Ontogeny of intestinal epithelium immune functions: developmental and environmental regulation.

Intestinal mucosa integrates primary digestive functions with immune functions such as pathogen surveillance, antigen transport and induction of mucosal immunity and tolerance. Intestinal adaptive immunity is elicited in organized mucosa-associated lymphoid tissue (O-MALT) that is composed of antigen-presenting cells and lymphocytes and achieved by effector cells widely distributed in mucosa (diffuse MALT or D-MALT). Interaction between the intestinal epithelium, the O-MALT and the diffuse MALT plays a critical role in establishing an adequate immune response. In regions associated to O-MALT, lympho-epithelial cross-talks lead to acquisition of a specific epithelial phenotype that contributes to O-MALT organization and functionality. Beyond the expression of several innate immune functions, the intestinal epithelium may directly take up and present antigens due to the expression of major histocompatibility complex (MHC) and MHC-related molecules. A complex genetic program that will be outlined in the present review controls the development of immune functions of the intestinal epithelium. The effect of environmental signals on the modulation of this ontogenetic program during development and neonatal life, from bioactive components of amniotic fluid to lactation and bacterial colonization, will be discussed.

Inhibition of Giardia intestinalis by extracellular factors from Lactobacilli: an in vitro study.

The aim of the present work was to evaluate the effect of spent culture supernatants of different strains of lactobacilli on giardia trophozoites. The growth of Giardia intestinalis strain WB, as well as the attachment to the human intestinal epithelial cell line Caco-2, was evaluated by using proliferation and adhesion assays with radiolabeled parasites. In addition, scanning electron microscopy and flow cytometric analysis were performed. The effect of spent culture supernatants from lactobacilli was strain dependent. Lactobacillus johnsonii La1 significantly inhibited the proliferation of G. intestinalis trophozoites. Although the effect was strongly pH dependent, it was not simply due to lactic acid. According to flow cytometric analysis, trophozoites were arrested in G(1) phase but neither significant necrosis nor apoptosis could be detected. Bacterial cells or their spent culture supernatants were unable to modify trophozoite attachment to Caco-2 cells. However, trophozoites treated with spent culture supernatants had little, if any, proliferative capacity. These results suggest that La1 produces some substance(s) able to inhibit proliferation of Giardia trophozoites. Partial characterization of the factors involved in the antigiardiasic action showed that they have a low molecular mass and are inactivated by heating. On this basis, it seems worthwhile to explore how colonization of the proximal small bowel with these lactic acid bacteria could interfere with giardiasis in vivo.

Endothelin: role in hypertension.

Endothelins (ET) are 21-aminoacid peptides produced ubiquitously, which were discovered originally as endothelial products. These peptides may play important roles in cardiovascular physiology and pathophysiology. As the pathophysiologic roles of endothelins in cardiovascular disease become increasingly apparent, the potential therapeutic use of endothelin antagonists or endothelin converting enzyme inhibitors is recognized. The main endothelin produced by the endothelium is ET-1. Endothelin-1 is overexpressed in the vascular wall of salt-dependent models of hypertension, such as DOCA-salt hypertensive rats, DOCA-salt-treated spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats, and in stroke-prone SHR, angiotensin II-infused rats and 1-kidney 1 clip Goldblatt hypertensive rats, but not in SHR, 2-K 1C hypertensive rats or L-NAME-treated rats. The vasoconstrictor effect of ET-1 may contribute to blood pressure elevation and its growth-promoting action to vascular hypertrophy in the hypertensive models which overexpress ET-1 in blood vessels. In rats without generalized activation of the endothelin system, expression of ET-1 is often enhanced in coronary arteries, which suggests a role for ET-1 in myocardial ischemia in hypertension. In rats overexpressing ET-1, ETA/B and ETA-selective antagonists lowered blood pressure slightly, and significantly reduced vascular growth, particularly of small arteries, suggesting that ET-1 has a direct effect on growth. Protection from renal injury and from stroke has also been demonstrated in hypertensive rats treated with endothelin antagonists. In normotensive human subjects endothelin-dependent tone can be shown in the forearm. In a study of mild hypertensive patients, the ETA/B antagonist bosentan reduced blood pressure similarly to an ACE inhibitor. Moderate to severe hypertensive patients presented enhanced expression of ET-1 mRNA in the endothelium of subcutaneous resistance arteries. In blacks with familial hypertension increased plasma levels of endothelin have been found. Thus, ET-1 may play a role in some experimental hypertensive models and in human hypertension. In summary, endothelial ET-1 may be overexpressed in the more severe forms of hypertension, and in certain special populations which may respond particularly well to endothelin antagonism. Endothelin antagonists may prove to be effective disease-modifying agents if in future clinical trials they are shown clinically to blunt vascular growth and endothelial dysfunction, reduce stroke and exert the cardioprotective and renal protective effects already reported in experimental hypertension. These agents could contribute to reduce the long-term complications of hypertension, which remains to be demonstrated in humans.

