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Ultrastructural aspects of the small intestinal lead toxicology. Part II. The small intestine goblet cells of rats during lead poisoning.

The purpose of the present study was to evaluate the detoxification significance of the small intestinal goblet cells in rats on prolonged treatment with 0.01% lead acetate in the drinking water. These goblet cells were analysed using a submicroscopic demonstration of heavy metals with the sulphide silver method and the X-ray microanalysis probe. Male Wistar rats, weighing 80 g, were sacrificed after 2, 30 and 60 d of exposure to oral administration of lead. The small intestines were perfused with Sörensen buffer with H2S, then blocks of tissue were removed from the border between the duodenum and jejunum and processed for transmission electron microscopy according to Grzybek (3) and Dancher (2). At first the silver containing salt precipitates were distributed in the extracellular space between epithelial cells after 2 d of the experiment. Treatment of rats with lead acetate for 30 d produced the characteristic appearance of the goblet cells at the electron microscopic level. The presence of lead in conjunction with the goblet cell membrane has been observed. If administration of lead to rats is continued longer than 30 d, in the mucus droplets located in the cytoplasm of goblet cells some deposits of silver salts may be demonstrated. For the electron probe X-ray microanalysis the bulk specimens were prepared using a critical point drying apparatus. The specimens were scanned along a line on the villous surface parallel to its long axis. The X-ray studies indicated that accumulation of lead in the epithelial cells increased during the time of experiment.

Animals↗

Regional blood flow and the localization of lymphoblasts in the small intestine of the mouse. I. Examination of normal small intestine.

The localization of 125I-UdR-labelled mesenteric lymphoblasts and the fraction of the cardiac output delivered to the small intestine was investigated in mice. When different regions of the small intestine were examined, the proportional delivery of the cardiac output and the localization of lymphoblasts were found to vary along the length of the small intestine. A significant correlation between these two phenomena was identified when both lymphoblast localization and the distribution of the cardiac output within the small intestine were studied concurrently. The intestinal localization of populations of unseparated or T-enriched mesenteric lymphoblasts and peripheral lymphoblasts all showed a similar degree of correlation with the fraction of the cardiac output delivered along the small intestine in spite of marked differences in their proclivity to accumulate in the gut. We conclude that there is an important relationship in normal animals between the level of lymphoblast accumulation within a particular region of the small intestine and the delivery of blood-borne cells to that region. This relationship could provide a physiological explanation for a antigen-independent yet non-uniform distribution of effector cells within the lamina propria of unimmunized animals.

Animals↗

[Guidelines on intestinal dysmicrobism (SIBO Small Intestine Bacterial Overgrowth)].

Bacterial flora consisting of Gram-positive and Gram-negative germs, aerobes and anaerobes, is distributed along the digestive tract in varying quantities from zero to a maximum of 10(12)/ml of endoluminal aspirate. This bacterial ecosystem counterbalances with the ecological niche of the host organism and harmonizes with the various digestive, secretory, motor, absorption and sensitivity functions of the entire intestine. This dynamic equilibrium between environment, bacterial flora and host may be interrupted due to a variety of complex reasons, leading to quantitative and qualitative modifications of the normal intestinal microbial flora that can cause Small Intestinal Bacterial Overgrowth (SIBO). SIBO is thus due to an invasion of the small intestine, from the upper part, by pathogenic strains of oro-alimentary origin, and from the lower part by colo-fecal germs through an incontinent Bauhin's valve. These germs alter the normal intestinal functions and give rise to a form of diarrhoea in which the characteristics of malabsorption prevail, with all the inherent diagnostic problems. The diagnostic gold standard is the culture of the duodenal-jejunal aspirate which, being difficult to perform and providing unreliable results, is not easily included in the daily clinical routine. Indirect tests include the breath test, which is widely accepted by patients but burdened by diagnostic doubts on the part of medical personnel. Diagnostic confirmation is therefore greatly conditioned by clinical subjectivity and objectivity, as well as by the response to medical therapy. In cases of declared malabsorption, medical therapy is necessary by means of appropriate diet, prebiotics, probiotics and antibiotics. The difficulty in identifying the specific bacterial population and the part of the digestive tract that is affected indicate the appropriateness of a broad-spectrum antibiotic therapy, capable of eradicating aerobes and anaerobes, preferably with a topical rather than a general action, frequently cause of undesired effects.

