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PubMed1988

Enhancement of the humoral immune response and resistance to bacterial infection in mice by the oral administration of a bacterial immunomodulator (OM-89).

We investigated the effects of an Escherichia coli-derived product (OM-89) in mice. The oral administration of OM-89 led to a significant (p less than 0.05, Student's t test) increase in the levels of IgA in intestinal secretions, which was at maximum 25 days after the end of the treatment, when a two-fold increase in IgA levels was observed. The i.p. inoculation of OM-89 induced the stimulation of anti-SRBC plaque-forming cells (PFC) in the spleen. The effect of OM-89 was dose-dependent and produced up to a 9-fold increase in PFC in the treated mice when compared to untreated controls. The oral administration of OM-89 proved to be effective in the enhancement of resistance to challenge i.p. inoculation with E. coli. 32% of OM-89-treated mice showed resistance to this experimental infection at minimal LD100. The combined effects of low environmental temperature and cyclophosphamide (CY) immunosuppression enabled us to enhance differences in survival rates in experiments on the modulation of resistance towards Pseudomonas aeruginosa infection. The oral treatment with the immunomodulator induced a significant (p less than 0.05, Student's t test) level of protection in CY-immunosuppressed mice to the intranasal infection with P. aeruginosa, when mice were kept at low environmental temperature right after the bacterial challenge. The protective effect of OM-89 treatment was dependent on both the environmental temperature and the timing of the experiment.

Adjuvants, Immunologic↗
PubMed2006

Contribution of polymeric immunoglobulin receptor to regulation of intestinal inflammation in dextran sulfate sodium-induced colitis.

BACKGROUND: Inflammatory bowel disease (IBD) affects approximately 4 million people worldwide and can be caused by dysregulated mucosal immune responses to the intestinal commensal microflora. Immunoglobulin A (IgA) is considered to be the principal antibody in intestinal secretions and functions to prevent commensals and pathogenic organisms from gaining access to epithelial cell surfaces. Immunoglobulin A deficiency in humans has been associated with celiac disease and ulcerative colitis. However, the precise role of IgA in the pathogenesis of these disorders is yet to be fully understood. METHODS: Mice with a targeted disruption in IgA production (IgA(-/-) mice) and polymeric immunoglobulin receptor (pIgR(-/-) mice) were analyzed for the contribution of secretory immunity in the pathogenesis of dextran sulfate sodium (2.5%)-induced colitis. RESULTS: It was found that dextran sulfate sodium-treated pIgR(-/-) mice displayed greater loss of bodyweight and had severe clinical illness compared to similarly treated IgA(-/-) mice and wild-type animals. Additionally, colonic tissues from the pIgR(-/-) mice exhibited progressively and significantly greater degrees of mucosal edema, ulceration, crypt abscesses and macrophage infiltration when compared to similarly treated IgA(-/-) mice and wild-type animals. CONCLUSIONS: The results indicate that secretory immunoglobulins contribute to protection of the colonic mucosa against dextran sulfate sodium-induced epithelial injury, although the isotype of the secretory immunoglobulin (IgA or IgM) may not be a decisive factor in such protection. Collectively, the pIgR and/or the secretory component are important for the maintenance of epithelial integrity and mucosal homeostasis in the colonic epithelium.

Animals↗
PubMed1996

Intranasal and intramuscular proteosome-staphylococcal enterotoxin B (SEB) toxoid vaccines: immunogenicity and efficacy against lethal SEB intoxication in mice.

