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Tachykinins: role in human gastrointestinal tract physiology and pathology.

Tachykinins (TKs) and their receptors (NK1, NK2 and NK3), which are diffusely expressed in the human gastrointestinal tract, represent an endogenous modulator system regulating enteric secretomotor functions, inflammatory and immune responses, and visceral hypersensitivity, mainly during pathological gut diseases. Pathophysiological implications of TKs in the digestive tract include changes in TK innervation, in the expression of TKs and TK receptors, which result in inflammation- and immune-induced disturbances of gut functions, such as dysmotility (diarrhoea/constipation), secretory diarrhoea and visceral hyperalgesia. Increasing evidence correlates all these TKergic system abnormalities with gastrointestinal diseases of different etiology (i.e. inflammatory bowel diseases, irritable bowel syndrome). Accordingly, TK receptors have been identified as novel targets for the development of new therapeutic agents for clinical use. Available preclinical findings have shown that TK antagonists could counteract the most significant symptoms characterizing these gut diseases.

Animals↗

Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans.

Ghrelin, a novel GH-releasing acylated peptide, was recently isolated from rat stomach. It stimulated the release of GH from the anterior pituitary through the GH secretagogue receptor (GHS-R). Ghrelin messenger RNA and the peptide are present in rat stomach, but its cellular source has yet to be determined. Using two different antibodies against the N- and C-terminal regions of rat ghrelin, we identified ghrelin-producing cells in the gastrointestinal tracts of rats and humans by light and electron microscopic immunohistochemistry and in situ hybridization combined with immunohistochemistry. Ghrelin-immunoreactive cells, which are not enterochromaffin-like cells, D cells, or enterochromaffin cells, accounted for about 20% of the endocrine cell population in rat and human oxyntic glands. Rat ghrelin was present in round, compact, electron-dense granules compatible with those of X/A-like cells whose hormonal product and physiological functions have not previously been clarified. The localization, population, and ultrastructural features of ghrelin-producing cells (Gr cells) indicate that they are X/A-like cells. Ghrelin also was found in enteric endocrine cells of rats and humans. Using two RIAs for the N- and C-terminal regions of ghrelin, we determined its content in the rat gastrointestinal tract. Rat ghrelin was present from the stomach to the colon, with the highest content being in the gastric fundus. Messenger RNAs of ghrelin and GHS-R also were found in these organs. Ghrelin probably functions not only in the control of GH secretion, but also in the regulation of diverse processes of the digestive system. Our findings provide clues to additional, as yet undefined, physiological functions of this novel gastrointestinal hormone.

Animals↗

[Cytogenetic and medical genetic research on families with a high predisposition for the development of cancer of the gastrointestinal tract].

Three families suspected of predisposition to tumor development in the gastrointestinal tract have been followed in a medico- and cytogenetical study. According to genealogical analysis, cancer predisposition was confirmed in one family only. However, both specific and non-specific signs of genome instability and possible malignant transformation of cells were identified in members of the other two families.

Adolescent↗

Recolonization and colonization resistance of the large bowel after three methods of preoperative preparation of the gastrointestinal tract for elective colorectal surgery.