English Abstract↗

Small intestinal metastasis from small cell lung cancer.

A 71-year-old man who had small cell lung cancer was referred to our institution. Before starting chemotherapy, anemia progressed and stool examination was positive for occult blood. An abdominal computed tomography scan with contrast medium enhancement of the gastrointestinal tract disclosed a small intestinal tumor. Histological examination after the surgery confirmed that the tumor was metastasis of lung cancer. The patient survived for 3 years after the resection. Although clinically apparent metastases of lung cancer to the small intestine are rare and are reported to have a poor prognosis, early detection and intervention might enhance the chance of survival.

Aged↗

Expression of mRNA for vasoactive intestinal peptide in rat small intestine.

Transplantation of small intestine is a neural model that permits studies of expression of the neuropeptide, vasoactive intestinal peptide, following extrinsic denervation, transection of intrinsic neural pathways, and an ischemic interval. Tissue levels of vasoactive intestinal peptide were examined at 3 months in ileum from a sham operation, in ileum after resection of proximal small intestine, in ileum after resection of proximal small intestine and extrinsic denervation, in ileum after resection of proximal small intestine and 30 min of ischemia, and in ileum obtained 3 months after ileal isografting in Lewis-to-Lewis combinations. Vasoactive intestinal peptide levels were increased in transplanted rat ileum, resection controls, denervation controls, and ischemic controls compared to sham-operated ileum (pANOVA < 0.01). The increased levels of this peptide were highest in denervation controls and lowest in ischemic controls. Northern blot analysis using rat vasoactive intestinal peptide cDNA identified a single 1.7-kb transcript in normal and transplanted rat ileum. The density of vasoactive intestinal peptide transcripts was increased in transplanted ileum (8450 +/- 540) compared to normal ileum (5790 +/- 620) (P < 0.01), and the ratio of this transcript to glyceraldehyde-3-phosphate dehydrogenase density units was also increased in transplanted ileum (0.81 +/- 0.08) compared to normal ileum (0.40 +/- 0.07; P < 0.01). Enhanced transcriptional regulation was the likely mechanism for increased tissue vasoactive intestinal peptide. The increased tissue levels appeared to be a response to extrinsic denervation and transection of intrinsic neural pathways, while an ischemic interval appeared to decrease tissue levels of the peptide.

Animals↗

Chemical and histochemical studies of normal and diseased human gastrointestinal tract. II. A comparison between histologically normal small intestine and Crohn's disease of the small intestine.

Comparative chemical and histochemical studies were performed on formalin-fixed, surgical specimens of human small intestine from cases of Crohn's disease and normal controls. The sialic acids of the crude glycoproteins isolated from normal ileum were significantly less neuraminidase-susceptible and more C4 substituted (P less than 0.01) than those of the glycoproteins isolated either from normal upper small intestine (duodenum and jejunum) or from cases of Crohn's disease of the ileum. Fractionation yielded two major sialic acid-containing fractions, eluting from DEAE-cellulose with 0.2 M or 0.3 M sodium chloride. Both fractions contained fucose, galactose, glucosamine and galactosamine in addition to sialic acids both with and without O-acyl substituents at position C4 and/or in the side-chain (side-chain O-acylated sialic acids were also detected by histochemical procedures). The fractions differed significantly from one another with respect to the neuraminidase susceptibility of their sialic acids (P less than 0.01), the percentage of C4 (P less than 0.01) and side-chain substituted sialic acids (P less than 0.05), and the molar fucose-sialic acid ratio (P less than 0.05). The O-acyl substitution patterns of the sialic acids of both the 0.2 M and 0.3 M fractions of the upper small intestine glycoproteins differed significantly from those of the corresponding fractions from normal ileum, while the sialic acids of the 0.2 M fractions from Crohn's disease of the ileum differed significantly from normal with respect to neuraminidase susceptibility (P less than 0.01) and percentage C4 substitution (P less than 0.01); the 0.3 M fractions differed only in the percentage of sialic acids substituted at C4. The differences between the sialic acids from the normal and Crohn's disease specimens were shown to be independent of either the anatomical origin of the specimen or the histopathological sub-group of the Crohn's disease specimens; no significant differences were noted between the sub-groups but all the sub-groups differed from normal.

