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Neuroendocrine cells in the gastrointestinal tract of wild boar.

The presence and the distribution of neuroendocrine cells in the gastrointestinal tract of adult wild boar were investigated. The endocrine cells have been identified by means of immunocytochemical techniques using antibodies against serotonin, gastrin, somatostatin, cholecystokinin (CCK), met-enkephalin (MET-ENK), gastric-inhibitory peptide (GIP) and glucagon. The number of positive cells for each antiserum in each region was evaluated. Results were compared with data present in the literature and obtained previously by us and other authors in swine and domestic mammals (Ceccarelli et al., 1985, 1987, 1990, 1991, 1995; Capella and Solcia, 1972; Domeneghini and Castaldo, 1981; Peranzi and Lehy, 1984; Krause et al., 1985).

Animals↗

Biochemical evidences for ribonucleic acid viral-like characteristics in malignant diseases of gastrointestinal tract and lung in humans.

It has been demonstrated that malignant diseases of the gastrointestinal tract and lung in humans possess three characteristics invariably found in ribonucleic acid tumor viruses: the presence of a ribonucleic acid directed deoxyribonucleic acid polymerase, reverse transcriptase; a high molecular weight ribonucleic acid with a sedimentation coefficient of 70 Svedberg units, and particulate elements with densities of 1.16 to 1.18 grams per milliliter sucrose gradient. Twelve of 17 carcinomas of the colon, three of five carcinomas of the stomach, all three carcinomas of the rectum and seven of ten carcinomas of the lung displayed detectable evidence of these viral-like entities. None of the corresponding normal tissues had positive reactions.

Cell Transformation, Neoplastic↗

Effect of hyperosmolar stimuli and coeliac disease on the permeability of the human gastrointestinal tract.

1. Oral loads have been used to assess the permeability of the human gastrointestinal tract, with lactulose (mol. wt. 342), raffinose (mol. wt. 504), stachyose (mol. wt. 666) and a fluoresceinlabelled dextran (mol. wt. 3000) as marker substances. Timed urinary recovery of these substances, which are not metabolized, was measured by quantitative paper chromatography and direct fluorimetry, and the results were used as an indication of passive intestinal permeability. 2. Results in healthy adults showed that permeability to these markers was dependent on molecular size, even after correction for aqueous diffusion differences, such that a profile of restricted permeability could be described for this range of markers. Interpretation in terms of conventional pore theory suggested the presence of more than one population of pores. 3. Ingestion of solutions made hyperosmotic by inclusion of glycerol resulted in a large increase in permeability, in a pattern that suggested an increase in either the size or frequency of a range of smaller pores. 4. A similar increase in permeability and alteration in the profile of restriction was found in patients with coeliac disease. 5. The possible location of such pores in the gastrointestinal mucosa is discussed in relation to the cell membrane, the intercellular junction, and the sites of cell exfoliation.

Celiac Disease↗

Distribution of Ca.LSU intron and acid protease production by Candida albicans strains isolated from gastrointestinal tract of diabetes children.

The association between the presence of self-splicing intron Ca.LSU and proteolytic activity of Candida albicans isolates was tested. Study included 95 C. albicans strains isolated from gastrointestinal tract of diabetes children. The strains with the intron (genotype B) displayed a significantly higher proteolytic activity (385.2+/-192U/L) than did strains without intron (genotype A) (119+/-115U/L) (p = 0.0000048).

Aspartic Acid Endopeptidases↗

[Genome analyses for precancerous lesions in the gastrointestinal tract].