[Post-sectional antral peptic ulcer and antrofundic re-anastomosis in rats (manifestation of a probable antrofundic neuroendocrine center)]. / Ulcera péptica antral postsección y reanastomosis antrofúndica en la rata (puesta de manifiesto de un probable centro neuroendócrino antrofúndico).

The antrum-fundic section and re-anastomosis (AESR), liberates, in Wistar male rats, genuine antral peptic ulcers. They start within 20 days. They are progressive evolution, penetrating into all gastric walls. Between 7 and 8 months, they involve near organs (spleen, liver, pancreas) and produce a great inflammatory reaction of the peripancreatic ganglions. The antral peptic ulcer is induced if the gastric lesser curvature's nerves are sectioned and a concomitant pyloroplasty is done or not. The gastric hemisection, if anterior or posterior, break out the peptic ulcer only on the same side of the antrum-fundic interruption. In all this situations, except in cases of concomitant pyloroplasty, it is proved a pronounced and significantly increase of the gastric (g/kg), but not pancreatic index. In the AFSR series with nervous section on the lesser curvature and without pyloroplasty, the percentage of antral peptic ulcers in 56%. It is postulated the probably existence, at an antrum-fundic level, of a neuroendocrine center. Its nullification or disturbance by the section and re-anastomosis procedure could generate the antral ulcer and other histologic changes (increase of the "G" cells, hyperplasia of the parietal, ECL and "A like" cells) by one or various hypothetical ways: 1. Direct action, nullifying the normal blocking function of somatostative over the "G" cells and or parietal cells. 2. Disturbing or nullifying the motor pump effect of the gastric antrum, and on this way, enhancing the duodenum-gastric reflux with all know deleterious effects of the bile in the antrum particularly in an acid milieu. 3. Modifying, in the opposite direction, the sensitivity by one hand, of the "G" cells mass and by the other one, of the parietal, ECL and "A like" cells. The depression of the fundic sensitivity will induce the hyperplasia of the "G" cells, the hypersecretion of gastrin and, "a posteriori", all the secretory effects and trophic characteristic of it. 4. Disturbing the prostaglandins secretion, perhaps through a deficit of the nervous innervation, with the resulting epiphenomenon of a cytoprotection deficit mediated through the mucus and bicarbonate production. It is probably that the proposed physiopathogenic mechanism are associated and that the final result, the antral peptic ulcer is the consequence of an increase of the aggressive factors (acid, bile) and a concomitant depression of the defensive factors (cytoprotection), starting normally by the prostaglandins through the mucus and bicarbonate secretion.

Ulcera péptica antral postsección y reanastomosis antrofúndica en la rata (puesta de manifiesto de un probable centro neuroendócrino antrofúndico). / [Post-sectional antral peptic ulcer and antrofundic re-anastomosis in rats (manifestation of a probable antrofundic neuroendocrine center)]

The antrum-fundic section and re-anastomosis (AESR), liberates, in Wistar male rats, genuine antral peptic ulcers. They start within 20 days. They are progressive evolution, penetrating into all gastric walls. Between 7 and 8 months, they involve near organs (spleen, liver, pancreas) and produce a great inflammatory reaction of the peripancreatic ganglions. The antral peptic ulcer is induced if the gastric lesser curvatures nerves are sectioned and a concomitant pyloroplasty is done or not. The gastric hemisection, if anterior or posterior, break out the peptic ulcer only on the same side of the antrum-fundic interruption. In all this situations, except in cases of concomitant pyloroplasty, it is proved a pronounced and significantly increase of the gastric (g/kg), but not pancreatic index. In the AFSR series with nervous section on the lesser curvature and without pyloroplasty, the percentage of antral peptic ulcers in 56

. It is postulated the probably existence, at an antrum-fundic level, of a neuroendocrine center. Its nullification or disturbance by the section and re-anastomosis procedure could generate the antral ulcer and other histologic changes (increase of the [quot ]G[quot ] cells, hyperplasia of the parietal, ECL and [quot ]A like[quot ] cells) by one or various hypothetical ways: 1. Direct action, nullifying the normal blocking function of somatostative over the [quot ]G[quot ] cells and or parietal cells. 2. Disturbing or nullifying the motor pump effect of the gastric antrum, and on this way, enhancing the duodenum-gastric reflux with all know deleterious effects of the bile in the antrum particularly in an acid milieu. 3. Modifying, in the opposite direction, the sensitivity by one hand, of the [quot ]G[quot ] cells mass and by the other one, of the parietal, ECL and [quot ]A like[quot ] cells. The depression of the fundic sensitivity will induce the hyperplasia of the [quot ]G[quot ] cells, the hypersecretion of gastrin and, [quot ]a posteriori[quot ], all the secretory effects and trophic characteristic of it. 4. Disturbing the prostaglandins secretion, perhaps through a deficit of the nervous innervation, with the resulting epiphenomenon of a cytoprotection deficit mediated through the mucus and bicarbonate production. It is probably that the proposed physiopathogenic mechanism are associated and that the final result, the antral peptic ulcer is the consequence of an increase of the aggressive factors (acid, bile) and a concomitant depression of the defensive factors (cytoprotection), starting normally by the prostaglandins through the mucus and bicarbonate secretion.