Crohn Disease↗

[Primary malignant melanoma of the small intestine].

The small intestine is a frequent site for metastases of cutaneous or ocular melanoma. When the latter are absent, the diagnosis of primary intestinal melanoma can be proposed. Primary malignant melanoma of the small intestine arises from melanoblastic cells of the neural crests, which migrate to the distal ileum through the omphalomesenteric canal. Incomplete regression of the later leads to persistence of Meckel's diverticulum. We report herein a case of malignant melanoma of the small intestine without evidence of a cutaneous and/or ocular origin. Based on its location in the distal ileum, we propose that this tumor be classified as a primary malignant melanoma of the small intestine.

Female↗

Characteristics of transport of fluoresceinated methotrexate in rat small intestine.

The small intestinal damage induced by the methotrexate (MTX) treatment results in malabsorption and diarrhea. The fluoresceinated methotrexate (F-MTX) may possibly be useful to study such effects of MTX on the small intestine. The purpose of this study is to characterize the transport of F-MTX in the small intestine in order to use it as a membrane transport and cellular marker of MTX. The transport of F-MTX in the rat small intestine (jejunum) was examined in the in vitro everted segments of the intestine. The uptake was pH-dependent and showed a maximal effect at pH 6.0, which was the same as the results of MTX previously reported. Further, it was temperature-dependent and was inhibited by metabolic inhibitors, dinitrophenol and sodium azide, and by MTX. The transport kinetics at pH 6.0 in the mucosal solution and at pH 7.4 in the serosal solution was saturable with Km of 0.48 +/- 0.23 microM and Vmax of 0.66 +/- 0.24 pmol/cm/min and in addition, the passive diffusion was observed there. These results suggested that the transport of F-MTX was energy-dependent and was mediated by the same transporter as that of MTX, although, in addition to it, other transport mechanism might contribute to the F-MTX transport. Therefore F-MTX will be of great use to investigate the MTX transport system in the normal and diseased states of small intestine, using various fluorescence techniques like visualization of membrane-associated transport proteins.

Animals↗

Small intestinal neoplasms.

Small intestinal neoplasms are uncommonly encountered in clinical practice. They may occur sporadically, in association with genetic diseases (e.g., familial adenomatous polyposis coli or Peutz-Jeghers syndrome), or in association with chronic intestinal inflammatory disorders (e.g., Crohn's disease or celiac sprue). Benign small intestinal tumors (e.g., leiomyoma, lipoma, hamartoma, or desmoid tumor) usually are asymptomatic but may present with intussusception. Primary malignancies of the small intestine-including adenocarcinoma, leiomyosarcoma, carcinoid, and lymphoma-may present with intestinal obstruction, jaundice, bleeding, or pain. Extraintestinal neoplasms may involve the intestine via contiguous spread or peritoneal metastasis. Hematogenous metastases to the intestine from an extraintestinal primary are unusual and are most typical of melanoma. Because the small intestine is relatively inaccessible to routine endoscopy, diagnosis of small intestinal neoplasms is often delayed for months after onset of symptoms. When the diagnosis is suspected, enteroclysis is the most useful imaging study. Small bowel endoscopy (enteroscopy) is increasingly widely available and may permit earlier, nonoperative diagnosis.

Biopsy, Needle↗

Mechanical remodeling of small-intestine submucosa small-diameter vascular grafts--a preliminary report.

