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A Paneth cell analogue in Xenopus small intestine expresses antimicrobial peptide genes: conservation of an intestinal host-defense system.

Antimicrobial peptides are a widespread component of host defense. We characterized the tissue distribution and cellular localization of expression of the magainin family of antimicrobial peptide genes in Xenopus laevis. Two genes from this family, magainin and PGLa, are expressed at high levels in the skin and throughout the gastrointestinal tract. Magainin and PGLa mRNAs are synthesized in the granular multinucleated cell (GMC) of the gastric mucosa, a cell shown previously to contain magainin and PGLa peptides by immunohistochemical methods. In addition, we have localized magainin and PGLa mRNAs to distinct cells of Xenopus small intestine. Further characterization of this large, granule-filled cell by electron microscopy demonstrates features in common with the Paneth cell of mammalian small intestine, previously identified as a site of expression of antimicrobial peptide genes of the defensin family in mouse and human. Our identification of granule-laden, eosinophilic intestinal cells in Xenopus as a site of magainin and PGLa antimicrobial peptide gene expression suggests that these cells are functional analogues of mammalian Paneth cells and further supports a conserved role of antimicrobial peptides in host defense of the vertebrate small intestine.

Animals↗

Evidence of an age-related decrease in intestinal responsiveness to vitamin D: relationship between serum 1,25-dihydroxyvitamin D3 and intestinal vitamin D receptor concentrations in normal women.

Although aged rats reportedly have reduced intestinal vitamin D receptor (VDR) concentrations, it is unclear whether an analogous age-related defect occurs in man. Thus, we assessed the interrelationship among serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], calcium absorption and intestinal VDR in 44 healthy, ambulatory women, ages 20-87 yr. Fractional calcium absorption was measured after oral administration of 45Ca (20 mg CaCl2 as carrier); serum 1,25-(OH)2D3, by the calf thymus binding assay; and serum intact PTH, by a two-site immunochemiluminometric assay. Vitamin D receptor concentration was measured, by a new immunoradiometric assay, in biopsy specimens taken from the second part of the duodenum during gastroduodenoscopy in 35 of the women. Despite an age-related increase in serum PTH (r = 0.48; P less than 0.001) and in serum 1,25-(OH)2D3 concentration (r = 0.32; P less than 0.05), intestinal VDR concentration decreased with age (r = -0.38; P = 0.03) and fractional calcium absorption did not change with age. Although a contribution of decreased 25-hydroxyvitamin D 1 alpha-hydroxylase activity to the blunting of the increase in serum 1,25-(OH)2D3 concentration late in life is not excluded, the data are far more consistent with impaired intestinal responsiveness to 1,25-(OH)2D3 action. This defect could lead to compensatory increases in PTH secretion and 1,25-(OH)2D3 production which maintain calcium absorption and serum ionic calcium, but at the expense of increased bone loss.

Adult↗

Intestinal bypass. Experimental study on the influence of the excluded intestinal segment.

Five groups of operated rats with 10% of the small intestine in continuity were studied. In one group the animals were subjected to 90% resection of the small intestine, and in the other groups a 90% jejuno-ileal bypass was performed. In two of the latter groups different lengths of the excluded intestinal segment was resected. The bypassed segment was anastomosed to the colon in three of the groups and to the skin as an ileostomy in one group. There were no differences in haemoglobin concentration, liver function parameters or fat absorption between the five groups, but measurements of body weight seem to indicate that the bypassed intestinal segment exerts a general harmful effect on the rats. This effect is more pronounced when the excluded segment is long, and the effect seems to be the same whether it is connected to the colon or to the skin. The mechanism for this effect is not fully ascertained.

Animals↗

Primary intestinal myopathy, a cause of chronic idiopathic intestinal pseudoobstruction syndrome (CIPS): clinicopathological studies of seven cases in children.

