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Testosterone metabolism by the rat gastrointestinal tract, in vitro and in vivo.

We have shown previously that the capacity of the jejunal mucosa to oxidise testosterone to the weaker androgen, androstenedione, by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD), is considerable. The present study extends these earlier observations by measuring 17 beta-HSD activity in different regions of the gastrointestinal tract, by investigating the potential for testosterone metabolism by slices and everted sacs of rat jejunum, and estimating the contribution of intestinal testosterone metabolites to circulating levels of plasma androgens, by portal vein sampling in the rat, in vivo. 17 beta-HSD activity in homogenates of gastric and duodenal mucosa was significantly higher than that in jejunum, and was also present in ileum and colon. In addition to androstenedione, slices and everted sacs of rat jejunum produced various metabolites, one of which was probably dihydrotestosterone. It was not, however, a major metabolite in vivo. It is suggested that 5 alpha-reduction may be favoured in vitro by a lower oxidation-reduction potential resulting from tissue anoxia. The major portal vein metabolite was androstenedione, the same major metabolite produced by mucosal homogenates. We conclude that oxidation of testosterone is the major metabolic pathway in intestinal mucosa and the capacity of the gastrointestinal tract to reduce the potency of testosterone is considerable. Our findings suggest that the gut, rather than the liver, is responsible for the failure of oral testosterone to provide effective androgen replacement therapy. The qualitative difference in testosterone metabolism between in vitro and in vivo preparations emphasises the need for caution in the interpretation of similar in vitro experiments.

17-Hydroxysteroid Dehydrogenases↗

Functional evaluation of the postoperative gastrointestinal tract using kinematic MR imaging: Quantitative assessment of peristaltic activity.

The purpose of this study is to demonstrate the feasibility of kinematic MR imaging in visualizing peristaltic activity in the reconstructed gastrointestinal tract with quantitative measurements. Sixteen patients with gastrointestinal reconstruction were studied with kinematic MR imaging using HASTE and/or true FISP. Peristaltic waves were noted in the retrosternal gastric segment after gastric pull through (frequency = 3.0 +/- 0.5 times/min, velocity = 2.6 +/- 0.6 mm/s) and in the residual antrum after cardiectomy (frequency = 3 times/min, velocity = 4.0 mm/s). Peristaltic waves were not apparent in the residual fundus after distal gastrectomy and in the reconstructed jejunum after pancreatoduodenectomy and gastrojejunostomy.

Aged↗

Lesions of the gastrointestinal tract of pigs infected with transmissible gastroenteritis.

Gross, subgross and histological lesions were studied in 103 pigs infected with transmissible gastroenteritis virus and killed at daily intervals for 14 days. Twenty-three pigs served as controls. Thirty-six pigs were given colchicine four hours prior to being killed in order to determine the mitotic activity in the gastrointestinal tract. The gross lesions consisted of dehydration, excessive milk curd in the stomach, focal hemorrhage in the submucosa of the diverticulum ventriculi of the stomach, fundic and pyloric congestion in severly dehydrated animals and thinning of the small intestinal wall. The major subgross lesion was a marked shortening of the villi in the lower duodenum, jejunum and ileum within 24 hours after exposure to the virus. Regrowth of the villi became evident on about the sixth day after infection. Histological examination of the small intestine revealed that the villus-height/crypt-depth ratio in the jejunum was reduced from 7:1 in normal pigs to less than 1:1 in infected pigs. Villous atrophy was less severe in the proximal duodenum and ileum. Cells covering the atrophic villi were flatened or cuboidal and did not have well defined brush borders. Inflammatory changes in the gastrointestinal tract were minimal at all stages of infection. Goblet cell numbers increased slightly in the recovery stage of the disease and small numbers of mononuclear cells accumulated in the lamina propria during regrowth of the villi. The number of metaphase nuclei in the small intestinal crypts of infected pigs was greater than in normal pigs.

Animals↗

Transgenic mice carrying a PSArasT24 hybrid gene develop salivary gland and gastrointestinal tract neoplasms.