Small-intestine submucosa (SIS) is cell-free, 100-mu-thick collagen derived from the small intestine. It has been used as a vascular graft and has the highly desirable ability to be remodeled to become histologically indistinguishable from native adjacent artery. To date there has been limited reporting of its preimplantation and explant mechanical properties as a vascular graft. In this study, compliance, elastic modulus, and burst pressure were measured on preimplant-tested 5- and 8-mm SIS grafts and two 60-day remodeled grafts. Seven prefabricated grafts were implanted in the carotid (n = 7) in dogs, which were sacrificed after 55-63 days. The animals (n = 4) weighed from 22 to 27 kg. One dog received a unilateral carotid graft, and 3 dogs received bilateral carotid grafts. The fabrication technique employed hand-suturing with either nonresorbable or resorbable sutures. None of the grafts had a patency failure. Angiograms taken at 1 month and just before explantation showed uniform flow and no dilation. At the time of explantation, all carotid grafts were found to be encased in fibrous tissue. The grafts made with nonresorbable sutures showed thicker tissue growth at the suture line compared with those made with the resorbable sutures. Along the suture line, the grafts made with resorbable sutures exhibited a more natural color than those sutured with nonresorbable sutures. When the explanted carotid grafts were slit open, the lumen was white, shiny, and glistening. The grafts sutured with nonresorbable sutures exhibited small areas of fibrin and red blood cells when the suture was within the lumen. The resorbable-sutured grafts did not exhibit this response. The mean compliance (percent diameter increase for a pressure rise from 80 to 120 mm Hg) was on average 4.6% (range, 2.9%-8.6%) for the 5-mm preimplant-tested grafts. For the 8-mm preimplant-tested grafts, the increase in diameter for the same pressure rise was 8.7%, on average (range, 7.2% to 9.5%). For comparison, the small-diameter SIS graft at the time of implantation was about one half as compliant as the adjacent dog carotid artery, about 4 times more compliant than a typical vein graft, and more than 10 times more compliant than synthetic vascular grafts. The compliance measured on two 60-day carotid grafts was 10.5% and 7.2%, respectively. This is midway between the original compliance value and the compliance of a typical canine carotid artery (14%), indicating that mechanical remodeling occurred. The modulus of elasticity (E) increased exponentially with increasing pressure according to E = E0e alpha P, where E0 is the zero-pressure modulus and alpha is the exponent that describes the rate of increase in E with pressure; the unit of measure for variables E, E0, and P is g/cm2. The mean value for E0 was 4106 gm/cm2 (range, 1348-5601). The mean value for alpha was 0.0059 (range, 0.0028-0.0125). At 100 mm Hg, the mean value for E was 8.03 x 10(6) dynes/cm2 (range, 4.95-15.7 x 10(6)). For a 60-day SIS graft implant, the elastic modulus at 100 mm Hg decreased from a high value at implant time to twice that of a typical native canine carotid artery. The mean burst pressure for 5.5-mm grafts was 3517 mm Hg (range, 2069-4654). The burst pressure of the remodeled carotid grafts averaged 5660 mm Hg. The burst pressure for a typical carotid artery is about 5000 mm Hg. The results of this preliminary study complement those of previous SIS-vascular-graft studies and add a new factor, namely that the mechanical properties of the remodeled graft approach those of the vessel it replaces.

Animals↗

The effect of dietary manipulation on hepatic lipid accumulation in rats undergoing small intestinal bypass.

Small intestinal bypass performed for morbid obesity produces hepatic fat infiltration which persists in some patients for more than 5 years. In an attempt to define causative and preventative factors of hepatic steatosis following small intestinal bypass, a rat model was developed. In this study, nutritionally obese rats underwent sham operations or bypass of 90 per cent of their small intestine and postoperatively were fed various diets to determine the effects of dietary manipulations on hepatic lipid content. After 30 days the rats were killed and their hepatic lipid content and lipogenic enzyme activity determined. In rats that underwent intestinal bypass neither a high fat, a high carbohydrate nor a high protein diet increased hepatic lipid content over that present in sham operated animals. A low (4.5 per cent) protein diet increased total hepatic lipid and hepatic triglyceride content. The increased triglyceride levels were not associated with significant changes in lipogenic enzyme activity and were associated with decreased serum triglycerides suggesting impaired triglyceride transport from the liver secondary to decreased lipoprotein formation as a possible etiologic mechanism. A significant inverse relationship was found between hepatic triglyceride content and hepatic protein content. These results support previous reports from human studies of hypoproteinemia associated with hepatic steatosis following small intestinal bypass.

Acetyl-CoA Carboxylase↗

Small intestinal metastasis from esophageal carcinoma associated with small intestinal obstruction: report of a case.