Intranasal or intramuscular (i.m.) immunization of mice and i.m. immunization of rabbits with formalinized staphylococcal enterotoxin B (SEB) toxoid in saline elicited higher anti-SEB serum immunoglobulin G (IgG) titers when the toxoid was formulated with proteosomes. In addition, intranasal immunization of mice with this proteosome-toxoid vaccine elicited high levels of anti-SEB IgA in lung and intestinal secretions, whereas the toxoid without proteosomes did not. Two i.m. immunizations with proteosome-toxoid plus alum also induced higher murine serum responses than alum-adjuvanted toxoid without proteosomes. Furthermore, proteosome-toxoid delivered intranasally in saline or i.m. with either saline or alum afforded significant protection against lethal SEB challenge in two D-galactosamine-sensitized murine models of SEB intoxication, i.e., the previously described i.m. challenge model and a new respiratory challenge model of mucosal SEB exposure. Efficacy correlated with the induction of high serum levels of anti-SEB IgG. In contrast, intranasal or i.m. immunization with toxoid in saline without proteosomes was not significantly protective in either challenge model. Proteosome-toxoid plus alum given i.m. also elicited more significant protection against respiratory challenge than the alum-adjuvanted toxoid alone. The capacity of proteosomes to enhance both i.m. and intranasal immunogenicity and efficacy of SEB toxoid indicates that testing such proteosome-SEB toxoid vaccines in the nonhuman primate aerosol challenge model of SEB intoxication prior to immunogenicity trials in humans is warranted. These data expand the applicability of the proteosome mucosal vaccine delivery system to protein toxoids and suggest that respiratory delivery of proteosome vaccines may be practical for enhancement of both mucosal and systemic immunity against toxic or infectious diseases.

Adjuvants, Immunologic↗
PubMed1992

Binding of nonmucoid Pseudomonas aeruginosa to normal human intestinal mucin and respiratory mucin from patients with cystic fibrosis.

Lung infections due to Pseudomonas aeruginosa and Pseudomonas cepacia are common in patients with cystic fibrosis. Initial colonization is due to nonmucoid P. aeruginosa, while later mucoid variants emerge and are associated with chronic infection. P. cepacia colonization tends to be more prevalent in older patients. The present study was conducted to discover whether highly purified mucins (from cystic fibrosis sputum and control intestinal secretions) exhibited specific binding of nonmucoid P. aeruginosa. In vitro solid phase microtiter binding assays (with or without a blocking agent) as well as solution phase assays were conducted. Bacteria bound to both mucins via bacterial pili, but no differences in binding capacity were noted between the mucins. Unlike P. cepacia (described in the accompanying manuscript) there was also no preferential binding of P. aeruginosa to mucins versus bovine serum albumin, casein, gelatin, or a host of structurally unrelated proteins and glycoproteins. Carbohydrate hapten inhibition studies did not suggest the existence of specific mucin carbohydrate receptors for P. aeruginosa. In solid phase assays a low concentration (0.05 M) of tetramethylurea abolished P. aeruginosa bacterial binding to both mucins as well as to BSA, whereas in solution phase assays mucin binding to bacteria was not completely disrupted by tetramethylurea. Specific monoclonal antipilus antibodies did not inhibit binding to a greater extent than did Fab fragments of normal mouse IgG. Binding of strains PAO1 and PAK (and isolated PAK pili) to buccal epithelial cells was not influenced by the presence of mucin in binding assay mixtures. Our findings do not support the widely held notion that specific mucin receptors are responsible for the attachment of P. aeruginosa pili, nor do they support the idea that there is a competitive interference by mucins of bacterial binding to respiratory cells. In patients with cystic fibrosis, it would seem unlikely therefore that initial colonization of the lungs by P. aeruginosa is due to a 'selective tropism' of these bacteria for respiratory mucin.

Bacterial Adhesion↗
PubMed2002

Treatment of postoperative peritonitis of small-bowel origin with continuous enteral nutrition and succus entericus reinfusion.