The impact of three current types of preoperative large bowel preparation on the microbial flora and the colonization resistance (CR) was investigated in 15 volunteers. In the first group a whole gut irrigation was performed without administration of antibiotics (group WGI). In the second group 0.5 g/l metronidazole and 1 g/l neomycin was added to the irrigation fluid (group WGI + AB). A whole gut irrigation with prior oral administration of 1 l mannitol 10% was performed in the third group. The antibiotic prophylaxis in this group consisted of two doses of 80 mg gentamicin i.v. and 500 mg metronidazole orally 24 h after lavage (group Mann + AB). One hour after the mechanical cleansing procedure was finished all volunteers were orally contaminated with one dose of an Escherichia coli test strain. The aerobic faecal reduction due to the cleansing procedure was 2-3 logs, while for the anaerobes it was 4-5 logs. The anaerobic flora in group WGI recovered within 24 h, while the aerobes showed a transient 'overgrowth' for the period of 2 days. The overgrowth of aerobes in group WGI + AB was observed for more than a week and the total numbers of aerobes started gradually to decline after the anaerobic flora had reached pretreatment levels at day three or four. Despite the normal numbers of anaerobes present 24 h after treatment, overgrowth of E. coli was seen in the group Mann + AB, probably due to residual mannitol left in the intestinal tract. The test strain of E. coli was excreted for a period of 1 week by the volunteers in the groups WGI and Mann + AB, but it was isolated for more than 10 weeks in the group WGI + AB. It is thought that all three methods of preoperative large bowel preparation decreased the CR of the gastrointestinal tract because of a disturbance of the interaction between aerobic and anaerobic microorganisms and alterations of the colonic wall. The anaerobic microflora, however, appeared to be primarily responsible for the maintenance of the CR. Antimicrobial prophylaxis should consist of a high dose, short term, systemic antibiotic regimen, not only because an adequate serum level of an appropriate drug at the time of operation substantially decreases the incidence of postoperative septic complications but also because a systemic regimen scarcely influences the CR of the gastrointestinal tract. beta-Aspartylglycine appeared to be a specific but not very sensitive marker for decreased CR.

Adult↗

The pattern of prion-related protein expression in the gastrointestinal tract.

Prion diseases or transmissible spongiform encephalopathies have been shown to be communicated by oral ingestion of the infectious agent. However, the exact route of transmission is still unknown. In order to better understand the pathophysiology of these diseases, it is crucial to identify cell types of peripheral tissues in which the infectious agent may propagate. Since expression of cellular prion protein (PrPc) is a prerequisite for prion replication, we determined the expression of PrPc in the mucosa of the gastrointestinal tract using immunohistochemistry. Expression of PrPc was negative or weak in the neck region of the gastric mucosa and moderate to strong in crypts of both the small and the large bowel. PrPc was found to be upregulated in the mucosa of patients with Helicobacter pylori gastritis. In contrast, PrPc staining appeared to be downregulated in patients with inflammatory disorders of the large bowel and it remained moderate to strong in inflammatory disorders of the small bowel. Our results support the notion that epithelial cells of the gastrointestinal tract may represent a possible target for prion entry and replication.

Digestive System↗

Circulating carcinoembryonic antigen immune complexes in sera of patients with carcinomata of the gastrointestinal tract.

The sera of patients with histologically proven carcinomata of the gastrointestinal tract were fractionated by gel filtration and the fractions assayed for the presence of free carcinoembryonic antigen (CEA) binding immunoglobulins and CEA immune complexes by radioimmuno-double-diffusion, using 125I-CEA as a marker. In eleven out of thirteen cases with disease recurrence, the presence of CEA-IgM complexes was observed, and in three out of thirteen cases the presence of CEA-IgG complexes, could be demonstrated. Free CEA-binding immunoglobulins could not be detected.

Adenocarcinoma↗

Metallic self-expanding stent application in the upper gastrointestinal tract: caveats and concerns.

Ten patients with a variety of upper gastrointestinal tract stenoses precluding conventional prostheses or associated with recurrent occlusions of these prostheses, had an expandable metal Z stent placed. All patients had successful insertion (esophagus, five; biliary, three; afferent loop, one; efferent loop, one), although there was a tendency for the prostheses to delivery distally (gut) or proximally (biliary tree). Despite patency rates for up to 6 months in the esophagus and 1 year in the biliary tree, additional data and design modifications are required before widespread utilization.

Catheterization↗

Cancer in south Louisiana. Part II: Gastrointestinal tract cancers.

Incidence rates for the most common cancers of the gastrointestinal tract are presented for the 5 geographic regions in South Louisiana for the period 1983-1986. The risk of colorectal cancer, the most frequent GI cancer in males and females, is uniformly lower in these regions of South Louisiana than in other areas of the United States. Gastric cancer rates are significantly high in black males, as are pancreatic cancer rates in whites of both sexes compared to national rates.