Clinicopathological data on seven instances of primary intestinal myopathy in children are reported. The ages of the patients ranged from eleven months to thirteen years. A persistent intestinal obstruction was the main and constant clinical feature. An ineffective intestinal propulsion was documented on manometric studies. Various urological abnormalities were present in three cases. One patient died and six survive but are dependent on enteral and parenteral nutrition. The morphological findings consisted of degenerative changes involving the muscular layers of the intestinal wall. These changes varied from cytoplasmic vacuolation to definite atrophy and disappearance of the muscular fibers. An extensive interstitial fibrosis underlined these atrophic changes in the late stages of the disease. A familial history was identified in three cases, one consistent with an autosomal dominant transmission.

Child↗

Stimulation of butyrate production in the large intestine of weaning piglets by dietary fructooligosaccharides and its influence on the histological variables of the large intestinal mucosa.

Fructooligosaccharides (FOS) reach the large intestine and are fermented into short-chain fatty acids (SCFA), lactate, and carbon dioxide. As the major energy source for the epithelial cells of the large intestine, n-butyrate stimulates the proliferation of cells as well as mineral and water absorption from the lumen. We examined the effect of dietary FOS supplementation on luminal SCFA production and its influence on the morphometrical variables of mucosa of the large intestine in commercially available pigs. Six weaning piglets were used. After 7 d of adaptation, three pigs were given a test diet containing FOS (10%) ad libitum for 10 d. The other three remained on the basal diet and were used as controls. At the end of the experiment, their large intestines were removed, and the cecum, gyri centripetales, gyri centrifugales, and rectum were separated. The contents of each portion were collected and measured for SCFA concentration, pH, and moisture. A micrometer was used to measure the crypt depth. The numbers of epithelial and mitotic cells in the crypt columns were also counted. The concentration of SCFA was significantly higher in piglets fed FOS than in the controls. The concentration of n-butyrate was markedly stimulated by FOS. The number of epithelial. mitotic, and mucin-containing cells was higher in piglets fed FOS than in the controls. Accordingly, the crypt depth was larger in the FOS-fed piglets. The luminal n-butyrate concentration showed a significantly positive correlation with the crypt depth and the number of epithelial, mitotic, and mucin-containing cells.

Animals↗

The influences of changes in temperature on intestinal lymph flow and relationship to operations for carcinoma of the intestine.

The effect of cooling, freezing and warming temperatures on the flow of lymph from the intestines was studied in dogs. When intestinal temperatures were dropped to an average of approximately 40 degrees F., an immediate decrease in lymph flow occurred to a mean value 33 per cent of control levels. With rewarming, lymph flow increased rapidly, rebounding to a level almost twice as great as that in controls. When the intestines were subjected to hypothermia to the point of freezing, lymph flow decreased immediately with flow rates dropping to only 6.6 per cent of control levels. Techniques for achieving freezing in these studies were inefficient, and uniform freezing was not always obtained. Again, with rewarming there was an immediate rise in lymph flow to levels significantly above those in controls. In hyperthermic studies to temperatures of 103 degrees F., a biphasic reaction was noted with an initial increase in lymph flow averaging 71 per cent higher than that in controls followed rapidly by a drop in lymph flow significantly below control levels. These experiments demonstrate that hypothermia, particularly below freezing temperatures, may rapidly decrease and virtually stop lymph flow from an intestinal segment. This suggests that hypothermia might be useful as an adjunctive measure in the operative management of patients with carcinomas of the gastrointestinal tract.

Animals↗

[Initial empirical antimicrobial therapy with piperacillin/tazobactam in intra-abdominal infections due to perforation of the large intestine and rectum and in postoperative complications after resection of the large intestine and rectum].