Pirenzepine as anti-inflammatory drug in a model of experimental colitis in rat.

Pirenzepine has been widely used for the treatment of gastric and duodenal ulcer. In this work we have proved that this drug could prevent the inflammatory reaction induced in the colon with an intraluminal stimuli as the acetic acid. These data suggest the cholinergic participation in the inflammatory colonic response.

Prevention of carrageenan-induced ulcerative colitis in the guinea pig by serum of bovine colostrum

La colitis ulcerosa inducida por administración oral de caragenina degradada en cobayos constituye un modelo experimental reinteradamente utilizado con el propósito de aclarar los mecanismos patogénicos participantes en la enfermedad inflamatoria intestinal. Se ha pretendido identificar a los factores agresores de la mucosa colónica enfatizando el estudio de cepas bacterianas asociadas al daño mucoso. El propósito del presente trabajo fue jerarquizar la importancia de los mecanismos protectores en la mucosa colónica. Los animales fueron divididos en tres grupos. Unos recibieron caragenina degradada al 5% en el agua de bebida. El segundo grupo recibió calostro bovino (100mg% p/v) junto con la caragenina degradada. Finalmente, un tercero recibió cultivos de Lactobacilos (10**7 células/ml) simultáneamente con la caragenina. Se realizarón evaluaciones clínicas, bacteriológicas y anatomopatológicas. El grupo de animales que recibió exclusivamente caragenina degradada desarrolló la enfermedad colónica con un aumento de bacterias coliformes fecales y disminución de bacterias anaerobias gram positivas. Los grupos que recibieron colostro o Lactobacilos simultáneamente con la caragenina se mantuvieron libres de enfermedad durante el tiempo que duró el experimento, mostrando un aumento significativo de bacterias anaerobias gram positivas. El mecanismo protector que previno el desarrollo de la enfermedad podría haberse logrado a través de una condición ecológica luminal óptima, mejorando la barrera mucosa o/y modulando la reacción inflamatoria-inmunológica del huésped

Pirenzepine as anti-inflammatory drug in a model of experimental colitis in rat.

Pirenzepine has been widely used for the treatment of gastric and duodenal ulcer. In this work we have proved that this drug could prevent the inflammatory reaction induced in the colon with an intraluminal stimuli as the acetic acid. These data suggest the cholinergic participation in the inflammatory colonic response.

Prevention of carrageenan-induced ulcerative colitis in the guinea pig by serum of bovine colostrum

La colitis ulcerosa inducida por administración oral de caragenina degradada en cobayos constituye un modelo experimental reinteradamente utilizado con el propósito de aclarar los mecanismos patogénicos participantes en la enfermedad inflamatoria intestinal. Se ha pretendido identificar a los factores agresores de la mucosa colónica enfatizando el estudio de cepas bacterianas asociadas al daño mucoso. El propósito del presente trabajo fue jerarquizar la importancia de los mecanismos protectores en la mucosa colónica. Los animales fueron divididos en tres grupos. Unos recibieron caragenina degradada al 5% en el agua de bebida. El segundo grupo recibió calostro bovino (100mg% p/v) junto con la caragenina degradada. Finalmente, un tercero recibió cultivos de Lactobacilos (10**7 células/ml) simultáneamente con la caragenina. Se realizarón evaluaciones clínicas, bacteriológicas y anatomopatológicas. El grupo de animales que recibió exclusivamente caragenina degradada desarrolló la enfermedad colónica con un aumento de bacterias coliformes fecales y disminución de bacterias anaerobias gram positivas. Los grupos que recibieron colostro o Lactobacilos simultáneamente con la caragenina se mantuvieron libres de enfermedad durante el tiempo que duró el experimento, mostrando un aumento significativo de bacterias anaerobias gram positivas. El mecanismo protector que previno el desarrollo de la enfermedad podría haberse logrado a través de una condición ecológica luminal óptima, mejorando la barrera mucosa o/y modulando la reacción inflamatoria-inmunológica del huésped (AU)