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1

Relationship between postprandial motor activity in the human small intestine and the gastrointestinal transit of food  

International Nuclear Information System (INIS)

Profiles for gastric emptying and colonic filling were determined in 20 normal volunteers by means of a gamma camera and dedicated minicomputer after ingestion of a radiolabeled solid meal. These were compared with intraluminal pressure activity, recorded simultaneously from three sites (each separated by 50 cm) in the small intestine by infusion manometry. Recordings were continued for at least 8 h or until all the radioactivity appeared in the colon. Colonic filling was approximately linear, occurring at an average rate of 16% of the meal residues per hour. There were significant inverse correlations (p less than 0.01) between the pressure activity in the proximal jejunum during the first 3 h after ingestion and the times taken for 50% and 80% of the meal residues to enter the colon, and direct correlations between total small intestinal pressure activity and the half-time for gastric emptying. Phase III of the interdigestive migrating motor complex appeared between 3 and 9 h after ingestion (when between 15% and 80% of the meal remained in the small intestine), but did not necessarily migrate to the next recording site until much later. The time of appearance of phase III in the proximal jejunum was directly correlated with the half-time for gastric emptying (p less than 0.05) and with the intraluminal pressure activity recorded at that site during the first 3 h after food ingestion (p less than 0.01). The time at which 80% of the meal residues had entered the colo of the meal residues had entered the colon was significantly shorter in 6 subjects, in whom a postprandial activity front appeared to migrate throughout the small bowel, compared with 13 subjects, in whom this did not occur (5.0 +/- 0.5 h vs. 7.0 +/- 0.4 h, p less than 0.01). These studies have shown that gastrointestinal transit of a solid meal is related to both fed and fasted intraluminal pressure activity in the small intestine

2

THE HUMAN INTESTINAL CYTOCHROME P450 “PIE”  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Cytochromes P450 (P450s) 3A, 2C, and 1A2 constitute the major “pieces” of the human liver P450 “pie” and account, on average, for 40, 25, and 18%, respectively, of total immunoquantified P450s (J Pharmacol Exp Ther 270:414–423, 1994). The P450 profile in the human small intestine has not been fully characterized. Therefore, microsomes prepared from mucosal scrapings from the duodenal/jejunal portion of 31 human donor small intestines were analyzed by Western blot using selective P45...

Paine, Mary F.; Hart, Heather L.; Ludington, Shana S.; Haining, Robert L.; Rettie, Allan E.; Zeldin, Darryl C.

2006-01-01

3

Effects of methotrexate on intestinal transit in rats  

International Nuclear Information System (INIS)

A study was designed to determine the effects of methotrexate (MTX) on rat intestinal transit. Adult male rats were implanted with indwelling cannulas in the proximal duodenum 5 to 7 days prior to experimentation. After recovery from surgery, groups of animals were treated with either saline (1.0 ml/kg/day) or MTX at 0.5, 1.25, 3.125, or 7.8 mg/kg/day (ip) for 3 consecutive days (Days 1-3). On each of the next 5 consecutive days (Days 4-8) weight and intestinal transit determinations were made in animals from each test group following a 24-hr fast. Intestinal transit was determined by measuring the progression of an intraduodenally administered bolus of radioactive chromium (Na251CrO4, 0.5 mu Ci) through the small intestine. When compared with saline-treated controls, intestinal transit was significantly (p less than 0.05) increased on 1 or more of the 5 test days in animals treated with doses of MTX greater than 0.5 mg/kg/day. When compared with animals treated with saline, animals treated with MTX lost a greater percentage of their initial body weight after the fast period. Plasma concentrations of MTX, determined at various time intervals after 3.125 mg/kg given daily for 1 to 3 consecutive days, peaked at 15 and 30 min after each injection and diminished to undetectable levels after 4 hr. The results indicate that 3 days of parenteral therapy with MTX significantly increases rat intestinal transit. The intestinal effects appear to transit. The intestinal effects appear to be transient and are proportional to the total dose of drug administered over the 3-day period. The intestinal effects of MTX occur from 1 to several days after peak plasma concentrations of drug and are associated with a reduced ability to sustain body weight after a 24-hr fast

4

Accurate measurement of intestinal transit in the rat  

Energy Technology Data Exchange (ETDEWEB)

A new method for quantifying intestinal transit was evaluated by comparison with two other popular techniques. The distribution of radiochromium (51Cr) throughout the small intestine of rats previously treated with saline (1.0 ml/kg s.c.), capsaicin (10 mg/kg s.c.), hexamethonium (20 mg/kg i.p.), D-ala2-met-enkephalinamide (1.0 microgram i.c.v.), or neostigmine (0.1 mg/kg i.p.) was quantified by (1) measuring the most distal intestinal segment reached by chromium, (2) calculating the slope produced by linear regression analysis on cumulative percent chromium that had passed through each segment, and (3) determining the geometric center of the distribution of chromium throughout the small intestine. It was concluded that the geometric center methods for quantifying intestinal transit provides the most sensitive and reliable measure of intestinal transit. Less sensitive techniques often fail to detect important effects of drugs on intestinal transit.

Miller, M.S.; Galligan, J.J.; Burks, T.F.

1981-11-01

5

Accurate measurement of intestinal transit in the rat  

International Nuclear Information System (INIS)

A new method for quantifying intestinal transit was evaluated by comparison with two other popular techniques. The distribution of radiochromium (51Cr) throughout the small intestine of rats previously treated with saline (1.0 ml/kg s.c.), capsaicin (10 mg/kg s.c.), hexamethonium (20 mg/kg i.p.), D-ala2-met-enkephalinamide (1.0 microgram i.c.v.), or neostigmine (0.1 mg/kg i.p.) was quantified by (1) measuring the most distal intestinal segment reached by chromium, (2) calculating the slope produced by linear regression analysis on cumulative percent chromium that had passed through each segment, and (3) determining the geometric center of the distribution of chromium throughout the small intestine. It was concluded that the geometric center methods for quantifying intestinal transit provides the most sensitive and reliable measure of intestinal transit. Less sensitive techniques often fail to detect important effects of drugs on intestinal transit

6

Effects of methotrexate on intestinal transit in rats  

Energy Technology Data Exchange (ETDEWEB)

A study was designed to determine the effects of methotrexate (MTX) on rat intestinal transit. Adult male rats were implanted with indwelling cannulas in the proximal duodenum 5 to 7 days prior to experimentation. After recovery from surgery, groups of animals were treated with either saline (1.0 ml/kg/day) or MTX at 0.5, 1.25, 3.125, or 7.8 mg/kg/day (ip) for 3 consecutive days (Days 1-3). On each of the next 5 consecutive days (Days 4-8) weight and intestinal transit determinations were made in animals from each test group following a 24-hr fast. Intestinal transit was determined by measuring the progression of an intraduodenally administered bolus of radioactive chromium (Na/sub 2//sup 51/CrO/sub 4/, 0.5 mu Ci) through the small intestine. When compared with saline-treated controls, intestinal transit was significantly (p less than 0.05) increased on 1 or more of the 5 test days in animals treated with doses of MTX greater than 0.5 mg/kg/day. When compared with animals treated with saline, animals treated with MTX lost a greater percentage of their initial body weight after the fast period. Plasma concentrations of MTX, determined at various time intervals after 3.125 mg/kg given daily for 1 to 3 consecutive days, peaked at 15 and 30 min after each injection and diminished to undetectable levels after 4 hr. The results indicate that 3 days of parenteral therapy with MTX significantly increases rat intestinal transit. The intestinal effects appear to be transient and are proportional to the total dose of drug administered over the 3-day period. The intestinal effects of MTX occur from 1 to several days after peak plasma concentrations of drug and are associated with a reduced ability to sustain body weight after a 24-hr fast.

Curd, C.D.; Manno, J.E.; Stewart, J.J.

