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Effect of emodin on small intestinal peristalsis of mice and relevant mechanism.

AIM: To investigate the effect of emodin on small intestinal peristalsis of mice and to explore its relevant mechanisms. METHODS: The effect of emodin on small intestinal peristalsis of mice was observed by charcoal powder propelling test of small intestine. The contents of motilin and somatostatin in small intestine of mice were determined by radioimmunoassay. The electrical potential difference (PD) related to Na+ and glucose transport was measured across the wall of reverted intestinal sacs. Na+-K+-ATPase activity of small intestinal mucosa was measured by spectroscopic analysis. RESULTS: Different dosages of emodin can improve small intestinal peristalsis of mice. Emodin increased the content of motilin, while reduced the content of somatostatin in small intestine of mice significantly. Emodin 0.2, 0.4, 0.8, and 1.6 g/L decreased PD when there was glucose. However, emodin had little effect when glucose was free. The Na+-K+-ATPase activity of small intestinal mucosa of mice in emodin groups was inhibited obviously. CONCLUSION: Emodin can enhance the function of small intestinal peristalsis of mice by mechanisms of promoting secretion of motilin, lowering the content of somatostatin and inhibiting Na+-K+-ATPase activity of small intestinal mucosa.

Animals↗

IEC-18, a nontransformed small intestinal cell line for studying epithelial permeability.

Small intestinal epithelium is leaky and allows permeation of hydrophilic molecules of various sizes. Passively absorbed hydrophilic permeability probes have been shown to permeate across intestinal epithelium mainly through the paracellular pathways. In this study we introduce microporous filter-grown IEC-18 epithelial cells, a nontransformed small intestinal cell line, as a in vitro model of intestinal epithelium for the study of epithelial permeability. IEC-18 cells, originally derived from native rat ileal crypts, form confluent epithelium when grown on hydrated collagen-coated Millicell-CM permeable inserts (Millipore Corp., Bedford, Mass.). With scanning and transmission electron microscopy, the presence of tight junctions and desmosomes between cells and the development of microvilli at the apical surface were confirmed. Immunofluorescent labeling of ZO-1 proteins and desmoplakins verified the presence of tight-junctional proteins (ZO-1) and desmosomes in the intercellular junctions of confluent IEC-18 epithelium. The net electrical resistance of IEC-18 epithelium (28 omega-cm2) was similar to resistance values obtained from small intestinal tissue with (50 to 100 omega-cm2) or without (20 to 45 omega-cm2) muscularis and serosal layers. Assessment of mannitol and dextran permeation revealed early "maturation" of paracellular pathway, with increasing restriction of permeation to both probes through day 4. Resistance across IEC-18 epithelium also reached plateau levels between 4 and 7 days. Permeability studies with various probes indicate that cross-sectional diameter rather than molecular weight of the probe is the important determinant of permeation rate. IEC-18 epithelium selectively restricted the permeation of probes proportional to probe size; permeation of larger probes such as albumin was negligible. We conclude that cultured IEC-18 epithelial cells, because of their native crypt origin, similarity in resistance to small intestinal epithelia, retention of ability to differentiate into villus-like enterocytes, and permeability characteristics, are a useful model of intestinal epithelium for the study of permeability and paracellular transport.

Animals↗

Small intestinal bacterial overgrowth in the symptomatic elderly.

OBJECTIVE: 1) To determine the prevalence of small intestinal overgrowth with colonic-type bacteria in symptomatic elderly subjects, particularly those without important "clues" such as clinically apparent predisposition or vitamin B12 deficiency, and 2) to investigate defense mechanisms such as gastric acidity, small intestinal motility, and luminal IgA in this setting. METHODS: Fifty-two symptomatic subjects without vitamin B12 deficiency or clinically apparent predisposition to bacterial overgrowth or disturbed mucosal immunity, including 22 subjects > or = 75 yr old, underwent culture of small intestinal luminal secretions. Indicator paper was used to measure fasting gastric pH. The presence of bacteria of confirmed nonsalivary origin in small intestinal secretions served as an index of small intestinal dysmotility. Small intestinal luminal IgA concentrations were measured by radial immunodiffusion. RESULTS: Small intestinal overgrowth with colonic-type flora was not present in any subject investigated for dyspepsia, irrespective of age. In subjects with chronic diarrhea, anorexia, or nausea, overgrowth with colonic-type flora (Enterobacteriaceae) was present in 0/12 (0%), 1/10 (10.0%), and 9/14 (64.3%) subjects aged < 50 yr, 50-74 yr, and > or = 75 yr, respectively. Enterobacteriaceae were not concurrently recovered from saliva of any subject > or = 75 yr old with small intestinal overgrowth with these bacteria. Fasting hypochlorhydria was present in only 1/9 (11.1%) such subjects. Luminal IgA concentrations were significantly greater in subjects > or = 75 yr old with bacterial overgrowth than in culture-negative subjects (p < or = 0.003). CONCLUSIONS: Small intestinal overgrowth with colonic-type bacterial should be considered in subjects > or = 75 yr old with chronic diarrhea, anorexia, or nausea, even in the absence of clues such as clinically apparent predisposition or vitamin B12 deficiency. Small intestinal dysmotility, rather than fasting hypochlorhydria or mucosal immunosenescence, probably is responsible for the prevalence of bacterial overgrowth in this group.