HYPOTHESIS: Proximal intestinal stomas established by the exteriorization of leaking anastomosis in the presence of peritonitis can be used to reinfuse succus entericus and provide adequate enteral nutrition. DESIGN: Retrospective analysis of prospectively gathered data from a cohort of consecutive patients admitted between January 1993 and December 1999 for postoperative peritonitis requiring laparotomy and the construction of one or more small-bowel stomas. SETTING: Tertiary referral center with a surgical intensive care unit experienced in the treatment of intra-abdominal sepsis and succus entericus reinfusion. PATIENTS: Twenty-one consecutive patients with postoperative peritonitis originating from a jejunal or ileal leak. We excluded patients with established enterocutaneous fistulae, abscesses amenable to percutaneous drainage or other conservative treatments, and postoperative peritonitis caused by ileocolic or ileorectal anastomosis. INTERVENTIONS: Early laparotomy with exteriorization of small-bowel leak(s), and continuous enteral nutrition (CEN) and succus entericus reinfusion (SER) via the distal portion of the stoma until gastrointestinal continuity was restored. MAIN OUTCOME MEASURES: Feasibility of CEN and SER with temporary, diverting small-bowel stomas and their associated postoperative morbidity and mortality rates. RESULTS: One patient died, and 14 experienced complications. For technical reasons, CEN and SER were discontinued early on in 7 patients. The mean duration of CEN and SER was 58 days and 61 days, respectively. Enteral feedings allowed the suppression of central venous access after a median of 28 days, with 82 days as a median time to restoration of intestinal continuity. CONCLUSIONS: Although the exteriorization of small-bowel leaks with CEN and SER is generally feasible and effective in the treatment of critically ill patients with peritonitis secondary to small-bowel leaks, it is associated with significant morbidity and mortality, in part relating to patients' underlying diseases.

Adult↗
PubMed1980

Remedial operation for alkaline reflux gastritis and associated postgastrectomy syndromes.

Alkaline reflux gastritis is being recognized with increasing frequency after operations that ablate the pylorus as a true sphincter. Medical management is generally ineffective for patients with severe reflux gastritis, but Roux-en-Y diversion of bile and of pancreatic and intestinal secretions provides gratifying results. We studied 100 patients who underwent remedial operation. Roux-en-Y gastrojejunostomy or Tanner's vs Roux-19 procedure gave good to excellent results in most of the 73 patients followed up for from one to six years. Reflux gastritis can occur in association with other postgastrectomy disorders. Fifteen patients with reflux gastritis also had severe dumping or postvagotomy diarrhea. Good to excellent results were obtained in most of these patients by Roux-en-Y diversion combined with an antiperistaltic jejunal segment.

Adult↗
PubMed1975

Intestinal mucosa of the platypus, Ornithorhynchus anatinus.

The intestinal mucosa of the platypus takes the form of numerous transverse surface folds. These folds are made up of a lamina propria covered by pseudostratified epithelium which lies on a thick modified basement membrane. The cells of the intestinal epithelium consist of columnar cells which generally resemble typical intestinal epithelium and cuboidal cells, which are undifferentiated in appearance, show few organelles and possess an electron lucent cytoplasm. Numerous desmosomes are found between the adjacent cell membranes of both cell types. Villi are absent and appear to be represented by the large surface folds. Intestinal glands are composed of columnar epithelium similar to that found in the intestinal glands of other mammalian species. Groups of these glands drain into common tubular ducts which follow a tortuous course and empty into the intestinal lumen between the surface folds. The peculiar morphological features of the platypus intestinal mucosa raise questions concerning traditional concepts of intestinal gland formation as well as the origin and migration of intestinal epithelium with regard to this particular species.

Animals↗
PubMed2001

Luminal morphology of the avian lower intestine: evidence supporting the importance of retrograde peristalsis for water conservation.