1985-10-01

7

Effects of methotrexate on intestinal transit in rats.  

Science.gov (United States)

A study was designed to determine the effects of methotrexate (MTX) on rat intestinal transit. Adult male rats were implanted with indwelling cannulas in the proximal duodenum 5 to 7 days prior to experimentation. After recovery from surgery, groups of animals were treated with either saline (1.0 ml/kg/day) or MTX at 0.5, 1.25, 3.125, or 7.8 mg/kg/day (ip) for 3 consecutive days (Days 1-3). On each of the next 5 consecutive days (Days 4-8) weight and intestinal transit determinations were made in animals from each test group following a 24-hr fast. Intestinal transit was determined by measuring the progression of an intraduodenally administered bolus of radioactive chromium (Na2(51)CrO4, 0.5 mu Ci) through the small intestine. When compared with saline-treated controls, intestinal transit was significantly (p less than 0.05) increased on 1 or more of the 5 test days in animals treated with doses of MTX greater than 0.5 mg/kg/day. When compared with animals treated with saline, animals treated with MTX lost a greater percentage of their initial body weight after the fast period. Plasma concentrations of MTX, determined at various time intervals after 3.125 mg/kg given daily for 1 to 3 consecutive days, peaked at 15 and 30 min after each injection and diminished to undetectable levels after 4 hr. The results indicate that 3 days of parenteral therapy with MTX significantly increases rat intestinal transit. The intestinal effects appear to be transient and are proportional to the total dose of drug administered over the 3-day period. The intestinal effects of MTX occur from 1 to several days after peak plasma concentrations of drug and are associated with a reduced ability to sustain body weight after a 24-hr fast. PMID:4065468

Curd, C D; Manno, J E; Stewart, J J

1985-10-01

8

A comparative evaluation of intestinal transit time of two dosage forms of Haritaki [Terminalia chebula Retz].  

Science.gov (United States)

Haritaki is praised as the best salutary drug which can be used in almost all ages of human life and is reputed for its Anulomana property. In Ayurveda, it has been mentioned that fruits of Haritaki when used in different forms give different type of actions. As the prime therapeutic utility of Haritaki is Anulomana, in the present study, two dosage forms of Haritaki fruits namely Churna and Vati were evaluated for intestinal transit time to evaluate its effect in two different dosage forms. Mature fruits were collected, authenticated, and processed as per classics to get Churna and Vati. Test drugs were administered in the dose of 550 mg/kg and evaluation on intestinal transit time was carried out by adopting kaolin expulsion test in mice. The results show that both the dosage forms of Haritaki significantly shortened intestinal transit time and between them Churna form is found to be better. PMID:23723658

Jirankalgikar, Yogesh M; Ashok, B K; Dwivedi, Rambabu R

2012-07-01

9

Scientists Grow, Implant Human Intestinal Tissue in Mice  

Science.gov (United States)

... on this page, please enable JavaScript. Scientists Grow, Implant Human Intestinal Tissue in Mice Research may provide ... many diseases and conditions that can cause intestinal failure, from genetic disorders appearing at birth to conditions ...

10

Compartmentalization of Aquaporins in the Human Intestine  

Directory of Open Access Journals (Sweden)

Full Text Available Improper localization of water channel proteins called aquaporins (AQP induce mucosal injury which is implicated in Crohn’s disease and ulcerative colitis. The amino acid sequences of AQP3 and AQP10 are 79% similar and belong to the mammalian aquaglyceroporin subfamily. AQP10 is localized on the apical compartment of the intestinal epithelium called the glycocalyx while AQP3 is selectively targeted to the basolateral membrane. Despite the high sequence similarity and evolutionary relatedness, the molecular mechanism involved in the polarity, selective targeting and function of AQP3 and AQP10 in the intestine is largely unknown. Our hypothesis is that the differential polarity and selective targeting of AQP3 and AQP10 in the intestinal epithelial cells is influenced by amino acid signal motifs. We performed sequence and structural alignments to determine differences in signals for localization and posttranslational glycosylation. The basolateral sorting motif “YRLL” is present in AQP3 but absent in AQP10; while Nglycosylation signals are present in AQP10 but absent in AQP3. Furthermore, the C-terminal region of AQP3 is longer compared to AQP10. The sequence and structural differences between AQP3 and AQP10 provide insights into the differential compartmentalization and function of these two aquaporins commonly expressed in human intestines.

Rajendram V. Rajnarayanan

2008-06-01

11

Alternative Functional In Vitro Models of Human Intestinal Epithelia  

Directory of Open Access Journals (Sweden)

Full Text Available Physiologically relevant sources of absorptive intestinal epithelial cells are crucial for human drug transport studies. Human adenocarcinoma-derived intestinal cell lines, such as Caco-2, offer conveniences of easy culture maintenance and scalability, but do not fully recapitulate in vivo intestinal phenotypes. Additional sources of renewable physiologically relevant human intestinal cells would provide a much needed tool for drug discovery and intestinal physiology. We sought to evaluate and compare two alternative sources of human intestinal cells, commercially available primary human intestinal epithelial cells (hInEpCs and induced pluripotent stem cell (iPSC-derived intestinal cells to Caco-2, for use in in vitro transwell monolayer intestinal transport assays. To achieve this for iPSC-derived cells, our previously described 3-dimensional intestinal organogenesis method was adapted to transwell differentiation. Intestinal cells were assessed by marker expression through immunocytochemical and mRNA expression analyses, monolayer integrity through Transepithelial Electrical Resistance (TEER measurements and molecule permeability, and functionality by taking advantage the well-characterized intestinal transport mechanisms. In most cases, marker expression for primary hInEpCs and iPSC-derived cells appeared to be as good as or better than Caco-2. Furthermore, transwell monolayers exhibited high TEER with low permeability. Primary hInEpCs showed molecule efflux indicative of P-glycoprotein transport. Primary hInEpCs and iPSC-derived cells also showed neonatal Fc receptor-dependent binding of immunoglobulin G variants. Primary hInEpCs and iPSC-derived intestinal cells exhibit expected marker expression and demonstrate basic functional monolayer formation, similar to or better than Caco-2. These cells could offer an alternative source of human intestinal cells for understanding normal intestinal epithelial physiology and drug transport.

AmandaLKauffman

2013-07-01

12

Relationship between small-intestinal transit rate and intestinal absorption of 14C-labelled mannitol and 51Cr-labelled ethylenediaminetetraacetic acid in healthy subjects  

International Nuclear Information System (INIS)

Although the small-intestinal transit rate is generally considered to influence the urinary excretion of markers of intestinal permeability, no study has until now formally addressed the importance of this influence in humans. Ten healthy subjects ingested a test solution containing 99mTc-DTPA, 14C-labelled mannitol and 51Cr-EDTA. After ingestion, the small-intestinal transit rate of 99mTc-DTPA was measured with the gamma camera technique. Urine was collected to measure the excretion of absorbed 14C-mannitol and 51Cr-EDTA. Moreover, the distribution volume and plasma clearance of 14C-mannitol and 51Cr-EDTA were determined in each subject. A positive correlation was found between mean small-intestinal transit time and urinary excretion of 14C-mannitol. The study did not show any correlation between small-intestinal transit rate and urinary excretion of 51Cr-EDTA. Urinary excretion of neither 14C-mannitol nor 51Cr-EDTA was affected by distribution volume or urine volume. A positive correlation was observed between plasma clearance and urinary excretion of 14C-mannitol, whereas plasma clearance did not influence the urinary excretion of 51Cr-EDTA. Small-intestinal transit rate seems to have a significant effect on urinary excretion of 14C-mannitol, whereas small-intestinal transit rate does not influence the tinal transit rate does not influence the timed urinary excretion of 51Cr-EDTA. 25 refs., 1 fig., 2 tabs