One of the basic therapeutic procedures in surgical intraabdominal infections is early administration of antimicrobial drugs. The basic requirement for the selection of antimicrobial drugs is a broad-spectum bactericide action with low toxicity. Within the framework of a retrospective non-comparative investigation the action of the betalactam antibiotic piperacillin combined with the betalactamase inhibitor tazobactam was tested which was used in the initial empirical antimicrobial treatment of 33 patients with intraabdominal infectious complications caused by perforation of the large bowel or dehiscence of the anastomosis on the large intestine or rectum. Twenty-eight patients developed diffuse inflammation of the peritoneum (caused by perforation of a diverticulum in 17, by dehiscence of the anastomosis on the large intestine and rectum after resection on account of carcinoma in 7, by a penetrating injury of the large bowel and rectum in 3 and by postirradiation necrosis of the rectum in one female patient). Five patients developed an intraabdominal abscess as a complication of diverticulitis of the large intestine or as a postoperative infectious complication after resection of the large bowel and rectum. All patients were operated (resection of the large bowel according to Hartmann, or stoma above the site of injury or dehiscence of the intestinal anastomosis or drainage of the abscess). After surgery administration of piperacillin/tazobactam (4.5 g, subsequently after 8 hours). The period of administration was on average 8 days (5 to 11 days). After surgery the contents of the peritoneal cavity were collected for bacteriological examination incl. evaluation of the sensitivity of the isolated bacteria to piperacillin/tazebactam. From the isolated pathogens 58% were Gram-negative aerobic bacteria, in 24% anaerobic bacteria and in 18% enterococci. In 3 patients antimicrobial treatment was because of resistance of isolated bacteria to piperacillin/tazobactam (Klebsiella species, Pseudomonas aeruginosa) combined with aminoglycosides (amikacin, netilmicin). Postoperative complications developed in 9 patients (27%), incl. 3 who died (9%). In patients with intraabdominal infection caused by perforation of the large bowel and rectum or dehiscence of the anastomosis after resection of the large bowel and rectum piperacillin/tazobactam is the antibiotic of choice for the initial empirical antimicrobial treatment on account of its great efficacy against the majority of isolated bacteria, its safety and low toxicity.

Abdominal Abscess↗

[Effect of mast cell activation on microcirculation of intestinal mucosa in inflamed small intestine of the rat].

Intravital microscopy and FITC-labeled erythrocytes were used to investigate villous perfusion in the rat small intestine in a model of inflammatory bowel disease. Inflammation was induced with s.c. application of Indomethacin. It has previously been demonstrated that systemic Indomethacin leads to an increase in villous blood flow in the small intestine of the rat. In order to determine whether mast cell activation may contribute to the increase in villous perfusion, Ketotifen was used to inhibit mast cell degranulation. We found that Ketotifen significantly reduced villous perfusion in the inflamed intestine, but had no effect in the control group. We conclude that mast cell activation is one of the mechanisms leading to hyperemia in the mucosa of the small intestine in this animal model. Further studies are required to determine whether mast cell stabilizers may be beneficial in the treatment of inflammatory bowel disease in man.

Animals↗

The relative lethality of intestinal bacteria for gnotobiotic rats with experimental intestinal strangulation.

In eight experiments utilizing 28 animals each, germfree rats with and without ischemically or hemorrhagically strangulated closed loop intestinal segments were contaminated with either one of four common intestinal anaerobic bacteria, or a combination of two or three bacteria previously found to be innocuous in pure culture. The results showed that: a) in pure culture, Bacteroides fragilis, Bacteroides melaninogenicus, and Peptostreptococcus anaerobius were innocuous; b) Fusobacterium necrophorum alone was a very lethal organism that produced intense, confluent, intraperitoneal, fibrous adhesions after four to six days; and c) mixed inoculum of Klebsiella pneumoniae, Bacteroides fragilis, and/or Streptococcus faecalis was found to be lethal for gnotobiotic rats with intestinal strangulation. It is concluded that Fusobacterium necrophorum is so patent that it should be specifically treated with antibiotics when suspected or known to be present in clinical specimens. This gnotobiotic animal model will be useful to delineate the lethality of known combinations of intestinal bacteria.

Animals↗

Neuronal intestinal dysplasia type B with massive small intestinal hemorrhage: report of one case.