Black People↗

[Non-epithelial tumors of gastrointestinal tract: diagnosis and surgical treatment].

Non-epithelial tumors of the gastrointestinal tract (GIT) are rare diseases, their rate is less than 2.6% of all tumors of this localization. Analysis of 271 clinical cases of non-epithelial tumors demonstrated that most of them (n = 174) belonged to smooth muscle tumors. Features of growth and localization of benign and malignant non-epithelial tumors were demonstrated. It was revealed that only morphologic study (frequently with histochemical methods) verified the diagnosis of neoplasm. The choice of the scope of surgical intervention depends on the localization, spread and morphology of tumor. Difficulties of verification before surgery lead to active surgical policy for non-epithelial GIT tumors.

Adult↗

Real-time PCR quantification of bovine lactase mRNA: localization in the gastrointestinal tract of milk-fed calves.

Lactase is a disaccharidase that is present in the brush-border membrane of the small intestine, hydrolyzes lactose to glucose and galactose, and is therefore important in milk-fed animals. Assays based on quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) in the bovine species have not yet been described. Therefore, we have developed an RT-PCR assay for the quantification of lactase mRNA levels and have tested its suitability in the bovine gastrointestinal tract of seven 5-d-old milk-fed calves. Primers for RT-PCR amplification of bovine lactase mRNA were designed in the 100% identical regions of species (rats, rabbits, humans) from which lactase sequences were available. Lactase mRNA was expressed relative to mean levels of 4 housekeeping genes (glyceraldehyde-3-phosphate dehydrogenase, beta-actin, ubiquitin, and 18S). The presence of lactase mRNA along the entire gastrointestinal tract was evaluated in samples that consisted of whole gut walls (mucosa plus submucosa). Furthermore, mRNA levels of lactase were measured in fractionized layers of jejunal and ileal mucosa (mainly containing villus tips or crypts) and ileal lamina propria (mainly containing Peyer's patches). Agarose gel electrophoresis of the lactase PCR product revealed a single band that corresponded to the single-amplified product as predicted by the melting curve analysis of the PCR. The amplified partial-bovine lactase sequence showed 87% similarity with human and rabbit sequences and 82% similarity with the rat sequence. Lactase mRNA was present in whole walls (consisting of mucosa and submucosa) of the entire small intestine, but was absent in esophagus, rumen, fundus, pylorus, and colon. Furthermore, lactase mRNA was detected in fractionized villus and crypt layers of jejunum and ileum, but levels were higher in the jejunum in villus than in crypt fractions. No lactase mRNA was detectable in the lamina propria fraction of the ileum containing mainly Peyer's patches. In conclusion, the developed RT-PCR method allows study of lactase mRNA levels.

Animals↗

Potential host-defense role of a human milk vitamin B-12-binding protein, haptocorrin, in the gastrointestinal tract of breastfed infants, as assessed with porcine haptocorrin in vitro.

BACKGROUND: Limited information exists on the biological role of a vitamin B-12-binding protein, haptocorrin, in human milk. The expression of haptocorrin by human mammary epithelial cells and its presence in human milk suggest a potential physiologic function in breastfed infants. OBJECTIVE: We investigated the extent to which haptocorrin could withstand proteolytic degradation and exert antimicrobial activity under in vitro conditions designed to simulate the gastrointestinal tract of breastfed infants. DESIGN: An in vitro model that simulates infant gastric and intestinal digestion was developed. The structural stability of porcine haptocorrin after exposure to digestive enzymes (pepsin and pancreatin) was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blot analysis, column chromatography, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The antimicrobial activity of haptocorrin was determined by incubating haptocorrin with enteropathogenic Escherichia coli O127 strain 2348/69 and monitoring bacterial growth. RESULTS: The structural analysis of haptocorrin exposed to enzymes did not show a decrease in molecular weight, which indicated that haptocorrin can survive proteolytic degradation. Both haptocorrin exposed to digestive enzymes and undigested haptocorrin inhibited the growth of enteropathogenic E. coli and did so to a similar extent. Thus, haptocorrin in vitro not only retains its structure after exposure to proteases but also exhibits antimicrobial activity. CONCLUSION: These results suggest that haptocorrin may exert a host-defense function against pathogens in the gastrointestinal tracts of breastfed infants.

