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Role of anaerobic flora in the translocation of aerobic and facultatively anaerobic intestinal bacteria.

It is thought that the normal enteric microflora acts not only to prevent intestinal colonization but also to prevent subsequent systemic dissemination of ingested, potentially pathogenic bacteria. To determine the relative roles of specific components of the intestinal bacterial flora in bacterial translocation out of the gut, mice were given various antimicrobial agents to selectively eliminate specific groups of intestinal bacteria. The cecal flora and the translocating bacteria in mesenteric lymph nodes were monitored both before and after oral inoculation with antibiotic-resistant Escherichia coli C25. Orally administered streptomycin selectively eliminated cecal facultative gram-negative bacilli, orally administered bacitracin-streptomycin eliminated all cecal bacterial species except low numbers of aerobic sporeformers, and parenterally administered metronidazole selectively eliminated cecal anaerobic bacteria. Compared with control mice, only metronidazole-treated mice had significantly increased rates of dissemination of intestinal bacteria into mesenteric lymph nodes, indicating that the exclusive absence of anaerobic bacteria facilitated the translocation of the intestinal facultative bacteria. In a parallel experiment with streptomycin-resistant E. coli C25 as a marker, parallel results were obtained. Metronidazole increased the translocation of the marker strain and the indigenous strains of intestinal bacteria. Thus, anaerobes appeared to play a key role in confining indigenous bacteria to the gut. However, intestinal colonization and translocation of E. coli C25 occurred most readily after bacitracin-streptomycin treatment, suggesting that in addition to anaerobic bacteria, other bacterial groups may play a role in limiting the intestinal colonization and extraintestinal dissemination of E. coli C25.

Administration, Oral↗

[Synchronous or metachronous extragastric neoplasms associated with gastric neoplasia. Common pathogenesis of gastric intestinal and colonic carcinoma?].

Coexistence of syncronous or metacronous extragastric carcinomas, particularly of the colon and small bowel may favour the hypothesis of a common origin with gastric carcinoma. Three cases of colonic carcinoma coexisting with early gastric cancer, are presented. The etiopathogenesis of intestinal-type gastric cancer and colonic cancer are discussed in the light of a possible common mechanism.

Aged↗

Comparative in vitro permeability of human vaginal, small intestinal and colonic mucosa.

Our previous experience with a continuous flow-through perfusion system has demonstrated its usefulness for studying diffusion kinetics of drugs across small intestinal mucosa for bioavailability/bioequivalence (BA/BE) studies. During the last decade, delivery of drugs to the colon for systemic absorption as well as for local delivery in certain colonic diseases, has been extensively investigated. For this reason, we sought to assess the in vitro comparative permeability of human vaginal, small intestinal and colonic mucosa using a flow-through perfusion method. It was clear from our studies that human colonic epithelium was statistically significantly (P<0.05) more permeable to water, 17beta-estradiol, arecoline and arecaidine than intestinal mucosa. However, both these mucosae were statistically significantly less permeable to the above four permeants than human vaginal mucosa. As previously shown for small intestinal mucosa, the low in vitro permeability of colonic mucosa to drugs with molecular weight >300Da may necessitate using other epithelial membranes, e.g. vaginal mucosa, as alternative barriers for in vitro BA/BE studies. We also concluded that the flow-through mucosal perfusion system used in our laboratory is therefore also potentially useful for determining the permeability of a therapeutic agent from the colon for registration purposes.

Adult↗

Identification of interstitial cells of Cajal. Significance for studies of human small intestine and colon.

