), PAF and cytokines, since the animal treatment with inhibitors of these mediators (MK 886, PCA 4248 and dexamethasone respectively) inhibited IL-1beta-induced neutrophil migration. The neutrophil migration induced by IL-1beta is dependent on mast cells and macrophages, since depletion of mast cells reduced the process whereas the increase of macrophage population enhanced the migration. Moreover, mast cells or macrophages stimulated with IL-1beta released a neutrophil chemotactic factor, which mimicked the neutrophil migration induced by IL-1beta. The chemotactic activity of the supernatant of IL-1beta-stimulated macrophages is due to the presence of LTB(4), since MK 886 inhibited its release. Moreover, the chemotactic activity of IL-1beta-stimulated mast cells supernatant is due to the presence of IL-1beta and TNF-alpha, since antibodies against these cytokines inhibited its activity. Furthermore, significant amounts of these cytokines were detected in the supernatant. In conclusion, our results suggest that neutrophil migration induced by IL-1beta depends upon LTB(4) released by macrophages and upon IL-1beta and TNFalpha released by mast cells.

Meningoencefalocele etmoidal / Meningoencefhalocele etmoidal

Se presenta un caso de meningoencefalocele etmoidal y se revisa la bibliografía de esta rara entidad. La incidencia de los encefaloceles es de 0,5/10.000 nacidos vivos, siendo el 80% de los mismos occipitales y el 20% restante divididos entre cefaloceles frontal y parietal. El encefalocele representa aproximadamente el 10 a 15% de los defectos del tubo neural. La patogénesis aún es poco clara, existiendo distintas interpretaciones desde 1938. El pronóstico y el tratamiento para los encefaloceles depende de las malformaciones asociadas, del tamaño, del sitio, del contenido del defecto y de la facilidad de la corrección quirúrgica. La ecografía 4D ha permitido en los últimos tiempos consolidar el diagnóstico de malformaciones fetales ya descritas en ecografía 2D. La ecografía 4D (tiempo real) nos permitió evaluar con detalle la patología descrita orientándonos al diagnóstico de meningocele etmoidal. La técnica facilita la adquisición de imágenes en distintos planos de rotación, distintos ejes y secuencias de cine. La posibilidad que los padres vean con el detalle 4D tiempo real la patología de su hijo nos dio la posibilidad de entablar una mejor relación médico-paciente, una aceptación por parte de los mismos de la patología y un seguimiento detallado del caso comunicado

A case of meningoencefhalocele etmoidal is presented and the bibliography of this unusual case is checked. The incidence of oncefhaloceles is 05/10.000 (born alive), being the 80% of the occipitals and the 20% remaining are divided into frontal and parietal encefhalocele. The encefhalocele represents approximately the 10 and 15% of the neural tube's defects. This is still not clear because there are many interpretations since 1938. The treatment depends in the malformations, size, site, defect contains and the surgery correction facility. The 4D scan allows consolidating the diagnostic of fetal malformations that 2D scan describe. The 4D scan (real time) has allowed the evaluation in detail of the following pathology, aimed at the diagnostic of meningocele etmoidal. The technique provides images in deferent's rotation plans, axis and video sequences. The possibility for the parents seeing in detail the pathology of his son in the real time 4D, gave us the possibility to make a better doctor-patient relationship acceptance of the palotology and a better monitoring of the case

Tumour necrosis factor-alpha and leukotriene B(4) mediate the neutrophil migration in immune inflammation.

1. We investigated the mediators responsible for neutrophil migration induced by ovalbumin (OVA) in immunized mice and the mechanisms involved in their release. 2. OVA administration promoted dose- and time-dependent neutrophil migration in immunized, but not in non-immunized mice, which was mediated by leukotriene B(4) (LTB(4)) and tumour necrosis factor (TNF)alpha, since it was inhibited by LTB(4) synthesis inhibitor (MK 886) or by LTB(4) receptor antagonist (CP 105,696), by dexamethasone and by antiserum to TNFalpha (82, 85, 63 and 87%, respectively). Confirming TNFalpha involvement, OVA challenge in immunized p55 TNF receptor deficient mice (p55(-/-)) did not promote neutrophil migration (control: 2.90 +/- 0.68; p55(-/-): 0.92+/-0.23 x 10(6) neutrophils cavity(-1)). 3. OVA-stimulated peritoneal cells from immunized mice released a neutrophil chemotactic factor which mimicked, in naive mice, neutrophil migration induced by OVA. 4. Supernatant chemotactic activity is due to TNFalpha and LTB(4), since its release was inhibited by MK 886 (93%) and dexamethasone (90%), and significant amounts of these mediators were detected. 5. TNFalpha and LTB(4) released by OVA challenge seem to act through a sequential mechanism, since MK 886 inhibited (88%) neutrophil migration induced by TNFalpha. Moreover, peritoneal cells stimulated with TNFalpha released LTB(4). 6. CD(4)(+) T cells are responsible for TNFalpha release, because the depletion of this subset prevented the release of TNFalpha (control: 400 +/- 25; immunized: 670 +/- 40; CD(4)(+) depleted: 435 +/- 18 pg ml(-1)). 7. In conclusion, neutrophil migration induced by OVA depends on TNFalpha released by CD(4)(+) cells, which acts through an LTB(4)-dependent mechanism.

A role for IL-18 in neutrophil activation.

IL-18 expression and functional activity has been identified in several autoimmune and infectious diseases. To clarify the potential role of IL-18 during early innate immune responses, we have explored the capacity of IL-18 to activate neutrophils. Human peripheral blood-derived neutrophils constitutively expressed IL-18R (alpha and beta) commensurate with the capacity to rapidly respond to IL-18. IL-18 induced cytokine and chemokine release from neutrophils that was protein synthesis dependent, up-regulated CD11b expression, induced granule release, and enhanced the respiratory burst following exposure to fMLP, but had no effect upon the rate of neutrophil apoptosis. The capacity to release cytokine and chemokine was significantly enhanced in neutrophils derived from rheumatoid arthritis synovial fluid, indicating differential responsiveness to IL-18 dependent upon prior neutrophil activation in vivo. Finally, IL-18 administration promoted neutrophil accumulation in vivo, whereas IL-18 neutralization suppressed the severity of footpad inflammation following carrageenan injection. The latter was accompanied by reduction in tissue myeloperoxidase expression and suppressed local TNF-alpha production. Together, these data define a novel role for IL-18 in activating neutrophils and thereby promoting early innate immune responses.

[Study of GH in patients suffering from sexual impotence and abnormal glucose tolerance test (author's transl)]. / Comportamento del GH in un gruppo di pazienti con intolleranza glucidica ed impotenza erettiva.

The correlation between dopamine-serotonin systems and sexual behaviour and the influence of these two amines on GH secretion is well known. We evaluated GH responses (maximum increase (delta) after OGTT and mean increase (delta M) after insulin test) in a group of 32 males suffering from erective impotence with impotence with abnormal reaction to a glucose tolerance test. Results were compared with those obtained in a group of 13 normal controls. No significant difference in basal values and dynamic responses between the two groups was present. Our data suggest that GH doesn't decrease the tolerance to glucose in these patients. The abnormal values observed during a glucose tolerance test may be due to some agent involved in the interactions between limbic system, ventral lateral and ventral medial hypothalamic nuclei and dopamine-serotonin systems. No influence by this system on GH secretion is evident.