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PubMed1988

Presence and characteristics of epidermal growth factor receptors in human fetal small intestine and colon.

In the present study, we demonstrate for the first time the presence of important concentrations of EGF binding sites in isolated epithelial cells of both human fetal small intestine and colon as early as 12 weeks gestation. The pattern of EGF binding in the small intestine between 12 and 17 weeks show that binding was significantly higher (2.5-fold) in younger fetuses than in older fetuses. Moreover, the fetal colon exhibited a much higher binding capacity (1.5-2.5 times) than corresponding intestinal cells for all age groups studied. Analysis of Scatchard representations reveal that the concentration of high- and low-affinity binding sites in colonic epithelial cells are twice the values observed in corresponding intestinal cells. The present data raise interesting possibilities as to the role of this growth factor in human fetal gut development.

Binding Sites↗
PubMed1991

Effects of Yersinia enterocolitica infection on rabbit intestinal and colonic goblet cells and mucin: morphometrics, histochemistry, and biochemistry.

The effects of Yersinia enterocolitica on intestinal goblet cells were investigated in New Zealand white rabbits. Animals infected with Y enterocolitica were compared with weight matched and pair fed controls. Goblet cell hyperplasia developed in the distal small intestine of infected rabbits on day 1, in the mid small intestine on day 3, and in the upper small intestine on day 6. In all regions hyperplasia persisted throughout the 14 day study. The degree of hyperplasia was greater in the distal small intestine than the upper and mid regions. Goblet cells in the proximal colon of infected animals seemed to respond as those in the distal small intestine. Thus goblet cell hyperplasia developed more rapidly and to a greater extent in the ileocaecal region where mucosal injury was most severe. These changes resulted directly from Y enterocolitica infection since goblet cell numbers did not increase in pair fed controls. Histochemically, goblet cell mucins from infected rabbits were unchanged at either six or 14 days. Biochemical analysis, however, established that purified mucins from animals on day 6 after infection were less sialylated (in the small intestine) and more sulphated (in the small intestine and proximal colon). In addition, mucins from the distal small intestine and the proximal colon seemed to contain fewer but longer oligosaccharide chains.

Amino Acids↗
PubMed2000

Active efflux kinetics of etoposide from rabbit small intestine and colon.

The aim of the present study was to investigate the directional transport kinetics of etoposide in rabbit intestinal tissues using side-by-side diffusion chambers. Etoposide is a routinely used mixed-mechanism 'efflux' inhibitor; however, its absorptive and secretory transport kinetics in rabbit intestinal tissues, a commonly used animal model, have not yet been reported. Kinetic studies revealed that the apical (AP) to basolateral (BL) (i.e. absorptive) transport of etoposide was not apparently mediated by specialized transporters, whereas secretion (i.e. BL to AP transport) by intestinal tissues was concentration dependent and saturable. Half-saturation constant values (K(m), mean+/-standard deviation (S.D.)) ranged from 53.6+/-35.8 microM to 168.7+/-127.3 microM, consistent with previous results from our group in intestinal tissues from other species and Caco-2 cell monolayers. Secretory permeability was greatest in the ileum, whereas values in the upper small intestine and colon were approximately equal, and represented only 50% of the value in the ileum. The ileal secretory transport of etoposide was temperature dependent, with the activation energy (E(a)) >4 kCal/mole at 5 microM, suggesting the involvement of the active, energy dependent mechanism. Etoposide inhibition by verapamil and saquinavir, known inhibitors of intestinal secretion, was characterized as competitive with K(i)'s equal to 193.0+/-164.4 microM and 72.6+/-53.5 microM, respectively. The current results demonstrate that the absorptive transport of etoposide in rabbit tissue was not mediated by specialized carriers, and that secretory transport was regionally dependent, mediated by a transporter or transporters, the K(m)'s were in the micromolar range, and involved the energy dependent mechanism(s). The relatively low k(m) of etoposide compared with its aqueous solubility (0.25-0.34 mM, pH 5-6.5, 25 degrees C) makes it the excellent mixed-mechanism competitive inhibitor for determining the secretory transport properties of putative drug substrates. Understanding the in vitro secretory transport kinetics of etoposide provides a mechanistic basis for ongoing studies exploring the functional role of 'efflux' in vivo.

ATP-Binding Cassette Transporters↗
PubMedDate not supplied

[Effect of Klebsiella Pneumoniae bacterial colonization of the gastrointestinal tract on the immune processes in mice after weaning].