BACKGROUND: Although prostate cancer is one of the most prevalent tumors in men, knowledge of its biology has been hindered by lack of animal models. We have attempted to develop a prostate cancer model utilizing transgenic mouse technology. EXPERIMENTAL DESIGN: Two lines of transgenic mice were derived from one cell stage embryos injected with a fusion gene consisting of a mutated (codon 12) ras gene driven by the human prostate specific antigen (PSA) promoter in an attempt to target the oncogene specifically to the mouse prostate gland. Nontransgenic FVB/N mice were used as controls. The animals were sacrificed for study between 4 and 55 weeks of age. RESULTS: All organs were normal except the salivary glands and gastrointestinal tracts, both of which developed carcinomas in animals older than 44 weeks. The salivary gland tumors were of ductal origin, exhibited a variable degree of differentiation, and were shown to contain abundant PSAras mRNA by in situ hybridization. The gastrointestinal tract tumors were undifferentiated but appeared to be of stromal origin. Both salivary gland and gastrointestinal tumors occasionally metastasized. No transgene expression could be demonstrated in the prostate gland by either reverse transcription-polymerase chain reaction or in situ hybridization. CONCLUSIONS: Lack of transgene expression by the prostate can be explained on the basis of the apparent species specificity previously observed for PSA. Expression in salivary gland is best attributed to identity between the nucleotide sequences of the PSA promoter and of a mouse glandular kallikrein normally secreted by the salivary gland.

Animals↗

[Endoscopy of the upper gastrointestinal tract].

Esophagogastroduodenoscopy (EGD) has replaced X-ray diagnosis as the standard method for assessment of the upper gastrointestinal tract. It also offers an array of minimally invasive treatment options. This contribution presents the requisite medical, technical, and human resources needed for EGD. The indication for this invasive procedure should always be carefully reviewed and contraindications excluded. EGD should be performed according to standardized procedures and well documented by noting distinctive features of peristalsis and describing alterations of mucosal size and surface texture. The endoscopic techniques of biopsy, chromoendoscopy, and percutaneous endoscopic gastrostomy should always be available in routine endoscopy.

Endoscopes, Gastrointestinal↗

Immunohistochemical study about the Flt-1/VEGFR1 expression in the gastrointestinal tract of mouse, rat, dog, swine and monkey.

Fms-like tyrosine kinase 1 (Flt-1) performs a subordinate effector role in mesenchymal angiogenesis and potentially serves an equally important functional role as a self-contained receptor in epithelial cells. In both endothelial cells and epithelial cells, Flt-1/vascular endothelial growth factor receptor 1 (VEGFR1) downstream signalling is involved in regulating cellular processes such as cytoskeletal changes and cellular survival protection. Cellular renewal of the gastrointestinal mucosa is based on these processes and might involve Flt-1/VEGFR1 pathway activities; the molecular mechanisms regulating these cellular dynamics remain unclear. This study was performed to investigate the presence and distribution of Flt-1/VEGFR1 in epithelial cells of the gastrointestinal tract by immunohistochemistry (IHC). Gastrointestinal tissues were taken from eight anatomical sites from mouse, rat, dog, swine and monkey. Present results revealed a cytosolic Flt-1/VEGFR1 staining pattern in mucosal epithelial cells for all investigated species. Non-epithelial structures also displayed a distinct Flt-1/VEGFR1 positivity and included vascular smooth muscle walls, enteric smooth muscle layers, the enteric nervous system and capillary endothelial cells. Diverse intensities of the Flt-1/VEGFR1 binding reaction within each species were observed in the intestinal mucosa with a strong immunoreaction in enterocytes and with a low protein expression in the ileum in most species. Crypt cells in the large intestine were mostly negative for Flt-1/VEGFR1. A peculiar and mainly intranuclear antibody binding reaction was found in Brunner's gland epithelial cells of mouse and rat whereas Brunner's glands of dog, swine and monkey remained completely negative. These results indicate a potential involvement of Flt-1/VEGFR1 in normal restitution of gastrointestinal structures in the species studied. Additionally, intranuclear Flt-1/VEGFR1 antibody binding in Brunner's glands of rodents may suggest a nuclear translocation of the transmembrane VEGFR1 which has not previously been described.

Animals↗

Does intake of highly demineralized water damage the rat gastrointestinal tract?