13

Small intestinal transit of spherical particles in the active rat  

International Nuclear Information System (INIS)

Reproducible measurements of small intestine transit for spherical particles of 0.5 ? to 1 mm diameter, have been accomplished in the conscious rat. A short cannula of polyethylene is surgically implanted into the duodenum and exists through the abdominal wall. After recovery, a bolus of saline containing colored or isotopically labeled particulate material and an internal standard of NaCr51O4 is introduced with a modified pipette tip that snugly fills the cannula to prevent back flow. The rats eat and drink during the transit period and are maintained on a reversed light cycle so that transit is measured during their physically active period. Glass microspheres of 1mm, 500 ?, and 50 ? were followed at 30 min, 1 hr, and 2 hr intervals by opening the intestine and photographing 1 cm segments along its length. Polymer beads of 500 ?, 125 ?, and 70 ? were labeled with 125I and located by freezing the exteriorized intestine and counting 1 cm segments in a gamma counter. Movement of the fluid bolus as detected by NaCr51O4 was reproducible with the fluid front moving through 59%, 73%, and 81% of the length at 30 min, 1 hr, and 2 hr. One millimeter to 125 ? glass and polymer beads moved with the fluid bolus. Evidence for separation of the fluid phase and particles under ? 100 ? is accumulating. It is hypothesized that small particles under a critical size may become lodged in the mucus lining of the intestinal

14

Human intestinal microbial metabolism of naringin.  

Science.gov (United States)

Naringin, a major flavonoid in citrus fruits, has been proved to be a promising antitussive candidate. It undertakes complicated metabolism. In this study, human intestinal microbial metabolism of naringin was studied in vitro. Six persons' fecal water, which have intestinal microbial enzyme, were used in the first experiment. Naringin was metabolized by fecal water into naringenin. Subsequently, 3-(4-hydroxyphenyl)propionic acid (4-HPPA) was produced with naringenin degradation by a person's fecal water. However, 4-HPPA was not detected after naringenin degradation by the other 5 subjects' fecal water and the reason might be that the degrading velocity of 4-HPPA exceeded the producing velocity. To confirm the difference in degrading 4-HPPA among human feces, 22 healthy persons' feces were used for incubation. In this second experiment, 15 persons' feces could degrade 4-HPPA, but the other 7 subjects' could not. Human feces showed different ability of degrading 4-HPPA, and there are no gender differences. These results may be helpful for explaining findings in pharmacological and toxicological studies and are groundwork for clinical studies. PMID:24935725

Zou, Wei; Luo, Yulong; Liu, Menghua; Chen, Si; Wang, Sheng; Nie, Yichu; Cheng, Guohua; Su, Weiwei; Zhang, Kejian

2014-06-17

15

Increased intestinal marker absorption due to regional permeability changes and decreased intestinal transit during sepsis in the rat  

International Nuclear Information System (INIS)

The intestinal barrier properties are impaired during inflammation and sepsis, but the mechanisms behind this are unknown and were therefore investigated during experimental sepsis in rats. The different-sized intestinal absorption markers 51Cr-labeled ethylenediaminetetraacetic acid (EDTA) and ovalbumin were gavaged to rats made septic by intra-abdominal bacterial implantation and to sham-operated rats. Regional tissue permeability was measured in diffusion chambers, and intestinal transit was evaluated by intestinal accumulation of gavaged 51Cr-EDTA. In comparison with the sham-operated rats, septic rats had higher 51Cr-EDTA levels in blood and urine and showed a prolonged intestinal transit. Septic rats also had a lower tissue permeability to both markers in the small intestines but higher permeability to ovalbumin in the colon. Rats receiving morphine to decrease intestinal motility showed similar changes, with a decreased intestinal transit and increased marker absorption. Thr results suggest that the increased intestinal absorption during sepsis was due to regional permeability changes and prolonged intestinal transit. 38 refs., 4 figs., 2 tabs

16

Gastric transit and small intestinal transit time and motility assessed by a magnet tracking system  

DEFF Research Database (Denmark)

ABSTRACT: BACKGROUND: Tracking an ingested magnet by the Magnet Tracking System MTS-1 (Motilis, Lausanne, Switzerland) is an easy and minimally-invasive method to assess gastrointestinal transit. The aim was to test the validity of MTS-1 for assessment of gastric transit time and small intestinal transit time, and to illustrate transit patterns detected by the system. Methods: A small magnet was ingested and tracked by an external matrix of 16 magnetic field sensors (4x4) giving a position defined by 5 coordinates (position: x, y, z, and angle: theta, phi). Eight healthy subjects were each investigated three times: (1) with a small magnet mounted on a capsule endoscope (PillCam); (2) with the magnet alone and the small intestine in the fasting state; and (3) with the magnet alone and the small intestine in the postprandial state. Results: Experiment (1) showed good agreement and no systematic differences between MTS-1 and capsule endoscopy when assessing gastric transit (median difference 1 min; range: 0-6 min) and small intestinal transit time (median difference 0.5 min; range: 0-52 min). Comparing experiments (1) and (2) there were no systematic differences in gastric transit or small intestinal transit when using the magnet-PillCam unit and the much smaller magnetic pill. In experiments (2) and (3), short bursts of very fast movements lasting less than 5% of the time accounted for more than half the distance covered during the first two hours in the small intestine, irrespective of whether the small intestine was in the fasting or postprandial state. The mean contraction frequency in the small intestine was significantly lower in the fasting state than in the postprandial state (9.90 min-1 vs. 10.53 min-1) (p=0.03). Conclusion: MTS-1 is reliable for determination of gastric transit and small intestinal transit time. It is possible to distinguish between the mean contraction frequency of small intestine in the fasting state and in the postprandial state.

Worsoe, Jonas; Fynne, Lotte

2011-01-01

17

A new approach to predict human intestinal absorption using porcine intestinal tissue and biorelevant matrices.  

Science.gov (United States)

A reliable prediction of the oral bioavailability in humans is crucial and of high interest for pharmaceutical and food industry. The predictive value of currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue and/or in vivo animal studies for human intestinal absorption, however, is often insufficient, especially when food-drug interactions are evaluated. Ideally, for this purpose healthy human intestinal tissue is used, but due to its limited availability there is a need for alternatives. The aim of this study was to evaluate the applicability of healthy porcine intestinal tissue mounted in a newly developed InTESTine™ system to predict human intestinal absorption of compounds with different chemical characteristics, and within biorelevant matrices. To that end, first, a representative set of compounds was chosen of which the apparent permeability (Papp) data in both Caco-2 cells and human intestinal tissue mounted in the Ussing chamber system, and absolute human oral bioavailability were reported. Thereafter, Papp values of the subset were determined in both porcine jejunal tissue and our own Caco-2 cells. In addition, the feasibility of this new approach to study regional differences (duodenum, jejunum, and ileum) in permeability of compounds and to study the effects of luminal factors on permeability was also investigated. For the latter, a comparison was made between the compatibility of porcine intestinal tissue, Caco-2 cells, and Caco-2 cells co-cultured with the mucin producing HT29-MTX cells with biorelevant samples as collected from an in vitro dynamic gastrointestinal model (TIM). The results demonstrated that for the paracellularly transported compounds atenolol, cimetidine, mannitol and ranitidine porcine Papp values are within 3-fold difference of human Papp values, whereas the Caco-2 Papp values are beyond 3-fold difference. Overall, the porcine intestinal tissue Papp values are more comparable to human Papp values (9 out of 12 are within 3-fold difference), compared to Caco-2 Papp values (4 out of 12 are within 3-fold difference). In addition, for the selected hydrophilic compounds a significant increase in the permeability was observed from duodenum to ileum. Finally, this study indicated that porcine jejunal tissue segments can be used with undiluted luminal samples to predict human intestinal permeability and the effect of biorelevant matrices on this. In conclusion, viable porcine intestinal tissue mounted in the InTESTine™ system can be applied as a reliable tool for the assessment of intestinal permeability in the absence and presence of biorelevant samples. This would enable an accessible opportunity for a reliable prediction of human intestinal absorption, and the effect of luminal compounds such as digested foods, early in drug development. PMID:25046168