The influence of intestinal colonization by the Klebsiella pneumonia strain 50/59 on the characteristics of local and humoral immunity has been studied on CBA mice after weaning. Bacteria have been introduced intragastrally in doses of 1 x 10(6) bacteria per mice. Observations have been performed in dynamics during 11 days. They have shown that intestinal colonization induces significant elevation of the concentration of IgA in serum, intestinal content and percentage of splenocytes, expressing receptors of IgA, IgM, CD4 on the 7th day. On the 11th day a significant decrease in these parameters was observed. A conclusion is made that intestinal colonization is not indifferent for the whole organism and induces complex influences on its immune system.

Animals↗
PubMed1996

Cysteine supplementation increases glutathione, but not polyamine, concentrations of the small intestine and colon of parenterally fed newborn rabbits.

The glutathione precursor cysteine is not contained in most total parenteral nutrition (TPN) formulations, and premature infants may not be capable of synthesizing cysteine because of a deficiency of cystathionase. Glutathione depletion may have negative effects on host defense against oxidative damage. Several studies have suggested that glutathione depletion induces ornithine decarboxylase activity and increases in polyamine concentrations. Since an inverse relationship between polyamine and glutathione concentrations has been suggested, the concentrations of both of these compounds may be altered in premature infants receiving TPN. We measured glutathione and polyamine concentrations of the small intestine and colon of prematurely delivered newborn rabbits administered TPN for 7 days after birth with or without added cysteine (75 or 150 mg kg-1 day-1). Maternally reared kits were also studied. Total glutathione concentrations in the gastrointestinal tract were significantly lower in kits administered cysteine-free TPN than in kits receiving cysteine or who were maternally reared. Polyamine concentrations did not differ among groups. Glutathione depletion of the small intestine and colon does occur during cysteine-free parenteral nutrition and may compromise intestinal defense against oxidant damage.

Animals↗
PubMed2000

Chemoprevention of colon cancer carcinogenesis by balsalazide: inhibition of azoxymethane-induced aberrant crypt formation in the rat colon and intestinal tumor formation in the B6-Min/+ mouse.

Non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin have been shown to suppress colon carcinogenesis and in some cases reduce the size of colorectal polyps. Balsalazide disodium (BSZ) is a colon-specific prodrug of the salicylate, 5-aminosalicylic acid. The aim of the present study was to test the chemopreventive activity of BSZ in two established animal models of colon tumorigenesis, azoxymethane-induced aberrant crypt formation in the rat and intestinal tumor formation in the B6-Min/+ mouse. Aberrant crypt foci (ACF) were induced in Fischer 344 rats via 2 subcutaneous injections of azoxymethane (20 mg/kg). BSZ was supplied in the drinking water for 8 weeks and ACF quantitated. B6-Min/+ mice were treated from 55 days of age for 90 days and intestinal tumors scored for number, size and location. BSZ treatment of AOM-injected rats reduced ACF formation in a dose-dependent manner by 60% with the greatest effect observed on ACF with 4 or more crypts. In B6-Min/+ mice a dose-dependent reduction of intestinal tumor number was observed which reached 80% in the distal small intestine and colon. A preliminary mechanistic study in cultured human colon cancer cells showed that both BSZ and 5-ASA inhibited colon cancer cell proliferation in vitro. However, 5-ASA but not BSZ produced changes consistent with the induction of apoptosis. BSZ produces a dose-dependent chemopreventive effect on colon carcinogenesis. A possible mechanism is consistent with the inhibition of cellular proliferation and the induction of apoptosis.

Aminosalicylic Acids↗
PubMed1995

Effects of novelty and conditioned fear on small intestinal and colonic motility and behaviour in the rat.

Novelty and conditioned fear were used to investigate the effects of psychological stress on fasting small intestinal and colonic myoelectric activity and their relation with behaviour in freely moving rats fitted with bipolar electrodes on proximal jejunum and colon. Rats in both novelty and conditioned fear groups spent a 15 min session in a novel box, where only rats in the fear group received unescapable, repeated foot shock (10 x 6 s, 0.5 mA). Behaviour in groups reexposed to the box on day 1 or day 7 indicated a profound difference in emotional state. Conditioned fear rats remained largely immobile, while novelty rats displayed active exploratory behaviour. Behaviour during conditioned fear did not differ significantly between rats reexposed to the box either 1 or 7 days after foot shock, while novelty animals appeared more aroused on day 7. Conditioned fear on day 1 caused a significant increase in colonic spike burst frequency compared to basal values in the home cage. A smaller but significant increase was found in novelty rats. In groups tested after 7 days, both novelty and conditioned fear resulted in small increases in colonic burst frequency that did not differ significantly from each other. No effects were found on the incidence of the fasting jejunal Migrating Motility Complex. Defecation was see only in conditioned fear rats, but did not differ quantitatively between day 1 and day 7. We conclude that, in the rat, colonic myoelectric spike burst activity is highly responsive to psychological stress, while the fasting pattern of small intestinal activity is more resistant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Effects of intrapartum penicillin prophylaxis on intestinal bacterial colonization in infants.