Highly demineralized water (hd-water) is used frequently in laboratories and on an industrial scale. However, no systematic data seem available as to whether hd-water has a toxic potential beyond the physical risks of drinking water (drowning, water intoxication). This study investigated the impact of hd-water on function and morphology of the rat's gastrointestinal tract. One group of rats received hd-water together with the usual diet ad libitum for 14 d. A second group was exposed to hd-water after withdrawal of food and water for 24 h. Both experiments had control groups which were treated identically except that hd-water was replaced by tap water. Histology showed no signs of erosion, ulceration or inflammation in the esophagus, stomach or jejunum. Body weights and the uptake of food and water were not significantly different between the hd-water exposures and controls for 14 d. Tissue alkaline phosphatase activity was unaltered, and the mitotic rate in the epithelium of the esophagus and stomach were not different between controls and rats on hd-water. Exposure to hd-water caused no changes in the km or Vmax values for the uptake o of alpha-methyl-D-glucose from the upper jejunum. There findings indicate no impact of hd-water on the function or morphology of the rat gastrointestinal tract. There is no need for additional safety regulations when working with hd-water which go beyond those considered adequate to prevent drowning and water intoxication.

Animals↗

Role of cyclooxygenase-2 in the carcinogenesis of gastrointestinal tract cancers: a review and report of personal experience.

Selective cyclooxygenase (COX)-2 inhibitors (coxibs) were developed as one of the anti-inflammatory drugs to avoid the various side effects of non-steroidal anti-inflammatory drugs (NSAIDs). However,coxibs also have an ability to inhibit tumor development of various kinds the same way that NSAIDs do. Many experimental studies using cell lines and animal models demonstrated an ability to prevent tumor proliferation of COX-2 inhibitors. After performing a randomized study for polyp chemoprevention study in patients with familial adenomatous polyposis (FAP),which showed that the treatment with celecoxib, one of the coxibs, significantly reduced the number of colorectal polyps in 2000, the U.S. Food and Drug Administration (FDA) immediately approved the clinical use of celecoxib for FAP patients. However, some coxibs were recently reported to increase the risk of serious cardiovascular events including heart attack and stroke. In this article we review a role of COX-2 in carcinogenesis of gastrointestinal tract, such as the esophagus, stomach and colorectum,and also analyze the prospect of coxibs for chemoprevention of gastrointestinal tract tumors.

Adenomatous Polyposis Coli↗

Current status of carcinoembryonic antigen (CEA) and CEA-S assays in the evaluation of neoplasm of the gastrointestinal tract.

Carcinoembryonic antigen (CEA) is heterogeneous and may represent a set of closely related glycoproteins which have been referred to as isomeric species of CEA. The existence of other CEA-related glycoproteins such as non-specific cross reacting antigen (NCA) has been recognized. Recently a highly purified homogeneous isomeric species of CEA described as CEA-S has shown differences in diagnostic results upon analysis of clinical sera as well as quantitative immunochemical differences. In a blind study of 308 sera, the CEA and CEA-S assays were compared. A significant difference in false positive results was observed between the CEA and CEA-S assay results. In contrast to the low but significant evidence of elevated CEA in sera of random normal persons and patients with liver disease or inflammatory disease of the gastrointestinal tract or lung, none of the sera had elevated concentrations of CEA-S. Among patients with tumor of the gastrointestinal tract that were considered surgically resectable, 46 percent were elevated using the CEA-S assay and only 34.7 percent were elevated above 5 nanograms per ml by the CEA assay. The CEA assays detect CEA-related molecules produced by lung, breast and other tumors; the CEA-S assay appears equally sensitive to CEA of gastrointestinal origin but detects only a small subgroup of breast, lung and, rarely, other types of tumors.

Carcinoembryonic Antigen↗

[Morphofunctional changes in gastrointestinal tract in patients with psoriasis accompanied by chronic opisthorchosis].

The paper covers clinical, morphological and functional aspects of gastrointestinal tract condition in patients with psoriasis accompanied by chronic opisthorchosis (CO). The authors examined 150 patients with psoriasis accompanied by CO, 100 patients having psoriasis without helminthiasis, 100 patients with CO and 30 healthy people. The gastric secretion was evaluated by means of the fractional test (both phases) with histamine stimulation; other diagnostic procedures included carbohydrate absorption evaluation (5-gram D-Xylose absorption test) and Kamer test of fat absorption. The morphological condition of the gastric and intestinal mucosa was investigated by means of light and electron microscopy. The study revealed gastric secretory dysfunction and malabsorption in small and large intestines in patients with psoriasis and CO, clarified the relation between the duration of psoriasis and opisthorchosis and gastric secretory dysfunction and determined dependence of small intestine malabsorption on such factors as stage, severity, degree of skin involvement and duration of psoriasis. The authors also established interrelation between the above malfunctions and gastric and intestinal structural abnormalities.