We herein summarize the reports on genetic changes in precancerous lesions in the gastrointestinal tract. It has been reported that with esophageal lesions such as dysplasia and Barrett's esophagus there is a high frequency of p53 mutations. Among gastric lesions, some cases of chronic atrophic gastritis have been shown to harbor K-ras mutations. p53 and APC mutations in intestinal metaplasia have also been demonstrated, as have APC mutations in flat adenomas. With colorectal lesions, it has been reported that K-ras, DCC, p53 mutations commonly occur while APC mutations are also seen in cases of adenoma-carcinoma. p53 and K-ras mutations have been demonstrated with serrated adenoma, and K-ras mutations with hyperplastic polyps APC mutations in familial polyposis coli, LKB1 mutations in Peutz-Jeghers syndrome, and SMAD4/DPC4 mutations in juvenile polyposis syndrome have been found. Besides these genes, other genetic changes likely occur in carcinogenesis among those with hereditary diseases. K-ras mutations in aberrant crypt foci and hMSH2 mutations in ulcerative colitis have been found. Research into the genetic changes associated with cancerous lesions should lead to the development of early diagnosis and treatment methods for gastrointestinal cancer as well as the improved comprehension of carcinogenesis.

Adenoma↗

Biopsy assessment of drug efficacy in the gastrointestinal tract.

When using biopsy pathology in clinical pharmacology to assess drug efficacy in the gastrointestinal tract, a number of questions must be answered: Is the biopsy necessary or more effective than macroscopic views by endoscopy? Can we extract maximal information from the specimen? Are there surrogate serum or other markers that give an overall measure of disease and/or improvement? Indeed, clinicopathological correlation is of paramount importance. If biopsy is to be used, it is important to utilize appropriate scoring systems. Many grading systems use continuous spectra, which are ordinal categorical variables and therefore a grading system of assigned 'numbers' which cannot be used in processes that require continuous variables such as linear regression. The use of grading vs a 'true' score with real numbers must be carefully considered, the site and number of biopsies must be precisely chosen and interobserver reproducibility of results evaluated before undertaking drug trials. Immunocytochemistry and in situ hybridization, however, can provide quantifiable molecular information related to mechanisms of drug action. The biopsy is of significant value as it is a true in vivo assessment if the above caveats are taken into account. However, further work is needed to determine sound histological criteria to assess the efficacy of drugs for use in gastrointestinal disease.

Biopsy↗

[The pharmacokinetic characteristics of theophylline in patients with chronic nonspecific intestinal diseases in relation to its routes of administration into the gastrointestinal tract].

Theophylline pharmacokinetics was investigated upon introduction of euphylline (0.15 g) at four levels of gastrointestinal tract: orally (20 patients), into the jejunum (15 patients) at enterogastroduodenoscopy, in the ileocecal area (8 patients) at colonoscopy and rectally (9 patients). Absorption speed depended on the variant of the gastrointestinal introduction rather than on the variant of chronic nonspecific intestinal disease, and appeared maximal in the drug introduction into the jejunum. Concentration and area under curve became maximal in minor participation of the liver in primary capture and biotransformation of theophylline. Reduced theophylline doses are recommended in lower hepatic metabolism of the drug, in hepatic hypofunction, in rectal route of administration.

Administration, Rectal↗

Population dynamics of ingested Clostridium difficile in the gastrointestinal tract of the Syrian hamster.

The population dynamics of Clostridium difficile in the hamster gastrointestinal tract were studied after intragastric inoculation with organisms and a 51Cr tracer. Seventy-eight percent of spores germinated within the small intestine within 1 hr. Germinated spores and vegetative cells both showed two phases of elimination from the hamster cecum--an initial phase of rapid death that was not affected by antibiotic treatment followed by a phase of complete inhibition of multiplication. The latter phase of inhibition was not seen in antibiotic-treated animals and was thus attributable to the indigenous flora. The 51Cr tracer mixed well with cecal contents and was eliminated exponentially with a dilution rate constant ranging from -0.46/hr to -0.31/hr in normal hamsters. The hamster cecum was therefore dynamically analogous to a continuous flow system, a finding supporting the concept that anaerobic continuous flow cultures are useful in vitro models of the cecal ecosystem.

Animals↗

Endoscopic management and follow up of Dieulafoy lesion in the upper gastrointestinal tract.

