There is increasing scientific and commercial interest in using beneficial microorganisms (i.e., probiotics) to enhance intestinal health. Of the numerous microbial strains examined, Lactobacillus rhamnosus GG has been most extensively studied. Daily intake of L. rhamnosus GG shortens the course of rotavirus infection by mechanisms that have not been fully elucidated. Comparative studies with germfree and conventional rats have shown that the microbial status of an animal influences the intestinal cell kinetics and morphology. The present study was undertaken to study whether establishment of L. rhamnosus GG as a mono-associate in germfree rats influences intestinal cell kinetics and morphology. L. rhamnosus GG was easily established in germfree rats. After 3 days of mono-association, the rate of mitoses in the upper part of the small intestine (jejunum 1) increased as much as 14 and 22% compared to the rates in germfree and conventional counterparts, respectively. The most striking alteration in morphology was an increase in the number of cells in the villi. We hypothesis that the compartmentalized effects of L. rhamnosus GG may represent a reparative event for the mucosa.

The pathophysiological mechanisms behind rotavirus-induced diarrhoea still remain incomplete. Current views suggest that the non-structural protein 4 (NSP4) of rotavirus and the enteric nervous system (ENS) participate in water secretion and diarrhoea. In the present work the role of nitric oxide (NO) in rotavirus infection and disease has been studied in vitro, mice and humans. Incubation of human intestinal epithelial cells (HT-29) with purified NSP4 but not with infectious virus produced NO2/NO3 accumulation in the incubation media. The NSP4-induced release of NO metabolites occurred within the first minutes after the addition of the toxin. Mice infected with murine rotavirus (strain EDIM) accumulated NO2/NO3 in the urine at the onset for diarrhoea. Following rotavirus infection, inducible nitric oxide synthetase (iNOS) mRNA was upregulated in ileum, but not in duodenum or jejunum of newborn pups within 5 days post-infection. A prospective clinical study including 46 children with acute rotavirus infection and age-matched controls concluded that rotavirus infection stimulates NO production during the course of the disease (P < 0.001). These observations identify NO as an important mediator of host responses during rotavirus infection.

In contrast to humans, adult but not infant small animals are resistant to rotavirus diarrhea. The pathophysiological mechanism behind this age-restricted diarrhea is currently unresolved, and this question was investigated by studying the secretory state of the small intestines of adult mice infected with rotavirus. Immunohistochemistry and histological examinations revealed that rotavirus (strain EDIM) infects all parts of the small intestines of adult mice, with significant numbers of infected cells in the ilea at 2 and 4 days postinfection. Furthermore, quantitative PCR revealed that 100-fold more viral RNA was produced in the ilea than in the jejuna or duodena of adult mice. In vitro perfusion experiments of the small intestine did not reveal any significant changes in net fluid secretion among mice infected for 3 days or 4 days or in those that were noninfected (37 ؎ 9 l · h ؊1 · cm ؊1 , 22 ؎ 13 l · h ؊1 · cm ؊1 , and 33 ؎ 6 l · h ؊1 · cm ؊1 , respectively) or in transmucosal potential difference (4.0 ؎ 0.3 mV versus 3.9 ؎ 0.4 mV), a marker for active chloride secretion, between control and rotavirus-infected mice. In vivo experiments also did not show any differences in potential difference between uninfected and infected small intestines. Furthermore, no significant differences in weight between infected and uninfected small intestines were found, nor were any differences in fecal output observed between infected and control mice. Altogether, these data suggest that rotavirus infection is not sufficient to stimulate chloride and water secretion from the small intestines of adult mice.Rotavirus (RV) is an important cause of acute gastroenteritis in young children and is also an important pathogen in several animal species. In contrast to the situation in humans, where symptomatic reinfections do occur in adults (1,23,30), most adult small animals show an age-dependent resistance to symptomatic RV infections (4,5,12,38). The pathophysiological mechanisms behind this age-dependent resistance are currently unresolved, but it has been proposed that they are due to compensatory fluid absorption by the larger colons of older animals. It has also been suggested that the low expression of proteolytic enzymes in newborn mice is a possible mechanism (13). Furthermore, an interesting observation is that the agedependent resistance in adult mice correlates with the lack of chemokine responses (28). We have previously shown that in infant mice, rotavirus infection gives rise to an increased fluid secretion and an increased transmucosal potential difference (PD), a marker for active chloride secretion (16). The aim of this study was to investigate the secretory state of the small intestines of adult mice. Using established (16,32,33) in vivo and in vitro methods, we measured net fluid transport and PD and found that in spite of virus infection, there was no evidence for chloride or water secretion from the small intestines of murine rotavirus-infected adult mice. This suggests that rotavirus infection in adult mice, in...

The aim of this study was to investigate the cell kinetics and epithelial structure in the intestinal tract in cohorts of young and old germfree (GF) and conventional AGUS rats of both sexes. The young rats were 35 days old and the old rats were 190 9 60 days old. All rats were fed the same diet and water ad libitum. At the beginning of the experiments, the rats were starved for 2.5 h. Thereafter, all animals were given vincristine 1 mg:kg intraperitoneally (i.p.) 4 h before they were sacri ced. Specimens from eight parts of the intestine were investigated. The cell kinetic parameters determined in the small intestine were percentage of cells in mitosis, growth fraction (GrF), total number of cells in the crypts and villi, depth of the crypts, height of villi and the crypt:villus (C:V) ratio. In the colon, the percentage of cells in mitosis, GrF and the total number of cells in the crypts, as well as depth of the crypts, were determined. Taken together, the effect of gender was most pronounced in the upper part of the small intestine, the effect of age was most pronounced in the lower small intestine, whereas the effect of microbial status was relatively more pronounced in the duodenum and in the large intestine. Thus, these factors are acting in a compartmentalized manner in the intestinal tract. In conclusion, gender, age and microbial status have to be taken into account when the compounds and conditions in uencing the intestinal morphometric parameters are studied.

No abstract