Aged↗

Griseofulvin absorption from different sites in the human small intestine.

The site-dependent small-intestinal absorption pattern of griseofulvin was investigated in man. Griseofulvin was chosen as a model substance having extremely low water solubility and moderate lipid solubility. A conventional steady-state perfusion technique (triple-lumen tubing system with a 20 cm test segment) was applied. Dissolved griseofulvin (10.0 mg L-1) was perfused (10 mL min-1) during 160 min into different parts of the small intestine with the middle of the test segment between 85 cm and 270 cm beyond the teeth. Each of the ten healthy volunteers was examined twice with the test segment localized in different regions to allow for intraindividual comparisons. Mean drug absorption rates calculated from intestinal aspirate concentrations were similar in the two intestinal parts (proximal, 15.0 +/- 5.9 micrograms (20 cm min)-1; distal, 16.2 +/- 4.3 micrograms (20 cm min)-1; mean +/- SD). Absorption rate was strongly correlated to the amount of griseofulvin offered to the test segment per unit time. Extrapolating these findings it follows that an amount of griseofulvin, once dissolved, would be absorbed completely (> 99%) along 100 cm of the small intestine. A significant, positive correlation between the rate of transmucosal fluid transport and the absorption rate of griseofulvin was observed in the distal parts investigated.

Adult↗

Intestinal loop lengthening--a technique for increasing small intestinal length.

A reproducible technique is described for doubling the length of a loop of small intestine, while simultaneously reducing its luminal diameter, and preserving the maximum amount of small bowel mucosa for intestinal adaptation. In pig experiments, 7 loops have been increased in length by the "intestinal loop lengthening" procedure, with survival of 5 of the 7 animals for a period of 16-26 wk. Leakage from the lengthened intestinal segment led to the death of one animal. At a second operation, or at termination of the experiment, all seven lengthened loops had a good blood supply and were patent along their full length. Histologic examination of 3 of the 4 specimens from the first phase of the study confirmed their viability. The potential application of intestinal loop lengthening in the management of the short gut syndrome is discussed.

Animals↗

BB-10010, an analog of macrophage inflammatory protein-1alpha, protects murine small intestine against radiation.

Irradiation of the small intestine can result in depletion of the epithelial stem cell compartment and is often the dose-limiting factor for radiotherapeutic treatment of tumors in the abdominal and pelvic region. Since mitotic cells are most sensitive to radiation, significant radioprotection can be achieved by reducing the number of cells in mitosis at the time of irradiation. We have previously shown that administration of macrophage inflammatory protein (MIP) -1alpha induces a transient 50% reduction in the number of mitotic cells in small intestinal crypts, including the stem cell region, and therefore, MIP-1alpha pretreatment before radiation exposure could result in a substantial reduction of the side effects associated with radiotherapy. Groups of adult mice were exposed to different doses of radiation (6, 8, 10, or 12 Gy), with or without prior administration of 200 microg BB-10010/kg 3 hr before irradiation and radiation damage was assessed by means of the microcolony survival assay. MIP-1alpha pretreatment resulted in significantly increased numbers of surviving crypts (10%) when compared to untreated irradiated animals. The observed radioprotective effects of MIP-1alpha in the small intestine should translate into reduced side effects in a clinically relevant radiotherapy context and could allow larger doses of radiation to be delivered to patients with tumors in the abdominal or pelvic region.

Animals↗

Light and electron microscopic immunocytochemical localization of vasoactive intestinal polypeptide VIP-like activity in the rat small intestine.