Early-onset group B streptococcal (GBS) infections remain a leading cause of morbidity and mortality in infants. To prevent the vertical transmission of GBS and neonatal GBS infection, guidelines recommend intrapartum penicillin or amoxicillin prophylaxis. This intrapartum antibiotic prophylaxis (IAP) is suspected to favor colonization by antibiotic-resistant bacteria. However, the effects of this prophylaxis on the patterns of acquisition of gastrointestinal bacterial flora in infants have never been studied. We collected stool samples from 3-day-old infants born to mothers who received intrapartum amoxicillin (antibiotic-exposed group; n = 25) and to untreated mothers (non-antibiotic-exposed group; n = 25). The groups were matched for factors known to affect intestinal microbial colonization: gestational age, type of delivery, and type of feeding. Qualitative and quantitative differential analyses of the bacterial flora in stool samples were performed. Similar numbers of infants in the non-antibiotic-exposed and antibiotic-exposed groups were colonized by aerobic bacteria and amoxicillin-resistant enterobacteria (75 and 77%, respectively) (P = 0.79). In contrast, significantly fewer infants in the antibiotic-exposed group than in the non-antibiotic-exposed group were colonized by anaerobic bacteria, especially Clostridium (12 and 40%, respectively) (P < 0.05). Regarding intestinal bacterial colonization, the differences between antibiotic-exposed and non-antibiotic-exposed infants were remarkably few. The only statistically significant effect was the reduced initial bacterial colonization by Clostridium in the antibiotic-exposed group. In our study, the use of IAP did not favor colonization by beta-lactam-resistant bacteria. However, further evaluations are required to highlight the potential risks of the widespread use of antibiotics to prevent early-onset GBS infection.

Ampicillin↗
PubMed1991

[Differentiation of intestinal candidial colonization from invasive candidiasis by measuring serum level of D-arabinitol in combination with oral administration of low dose amphotericin B].

The measurement of D-arabinitol in serum has been reported to be useful for the diagnosis of invasive candidiasis. However, excessive proliferation of Candida species in intestinal tract often leads false positive result of serum D-arabinitol. Based on the evidence that amphotericin B (AMPH) is scarcely absorbed from intestinal tract and inhibits the proliferation of Candida species only in intestinal tract, we have developed a simple differentiation method of intestinal candida colonization from invasive candidiasis by measuring serum level of D-arabinitol in combination with oral administration of low dose AMPH. AMPH, 600 mg/day for 2 days was orally administered to five patients with hematological malignancies who showed more than 1.7 mumol/mg of D-arabinitol/creatinine ratio (D/C ratio) in serum without any evidence of invasive candidiasis. D/C ratios were markedly decreased and normalized after the oral administration of low dose AMPH. While, in a patient with invasive candidiasis in whom Candida species was detected by blood cultures, D/C ratio remained unchanged in spite of oral administration of AMPH. These observations suggest that this method is a simple and reliable diagnostic method to distinguish intestinal candida colonization from true invasive candidiasis.

Administration, Oral↗
PubMed2004

Wnts as essential growth factors for the adult small intestine and colon.

The study of physiologic functions of Wnt proteins has been complicated by the redundant nature of the families encoding the Wnt factors and their Frizzled receptors. Adenoviral expression of the secreted Wnt antagonist Dickkopf-1 (Dkk1) was used to achieve fully conditional inhibition of canonical Wnt signaling in adult mice. Systemic expression of Dkk1 resulted in rapid inhibition of Wnt target gene expression and of proliferation of the small intestine and colon, loss of proliferative crypts, and eventual inflammation and architectural degeneration. These studies indicate an essential requirement for extracellular Wnt signaling in the maintenance of adult small intestine and colon proliferation. The essential role of Wnt signaling in ongoing proliferation in the colon suggests potential clinical applications in mucosal repair for inflammatory bowel diseases and underscores the utility of adenoviral strategies for conditional ablation of gene function in adult organisms.

Adenoviridae↗
PubMed1987

The significance of colonic mucosa (intestinal metaplasia) involving the urinary tract.

Although colonic type goblet cells are a relatively common component of reactive urothelial lesions and well-differentiated adenocarcinomas, complete replacement of areas of urothelium by benign appearing intestinal mucosa is a rare condition. All of the 11 documented cases occurred in association with abnormalities leading to chronic irritation and/or infection. In the three cases where the reported period of observation exceeded 2 years, all patients developed carcinoma. Despite its innocuous histology, widespread intestinal metaplasia apparently identifies a disturbed urothelium at high risk for cancer.