The small intestine is rarely involved with metastatic tumors from outside the abdomen, and few case reports have been documented in the literature. We describe herein what to our knowledge is the third case of a solitary metastasis from squamous cell carcinoma (SCC) of the esophagus being found in the jejunum, causing small intestinal obstruction.

Carcinoma, Squamous Cell↗

Risk factors for small intestine cancer.

Small intestine cancer is relatively rare. Clinical reports have suggested that several medical conditions may predispose to increased occurrence of this cancer, but otherwise its etiology is unknown. In one of the first case-control studies of this cancer, we compared questionnaire responses provided by next-of-kin of 430 persons who died of small intestine cancer cf921 controls who died of other causes. Subjects were identified from decedents included in the 1986 United States National Mortality Followback Survey. The questionnaires sought information on demographic and lifestyle characteristics, including diet and use of tobacco and alcohol. Tobacco and alcohol consumption were unrelated to risk of small intestine cancer, but weekly or more frequent consumption of red meat and monthly or more frequent intake of salt-cured/smoked foods were associated with two- to three fold increases in risk. The findings suggest that dietary factors probably are involved in risk of small intestine cancer, but additional research in other settings is required to clarify the determinants of these rare cancers.

Adult↗

[Histological findings following experimental resection of the small intestine].

The small intestine remaining after resection of up to 50% of the small intestine in young rats was studied continuously in serial sections. Morphological changes in the area of the serous surface, the strength of the musculature, the number and length of villi per section and the surface index were scrutinized. Statistical evaluation and the discussion (with the results of authors who have been concerned with the same problem) showed that a true hyperplasia of the mucosa and of the whole gut wall with an increase in the number of villi occurs in animals with a resectioned small intestine. Thus it could be demonstrated that functional integrity is restored by morphological changes in the residual gut which are based on hyperplasia and hypertrophy.

Animals↗

Small intestinal dysmotility following abdominal irradiation in the rat small intestine.

Abdominal symptoms such as diarrhoea, abdominal cramps and vomiting are common during and after abdominal radiotherapy for gynaecological and pelvic malignancy. It has recently been recognized that small intestinal dysmotility may contribute to these symptoms but the underlying mechanisms are unclear in part because of the technical difficulties inherent in performing studies in irradiated small intestine. The aim of the current study was to evaluate small intestinal motor activity using perfused micromanometric techniques in 6-8-cm segments of ileum during arterial perfusion with isotonic oxygenated fluorocarbon solution. Intestinal segments from six rats were studied 4 days after treatment with 10 Gy abdominal irradiation. Ileal segments from nine nonirradiated animals acted as controls. For each experiment the total number of pressure waves, high-amplitude (> 20 mmHg, long-duration > 6 sec) pressure waves, and long (> 20 associated) bursts of pressure waves were determined. Irradiation had no effect on the overall number of pressure waves, but increased high-amplitude long-duration (HALD) pressure waves (248 vs 7, P < 0.01). In control animals HALD waves were localized to a single recording site but after radiotherapy 74% of HALD waves were temporally associated with similar pressure waves in other manometric channels. Forty-seven per cent of associated HALD waves migrated aborally. Retrograde migration of HALD waves was seen in five segments following irradiation. Irradiation abolished bursts of > 20 pressure waves.

Abdomen↗

The recognition system of dietary fatty acids by the rat small intestinal cells.

Small intestinal epithelial cells interact with a rather high concentration of fatty acids derived from the diet. These fatty acids directly or indirectly regulate the functions of the small intestine. We report here that linoleic acid and oleic acid markedly increased the influx of 45Ca2+ into the small intestinal epithelial cell line (IEC 6). By contrast, octanoic acid, methyl linoleate, and linolyl alcohol had no effect on the influx. Acidic amino acids, methyl linoleate, and linolyl alcohol, inhibited the linoleic acid-induced influx of 45Ca2+, indicating that activation of the influx by linoleic acid depended on the chain length and was affected by the presence of a carboxyl group. Of the gastrointestinal hormones, somatostatin specifically inhibited the linoleic acid-induced influx of 45Ca2+.

Amino Acids↗