BACKGROUND AND STUDY AIMS: Dieulafoy's lesion is an important cause of upper gastrointestinal bleeding, and the safety and efficacy of endoscopic treatment have been widely accepted. The aim of this study was to evaluate the effectiveness of endoscopic management, including hemoclipping and injection methods, for bleeding Dieulafoy lesions in the upper gastrointestinal tract. PATIENTS AND METHODS: Between 1995 and 2003, 61 patients with bleeding Dieulafoy lesions underwent endoscopic treatment. The available hemostatic methods were hemoclipping, hypertonic saline-epinephrine injection, and pure ethanol injection. Clinical data, endoscopic features, and treatment outcome were analyzed retrospectively. RESULTS: Comorbid conditions were present in 39 patients (64 %). Active bleeding was noted in 20 patients (33 %). Hemoclipping was a selected treatment in 48 patients (79 %). Initial hemostasis was achieved in 61 patients (100 %). One patient had rebleeding 6 days after the initial procedure but was successfully treated endoscopically. The 30-day mortality was 0 %. During follow-up, for a mean of 47 months, 15 patients (25 %) died of causes unrelated to the Dieulafoy lesion. Two patients had recurrent bleeding due to non-Dieulafoy gastric ulcer, and responded to endoscopic therapy. We encountered no patients who required surgery. CONCLUSIONS: Dieulafoy lesion can be successfully managed by endoscopic treatment. The long-term outcome is acceptable.

Adolescent↗

Bioadhesive fluorescent microspheres as visible carriers for local delivery of drugs. II: Uptake of insulin-loaded PCEFB/PLGA microspheres by the gastrointestinal tract.

Uptake of novel inherently fluorescent microspheres composed of a luminescent polyanhydride, poly[p-(carboxyethylformamido)-benzoic anhydride] (PCEFB), and poly(lactide-co-glycolide) (PLGA) (2:1, weight ratio) by the gastrointestinal tract was evaluated by fluorescent microscopy. Oral efficiency of the incorporated insulin also was determined by measuring reduction of plasma glucose levels after feeding diabetic rats with a single dose of the microspheres. We found that PCEFB/PLGA microspheres could adhere to the intestinal epithelium and traverse the absorptive cells. A large number of the spheres were observed in spleen, whereas few were detected in liver within the evaluated period of time. Apparent reduction of the plasma glucose levels was observed over a span of 6 h postfeeding. The unique properties of the delivery system such as biodegradability, bioadhesivity, and inherently luminescent characteristics render it an ideal "visible" tracer for monitoring oral fate of polymeric microspheres.

Adhesives↗

Reactive nodular fibrous pseudotumors of the gastrointestinal tract: report of 8 cases.

Eight cases of reactive nodular fibrous pseudotumor of the gastrointestinal tract are presented. The patients included 6 males and 2 females between the ages of 1 and 68 years (mean age 41.5 years). Three tumors involved the small intestine, and 5 of the investigated lesions were located in the large bowel. Of these, 2 originated in the sigmoid colon, 1 in the cecum, 1 in the appendix, and 1 in the large bowel not otherwise specified. The tumors' size varied from 3 to 10 cm in the greatest diameter (mean 6.2 cm). Histologically they were composed of stellate or spindle shaped cells resembling fibroblasts arranged haphazardly or in intersecting fascicles, embedded in a collagen-rich stroma, with sparse intralesional mononuclear cells frequently arranged in lymphoid aggregates. Immunohistochemically, the lesions were positive for vimentin (7/7), smooth muscle actin (8/8), muscle-specific actin (5/7), cytokeratins AE1/AE3 (6/7), and CAM 5.2 (1/7), and antigen CD68 (1/7). No case (0/8) reacted positively with antibody to CD117 (c-kit). Genetically no substitutions, deletions, or insertions occurred in exon 11 in all analyzed samples. Likewise, no deletions or insertions in part of exon 9 were observed. Ultrastructurally the tumor cells revealed features typical of myofibroblasts. According to the morphologic, immunohistochemical, and ultrastructural features mentioned above, especially to the positivity of low-molecular-weight cytokeratins, we propose this lesion to be related to a proliferation of multipotential subserosal cells rather than ordinary myofibroblasts or fibroblasts.