Carcinoma↗
PubMed2000

Flow cytometric analysis of colonic and small intestinal mucosal lymphocytes obtained by endoscopic biopsy in the healthy dog.

Flow cytometric analysis of the lymphocyte population of the gut could provide useful information on the immune cells present in the gut that would not be easily obtained in tissue sections. However, little is known of the normal lymphocyte population in the canine gut as determined by flow cytometry, which allows for simultaneous staining of multiple cell surface antigens and identification of specific lymphocytic subsets. Therefore, intraepithelial lymphocytes were obtained from biopsies of the healthy canine proximal small intestine and colon taken with an endoscope, and flow cytometric analysis was used to characterize the lymphocyte subsets present. Endoscopic biopsy of the intestine is a minimally invasive technique commonly used for diagnostic purposes. Although CD3+ lymphocytes were the most abundant subset in both colon and small intestine, CD3+/CD8- lymphocytes predominated in the proximal small intestine, whereas CD3+/CD8+ lymphocytes did in the colon. Canine CD8+ intraepithelial lymphocytes were predominantly CD8alphabeta+ in both small intestine and colon. CD4+ intraepithelial lymphocytes were always much less numerous than CD8+ intraepithelial lymphocytes. As in man, a majority of intraepithelial lymphocytes expressed the T-cell receptor, TCRalphabeta, but TCRgammadelta was expressed by a third of intraepithelial T-cells in the proximal small intestine, and approximately 15% of those in the colon. Very few CD21+ lymphocytes were detected in samples of healthy canine colon and small intestinal intraepithelial cells. We have showed that canine intraepithelial lymphocytes are regionally specialized, and that those from the small intestine are unique in comparison to those of other species such as man and rodents due to the large numbers of CD3+/CD8- intraepithelial lymphocytes. This study provides a baseline for comparison with intraepithelial lymphocytes obtained from canine patients with intestinal disease.

Animals↗
PubMed1995

Colonization ability & intestinal pathology of rabbits orally fed with Vibrio cholerae O139 Bengal.

The colonization ability of a representative epidemic strain of V. cholerae O139 Bengal was studied in the oral rabbit colonization model and the nature of colonization in the ileal and jejunal tissues was examined ultrastructurally. Results of the colonization study and ileal loop assay indicated that the strain proliferates and colonizes the small intestine of the rabbit mucosal surface. Further, the electronmicroscopic study revealed the disruptive effect of the strain on the apical membrane of the epithelial cells. The results of this study suggested that apart from colonization, invasion of the bacteria was important in the pathogenesis of V. cholerae O139 mediated infections.

Animals↗
PubMed1996

Availability of calcium for absorption in the small intestine and colon from diets containing available and unavailable carbohydrates: an in vitro assessment.

An in vitro method simulating conditions in the small intestine and colon was used to study the effects of various carbohydrates on Ca release from basal diet (BD) containing dairy products. During enzymatic digestion of BD, 28.5 +/- 0.3% of the Ca was released. This was reduced by 3, 22 and 27% by adding bread, psyllium or pectin to BD, respectively (P < 0.05). After enzymatic digestion, the residue from BD was fermented releasing 11.9 +/- 1.2% of the Ca, a value which was significantly less than with pectin (13.7 +/- 0.9%) and greater than with psyllium (4.4 +/- 0.2%) addition. The total Ca release ranged from 26.5 +/- 0.8 to 42.2 +/- 1.0% with bread>BD>pectin>psyllium. Lactulose did not differ significantly from BD. These results suggest that carbohydrates may bind Ca and reduce its availability for absorption in the small intestine. However, if the carbohydrate is fermented, bound Ca may be released for potential absorption in the colon, whereas less fermented carbohydrates may continue to bind Ca in the colon. The in vitro method described may be useful for estimating total Ca availability. However, studies in humans are required to validate these results.

Biological Availability↗
PubMed1990

Net fluid secretion and impaired villous function induced by colonization of the small intestine by nontoxigenic colonizing Escherichia coli.