Adult↗

Inhibition of Clostridium perfringens by a novel strain of Bacillus subtilis isolated from the gastrointestinal tracts of healthy chickens.

The objectives of this study were to isolate beneficial strains of microorganisms from the gastrointestinal tracts of healthy chickens and to screen them against Clostridium perfringens, a causative agent of necrotic enteritis in poultry. One of the bacteria isolated, a strain of Bacillus subtilis, was found to possess an anticlostridial factor that could inhibit the C. perfringens ATCC 13124 used in this study. The anticlostridial factor produced by B. subtilis PB6 was found to be fully or partially inactivated in the presence of pronase, trypsin, and pepsin. In contrast, the antimicrobial activity of the anticlostridial factor was not affected by treatment at 100 or 121 degrees C or by treatment with any of the organic solvents used in the study. The optimum growth temperature and optimum pH for production of the anticlostridial factor were 37 degrees C and 6.20, respectively. Using the mass spectroscopy-mass spectroscopy technique, the apparent molecular mass of the anticlostridial factor was estimated to be in the range from 960 to 983 Da. In terms of the antimicrobial spectrum, the anticlostridial factor was inhibitory toward various strains of C. perfringens implicated in necrotic enteritis in poultry, Clostridium difficile, Streptococcus pneumoniae, Campylobacter jejuni, and Campylobacter coli.

Animals↗

[Electric stimulator for the gastrointestinal tract].

A theoretical possibility of creating an autonomous electric stimulator for the gastrointestinal tract is discussed. The feasibility of using a galvanic element with two dissimilar electrodes and gastrointestinal medium instead of the intravenous power source (galvanic battery) is contemplated.

Digestive System↗

Symptomatic, endoscopic and histological assessment of upper gastrointestinal tract in renal transplant recipients.

AIM: To assess the prevalence of gastrointestinal symptoms, endoscopic findings, and histological abnormalities in renal transplant recipients. SETTING: Teaching hospital in northern Jordan. METHODS: Seventy-six renal transplant recipients with stable renal function were interviewed for gastrointestinal symptoms, and underwent upper gastrointestinal endoscopy; gastric antral biopsies were evaluated for inflammatory changes and the presence of Helicobacter pylori. One hundred consecutive patients attending the general medical outpatient for various medical problems served as controls; 41 of them consented to undergo endoscopy and biopsy examination. RESULTS: Upper gastrointestinal symptoms were present in 50% of patients compared to 47% of controls (p=0.80). Endoscopic abnormalities were found in 71% versus 63.4%. One patient in each group had duodenal ulcer. H. pylori were found in 60.5% versus 46.3% (p=0.20), and histological gastritis in 40 (52.6%) with acute inflammatory changes in 22 (28.9%), compared to 21 (51.2%) and 15 (36.6%) controls, respectively. Monilial and cytomegalovirus esophagitis were found in 2 (2.6%) and one patient, respectively. CONCLUSIONS: Prevalence of gastrointestinal symptoms and endoscopic and histological findings in stable renal transplant recipients are similar to those in controls. Also, there was no increase in opportunistic infections of the gastrointestinal tract or of gastric H. pylori in these patients.

Age Distribution↗

[The parietal mucin microbial population in different sections of the human gastrointestinal tract].