Animals↗

Upper gastrointestinal tract and abdomen: water as an orally administered contrast agent for helical CT.

PURPOSE: To evaluate the use of orally administered water as a negative contrast agent and intravenously administered glucagon in helical computed tomography (CT) of the upper abdomen. MATERIALS AND METHODS: Ninety-eight adult patients underwent 102 helical CT examinations. Patients received 700 mL of water orally 30 minutes before and another 350 mL of water orally with 1 mg of glucagon intravenously just before CT. The amount of water actually ingested was recorded. Luminal distention at five sites was graded on a three-point scale; depiction of six normal anatomic structures was evaluated. RESULTS: Luminal distention improved with the amount of water ingested in four of the five sites (P < .03 in three sites). Depiction of all six normal anatomic structures improved with increasing luminal distention (P < .001). The normal duodenal papilla was seen in 42% (83 of 198) of the examinations. Of 87 patients who had previously undergone CT with positive oral contrast agents, 89% (n = 77) preferred the water, 11% (n = 10) had no preference, and none preferred the positive agent (P < .001). Upper gastrointestinal tract abnormalities were easily recognized and depicted. CONCLUSION: Water is an efficacious negative contrast agent for evaluation of the upper gastrointestinal tract during helical CT.

Administration, Oral↗

The justification for surgical treatment of metastatic melanoma of the gastrointestinal tract.

Fifty-six patients with symptomatic metastatic melanoma of the gastrointestinal tract (GIT) treated surgically at the Sydney Melanoma Unit between 1974 and 1989 were reviewed. The majority of these patients presented with abdominal pain or symptoms of anemia. The small intestine was the site of metastasis in more than 80 per cent. The mean over-all survival time was 11.7 months (range of one to 60 months) after surgical treatment of a first metastasis to the GIT and 3.6 months (range of zero to 12 months) postoperatively for a second GIT metastasis. Forty-four of the patients reported complete relief of their symptoms postoperatively. The results suggest that an aggressive approach to symptomatic GIT metastases from malignant melanoma is justified both to relieve distressing symptoms and to prolong life.

Adolescent↗

[Acute insufficiency of the gastrointestinal tract in patients with severe gunshot injury].

Acute insufficiency of the gastrointestinal tract (GIT) in patients with severe gunshot injuries is an important link of pathogenesis of the polyorganic insufficiency syndrome. The character of the wound, the numerical score objective assessment of the injury severity and severity of the patient's state are considered to be criteria of early diagnosis of a risk of the development of acute insufficiency of GIT. The specific feature of "general" intensive therapy of acute insufficiency of GIT in severe gunshot traumas is the necessary application of regional anesthesia, sympatholytics, anticholinesterase agents and H2-blockers. Intensive "enteral" therapy of acute insufficiency of GIT in severe gunshot wounds includes the measures resulting in improvement of microcirculation, tissue respiration in organs of GIT, decompression of the stomach, local defense of mucosa, detoxication and early enteral balanced nutrition. The described method of treatment of wounded to the stomach used at specialized medical institutions resulted in 6.2 less lethality among this category of patients.

Abdominal Injuries↗

Overexpression of M68/DcR3 in human gastrointestinal tract tumors independent of gene amplification and its location in a four-gene cluster.