Westerhout, Joost; van de Steeg, Evita; Grossouw, Dimitri; Zeijdner, Evelijn E; Krul, Cyrille A M; Verwei, Miriam; Wortelboer, Heleen M

2014-10-15

18

Human Intestinal Ischemia-Reperfusion–Induced Inflammation Characterized  

Science.gov (United States)

Human intestinal ischemia-reperfusion (IR) is a frequent phenomenon carrying high morbidity and mortality. Although intestinal IR-induced inflammation has been studied extensively in animal models, human intestinal IR induced inflammatory responses remain to be characterized. Using a newly developed human intestinal IR model, we show that human small intestinal ischemia results in massive leakage of intracellular components from ischemically damaged cells, as indicated by increased arteriovenous concentration differences of intestinal fatty acid binding protein and soluble cytokeratin 18. IR-induced intestinal barrier integrity loss resulted in free exposure of the gut basal membrane (collagen IV staining) to intraluminal contents, which was accompanied by increased arteriovenous concentration differences of endotoxin. Western blot for complement activation product C3c and immunohistochemistry for activated C3 revealed complement activation after IR. In addition, intestinal IR resulted in enhanced tissue mRNA expression of IL-6, IL-8, and TNF-?, which was accompanied by IL-6 and IL-8 release into the circulation. Expression of intercellular adhesion molecule-1 was markedly increased during reperfusion, facilitating influx of neutrophils into IR-damaged villus tips. In conclusion, this study for the first time shows the sequelae of human intestinal IR-induced inflammation, which is characterized by complement activation, production and release of cytokines into the circulation, endothelial activation, and neutrophil influx into IR-damaged tissue. PMID:20348235

Grootjans, Joep; Lenaerts, Kaatje; Derikx, Joep P.M.; Matthijsen, Robert A.; de Bruïne, Adriaan P.; van Bijnen, Annemarie A.; van Dam, Ronald M.; Dejong, Cornelis H.C.; Buurman, Wim A.

2010-01-01

19

Defence capabilities of human intestinal epithelial cells  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The epithelial cells lining the intestinal mucosa separate the underlying tissue from components of the intestinal lumen. Innate immunity mediated by intestinal epithelial cells (IECs) provides rapid protective functions against microorganisms. Innate immunity also participates in orchestrating adaptive immunity. Key components in innate defence are defensins. To study the production of defensins and how it is affected by intestinal inflammation IECs were isolated from the small and large int...

Fahlgren, Anna

2003-01-01

20

[Effect of tiropramide chlorhydrate on intestinal transit time in patients with irritable colon syndrome].  

Science.gov (United States)

The effect of tiropramide hydrochloride--a new spasmolytic drug with calmodulin-independent activity--in correcting alterations of intestinal transit, has been investigated in 40 IBS patients (20 with accelerated and 20 with delayed transit time). Intestinal transit has been evaluated by means of radioopaque markers. Tiropramide hydrochloride, at a dose of 100 mg t.i.d. for 4 weeks, was found significantly more effective than placebo both in normalizing intestinal transit time and in inducing symptomatic relief. PMID:4000532

Passaretti, S; Fesce, E; Fanti, L; Bierti, L; Bruno, L; Rossini, G; Mazzotti, G; Ideo, G; Tittobello, A

1985-05-12

 
 
 
 
21

Nutrient regulation of human intestinal sugar transporter (SGLT1) expression.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

BACKGROUND: The activity of most intestinal nutrient transporters is adaptively regulated by the type and amounts of nutrients entering the intestinal lumen. The concentration and activity of the intestinal Na+/glucose cotransporter (SGLT1) are regulated by dietary sugars in most animal species. The activity and abundance of SGLT1 in biopsy specimens removed from human jejunal regions exposed to, and having limited access to, luminal nutrients have been measured and compared. AIMS: To study t...

Dyer, J.; Hosie, K. B.; Shirazi-beechey, S. P.

1997-01-01

22

A Revised Model for Dosimetry in the Human Small Intestine  

Energy Technology Data Exchange (ETDEWEB)

A new model for an adult human gastrointestinal tract (GIT) has been developed for use in internal dose estimations to the wall of the GIT and to the other organs and tissues of the body from radionuclides deposited in the lumenal contents of the five sections of the GIT. These sections were the esophasgus, stomach, small intestine, upper large intestine, and the lower large intestine. The wall of each section was separated from its lumenal contents.

John Poston; Nasir U. Bhuiyan; R. Alex Redd; Neil Parham; Jennifer Watson

2005-02-28

23

A Revised Model for Dosimetry in the Human Small Intestine  

International Nuclear Information System (INIS)

A new model for an adult human gastrointestinal tract (GIT) has been developed for use in internal dose estimations to the wall of the GIT and to the other organs and tissues of the body from radionuclides deposited in the lumenal contents of the five sections of the GIT. These sections were the esophasgus, stomach, small intestine, upper large intestine, and the lower large intestine. The wall of each section was separated from its lumenal contents

24

Human placental alkaline phosphatase in liver and intestine  

International Nuclear Information System (INIS)

Three distinct forms of human alkaline phosphatase, presumably isozymes, are known, each apparently associated with a specific tissue. These are placental, intestinal, and liver (kidney and bone). The authors have used a specific immunoassay and HPLC to show that placental alkaline phosphatase is also present in extracts of liver and intestine in appreciable amounts

25

Intestinal and hepatic metabolism of glutamine and citrulline in humans.  

Science.gov (United States)

Glutamine plays an important role in nitrogen homeostasis and intestinal substrate supply. It has been suggested that glutamine is a precursor for arginine through an intestinal-renal pathway involving inter-organ transport of citrulline. The importance of intestinal glutamine metabolism for endogenous arginine synthesis in humans, however, has remained unaddressed. The aim of this study was to investigate the intestinal conversion of glutamine to citrulline and the effect of the liver on splanchnic citrulline metabolism in humans. Eight patients undergoing upper gastrointestinal surgery received a primed continuous intravenous infusion of [2-(15)N]glutamine and [ureido-(13)C-(2)H(2)]citrulline. Arterial, portal venous and hepatic venous blood were sampled and portal and hepatic blood flows were measured. Organ specific amino acid uptake (disposal), production and net balance, as well as whole body rates of plasma appearance were calculated according to established methods. The intestines consumed glutamine at a rate that was dependent on glutamine supply. Approximately 13% of glutamine taken up by the intestines was converted to citrulline. Quantitatively glutamine was the only important precursor for intestinal citrulline release. Both glutamine and citrulline were consumed and produced by the liver, but net hepatic flux of both amino acids was not significantly different from zero. Plasma glutamine was the precursor of 80% of plasma citrulline and plasma citrulline in turn was the precursor of 10% of plasma arginine. In conclusion, glutamine is an important precursor for the synthesis of arginine after intestinal conversion to citrulline in humans. PMID:17347276

van de Poll, Marcel C G; Ligthart-Melis, Gerdien C; Boelens, Petra G; Deutz, Nicolaas E P; van Leeuwen, Paul A M; Dejong, Cornelis H C

2007-06-01

26

Phytase activity in the human and rat small intestine.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Phytate is the major storage form of phosphorus in seeds and so is a common dietary constituent. Excessive ingestion of undegraded phytates can cause mineral deficiencies in humans. In addition, phytic acid is antineoplastic in animal models of both colon and breast carcinoma. There have been no previous studies quantifying phytase activity in the human small intestine although it is present in animals. Small intestinal phytase and alkaline phosphatase activity and distribution was measured i...