Tissue from the lower intestine of two species of sparrow, the house sparrow Passer domesticus and savannah sparrow Passerculus sandwichensis was sectioned in an unbiased manner and examined quantitatively using stereology. The tissue was processed for light microscopy, and scanning and transmission electron microscopy to examine the extent to which microvilli enhanced the epithelial surface area of the cecae, rectum, and coprodeum. Parameters measured included individual microvillus surface area, microvilli packing density, and absolute surface area. In both species, the average surface area, packing density, and absolute surface area of microvilli decreased distally along the rectum and coprodeum. All three measured variables were not statistically significant (P > 0.05) between species. Surface area amplification on the cecae due to microvilli was low, and approximated values equivalent to distal regions of the rectum and coprodeum. In the cecae, microvilli within the savannah sparrow had a significantly higher (P < 0.05) individual surface area, packing density, and absolute surface area than in the house sparrow. The functional implications of a change in microvilli population are discussed in relation to retrograde peristalsis within the lower intestine of birds.

Animals↗
PubMed1983

Prevention of postoperative renal failure in patients with obstructive jaundice--the role of bile salts.

Preoperative administration of the simple bile salt sodium deoxycholate has been shown in this study to prevent postoperative endotoxaemia and renal failure in patients with obstructive jaundice. Fifty-four per cent of jaundiced patients not given the salt were found to have systemic endotoxaemia, associated with renal impairment in two-thirds of the cases. No patient given sodium deoxycholate 500 mg 8 hourly for 48 hours before operation had portal or systemic endotoxaemia, and none had evidence of renal impairment (P less than 0 X 02, X2 with Yates' correction). The incidence of endotoxaemia in untreated jaundiced patients was very significantly greater than in non-jaundiced patients undergoing elective upper abdominal surgery (P less than 0 X 005), but this difference is abolished by the prophylactic administration of the oral bile salt. The mechanism of action of bile salts in preventing endotoxin absorption from the small bowel has been investigated, and the lack of any significant alteration in the small bowel microbial flora in obstructive jaundice suggests that a direct effect on the endotoxin molecule is involved. Nearly 20 per cent of patients with obstructive jaundice still develop postoperative renal insufficiency, but preoperative prophylactic use of sodium deoxycholate should reduce this very significantly.

Acute Kidney Injury↗
PubMed1994

Short bowel syndrome: metabolic and surgical management.

The management of short bowel syndrome requires long-term nutritional support and monitoring, medication, and occasionally additional surgical procedures. Constant attention is required to ensure adequate adaptation of the gut. This article reviews the normal function of the small bowel, adaptation following resection, total parenteral and enteral nutrition, and the role of adjunctive surgical procedures in the management of short bowel syndrome.

Adaptation, Physiological↗
PubMed2006

Novel colon-specific microspheres with highly dispersed hydroxycamptothecin cores: their preparation, release behavior, and therapeutic efficiency against colonic cancer.

To increase therapeutic efficiency of hydroxycamptothecin (HCPT) against colonic cancer and decrease its side-effects, highly dispersed HCPT was first incorporated in fast release microspheres. HCPT in the microspheres showed a solubility two times larger, and its cumulative release rate for 24 h in simulated colonic juice 140 times higher than that of free HCPT. The microspheres were then coated with a layer of Eudragit S100 by air suspension spray-drying method with a self-designed device to obtain colon-specific microspheres (HCPT-CSMS). The mean particle size of the microspheres was 200 microm before coating and 230 microm after coating. The in vitro cumulative release results for HCPT-CSMS in simulated gastric juice for 2 h, in simulated enteric juice for 4 h, and in simulated colonic juice for 18 h showed that over 60% of total HCPT released in simulated colonic juice in the initial 5 h. Animal tests with per os (po) administration showed that free HCPT was mainly absorbed in stomach and small intestine, while the HCPT in HCPT-CSMS was mainly delivered and absorbed in colon. po administration of HCPT-CSMS to nude mice with colonic cancer showed a cancer inhibition rate of 61.4% compared to 39.8% for free HCPT.

Animals↗
PubMed1978

Hepatic disposition and biliary excretion of the organic cations thiazinamium and thiazinamium sulfoxide in rats.