Vasoactive intestinal polypeptide nerve processes and cell bodies were identified by electron microscopic immunocytochemistry in the rat small intestine. Labeled nerve processes were numerous in the inner circular smooth muscle coat and mainly in the mucosa, but were absent in the longitudinal muscle layer. Submucosal blood vessels were often surrounded by immunoreactive vasoactive intestinal polypeptide positive nerves, in close associations (distance less than 40 mn) to blood vessel basement membranes and to smooth muscle cells. In the ganglia of the myenteric and submucous plexuses, labeled fibers surrounded unstained neural cell bodies. The synaptic vesicles of vasoactive intestinal polypeptide positive terminals were 35-40 nm in diameter and some dense core vesicles (80-120 nm in diameter) were also observed in the same profiles. These observations suggest that vasoactive intestinal polypeptide nerves may participate in regulating smooth muscle activity and local blood flow in the small intestine.

Animals↗

Intestinal ammonium production in the rat: the role of the colon, small intestine, and circulating glutamine.

The intestinal ammonium production and the intestinal uptake of circulating glutamine were investigated in anesthetized intact rats and rats with resected small intestine or colon by simultaneous measurements performed on portal and arterial blood. It was shown that ammonium release into the portal blood by the small intestine is of equal magnitude to that released by the colon, and that circulating glutamine participates in ammonium production by the small intestine. Increased levels of circulating glutamine induced by its i.v. infusion to intact rats were not accompanied by an increase in intestinal ammonium production.

Ammonia↗

Survival rates for horses undergoing stapled small intestinal anastomosis: 84 cases (1988-1997).

OBJECTIVE: To determine whether location and type of small intestinal anastomosis and other variables were associated with short- and long-term survival rates in horses undergoing stapled small intestinal anastomosis. DESIGN: Retrospective study. ANIMALS: 84 horses that underwent small intestinal anastomosis. PROCEDURE: Medical records from 1988 to 1997 were examined for horses that underwent stapled small intestinal anastomosis. Horses were allotted into 4 groups: jejunojejunostomy (n = 27), jejunoileostomy (11), jejunoileocecostomy with small intestinal resection (20), and jejunoileocecostomy without small intestinal resection (26). Survival rates and other variables were determined. RESULTS: Horses that underwent jejunoileocecostomy without resection had a significantly higher survival rate at all intervals than did horses in the other 3 groups. At 180 and 365 days after surgery, horses that underwent jejunojejunostomy had a significantly lower survival rate than those that underwent jejunoileocecostomy with intestinal resection. Horses that underwent jejunoileocecostomy with intestinal resection had a significantly higher survival rate at 1 year, compared with the combined jejunojejunostomy and jejunoileostomy groups. Preoperative heart rate was inversely associated with survival rate. Overall survival rates at discharge and 1 year were 81 and 56%, respectively. For horses that underwent small intestinal resection, survival rates at discharge and 1 year were 65 and 47%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Horses that underwent anastomosis of the small intestine to the cecum without resection had the highest survival rate, compared with horses that required intestinal resection. In some instances, resection and anastomosis involving the cecum had better prognosis than resections involving 2 segments of the small intestine.

Anastomosis, Surgical↗

[Morphofunctional alterations of the small intestine in patients with psoriasis and concomitant chronic opisthorchiasis].

To characterize the small intestine clinically and functionally in psoriasis combination with chronic opisthorhiasis, 60 patients were examined with this combination, 45 with psoriasis but no helminthosis, 30 patients with chronic opisthorchiasis and 15 healthy subjects. Small intestinal absorption was studied by fat and carbohydrates absorption; bioelectric small intestinal activity--by electroenterography. Absorption in the small intestine of patients with mixed pathology was impaired. Pathogenetic mechanisms of such impairment were the following: low amplitude of bioelectrical activity of the small intestine, subnormal concentration of bile acids in the vesical bile, defects in microbial biocenosis of the intestine, structural disorders of the upper small intestine. Abnormal absorption in the small intestine correlated with psoriasis clinical picture (stages, duration, size of the lesion, disease severity).

Adult↗

[Parallel morphological and functional research on chronic enterocolitis patients using the authors' own method for the simultaneous performance of perfusion and biopsy of the small intestine].