Neuronal intestinal dysplasia type B is characterized by poor intestinal motility that usually results in constipation. Massive gastrointestinal hemorrhage is very unusual as the initial presentation in this disease entity. We report on a 3-year-and-7-month-old boy who had experienced two episodes of life-threatening lower gastrointestinal hemorrhage and high fever. Technetium-99m labeled red blood cell scan and the Meckel's diverticulum scan failed to demonstrate the bleeding point. The results of panendoscopy and colonoscopy were negative. Laparotomy revealed a 70 cm-long thick-walled intestine (from 100 cm to 170 cm below the Treitz ligament) with cord like material formed by mucosa debris, blood clot and mucus. Pathology report revealed hyperplastic nerve bundles in submucosal plexus with giant ganglion formation, consistent with neuronal intestinal dysplasia type B.

Child, Preschool↗

Intestinal metastases from renal cell carcinoma: a rare cause of intestinal obstruction and bleeding.

Intestinal metastases from renal cell carcinoma (RCC) are rare. Clinical presentation includes intestinal obstruction, bleeding, or perforation. Management should be aggressive, since the prognosis of RCC is unpredictable and metastasectomy can extend patient survival. We present a patient with intestinal obstruction and bleeding caused by intestinal metastases from renal cell carcinoma and summarize the surgical procedures employed. The relevant literature is briefly reviewed.

Aged↗

[Intestinal T-cell lymphoma (so-called malignant histiocytosis of the intestine) complicated by multiple perforations].

We describe a case of intestinal T-cell lymphoma which was histologically diagnosed of malignant histiocytosis of the intestine. A 47-year-old man was admitted to our hospital because of fever and generalized lymphadenopathy. Mild anemia, leukocytosis, positive CRP and a high level of LDH were noted. Pathological finding of the lymph node was compatible with dermatopathic lymphadenopathy with a slight increase in atypical lymphoid cells. At the 14th day after admission, he suffered from abdominal pain and was diagnosed as having perforative peritonitis. In laparotomy, the infiltration of histiocyte-like atypical cells were found around a site of small perforation of the terminal ileum. The findings were compatible with that of malignant histiocytosis of the intestine (MHI). He had recurrent perforations of the small intestine and died of peritonitis and sepsis at the 42nd day. Southern blot analysis of the biopsied lymph node showed TCR-beta gene rearrangement. Some patients diagnosed clinically and pathologically as having MHI may have a T-cell lymphoma like our case.

Histiocytic Sarcoma↗

Digestive enzymes of the mucosa of the small intestine and trypsin and chymotrypsin proteolytic activity of the intestinal contents of germ-free, monocontaminated and conventional rabbits.

The activity of the membrane-bound enzymes of the microvillous zone of the entreocytes (maltase, sucrase, trehalase, lactase, cellobiase, alkaline phosphatase and leucylaminopeptidase) was studied in mucosal smears from the proximal jejunum, ileum, caecum and sigmoid flexure in a group of control (C) (8) and germ-free (GF) (7) rabbits. The trypsin and chymotrypsin activity of the contents of the ileum, caecum and sigmoid flexure was studied in 6 C, 5 GF and 5 monocontaminated (MC) rabbits. In summing up it can be stated that the individual membrane-bound enzymes have a different gradient in the various intestinal segments of C and GF rabbits and that they differ reciprocally in character. The maximum statistically significant differences between GF and C rabbits were found in the ileum; in the jejunum they were somewhat smaller and in the caecum smaller still (in this localization the difference was C versus GF). Striking differences in the proportion of the individual disaccharidases were found inthe jejunum and ileum of C rabbits compared with GF rabbits, in which, in both these segments of small intestine the relationship maltase greater than sucrase greater than trehalase greater than lactase was preserved. The proteolytic activity of the intestinal contents likewise had a different gradient character in C, MC and GF rabbits. The maximum activities (especially trypsin) were found in MC animals. The microbial flora is one of the factors regulating the enzymatic activities of the microvillous zone of the enterocytes and it also significantly influences the proteolytic activity of the intestinal contents. This influence is particularly marked in the distal part of the alimentary tube.

Animals↗

[Metabolites of the intestinal microflora in the diagnosis of intestinal dysbacteriosis].