Microbiological examinations of the human-colon parietal mucin were made in different sections of the human gastrointestinal tract (GIT). Biopsy samples of the human colon mucus tunic were used as the research material. Convincing data were found by research on the importance of the anatomic-and-morphological factor in shaping-up of microbiocenosis of the colon-wall parietal mucin. It was established that, depending on a GIT section, not only the quantitative and qualitative composition of normal microflora but also the nature of inter-microbe interactions are subject to changes. In particular, biopsy materials of the small-intestine parietal mucin are much different from that of the colon. The colon section from the ascending colon to the sigmoid colon has, with some exceptions, an identical microbial composition. At the same time, the rectum is significantly different from other colon sections. The results are suggestive of the below cluster-type pattern of parietal biological material: microorganisms are clustered as small domains with certain specific and quantitative compositions. It was established that, although feces and parietal mucin have a similar species composition of microorganisms, still, there is a number of essential differences between them in as far as the frequency ratio and the microorganism concentration are concerned, which signifies a certain degree of isolation of the above biopsy materials. Finally, a certain isolation degree of the feces biopsy materials and of the parietal ones was established.

Bacteria↗

The gastrointestinal tract: a major site of antioxidant action?

Diets rich in fruits and vegetables delay the onset of many age-related diseases, and contain a complex mixture of antioxidants (including ascorbate, carotenoids, vitamin E and other phenolics such as the flavonoids). However, diet also contains pro-oxidants, including iron, copper, H2O2, haem, lipid peroxides and aldehydes. Nitrite is frequently present in diet, leading to generation of reactive nitrogen species in the stomach. In considering the biological importance of dietary antioxidants, attention has usually focussed on those that are absorbed through the gastrointestinal tract into the rest of the body. In the present paper we develop the argument that the high levels of antioxidants present in certain foods (fruits, vegetables, grains) and beverages (e.g. green tea) play an important role in protecting the gastrointestinal tract itself from oxidative damage, and in delaying the development of stomach, colon and rectal cancer. Indeed, carotenoids and flavonoids do not seem to be as well absorbed as vitamins C and E. Hence their concentrations can be much higher in the lumen of the GI tract than are ever achieved in plasma or other body tissues, making an antioxidant action in the GI tract more likely. Additional protective mechanisms of these dietary constituents (e.g. effects on intercellular communication, apoptosis, cyclooxygenases and telomerase) may also be important.

Animals↗

Malignant melanoma of the gastrointestinal tract presenting as a bleeding gastric ulcer.

Malignant melanoma involving the gastrointestinal tract is diagnosed antemortem in only a small percentage of patients with the disease. Presenting symptoms are often non-specific, causing a diagnostic problem. The vast majority of such melanomas are metastatic from a cutaneous primary, however there is evidence that the tumour can arise de novo in the gastrointestinal system. We report a 74-year-old man with malignant melanoma with an unusual presentation simulating a symptomatic gastric ulcer. He presented with epigastric pain, haematemesis and melaena. Explorative laparotomy revealed a large ulcerated tumour with several pigmented satellite nodules in the proximal stomach, multiple ileal nodules and widespread nodal and liver metastases. Proximal gastrectomy and limited small bowel resection was performed. Histology revealed the tumour to be composed of nests of epithelioid cells with melanin pigment. The tumour cells showed immunohistochemical positivity for S100 protein and HMB45 antibodies. This report emphasizes that melanoma should be a diagnostic consideration in patients with gastric ulcer.

Aged↗

EGF content in the gastrointestinal tract of rats: effect of age and fasting/feeding.

Immunoreactive rat epidermal growth factor (EGF) was measured in the pancreas and in the mucosa and lumen of the stomach, duodenum, jejunum, midjejunum, ileum, and colon of fed or fasted 5- and 12-day-old suckling, and 3- to 4-month-old adult male rats using a homologous radioimmunoassay. The EGF levels in the pancreas in sucklings were lower than in adults and were unaffected by fasting. Both gastrointestinal mucosal and luminal EGF levels were higher in suckling rats than in adults. Fasting caused a significant decrease in gastrointestinal levels of EGF in the suckling rats but resulted in minimal changes in the adults. Our results show that the content of EGF in gastrointestinal tract is dependent on both age and dietary status. Together with the fact that milk contains a large amount of EGF (O. Koldovský and W. Thornburg, J. Pediatr. Gastro. Nutr. 6: 172-196, 1987) and that labeled EGF is absorbed to a considerable extent by the gastrointestinal tract of suckling rats (P.A. Gonella et al., J. Clin. Invest. 80: 22-32, 1987: W. Thornburg et al., Am. J. Physiol. 246: G80-G85, 1984), our present study implicates milk as an important source of EGF in the suckling period.

Age Factors↗