BACKGROUND: Interstitial cells of Cajal (ICC) were described a century ago by Ramón y Cajal a.o. as primitive neurons in the intestines. In the period 1900-1960 a large number of light microscopical studies of ICC were published, in which ICC were identified by heir characteristic morphology. After 1960 electron microscopical studies emphasized similarities between ICC and fibroblasts. In our early studies of ICC in the external musculature of mouse small intestine, we identified ICC by their characteristic morphology and topography, and we analyzed the relation between ICC, autonomic nerves and smooth muscle. These studies strongly suggested that ICC were fundamental regulators of external muscle function. These hypotheses have since been supported by independent morphological and electrophysiological evidence, strongly suggesting a pacemaker role of some ICC populations as well as other regulatory functions (mechanoreceptive, mediating inhibitory nervous input). In spite of this possible fundamental importance for G-I motility, ICC have not been adequately described or even identified in human intestine, and hence, never included in ultrastructural studies of G-I neuropathology. This survey presents the concepts of ultrastructure necessary for identification and morphological studies of ICC in human intestine. METHODOLOGY: Several light microscopical methods have been claimed selective for intestinal ICC (and nerves), including vital methylene blue, Golgi methods, silver impregnations and ZIO-methods. Unfortunately, even the most reliable of them (ZIO, vital methylene blue) do not work at all in some animal species and in some, regions of the intestinal wall. In our hands, the best results have been obtained in mouse small intestine with vital methylene blue staining (AP only) and with ZIO methods (all levels of the musculature). None of them have yet proved their value in human intestine, although we have occasionally stained ICC-SMP in human colon with ZIO methods. Optimal ultrastructural preservation of ICC for TEM studies in laboratory animals, has been achieved by fixation by vascular perfusion. In humans, the ultrastructural preservation was satisfactory, but not ideal, after optimizing the immersion fixatives (Karnovsky-types, addition of picrate). RESULTS AND DISCUSSION: General architecture of musculature externa. ICC differ markedly in their organization and ultrastructure from one part of the gut and from one region to another. For understanding the extent and distribution of ICC plexuses it is therefore critical to preserve a stringency and uniformity with respect to terminologies and descriptions of topography. Auerbach's plexus (AP) designates the ganglionated plexus between the main muscle layers in small and large intestine, whereas we prefer to use the term myenteric plexus for all nerves in the external muscle. The deep muscular plexus (DMP) designates the two-dimensional, non-ganglionated nerve plexus between the thick outer and thin inner subdivision of the circular muscle layer in the small intestine. In our material a similar plexus was not present in colon. The submuscular plexus (SMP) indicates the non-ganglionated, two-dimensional nerve plexus present at the submucosal surface of the colonic circular muscle. The circular muscle in small- and large intestine of large animals (dogs, humans) is organized into lamellae, separated by main septa piercing the whole layer. Both in the small intestine and colon the innermost circular muscle cells, are smaller, and, particularly in colon, more irregular than the bulk of the circular muscle. Identification of ICC in laboratory animals. By TEM ICC are distinguishable as a separate cell type in the small- and large intestine of all species investigated.(ABSTRACT TRUNCATED)

Animals↗

The postnatal development of the alimentary canal in the opossum. III. Small intestine and colon.

The duodenum of the newborn opossum exhibits a patent lumen containing scattered elongate villi, whereas the distal segments of the small intestine are smaller in diameter and are filled with short immature villi. The muscularis externa through the small intestine consists of a single layer of myoblasts. Interposed between the intestinal lining epithelium and the muscularis externa is an extensive capillary bed that occupies a considerable proportion of the intestinal wall. Additional villi appear to form during the postnatal period as a result of evaginations of the epithelium, together with underlying connective tissue and vasculature, into the intestinal lumen. Intestinal glands are not observed until 8.5cm, and are shallow in depth even in the adult. The epithelium of the entire small intestine is modified for absorption until just prior to weaning. The principal intestinal lining cells show an extensive apical endocytic complex, large supranuclear vacuoles and numerous cytoplasmic inclusions. Intestinal epithelial cells of the colon also appear to be modified for absorption during the first two weeks after birth. Although goblet cells and Paneth cells are present during the suckling period, they do not comprise a significant population in the intestinal epithelium until after weaning. In contrast to the small intestine, goblet cells are numerous in the colon by the ninth postnatal day. The significance of macromolecular absorption and the possibility of passive immunity being transmitted in the opossum during suckling are discussed and related to similar events that occur in the slckling young of several eutherian species. The possible functional significance of two large membranes that develop in the lamina propria of the intestines after weaning also is discussed.

Animals↗

Comparative intestinal and colonic absorption of [4-14C] cholesterol in the rat.

[4(-14)C] Cholesterol was administered as an aqueous emulsion with triolein and dry non-fat milk either directly into the upper duodenum or into the ileocaecal junction of lymph duct cannulated rats. Lymph flow rates were similar in the two groups of animals. Whereas ca. 53% of the administered tracer dose of cholesterol was absorbed when introduced into the upper small intestine, only 0.06% appeared in lymph when administered into the caecum. Furthermore, less than 0.01% of the administered isotope was detected in urine and blood. The data demonstrate that the large intestine does not contribute significantly to the absorption of exogenous cholesterol in the rat.

Animals↗

[Cell kinetics in intestinal metaplasia and gastric carcinoma].

48 specimens of gastric mucosa, including those of normal mucosa, intestinal metaplasia, atypical hyperplasia and carcinoma, were studied with in vitro 3H-TdR double labeling autoradiographic technique. On the basis of cell kinetics, intestinal metaplasia might be divided into two types: Type A consisted of those cases in which the values of LI, Ts and Tc were approximately closer to those of normal mucosa. The labeling cells appeared in the lower two thirds of the intestinalized glands, including small intestinal type and the complete type of colonic intestinal metaplasia. In type B, the average values of LI were higher. Ts and Tc values approximated those found in carcinoma a. Type B consisted mostly of the incomplete type of colonic intestinal metaplasia. The above evidence suggests that type B intestinal metaplasia is precancerous.