Iqbal, T. H.; Lewis, K. O.; Cooper, B. T.

1994-01-01

27

Phytase activity in the human and rat small intestine.  

Science.gov (United States)

Phytate is the major storage form of phosphorus in seeds and so is a common dietary constituent. Excessive ingestion of undegraded phytates can cause mineral deficiencies in humans. In addition, phytic acid is antineoplastic in animal models of both colon and breast carcinoma. There have been no previous studies quantifying phytase activity in the human small intestine although it is present in animals. Small intestinal phytase and alkaline phosphatase activity and distribution was measured in vitro in mucosal homogenates from two human small intestinal specimens obtained from transplant donors. Rat intestine was also studied for comparison. Phytase activity was found in human small intestine at low values (30 times less than that in rat tissue and 1000-fold lower than alkaline phosphatase in the same tissue). The activity was greatest in the duodenum and lowest in the ileum. In conclusion, the normal human small intestine has very limited ability to digest undegraded phytates. Although this may have adverse nutritional consequences with respect to metabolic cation imbalances, the presence of undigested phytate in the colon may protect against the development of colonic carcinoma. PMID:7959229

Iqbal, T H; Lewis, K O; Cooper, B T

1994-09-01

28

Three-Dimensional Coculture Of Human Small-Intestine Cells  

Science.gov (United States)

Complex three-dimensional masses of normal human epithelial and mesenchymal small-intestine cells cocultured in process involving specially designed bioreactors. Useful as tissued models for studies of growth, regulatory, and differentiation processes in normal intestinal tissues; diseases of small intestine; and interactions between cells of small intestine and viruses causing disease both in small intestine and elsewhere in body. Process used to produce other tissue models, leading to advances in understanding of growth and differentiation in developing organisms, of renewal of tissue, and of treatment of myriad of clinical conditions. Prior articles describing design and use of rotating-wall culture vessels include "Growing And Assembling Cells Into Tissues" (MSC-21559), "High-Aspect-Ratio Rotating Cell-Culture Vessel" (MSC-21662), and "In Vitro, Matrix-Free Formation Of Solid Tumor Spheroids" (MSC-21843).

Wolf, David; Spaulding, Glen; Goodwin, Thomas J.; Prewett, Tracy

1994-01-01

29

Diclofenac toxicity in human intestine ex vivo is not related to the formation of intestinal metabolites.  

Science.gov (United States)

The use of diclofenac (DCF), a nonsteroidal anti-inflammatory drug, is associated with a high prevalence of gastrointestinal side effects. In vivo studies in rodents suggested that reactive metabolites of DCF produced by the liver or the intestine might be responsible for this toxicity. In the present study, precision-cut intestinal slices (PCIS) prepared from the jejunum of 18 human donors were used as an ex vivo model to investigate whether DCF intestinal metabolites are responsible for its intestinal toxicity in man. PCIS were incubated with a concentration range of DCF (0-600 µM) up to 24 h. DCF (?400 µM) caused direct toxicity to the intestine as demonstrated by ATP depletion, morphological damage, caspase 3 activation, and lactate dehydrogenase leakage. Three main metabolites produced by PCIS (4'-hydroxy DCF, 5-hydroxy DCF, and DCF acyl glucuronide) were detected by HPLC. Protein adducts were detected by immunohistochemical staining and showed correlation with the intestinal metabolites. DCF induced similar toxicity to each of the samples regardless of the variation in metabolism among them. Less metabolites were produced by slices incubated with 400 µM DCF than with 100 µM DCF. The addition of the metabolic inhibitors such as ketoconazole, cimetidine, or borneol decreased the metabolite formation but increased the toxicity. The results suggest that DCF can induce intestinal toxicity in human PCIS directly at therapeutically relevant concentrations, independent of the reactive metabolites 4'-OH DCF, 5-OH DCF, or diclofenac acylglucuronide produced by the liver or formed in the intestine. PMID:24770551

Niu, Xiaoyu; de Graaf, Inge A M; Langelaar-Makkinje, Miriam; Horvatovich, Peter; Groothuis, Geny M M

2015-01-01

30

A comparative evaluation of intestinal transit time of two dosage forms of Haritaki [Terminalia chebula Retz.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Haritaki is praised as the best salutary drug which can be used in almost all ages of human life and is reputed for its Anulomana property. In Ayurveda, it has been mentioned that fruits of Haritaki when used in different forms give different type of actions. As the prime therapeutic utility of Haritaki is Anulomana, in the present study, two dosage forms of Haritaki fruits namely Churna and Vati were evaluated for intestinal transit time to evaluate its effect in two different dosage forms. ...

Jirankalgikar, Yogesh M.; Ashok, B. K.; Dwivedi, Rambabu R.

2012-01-01

31

Intestinal pathology in human metagonimiasis with ultrastructural observations of parasites.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A human case of intestinal metagonimiasis that was incidentally found during the histological examination of a resected segment of jejunum was described. The small adults trematode of Metagonimus yokogawai were found free in jejunal lumen as well as impacted in intervillous spaces. Histologically intestinal lesions were massive lymphoplasmacytic and eosinophilic infiltration in stroma, erosion of neanby enterocytes, goblet cell depletion and occasional villous edema. Scanning electron microsc...

Chi, J. G.; Kim, C. W.; Kim, J. R.; Hong, S. T.; Lee, S. H.

1988-01-01

32

Chloride dependent amino acid transport in the human small intestine.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Carriers of beta amino acids and imino acids in the small intestine of rabbits and guinea pigs are chloride dependent, and a cotransport of chloride, sodium, and 2-methyl-aminoisobutyric acid has been shown. This study examines the chloride dependence of amino acid transport in the human small intestine. The steady state tissue uptake of amino acids, given as the ratio between substrate concentration in intracellular and extracellular water after 35 minutes incubation at 37 degrees C, was det...

Munck, L. K.

1995-01-01

33

Reprogramming of the human intestinal epigenome by surgical tissue transposition  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Extracellular cues play critical roles in the establishment of the epigenome during development and may also contribute to epigenetic perturbations found in disease states. The direct role of the local tissue environment on the post-development human epigenome, however, remains unclear due to limitations in studies of human subjects. Here, we use an isogenic human ileal neobladder surgical model and compare global DNA methylation levels of intestinal epithelial cells pre- and post-neobladder ...

Lay, Fides D.; Triche, Timothy J.; Tsai, Yvonne C.; Su, Sheng-fang; Martin, Sue Ellen; Daneshmand, Siamak; Skinner, Eila C.; Liang, Gangning; Chihara, Yoshitomo; Jones, Peter A.

2014-01-01

34

Infant intestinal Enterococcus faecalis down-regulates inflammatory responses in human intestinal cell lines  

Directory of Open Access Journals (Sweden)

Full Text Available AIM: To investigate the ability of Lactic acid bacteria (LAB to modulate inflammatory reaction in human intestinal cell lines (Caco-2, HT-29 and HCT116. Different strains of LAB isolated from new born infants and fermented milk, together with the strains obtained from culture collections were tested.METHODS: LABs were treated with human intestinal cell lines. ELISA was used to detect IL-8 and TGF-? protein secretion. Cytokines and Toll like receptors (TLRs gene expression were assessed using RT-PCR. Conditional medium, sonicated bacteria and UV killed bacteria were used to find the effecter molecules on the bacteria. Carbohydrate oxidation and protein digestion were applied to figure out the molecules’ residues. Adhesion assays were further carried out.RESULTS: It was found that Enterococcus faecalis is the main immune modulator among the LABs by downregulation of IL-8 secretion and upregulation of TGF-?. Strikingly, the effect was only observed in four strains of E. faecalis out of the 27 isolated and tested. This implies strain dependent immunomodulation in the host. In addition, E. faecalis may regulate inflammatory responses through TLR3, TLR4, TLR9 and TRAF6. Carbohydrates on the bacterial cell surface are involved in both its adhesion to intestinal cells and regulation of inflammatory responses in the host.CONCLUSION: These data provide a case for the modulation of intestinal mucosal immunity in which specific strains of E. faecalis have uniquely evolved to maintain colonic homeostasis and regulate inflammatory responses.