Thirty two patients were studied with chronic enterocolitis and 9 patients without any small intestinal diseases, with normal histomorphological picture of small intestinal mucosa--control group. The method of simultaneous performance of perfusion and biopsy of small intestine was used. Glucose resorption rate in small intestine was studied and histomorphological, electron--microscopic and enzymologic (disaccharidases) studies were carried out on jejunal mucosa. Data about chronic enterocolitis without atrophy were established in 17 patients, in 10--initial partial atrophy, in 5--advanced partial and subtotal atrophy of jejunal mucosa. Reduced glucose resorption rate was established in small intestine in the patients with chronic enterocolitis as compared with that of the control group. Glucose resorption rate correlates with the severity of the histomorphological changes in small intestinal mucosa. Disturbed resorption rate was established via jejuno--perfusion in patients with clinically not manifested syndrome of malresorption and absence of histomorphological changes in small intestinal mucosa, but with established ultrastructural changes in enterocytes.

Adult↗

Colonization by lactobacilli of piglet small intestinal mucus.

The colonization potential of lactobacilli was investigated using small intestinal mucus extracts from 35-d-old pigs. Mucus-secreting tissue from the small intestine of piglets was gently rinsed to remove contents and then shaken in buffer to release mucus from the surface. Numbers of lactobacilli in different portions of the small intestine of 35-d-old pigs were enumerated. Also, mucus isolated from the small intestine of pigs was investigated for its capacity to support the growth of lactobacilli. Results indicated that Lactobacillus spp. inhabit the mucus layer of the small intestine and can grow and adhere to ileal mucus. From adhesion studies of Lactobacillus fermentum 104R to mucus analysed by Scatchard plot, it is suggested that an associating system showing positive cooperativity is involved. Proteinaceous compounds(s) involved in the adhesion to mucus were detected in the spent culture fluid from the growth of strain 104R. Studies are continuing in order to identify and characterize the adhesion-promoting protein(s). From the data, it is proposed that lactobacilli colonize the mucus layer of the small intestine of pigs.

Animals↗

Species difference in nisoldipine oxidation activity in the small intestine.

Species difference in nisoldipine oxidation activities was investigated using small intestinal microsomes of rats, guinea pigs, dogs, monkeys and humans. The oxidation activities were estimated by measuring metabolites formation (BAY o 3199 and BAY r 9425) of nisoldipine. For the preparation of small intestinal microsomes of various animal species, the effect of protease inhibitors was preliminarily investigated. The formation of BAY o 3199 significantly increased in the rat small intestinal microsomes prepared with trypsin inhibitor. Using the trypsin inhibitor-treated small intestinal microsomes of various animals, metabolic intrinsic clearances (CL(int, in vitro)) for BAY o 3199 and BAY r 9425 formations were estimated based on an Eadie-Hofstee plot. The total CL(int,in vitro) estimated by the sum of CL(int, in vitro) for both formations in the small intestines of all species was much lower than that in the liver. There was a marked species difference in the nisoldipine oxidation activities in the small intestines, with the rank order being humans=monkeys>dogs>rats>guinea pigs, versus the following order in the liver: rats>monkeys=guinea pigs>humans>dogs. The formations of both BAY o 3199 and BAY r 9425 in the human intestinal microsomes were inhibited by pretreatment with troleandomycin (TAO) and antiserum against CYP3A4. Similar inhibition profile by TAO was obtained from the monkey intestinal microsomes. These results implied that monkeys would be a good predictor of human small intestinal metabolism for CYP3A4 substrates.

Journal Article↗

Comparative analysis of adult and fetal human small intestinal microvilli.

The aim was to study the development of human small intestinal microvillus membranes. We compared the protein patterns of human fetal and adult small intestinal microvillus membranes using the high-resolution technique of sodium dodecyl sulphate-polyacrylamide gel electrophoresis. We also examined the synthesis of brush border membrane proteins from the adult small intestine using small intestinal biopsy organ culture 35S-methionine uptake and subsequent gel electrophoresis. We observed that the fetal and colonic microvillus membranes were similar, but differed in certain respects from adult small intestinal microvillus membranes. The jejunal biopsy organ culture revealed that synthesised brush border membrane proteins could be recognized by gel electrophoresis.

Adult↗

Primary lymphomas of the small intestine: east-west contrast.