Adult↗

CDX2-regulated expression of iron transport protein hephaestin in intestinal and colonic epithelium.

BACKGROUND & AIMS: The homeobox transcription factor CDX2 has a key role in intestinal development and differentiation. Mice heterozygous for Cdx2 inactivation develop colonic polyps with epithelial cells showing gastric or squamous differentiation. Loss of CDX2 expression is seen in some poorly differentiated colon carcinomas in humans. Conversely, ectopic CDX2 expression in the stomach of transgenic mice promotes intestinal metaplasia, and CDX2 expression often is seen in intestinal metaplasia in stomach and esophagus. To enhance knowledge of CDX2 function, we sought to define CDX2-regulated genes. METHODS: HT-29 and WiDr colorectal cancer (CRC) cells with low endogenous CDX2 expression were transduced with a CDX2 expression vector, and gene expression changes were assessed by microarrays. RESULTS: The gene for ceruloplasmin-related iron transport protein hephaestin (HEPH) was induced by CDX2 in HT-29 and WiDr. In other CRC lines and human and mice tissues, endogenous HEPH expression was linked to CDX2 expression. Activation of CDX2 rapidly induced HEPH expression, and RNA interference-mediated inhibition of CDX2 led to lower HEPH expression. Studies with HEPH reporter gene constructs and chromatin-immunoprecipitation approaches suggested that CDX2 directly regulates HEPH transcription. In CRC cells, CDX2 induction suppressed intracellular iron levels, consistent with the view that HEPH regulates iron export. CDX2 expression was modulated in response to changes in intracellular iron levels, implying a regulatory pathway in which increased iron levels lead to increased expression of CDX2 and HEPH and enhanced iron export. CONCLUSIONS: CDX2 has a key role in regulating HEPH expression and iron levels in intestinal cells.

Animals↗

[Characteristics of microorganisms colonizing human intestine].

Introduction of novel methods of microbial diagnostics has considerably broadened our conceptions on the qualitative and quantitative variety of microorganisms inhabiting human gastrointestinal tract. In this review morphological and functional properties of obligate anaerobic bacteria (bifidobacteria, lactobacilli, eubacteria, peptostreptococci, clostridia, bacteroids, fusobacteria) and facultative anaerobic microorganisms (enterobacteria, staphylococci, streptococci, yeast-like fungi of the genus Candida) capable of colonizing human intestine are briefly characterized.

Bacteria, Anaerobic↗

Colonic chemobezoar--intestinal obstruction due to barium inspissation.

A 72-year-old man presented with constipation of 45 days' duration, with history suggestive of recurrent episodes of subacute intestinal obstruction relieved by passage of fluid and flatus; he had noticed an abdominal lump 30 days prior. Examination revealed a lump corresponding to the contours of the entire large intestine. X-ray showed barium outlining the colon. Enquiry revealed that he had undergone a barium enema study 10 days prior to appearance of the lump. The diagnosis of barium inspissation was confirmed at laparotomy; total colectomy with ileo-rectal anastomosis was done.

Aged↗

Polyethylene glycol 900 permeability of rat intestinal and colonic segments in vivo and brush border membrane vesicles in vitro.

Increased intestinal absorption of medium-sized aqueous probes has been found in patients with a variety of disorders. We studied the physiologic control mechanisms, intestinal regions, and effects of lumenal factors on the intestinal absorption of polyethylene glycol (PEG) 900 in the rat in vivo and in rabbit brush border membrane vesicles (BBMVs). The kinetics of PEG 900 intestinal absorption were compatible with simple passive diffusion. Because transport across BBMVs was minimal, we concluded that transport of PEG 900 is mostly through the paracellular tight junctions. Absorption was highest in the midcolon (104.3 +/- 9.5 mumol/100 mg protein per hour vs 9.1 +/- 1.2 mumol/100 mg protein per hour in the jejunum). Absorption was decreased by higher lumenal osmolarity (greater than 400 mOsm/L) after the additions of 2.5 to 5.0 mmol/L chenodeoxycholate or 2.5 mmol/L lysolecithin, or at higher lumenal flow rates (greater than 1 ml/minute), higher lumenal pressure (7.5 cm H2O),or higher lumenal pH (8.0). Lipid solubility of PEG 900 was less than 0.00079%. Under all experimental conditions, PEG net absorption followed changes in water transport. When water transport changed from absorption to secretion, PEG absorption decreased. When water absorption increased, PEG 900 absorption increased in parallel. We conclude that PEG 900 is absorbed by passive diffusion that is modulated by solvent drag and is maximal in the midcolon. Transport directly across cell membranes is mimimal, but overall PEG 900 permeability is closely linked to water absorption by solvent drag and takes place primarily through the paracellular junctions. We propose that these features and mechanisms of PEG 900 transport make PEG 900 a suitable probe molecule for studying intestinal permeability changes.