The disappearance from plasma and the excretion in bile of the monoquaternary thiazinamium (administered as the iodide) and one of its polar metabolites, thiazinamium sulfoxide (also administered as the iodide), were studied in the rat after intravenous injection to obtain more information on hepatic transport mechanisms for organic cations. Both compounds exhibited an extremely rapid plasma disappearance, partly due to a rapid liver uptake. After injection of thiazinamium iodide and thiazinamium sulfoxide iodide, 36 and 47%, respectively, of the administered dose were excreted in bile during 1 hr. TLC analysis of the bile showed at least two unidentified polar metabolites in addition to thiazinamium sulfoxide and only 3.8% unchanged thiazinamium after administration of thiazinamium iodide. The same metabolites were found after injection of thiazinamium sulfoxide iodide. Urinary excretion and intestinal secretion were 18 and 12%, respectively, for thiazinamium sulfoxide iodide and 27 and 9%, respectively, of the dose for thiazinamium iodide. It is concluded that, in spite of unequal physicochemical features, thiazinamium iodide and thiazinamium sulfoxide iodide differ only slightly in hepatic uptake and metabolism.

Animals↗
PubMed1988

Undifferentiated columnar cells on the gastric interfoveolar crest: a previously undescribed observation.

We have observed and defined morphometrically and histochemically an entity composed of groups of undifferentiated columnar cells on the interfoveolar crest of gastric mucosa. These cells are clearly distinct from either normal foveolar cells or regenerative epithelial cells associated with ulcer healing. They show a close association with atrophic gastritis, particularly in the presence of type 3 sulphomucin-secreting intestinal metaplasia. We have termed this the gastric tip lesion since it is observed only on the tips of the mucosal folds. This has not been described previously. We propose that these cells are the precursors of type 3 intestinal metaplasia and may also provide a link between this type of intestinal metaplasia and the intestinal variant of gastric adenocarcinoma.

Adenocarcinoma↗
PubMed1989

Undifferentiated columnar cells in colorectal adenomas and familial adenomatous polyposis.

We have observed and defined morphometrically and histochemically groups of undifferentiated columnar cells within the surface epithelium in colorectal mucosa. They were present within both non-polypoid and polypoid mucosa in familial adenomatous polyposis, and within non-hereditary adenomatous polyps of the colon and rectum. The cells show some evidence of proliferative activity and appear similar to cells previously described in the stomach which were proposed as precursors to type 3 sulphomucin-secreting intestinal metaplasia in atrophic gastritis. To our knowledge, these observations have not been previously described. It is possible that the cells represent the cellular basis of the shift in the proliferative zone from the normal site at the crypt base to the colorectal mucosal surface, which is known to precede adenomatous polyp formation. The cells may therefore be involved in the early stages of colorectal adenoma formation.

Adenomatous Polyposis Coli↗
PubMed2002

Chimeric recombinant hepatitis E virus-like particles as an oral vaccine vehicle presenting foreign epitopes.

Many viral and bacterial pathogens establish infections through mucosal surfaces in their initial stage. However, only a few nonreplicating molecules successfully induce strong mucosal immune reaction without the addition of adjuvants by oral administration. To overcome this difficulty, we investigated whether hepatitis E virus-like particles (HEV-VLPs) could be utilized as a carrier molecule for foreign antigenic epitopes and to stimulate mucosal immunity without the need for adjuvants. To accomplish this goal, we incorporated a B cell epitope tag, consisting of 11 amino acids at the C-terminal of HEV-VLP. The chimeric VLP showed morphology similar to that of the mature HEV virion and VLP. The inserted epitope was reactive with a specific monoclonal antibody in the VLP form, suggesting that it was exposed on the surface of the VLP. After oral administration without adjuvant, this chimeric HEV induced significant levels of specific IgG and IgA to both the inserted epitope and HEV-VLP in intestinal secretions. These humoral immune responses were observed as early as 2 weeks after the first immunization. These results suggest the potential of HEV-VLP as a mucosal vaccine carrier vehicle for the presentation of antigenic epitopes through oral administration.

Administration, Oral↗