Primary small intestinal lymphoma (PSIL) represents a heterogenous group of disorders with variable clinical and pathologic features and a characteristic age, socioeconomic, and geographic distribution. In developed countries, PSIL usually occurs as a localized ileal tumor, shows a bimodal age distribution, and most frequently presents with abdominal pain and obstructive symptoms. Histologically, most of these tumors are diffuse histiocytic, lymphocytic, or undifferentiated lymphomas. Other variants of PSIL, collectively referred to as immunoproliferative small intestinal disease, occur most often among young patients of poor socioeconomic status in Third World countries, mostly in the Middle East and Mediterranean area. They are characterized by involvement of long loops of the upper small intestine and commonly present with abdominal pain, diarrhea, malabsorption, and clubbing of the fingers. A subgroup of these patients shows a serological abnormality with the appearance of part of the alpha heavy chain of IgA in the serum. Histologically, the lesion appears as a dense diffuse lymphoplasmacytic infiltrate of the mucosa of the upper jejenum or duodenum. A form of malignant lymphoma of true histiocytic origin complicates long-standing celiac disease. The contrasting clinical, epidemiological, histopathological, and immunological features of these variants of PSIL raise interesting questions about the pathogenesis of small bowel lymphoma.

Adolescent↗

Small intestinal transplantation in nonhuman primates.

Small intestinal transplantation represents a potentially therapeutic procedure for individuals with short gut syndrome. The purpose of this study was to develop a model for small intestinal transplantation in primates that is: technically feasible without microsurgery; consistent in the prevention of allograft rejection; functional in terms of nutrient absorption; and compatible with harvest for multiple organ procurement. First, autotransplantations on four rhesus monkeys were performed in order to study a variety of harvesting techniques and vascular anastomoses. Then, a study was performed with 14 heterotopic allotransplants in 4 baboons and 10 rhesus primates. The successful donor model consisted of division of the pancreas, harvesting the small bowel with a superior mesenteric artery and portal vein pedicle. The allograft vascular pedicle was anastomosed to the recipient's common iliac vessels in end-to-side fashion. The graft was transplanted as an out-of-continuity loop, both ends being exteriorized as stomas providing access for absorption studies and biopsy. Three immunosuppressive regimens were tested: (1) cyclosporine A (CyA) 20 mg/kg/d, solumedrol (SML) 2 mg/kg/d, and graft irradiation (150 rad) (n = 4); (2) CyA 20 mg/kg/d and SML 2 mg/kg/d (n = 3); and (3) CyA 40 mg/kg/d, SML 2 mg/kg/d, and azathioprine 5 mg/kg/d (n = 3). There were 4 deaths due to technical error in the first 24 hours. Weekly graft biopsy, serum CyA levels, complete blood count, and automated 24-channel serum analysis were performed. Grafts surviving greater than 14 days underwent absorption study via luminal perfusion with sucrose, maltose, dextrose, Pregestimil, xylose, and cyclosporine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differential expression of glutathione S-transferase isoenzymes in murine small intestine and colon.

Glutathione (GSH) S-transferase (GST) isoenzymes of the small intestine and colon of female A/J mice have been purified and characterized to determine their interrelationships with other murine GSTs. Cytosolic GST activity in the small intestine was at least due to six isoenzymes with isoelectric points (pI) of 9.5, 9.3, 9.1, 8.5, 6.2 and 5.5. Small intestine isoenzymes with pI values of 9.5, 9.3, 8.5, and 6.2 were identical to the mGSTA1-1 (Alpha class), mGSTP1-1 (Pi class), mGSTM1-1 (Mu class) and mGSTA4-4 (Alpha class), respectively, of other A/J mouse tissues on the basis of their reverse-phase HPLC elution profile, immunological cross-reactivity and/or N-terminal region amino acid sequence. Even though GST9.1 of the small intestine cross-reacted with the antibodies raised against Pi class GST, reverse-phase HPLC and N-terminal amino acid sequence analyses suggested that this isoenzyme may be structurally different from mGSTP1-1 as well as mGSTP2-2. Likewise, despite immunological similarity with the Mu class GSTs, small intestine GST5.5 appeared to be different from other Mu class murine GSTs characterized previously. Cytosolic GST activity in the colon was mainly due to four isoenzymes with pI values of 9.8, 9.4, 6.6 and 5.8. While the identity of colon GST6.6 could not be established due to its low abundance, GST9.8, GST9.4 and GST5.8 were identical to mGSTP1-1, mGSTM1-1 and mGSTA4-4, respectively, of other A/J mouse tissues including the small intestine. Isoenzymes corresponding to small intestine GST9.1 and GST5.5 could not be detected in the colon. The results of the present study indicate that the small intestine of female A/J mice is better equipped for protection against toxic effects of electrophiles than colon.

Animals↗