Shugui Wang, Lydia Hui Mei Ng, Wai Ling Chow, Yuan Kun Lee

2008-02-01

35

Intestinal-fatty acid binding protein and lipid transport in human intestinal epithelial cells.  

Science.gov (United States)

Intestinal-fatty acid binding protein (I-FABP) is a 14-15 kDa cytoplasmic molecule highly expressed in the enterocyte. Although different functions have been proposed for various FABP family members, the specific function of I-FABP in human intestine remains unclear. Here, we studied the role of I-FABP in molecularly modified normal human intestinal epithelial cells (HIEC-6). cDNA transfection resulted in 90-fold I-FABP overexpression compared to cells treated with empty pQCXIP vector. The high-resolution immunogold technique revealed labeling mainly in the cytosol and confirmed the marked phenotype abundance of I-FABP in cDNA transfected cells. I-FABP overexpression was not associated with alterations in cell proliferation and viability. Studies using these transfected cells cultured with [14C]oleic acid did not reveal higher efficiency in de novo synthesis or secretion of triglycerides, phospholipids, and cholesteryl esters compared to cells treated with empty pQCXIP vector only. Similarly, the incubation with [35S]methionine did not disclose a superiority in the biogenesis of apolipoproteins (apo) A-I, A-IV, B-48, and B-100. Finally, cells transfected with I-FABP did not exhibit an increased production of chylomicrons, VLDL, LDL, and HDL. Our observations establish that I-FABP overexpression in normal HIEC-6 is not related to cell proliferation, lipid esterification, apo synthesis, and lipoprotein assembly, and, therefore, exclude its role in intestinal fat transport. PMID:16297872

Montoudis, Alain; Delvin, Edgard; Menard, Daniel; Beaulieu, Jean-François; Jean, Dominic; Tremblay, Eric; Bendayan, Moise; Levy, Emile

2006-01-01

36

Toxicological significance of azo dye metabolism by human intestinal microbiota.  

Science.gov (United States)

Approximately 0.7 million tons of azo dyes are synthesized each year. Azo dyes are composed of one or more R?-N=N-R? linkages. Studies have shown that both mammalian and microbial azoreductases cleave the azo bonds of the dyes to form compounds that are potentially genotoxic. The human gastrointestinal tract harbors a diverse microbiota comprised of at least several thousand species. Both water-soluble and water-insoluble azo dyes can be reduced by intestinal bacteria. Some of the metabolites produced by intestinal microbiota have been shown to be carcinogenic to humans although the parent azo dyes may not be classified as being carcinogenic. Azoreductase activity is commonly found in intestinal bacteria. Three types of azoreductases have been characterized in bacteria. They are flavin dependent NADH preferred azoreductase, flavin dependent NADPH preferred azoreductase, and flavin free NADPH preferred azoreductase. This review highlights how azo dyes are metabolized by intestinal bacteria, mechanisms of azo reduction, and the potential contribution in the carcinogenesis/mutagenesis of the reduction of the azo dyes by intestinal microbiota. PMID:22201895

Feng, Jinhui; Cerniglia, Carl E; Chen, Huizhong

2012-01-01

37

A model for Vibrio cholerae colonization of the human intestine  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Vibrio cholerae is a strict human pathogen that causes the disease cholera. It is an old-world pathogen that has re-emerged as a new threat since the early 1990s. V. cholerae colonizes the upper, small intestine where it produces a toxin that leads to watery diarrhea, characterizing the disease [36]. The dynamics of colonization by the bacteria of the intestines are largely unknown. Although a large initial infectious dose is required for infection, data suggests that only a smaller sub-popul...

Spagnuolo, Anna Maria; Dirita, Victor; Kirschner, Denise

2011-01-01

38

Molecular Epidemiology of Human Intestinal Amoebas in Iran  

Directory of Open Access Journals (Sweden)

Full Text Available Many microscopic-based epidemiological surveys on the prevalence of human intestinal pathogenic and non-pathogenic protozoa including intestinal amoeba performed in Iran show a high prevalence of human intestinal amoeba in different parts of Iran. Such epidemiological studies on amoebiasis are confusing, mainly due to recently appreciated distinction between the Entamoeba histolytica, E. dispar and E. moshkovskii. Differential diagnosis can be done by some methods such as PCR-based methods, monoclonal antibodies and the analysis of isoenzyme typing, however the molecular study of these protozoa in Iran is low. Based on molecular studies, it seems that E. dispar is predominant species especially in the central and northern areas of Iran and amoebiasis due to E. histolytica is a rare infection in the country. It is suggested that infection with E. moshkovskii may be common among Iranians. Considering the importance of molecular epidemiology of amoeba in Iran and also the current data, the present study reviews the data currently available on the molecular distribution of intestinal human amoeba in Iran.

M Rezaian

2012-09-01

39

Microbial contact during pregnancy, intestinal colonization and human disease.  

Science.gov (United States)

Interaction with colonizing intestinal bacteria is essential for healthy intestinal and immunological development in infancy. Advances in understanding early host-microbe interactions indicate that this early microbial programming begins in utero and is substantially modulated by mode of birth, perinatal antibiotics and breastfeeding. Furthermore, it has become evident that this stepwise microbial colonization process, as well as immune and metabolic programming by the microbiota, might have a long-lasting influence on the risk of not only gastrointestinal disease, but also allergic, autoimmune and metabolic disease, in later life. Modulating early host-microbe interaction by maternal probiotic intervention during pregnancy and breastfeeding offers a promising novel tool to reduce the risk of disease. In this Review, we describe the current body of knowledge regarding perinatal microbial contact, initial intestinal colonization and its association with human disease, as well as means of modulating early host-microbe interaction to reduce the risk of disease in the child. PMID:22890113

Rautava, Samuli; Luoto, Raakel; Salminen, Seppo; Isolauri, Erika

2012-10-01

40

Ricin Crosses Polarized Human Intestinal Cells and Intestines of Ricin-Gavaged Mice without Evident Damage and Then Disseminates to Mouse Kidneys  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Ricin is a potent toxin found in the beans of Ricinus communis and is often lethal for animals and humans when aerosolized or injected and causes significant morbidity and occasional death when ingested. Ricin has been proposed as a bioweapon because of its lethal properties, environmental stability, and accessibility. In oral intoxication, the process by which the toxin transits across intestinal mucosa is not completely understood. To address this question, we assessed the impact of ricin o...

Flora, Alyssa D.; Teel, Louise D.; Smith, Mark A.; Sinclair, James F.; Melton-celsa, Angela R.; O’brien, Alison D.

2013-01-01

 
 
 
 
41

Development of the Human Infant Intestinal Microbiota  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Almost immediately after a human being is born, so too is a new microbial ecosystem, one that resides in that person's gastrointestinal tract. Although it is a universal and integral part of human biology, the temporal progression of this process, the sources of the microbes that make up the ecosystem, how and why it varies from one infant to another, and how the composition of this ecosystem influences human physiology, development, and disease are still poorly understood. As a step toward s...

Palmer, Chana; Bik, Elisabeth M.; Digiulio, Daniel B.; Relman, David A.; Brown, Patrick O.