Animals↗

Evaluation of the efficacy of oil-emulsion bacterins for reducing fecal shedding of Salmonella enteritidis by laying hens.

Two replicate experiments were conducted to test the efficacy of two different Salmonella enteritidis oil-emulsion bacterins (an experimentally prepared acetone-killed vaccine and a commercially available vaccine) for protecting laying hens against intestinal colonization following oral exposure to S. enteritidis. Each vaccine was administered twice (4 weeks apart), and all hens were challenged with 10(8) cells of a nalidixic-acid-resistant S. enteritidis strain 2 weeks after the second vaccination. Fecal samples from vaccinated and unvaccinated control hens were cultured at three weekly intervals post-challenge to determine the incidence of intestinal colonization and the numbers of S. enteritidis shed into the environment. Both vaccines significantly reduced the incidence of intestinal colonization (P < 0.05) and the mean number of S. enteritidis cells shed in the feces (P < 0.01) at 1 week post-challenge. However, the degree of protection afforded by vaccination was only partial, as more than half of the vaccinated hens still shed substantial numbers of S. enteritidis. If used in conjunction with other flock sanitation and infection-monitoring strategies, vaccination with bacterins could potentially reduce the overall level of environmental contamination and thereby also reduce the horizontal transmission of S. enteritidis within and between laying flocks.

Animals↗

[Study on the intestinal microbial colonization resistance in patients with chronic severe hepatitis].

OBJECTIVE: To investigate the changes of microbial colonization resistance of the bowel in patients with chronic severe hepatitis. METHODS: The fecal flora bifidobacteria, enterobacteriaceae, enterococci, and yeasts of subjects (chronic severe hepatitis, chronic hepatitis, and healthy volunteers) were quantitatively and qualitatively analyzed by Mitsuoka's methods. While the ratio of bifidobacterium to enterobacteriaceae ( B/E ratio ) was calculated. RESULTS: The number of bifidobacteria and the B/E ratio in chronic severe hepatitis group was significantly deceased compared with that of the control group (P<0.001). The number of enterobacteriaceae and yeasts was significantly increased compared with that of control group (P<0.001 and P<0.01, respectively). CONCLUSIONS: The results suggest that the intestinal microbial colonization resistance in patients with chronic severe hepatitis is seriously impaired.

Bifidobacterium↗

Quantitative distribution of NADPH-diaphorase-positive myenteric neurons in different segments of the developing chicken small intestine and colon.

NADPH-diaphorase (NADPH-d) was used as a marker for neuronal nitric oxide synthase in order to investigate the nitrergic neurons of the developing myenteric ganglia on whole-mount preparations in the proximal and distal segments of the small intestine and in the colon of the chicken embryo, between incubation days 12 and 19. Neurons that were positive for NADPH-d were counted in randomly selected myenteric ganglia. The data obtained from each area and each age group were subjected to two-way analysis of variance (ANOVA) and the Student-Newman-Keuls test. Between incubation days 12 and 19, the originally narrow-meshed myenteric plexus with its high ganglionic density progressively became wide-meshed and the ganglionic density decreased significantly. Quantitative analysis further revealed a significant decrease in the NADPH-d-positive nerve cell density with age. At the same time, the constant or even increasing number of nitrergic cells per ganglion may indicate that the decreasing cell density may be a result of the growth of the bowel with decreasing ganglion density rather than a decrease in the total number of myenteric nitrergic cells. Regional differences in the dynamics of the quantitative changes were revealed. A significant decrease in the nitrergic cell number appeared earlier in the proximal than in the distal segments of the small intestine or in the colon. In contrast, the significant decline of the ganglionic density was first noticed in the colon at the same time.

Animals↗

Intestinal spirochaetes colonizing aborigines from communities in the remote north of Western Australia.

Intestinal spirochaetal bacteria were isolated from 59 of 181 (32.6%) faecal samples obtained from Aboriginal children and a few adults living in communities in the Kimberley region in the north of Western Australia. Colonization was more common in young Aborigines between 2 and 18 years of age than it was in adults, or in babies and children less than 2 years of age. Three of 22 Aboriginal children who were sampled on two consecutive years were colonized on both occasions. None of four other children were found to be consistently colonized with the bacteria when sampled on three sequential years, but three were positive on two consecutive visits and the other child was positive on the first and third sampling. Most Aboriginal children had abnormal or watery stools, and both abnormal and watery stool samples were significantly more likely to contain spirochaetes than were normal samples. However, it was not possible to prove that the spirochaetes were the cause of the diarrhoea. In contrast, spirochaetes were only recovered from 8 of 695 (1.2%) faecal samples that were obtained from other mainly non-Aboriginal children and adults in Western Australia or the Northern Territory of Australia, even though most of these individuals were suffering from gastrointestinal disturbances.

Adolescent↗