The role of colonizing bacteria in the small bowel in causing diarrhea remains unclear. We examined whether colonizing, nontoxigenic Escherichia coli could alter small bowel function by determining net water and electrolyte fluxes and sucrase activity in colonized and noncolonized ileal segments by using the reversible-ileal-tie adult rabbit model. Colonization of the ileum with nontoxigenic E. coli for greater than or equal to 72 h at greater than or equal to 10(4)/cm2 was associated with significant functional derangements, as follows: (i) overt liquid diarrhea in 50% of animals colonized at greater than 10(4)/cm2; (ii) reversal of normal net ileal absorption to net secretion of water, sodium, and chloride; and (iii) significant decrease in mucosal sucrase activity. We conclude that small bowel colonization by colonizing, nontoxigenic E. coli impairs water and electrolyte absorption and sucrase activity in the absence of recognized enterotoxin, cytotoxin, invasion, or effacement traits.

Animals↗
PubMed1988

Rabbit intestinal and colonic mucins: isolation, partial characterization, and measurement of secretion using an enzyme-linked immunoassay.

Mucin was purified separately from the upper, mid, and distal small intestine and the proximal colon of the rabbit. The carbohydrate profiles of the three intestinal mucins were the same but differed from that of the colonic mucin, which contained less N-acetylgalactosamine but more sialic acid. All four mucins had similar polymeric structures composed of large, heterogeneous glycoprotein monomers and a smaller protein of Mr approximately 120,000, held together by disulphide bonds. The three intestinal mucins, however, were more resistant to dissociation by thiol reduction or degradation by proteolysis than colonic mucin. An antibody against a pool of the purified mucins was developed in guinea pigs and used to establish an enzyme-linked immunosorbent assay (ELISA). The antibody was highly specific for rabbit intestinal and colonic mucins, showing no cross-reactivity with nonmucin components of rabbit intestinal and colonic tissue, and very little or no reactivity with purified intestinal mucins from other species. The four purified rabbit mucins had the same affinity for the antibody and similar numbers of antigenic determinants. Antigenicity was apparently associated with the protein moeity of the mucins and was critically dependent on three-dimensional conformation, since proteolysis decreased the number of antigenic determinants while thiol reduction abolished antigen-antibody affinity. Using the ELISA, the tissue mucin content and the rate of mucin secretion were found to be significantly higher in the proximal colon that in the three regions of the intestine, which were the same.

Animals↗
PubMed1993

[Importance of the colon in intestinal adaptation. Study with the proliferating cell nuclear antigen].

Proliferating cell nuclear antigen (PCNA) is an auxiliary protein to DNA polymerase delta necessary for tissue cellular proliferation. The colon releases several peptides or hormones which are probably related to intestinal proliferation. Colonic resection determines adaptive changes in the remnant bowel. In the present study, proliferative changes after colectomy were studied by means of the murine monoclonal PC10 antibody. A control group (n = 10 rats) and a 75% proximal colon resection group (n = 10 rats) were studied. 14 days after resection, jejunal, ileal and colon samples were taken and assayed for PCNA. Relationship between immunostained nuclei and the total number of nuclei was determined. The three intestinal segments showed statistically significant increases (p < 0.001) in the number of immunostained nuclei. PCNA proliferative index was greater in the remnant large bowel.

Adaptation, Physiological↗
PubMed2006

Endemic extended-spectrum beta-lactamase-producing Klebsiella pneumoniae at an intensive care unit: risk factors for colonization and infection.

A prospective cohort study was undertaken to describe the epidemiology of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBLKp) acquisition at an intensive care unit (ICU) in a non-outbreak setting. Surveillance for ESBLKp colonization and infection was performed in patients admitted at the ICU from January, 2000, to May, 2001. Screening for ESBLKp intestinal colonization was done by culturing rectal swab specimens at admission, 72 hr after admission and weekly until discharge or detection of ESBLKp. The incidence of ESBLKp intestinal colonization was 5.8/1,000 patient-days (95%CI, 3.4-10.1), and of ESBLKp infection was 1.7/1,000 patient-days (95%CI, 0.7-4.2). Use of vancomycin (OR 6.6; 95%CI, 1.73-25.28), amphotericin B (OR 12.0; 95%CI, 1.79-80.51), metronidazole (OR 5.3; 95%CI, 1.10-25.65), and ciprofloxacin (OR 0.1; 95%CI, 0.01-0.97) were independently associated with ESBLKp intestinal colonization. Previous ESBLKp colonization (OR 60.6; 95%CI, 56.33-578.73) was independently associated with ESBLKp infection. Each ICU-acquired ESBLKp isolate belonged to a different genotype by ERIC-PCR or pulsed-field gel electrophoresis (PFGE) and had a different plasmid profile, suggesting that cross transmission was not the main source for ESBLKp acquisition. Factors associated with ESBLKp in the non-outbreak setting were different from those previously reported during outbreaks. Intestinal ESBLKp colonization was confirmed as a risk factor for infection by this pathogen.

Cohort Studies↗