2007-01-01

42

Vincristine alters myoelectric activity and transit of the small intestine in rats  

International Nuclear Information System (INIS)

We investigated the motility of the small intestine in unanesthetized rats receiving vincristine (0.075, 0.50, 0.75 mg/kg i.v.). Motility was determined by two methods: myoelectric activity was monitored with indwelling bipolar electrodes, and intestinal transit was measured by the movement of radiochromium (Na51CrO4). Only the animals injected with the two higher doses had two distinct patterns of altered intestinal myoelectric activity within 2 h of drug administration. The first alteration occurred 44 +/- 6 min after vincristine administration and consisted of a marked increase in action potential activity with disruption of the migrating myoelectric complex. The second alteration consisted of a reappearance of the activity front of the migrating myoelectric complex with a significantly shorter periodicity. A marked reduction in spike activity occurred 3 days after vincristine injection in 3 of 10 animals receiving vincristine. A biphasic response was noted in intestinal transit. Disrupted activity front formation was associated with a significant delay in small bowel transit. In contrast, frequent activity front formation in rats was associated with significantly hastened transit. In summary, vincristine administration induces alterations of myoelectric activity of the small intestine in fasted rats and is associated with changes in intestinal transit

43

Intestinal-fatty acid binding protein and lipid transport in human intestinal epithelial cells  

International Nuclear Information System (INIS)

Intestinal-fatty acid binding protein (I-FABP) is a 14-15 kDa cytoplasmic molecule highly expressed in the enterocyte. Although different functions have been proposed for various FABP family members, the specific function of I-FABP in human intestine remains unclear. Here, we studied the role of I-FABP in molecularly modified normal human intestinal epithelial cells (HIEC-6). cDNA transfection resulted in 90-fold I-FABP overexpression compared to cells treated with empty pQCXIP vector. The high-resolution immunogold technique revealed labeling mainly in the cytosol and confirmed the marked phenotype abundance of I-FABP in cDNA transfected cells. I-FABP overexpression was not associated with alterations in cell proliferation and viability. Studies using these transfected cells cultured with [14C]oleic acid did not reveal higher efficiency in de novo synthesis or secretion of triglycerides, phospholipids, and cholesteryl esters compared to cells treated with empty pQCXIP vector only. Similarly, the incubation with [35S]methionine did not disclose a superiority in the biogenesis of apolipoproteins (apo) A-I, A-IV, B-48, and B-100. Finally, cells transfected with I-FABP did not exhibit an increased production of chylomicrons, VLDL, LDL, and HDL. Our observations establish that I-FABP overexpression in normal HIEC-6 is not related to cell proliferation, lipid esterification, apo synthesis, and lipoprotein assembly, and, therefore, exclude its role in mbly, and, therefore, exclude its role in intestinal fat transport

44

Isolation and longterm culture of human intestinal microvascular endothelial cells.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Microvascular endothelial cells play an important part in inflammation as well as in organ specific leucocyte traffic, and may be functionally different from large vessel endothelium in this respect. This study therefore established a method for isolation and longterm culture of human intestinal microvascular endothelial cells (HIMEC). After dissociation by collagenase/dispase/DNase of mucosal and submucosal tissue obtained from normal adult jejunum, cells were plated and cultured to subconfl...

Haraldsen, G.; Rugtveit, J.; Kvale, D.; Scholz, T.; Muller, W. A.; Hovig, T.; Brandtzaeg, P.

1995-01-01

45

Effects of capsaicin on human intestinal cell line Caco-2  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The influence of capsaicin processing on human intestinal cell line Caco-2 was examined by measuring transepithelial electrical resistance (TER). There was an increase in permeability at high concentration (200 to 500 ?M) of capsaicin, and the effect was inhibited by pretreatment of capsazepine, which is a competitive antagonist of the vanilloid receptor 1 (VR1). LDH-activity as well as changes in intracellular Ca2+ were determined to know whether or not capsaicin affected TER activity throu...

Isoda, Hiroko; Han, Junkyu; Tominaga, Makoto; Maekawa, Takaaki

2001-01-01

46

Diet and the development of the human intestinal microbiome  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The important role of the gut microbiome in maintaining human health has necessitated a better understanding of the temporal dynamics of intestinal microbial communities as well as the host and environmental factors driving these dynamics. Genetics, mode of birth, infant feeding patterns, antibiotic usage, sanitary living conditions and long term dietary habits contribute to shaping the composition of the gut microbiome. This review focuses primarily on diet, as it is one of the most pivotal ...

Voreades, Noah; Kozil, Anne; Weir, Tiffany L.

2014-01-01

47

Macropinocytosis in Shiga toxin 1 uptake by human intestinal epithelial cells and transcellular transcytosis  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Shiga toxin 1 and 2 production is a cardinal virulence trait of enterohemorrhagic Escherichia coli infection that causes a spectrum of intestinal and systemic pathology. However, intestinal sites of enterohemorrhagic E. coli colonization during the human infection and how the Shiga toxins are taken up and cross the globotriaosylceramide (Gb3) receptor-negative intestinal epithelial cells remain largely uncharacterized. We used samples of human intestinal tissue from patients with E. coli O157...

Malyukova, Irina; Murray, Karen F.; Zhu, Chengru; Boedeker, Edgar; Kane, Anne; Patterson, Kathleen; Peterson, Jeffrey R.; Donowitz, Mark; Kovbasnjuk, Olga

2008-01-01

48

Evolution of Symbiotic Bacteria in the Distal Human Intestine  

Science.gov (United States)

The adult human intestine contains trillions of bacteria, representing hundreds of species and thousands of subspecies. Little is known about the selective pressures that have shaped and are shaping this community's component species, which are dominated by members of the Bacteroidetes and Firmicutes divisions. To examine how the intestinal environment affects microbial genome evolution, we have sequenced the genomes of two members of the normal distal human gut microbiota, Bacteroides vulgatus and Bacteroides distasonis, and by comparison with the few other sequenced gut and non-gut Bacteroidetes, analyzed their niche and habitat adaptations. The results show that lateral gene transfer, mobile elements, and gene amplification have played important roles in affecting the ability of gut-dwelling Bacteroidetes to vary their cell surface, sense their environment, and harvest nutrient resources present in the distal intestine. Our findings show that these processes have been a driving force in the adaptation of Bacteroidetes to the distal gut environment, and emphasize the importance of considering the evolution of humans from an additional perspective, namely the evolution of our microbiomes. PMID:17579514

Ley, Ruth E; Lozupone, Catherine A; Hamady, Micah; Martens, Eric C; Henrissat, Bernard; Coutinho, Pedro M; Minx, Patrick; Latreille, Philippe; Cordum, Holland; Van Brunt, Andrew; Kim, Kyung; Fulton, Robert S; Fulton, Lucinda A; Clifton, Sandra W; Wilson, Richard K; Knight, Robin D; Gordon, Jeffrey I

2007-01-01

49

Dual system of intestinal thiamine transport in humans  

International Nuclear Information System (INIS)

The transport of thiamine across the intestine has been characterized in rats but has not been adequately studied in humans. To determine the kinetics of thiamine intestinal transport directly in humans, mucosal tissues were obtained during routine endoscopy from normal-appearing sites at the second portion of the duodenum. With 3H-dextran as the marker of adherent volume, the uptake of 14C-thiamine hydrochloride by the excised mucosa was measured in vitro. By this method thiamine uptake was linear with tissue weight and with incubation time up to 5 min. Results showed that at low thiamine concentrations (0.2 to 2.0 microM), uptake was saturable whereas at high concentrations (5 to 50 microM), uptake was linear with thiamine concentrations. Pyrithiamine, anoxia, N-ethylmaleimide, and replacement of sodium chloride by mannitol reduced the uptake of 0.5 microM thiamine by 42%, 37%, 32% and 35%, respectively (p less than 0.05) but had no effect on the uptake of 20 microM thiamine. These data suggest that, as in the rat, the intestinal transport of thiamine in humans proceeds by a coexistent dual system. At physiologic concentrations, thiamine is transported primarily by an energy-requiring, sodium-dependent active process, whereas at higher pharmacologic concentrations thiamine uptake is predominantly a passive process