Adult↗

Stress and the gastrointestinal tract.

Stress, defined as an acute threat to homeostasis, evokes an adaptive or allostatic response and can have both a short- and long-term influence on the function of the gastrointestinal tract. The enteric nervous system is connected bidirectionally to the brain by parasympathetic and sympathetic pathways forming the brain-gut axis. The neural network of the brain, which generates the stress response, is called the central stress circuitry and includes the paraventricular nucleus of the hypothalamus, amygdala and periaqueductal gray. It receives input from the somatic and visceral afferent pathways and also from the visceral motor cortex including the medial prefrontal, anterior cingulate and insular cortex. The output of this central stress circuit is called the emotional motor system and includes automatic efferents, the hypothalamus-pituitary-adrenal axis and pain modulatory systems. Severe or long-term stress can induce long-term alteration in the stress response (plasticity). Corticotropin releasing factor (CRF) is a key mediator of the central stress response. Two CRF receptor subtypes, R1 and R2, have been described. They mediate increased colonic motor activity and slowed gastric emptying, respectively, in response to stress. Specific CRF receptor antagonists injected into the 0 block these visceral manifestations of stress. Circulating glucocorticoids exert an inhibitory effect on the stress response by receptors located in the medial prefrontal cortex and hippocampus. Many other neurotransmitters and neuroimmunomodulators are being evaluated. Stress increases the intestinal permeability to large antigenic molecules. It can lead to mast cell activation, degranulation and colonic mucin depletion. A reversal of small bowel water and electrolyte absorption occurs in response to stress and is mediated cholinergically. Stress also leads to increased susceptibility to colonic inflammation, which can be adaptively transferred among rats by sensitized CD4(+) lymphocytes. The association between stress and various gastrointestinal diseases, including functional bowel disorders, inflammatory bowel disease, peptic ulcer disease and gastroesophageal reflux disease, is being actively investigated. Attention to the close relation between the brain and gut has opened many therapeutic avenues for the future.

Adaptation, Psychological↗

Distribution of galanin-immunoreactive nerves in the canine gastrointestinal tract.

The distribution of nerves containing galanin immunoreactivity (GAL-IR) in the canine gastrointestinal tract was determined by immunohistochemistry. GAL-IR was observed in nerve cell bodies and nerve fibers in all layers of the lower esophagus, gastric antrum, pylorus, ileum, and colon, and in the sphincters of lower esophagus and pylorus. There were numerous GAL-IR-containing nerve cell bodies in the myenteric plexus of gastric antrum. GAL-IR nerve somata were also common in the myenteric plexus of lower esophagus, ileum, pylorus, and colon, and in the submucous plexus of stomach, ileum, and colon. GAL-IR-positive nerve fibers were also observed around submucous blood vessels of the stomach. GAL-IR nerves are distributed more widely in the canine enteric nervous system than previously recognized.

Animals↗

Changes of substance P and somatostatin contents in the gastrointestinal tract of streptozotocin diabetic rats.

Substance P and somatostatin contents were measured in the gastrointestinal tract of streptozotocin diabetic rats, 1 month after streptozotocin administration (60 mg/kg), and of age-matched controls with radioimmunoassay. Substance P and somatostatin contents were statistically increased in the extrafundus of the diabetic stomach, but not in the diabetic fundus. Substance P was significantly decreased in the diabetic ileum and caecum. Similarly, somatostatin was decreased in the diabetic caecum. Contrarily, slight increase of somatostatin contents in the diabetic duodenum, jejunum and proximal colon was not statistically significant.

Animals↗

Intraoperative tissue oximetry in the human gastrointestinal tract.