The procedures most widely used in investigation of intestinal microflora activity are briefly reviewed. The original findings relating to investigation of intestinal microflora and isolation of certain bacterial metabolites from rats with self-filling jejunal loop are presented as an example. Marked correlation between isolation of certain bacterial metabolites and self-filling jejunal loop microflora was observed. The authors consider advisable that biochemical and bacteriological methods for investigation of intestinal microflora be combined. When there are shifts in the number and ratio of the produced metabolites, invasive diagnostic methods including intubation and bacteriological examination of the small intestine are recommended.

Animals↗

Effect of restricting a balanced diet on rat intestinal disaccharidase activity and intestinal architecture.

The effects of malnutrition on the gastrointestinal tract have been previously investigated in animal models using dietary protein restriction. Because malnutrition is clinically a consequence of reduced dietary intake of all macronutrients, we investigated the effect of restricting a balanced diet on intestinal disaccharidases and histologic conditions of rats. Our diet-restricted animals gained less weight (13 +/- 9 gm) than the control animals (158 +/- 27 gm) over the 5-week study. The proximal, middle, and distal small intestinal segments from the experimental animals had reduced mucosal protein content (15 +/- 4 mg vs. 24 +/- 7 mg). In these segments the total amount of maltase was slightly decreased, whereas sucrase and lactase activities were normal or increased. The intestinal villus/crypt ratios were similar in the experimental and control animals. Mucosal cell height was significantly reduced in the diet-restricted groups; however, cell width was normal. We conclude that severely diet-restricted animals have mucosal protein loss caused in part by reduced cell height, but that the disaccharidase enzyme activities are normal. Diet-restricted animals appear to have sufficient intestinal enzymes to support a normal amount of disaccharide hydrolysis.

Animals↗

Intestinal absorption of alpha-methyldopa: in vitro mechanistic studies in rat small intestinal segments.

The mechanism of intestinal uptake of alpha-methyldopa (Aldomet) was investigated using isolated segments of rat small intestine. Incubations were limited to 2 to 5 min as histological examination of the tissue showed significant loss of structural integrity after 10 to 20 min at 37 degrees C. alpha-Methyldopa in the tissue was extracted and assayed by high-pressure liquid chromatography. Corrections were applied for uptake into extracellular spaces using inulin (14C). Uptake was temperature- and concentration-dependent (Km congruent to 10 mM), was dependent on the location in the small intestine and was inhibited by ouabain (2 mM) or lack of sodium or glucose in the incubation medium. alpha-Methyldopa uptake also was inhibited by other neutral amino acids. The mucosal cell layer accounted for approximately 50% of the total drug accumulated in the tissue. Uptake was less when the serosal surface was exposed than when the tissue was everted. The similarity in uptake parameters between alpha-methyldopa and L-phenylalanine (parallel experiments) suggests that alpha-methyldopa is principally absorbed into rat small intestinal mucosal cells via an amino acid transport system.

Amino Acids↗

Evidence of increased intestinal synthesis and extracellular deposition of IgM in primary biliary cirrhosis. An immunofluorescence study of liver and small-intestinal biopsy specimens.

Direct immunofluorescence showed intense extracellular granular deposition of IgM and C3 in liver and small-intestinal biopsy specimens from patients with primary biliary cirrhosis. In contrast, IgM deposits were not observed in liver tissue from patients with other liver diseases, whereas small-intestinal IgM deposits were seen also in 2 of 17 patients with various intestinal disorders. The tissue deposition of IgM did not vary with plasma IgM levels, degree of cholestasis, or histological stage of the disease but seemed to reflect an abnormal property of the IgM molecule. The number of IgM-positive mononuclear cells in intestinal mucosa from patients with primary biliary cirrhosis was markedly increased, suggesting increased local synthesis of IgM. Deposition of IgM with complement-activating ability might contribute to the development of tissue damage in primary biliary cirrhosis. In addition, the apparent specificity of these IgM deposits in liver for primary biliary cirrhosis might be of diagnostic value when histological classification is difficult.

Aged↗