Fas-mediated apoptosis is an important regulator of cell survival, and abnormalities in this system have been shown to result in a number of human pathological conditions. A secreted member of the tumor necrosis factor receptor superfamily, DcR3, was recently reported to be amplified in human lung and colon cancers as a negative regulator of Fas-mediated apoptosis. We identified this gene, which we call M68. M68 genomic DNA, mRNA, and protein levels were examined in a series of human gastrointestinal tract tumors. Using M68 immunohistochemistry and a scoring system similar to that used for HER-2/neu, we found that M68 protein was overexpressed in 30 of 68 (44%) human adenocarcinomas of the esophagus, stomach, colon, and rectum. Tumors examined by Northern blot revealed M68 mRNA highly elevated in a similar fraction of primary tumors from the same gastrointestinal tract regions, as well as in the colon adenocarcinoma cell lines SW480 and SW1116. Further, we found M68 protein to be overexpressed in a substantial number of tumors in which gene amplification could not be detected by fluorescence in situ hybridization or quantitative genomic PCR, suggesting that overexpression of M68 may precede amplification in tumors. Finally, we find that M68 lies within a four-gene cluster that includes a novel helicase-like gene (NHL) related to RAD3/ERCC2, a plasma membrane Ras-related GTPase and a member of the stathmin family, amplification or overexpression of which may also contribute to cell growth and tumor progression.

ADP-Ribosylation Factors↗

Radiation doses to patients during contrast examinations of the gastrointestinal tract.

Radiation doses received by patients undergoing radiological examinations of the gastrointestinal tract have been measured in 405 patients at two major hospitals in Nairobi using thermoluminescent LiF dosimeters. Skin-entry doses were found to be high at one of the facilities (A) and very high at the other (B). Barium meal delivered mean doses of 77 mGy (7.7 rad) and 558 mGy (55.8 rad) at facilities A and B respectively, while the corresponding mean values for barium enema were 93 mGy (9.3 rad) and 712 mGy (71.2 rad). Differences between the two hospital mean doses were highly significant (p < 0.001). Doses to the thyroid gland and the gonads were also generally higher than those reported in other similar studies. Poor performance of old and ill-maintained radiological equipment, among other possible factors, is suggested to be the main cause of excessive patient exposure. Radiation risks to patients are considered in the context of such high doses being received by a generally young patient population. The authors suggest that there ought to be limits on the extent to which social and economic considerations in the provision of radiological services should be allowed to compromise sound principles in the radiation protection of the patient. It is recommended that increased efforts be directed at establishing and supporting quality assurance programmes for the performance testing of radiological equipment in Africa.

Adolescent↗

Autoradiographic study of motilin binding sites in the rabbit gastrointestinal tract.

Although motilin receptors have been demonstrated by ligand binding studies, there have been no morphological studies of motilin binding site distribution. Light microscopic macro- and micro-autoradiography using highly purified iodinated Tyr23 canine motilin (10(-10) M) was carried out on the gastric antrum, duodenum, cecum and distal colon of the rabbit. Motilin binding sites were found on the smooth muscle layers of the gastric antrum, duodenum and colon, but no positive binding reaction was detected in that of the cecum. Specific binding sites were particularly abundant in the circular muscle layers, with low concentrations in the longitudinal muscle layers of the gastric antrum, duodenum and colon. No motilin binding sites were found in the mucosa of the gastrointestinal tract and pancreas. The intensity of the positive reaction was inhibited when the tissue was incubated with 10(-8) M unlabeled motilin and was completely abolished by 10(-7) M unlabeled motilin. These results are consistent with the difference in contractile response to motilin between the muscle layers of the gastrointestinal tract.

Animals↗

Continuous single-layer serosubmucosal anastomosis in the upper gastrointestinal tract.

In a 4-year period, 100 anastomoses in the upper gastrointestinal tract were fashioned using a single serosubmucosal layer of continuous polydioxanone. One patient required revisional surgery because of anastomotic stricture after partial gastrectomy, but there was no other complication related to the anastomosis. This technique is simple, safe, and quick to perform.

Anastomosis, Surgical↗