Tissue oxygen tension was measured using a modified Clark oxygen electrode in the gastrointestinal tract of 33 patients undergoing laparatomy. The electrode, which incorporated a thermistor, had a linear response to oxygen tension (r = 0.995, p less than 0.001). The patients were all maintained on an inspired oxygen concentration of 33 +/- 3% and had a mean arterial oxygen tension (PaO2) of 124.9 +/- 31.9 mm Hg. Tissue oxygen tension measurements (mm Hg, mean +/- SD) were recorded from the serosal surfaces of the stomach (46.3 +/- 15.4), mid-ileum (36 +/- 9.7), terminal ileum (33.5 +/- 11.5), cecum (30.3 +/- 7.4), transverse colon (38.5 +/- 10), descending colon (29.3 +/- 11), and sigmoid colon (39.2 +/- 7.7) and tended to increase with increasing PaO2 (r = 0.70, p less than 0.001). Arterial occlusion resulted in a gradual decrease in tissue oxygen tension. It is concluded that intraoperative tissue oxygen tension measurement is feasible, and that the technique may have clinical applications in the assessment of intestinal viability.

Adult↗

Dose rate-dependent sparing of the gastrointestinal tract by fractionated total body irradiation in dogs given marrow autografts.

PURPOSE: We compared gastrointestinal toxicity of single vs. fractionated total body irradiation (TBI) administered at dose rates ranging from 0.021 to 0.75 Gy/min in a canine model of marrow transplantation. METHODS AND MATERIALS: Dogs were given otherwise marrow-lethal single or fractionated TBI from dual 60Co sources at total doses ranging from 8-18 Gy and delivered at dose rates of 0.021, 0.05, 0.10, 0.20, 0.40, and 0.75 Gy/min, respectively. They were protected from marrow death by infusion of previously stored autologous marrow cells and they were given intensive supportive care posttransplant. The study endpoint was 10-day mortality from gastrointestinal toxicity. Logistic regression analyses were used to jointly evaluate the effects of dose rate, total dose, and delivery regimen on toxicity. RESULTS AND CONCLUSION: With increasing dose rates, mortality increased for either mode of delivery of TBI. With dose rates through 0.10 Gy/min, mortality among dogs given single vs. fractionated TBI appeared comparable. Beginning at 0.20 Gy/min, fractionation appeared protective for the gastrointestinal tract. Results in dogs given TBI at 0.40 and 0.75 Gy/min, respectively, were comparable, and dose fractionation permitted the administration of considerably higher total doses of TBI than were possible after single doses, an increment that was on the order of 4.00 Gy. The data indicate that the impact of fractionating the total dose at high dose rates differs from the effect of fractionation at low dose rates.

Animals↗

Bacterial translocation from the gastrointestinal tract.

Bacterial translocation is defined as the passage of viable indigenous bacteria from the gastrointestinal tract to extraintestinal sites, such as the mesenteric-lymph-node complex, liver, spleen and bloodstream. Three major mechanisms promote bacterial translocation: intestinal bacterial overgrowth, deficiencies in host immune defenses and increased permeability or damage to the intestinal mucosal barrier.

Animals↗

Inflammatory fibroid polyps of gastrointestinal tract. Evolution of histologic patterns.

Fifteen cases of inflammatory fibroid polyps (IFPs) of the gastrointestinal tract were subjected to histopathologic analysis. Six of them were from the small intestines and the remainder from the stomach. Their size ranged from 0.2 to 12.0 cm in maximum cross-section. The polyps were classified into four groups, based on histology and size. The nodular stage (average: 0.4 cm) showed nodules of immature fibroblasts with a loose myxoid background resembling a tactile corpuscle of Meissner. The fibrovascular stage (average: 1.5 cm) demonstrated concentric aggregations of mature fibroblasts, with endothelial proliferation and eosinophilic infiltration. When the polyps became larger (average: 4.8 cm), the histologic patterns were modified, evolving into the sclerotic or edematous stage by either collagenization or vascular compromise following intestinal obstruction. This study suggests that histologic patterns of IFPs may represent an evolutional change when size is increased.

Adult↗