50

The human commensal Bacteroides fragilis binds intestinal mucin  

Science.gov (United States)

The mammalian gastrointestinal tract harbors a vast microbial ecosystem, known as the microbiota, which benefits host biology. Bacteroides fragilis is an important anaerobic gut commensal of humans that prevents and cures intestinal inflammation. We wished to elucidate aspects of gut colonization employed by B. fragilis. Fluorescence in situ hybridization was performed on colonic tissue sections from B. fragilis and Escherichia coli dual-colonized gnotobiotic mice. Epifluorescence imaging reveals that both E. coli and B. fragilis are found in the lumen of the colon, but only B. fragilis is found in the mucosal layer. This observation suggests that physical association with intestinal mucus could be a possible mechanism of gut colonization by B. fragilis. We investigated this potential interaction using an in vitro mucus binding assay and show here that B. fragilis binds to murine colonic mucus. We further demonstrate that B. fragilis specifically and quantitatively binds to highly purified mucins (the major constituent in intestinal mucus) using flow cytometry analysis of fluorescently labeled purified murine and porcine mucins. These results suggest that interactions between B. fragilis and intestinal mucin may play a critical role during host-bacterial symbiosis. PMID:21664470

Huang, Julie Y.; Lee, S. Melanie; Mazmanian, Sarkis K.

2011-01-01

51

Enteropathogenic Escherichia coli inhibits intestinal vitamin B1 (thiamin) uptake: studies with human-derived intestinal epithelial Caco-2 cells  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Infection with the gram-negative enteropathogenic Escherichia coli (EPEC), a food-borne pathogen, represents a significant risk to human health. Whereas diarrhea is a major consequence of this infection, malnutrition also occurs especially in severe and prolonged cases, which may aggravate the health status of the infected hosts. Here we examined the effect of EPEC infection on the intestinal uptake of the water-soluble vitamin B1 (thiamin) using an established human intestinal epithelial Cac...

Ashokkumar, Balasubramaniem; Kumar, Jeyan S.; Hecht, Gail A.; Said, Hamid M.

2009-01-01

52

Blimp1 regulates the transition of neonatal to adult intestinal epithelium  

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In many mammalian species, the intestinal epithelium undergoes major changes that allow a dietary transition from mother's milk to the adult diet at the end of the suckling period. These complex developmental changes are the result of a genetic programme intrinsic to the gut tube, but its regulators have not been identified. Here we show that transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp1) is highly expressed in the developing and postnatal intestinal epithelium u...

Muncan, Vanesa; Heijmans, Jarom; Krasinski, Stephen D.; Bu?ller, Nike? V.; Wildenberg, Manon E.; Meisner, Sander; Radonjic, Marijana; Stapleton, Kelly A.; Lamers, Wout H.; Biemond, Izak; Den Bergh Weerman, Marius A.; O Carroll, Do?nal; Hardwick, James C.; Hommes, Daniel W.; Den Brink, Gijs R.

2011-01-01

53

Rates of intestinal absorption of molybdenum in humans  

International Nuclear Information System (INIS)

The intestinal absorption of molybdenum in healthy human volunteers has been measured by simultaneous oral and intravenous administration of the stable isotopes 95Mo and 96Mo, and the results were analysed using the convolution integral technique. The results showed that molybdenum ingested in liquid form was rapidly and totally absorbed into the circulation under ordinary intake regimes. The rates and extent of absorption were lower for composite meals, and also for increasing levels of administration. This information can be helpful in the application of the new ICRP model of the human alimentary tract

54

Rates of intestinal absorption of molybdenum in humans  

Energy Technology Data Exchange (ETDEWEB)

The intestinal absorption of molybdenum in healthy human volunteers has been measured by simultaneous oral and intravenous administration of the stable isotopes {sup 95}Mo and {sup 96}Mo, and the results were analysed using the convolution integral technique. The results showed that molybdenum ingested in liquid form was rapidly and totally absorbed into the circulation under ordinary intake regimes. The rates and extent of absorption were lower for composite meals, and also for increasing levels of administration. This information can be helpful in the application of the new ICRP model of the human alimentary tract.

Giussani, Augusto [Dipartimento di Fisica, Universita degli Studi di Milano, and INFN, Sezione di Milano, via Celoria 16, 20133 Milan (Italy)]. E-mail: augusto.giussani@gsf.de; Arogunjo, Adeseye M. [Department of Physics, Federal University of Technology, P.M.B. 704, Akure, Ondo State (Nigeria); Claire Cantone, Marie [Dipartimento di Fisica, Universita degli Studi di Milano, and INFN, Sezione di Milano, via Celoria 16, 20133 Milan (Italy); Tavola, Federico [Dipartimento di Fisica, Universita degli Studi di Milano, and INFN, Sezione di Milano, via Celoria 16, 20133 Milan (Italy); Veronese, Ivan [Dipartimento di Fisica, Universita degli Studi di Milano, and INFN, Sezione di Milano, via Celoria 16, 20133 Milan (Italy)

2006-06-15

55

Síndrome estreñimiento: métodos para medir la velocidad de tránsito intestinal / Constipation syndrome: methods for measuring the speed of intestinal transit  

Scientific Electronic Library Online (English)

Full Text Available SciELO Peru | Language: Spanish Abstract in spanish En el presente artículo, recuerdo lo que presenté, en un simposio llevado a cabo en nuestra Sociedad sobre el síndrome estreñimiento, en relación con la definición y los factores determinantes de este síndrome, y, además, con los métodos que hemos creado para medir en forma fisiológica la velocidad [...] del tránsito intestinal, especialmente colónico. Abstract in english In the present article, I remind what I presented, in a symposium performed in our Society on the constipation syndrome, in relation with the definition and the determinant factores of this syndrome, and, in addition, with the methods we have created to determine physiologically the velocity of the [...] intestinal transit, specially colonic.

Raúl, León-Barúa.

2012-01-01

56

Effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function in healthy humans  

DEFF Research Database (Denmark)

BACKGROUND: Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth muscle cells of the gastrointestinal tract. Little is known about the effect of glyceryl trinitrate on gastric emptying and no data exist on the possible effect of glyceryl trinitrate on small intestinal transit. AIM: To examine the effect of intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor function after a meal in healthy humans. METHODS: Nine healthy volunteers participated in a placebo-controlled, double-blind, crossover study. Each volunteer was examined during intravenous infusion of glyceryl trinitrate 1 microg/kg x min or saline. A gamma camera technique was used to measure gastric emptying and small intestinal transit after a 1600-kJ mixed liquid and solid meal. Furthermore, duodenal motility was assessed by manometry. RESULTS: Glyceryl trinitrate did not change gastric mean emptying time, gastric half emptying time, gastric retention at 15 min or small intestinal mean transit time. Glyceryl trinitrate did not influence the frequency of duodenal contractions, the amplitude of duodenal contractions or the duodenal motility index. CONCLUSIONS: Intravenous infusion of glyceryl trinitrate 1 microg/kg x min does not induce major changes in gastric or small intestinal motor function after a 1600-kJ meal in healthy volunteers.

Madsen, Jan Lysgård; Fuglsang, Stefan

2006-01-01

57

Human Milk Hyaluronan Enhances Innate Defense of the Intestinal Epithelium*  

Science.gov (United States)

Breast-feeding is associated with enhanced protection from gastrointestinal disease in infants, mediated in part by an array of bioactive glycan components in milk that act through molecular mechanisms to inhibit enteric pathogen infection. Human milk contains hyaluronan (HA), a glycosaminoglycan polymer found in virtually all mammalian tissues. We have shown that synthetic HA of a specific size range promotes expression of antimicrobial peptides in intestinal epithelium. We hypothesize that hyaluronan from human milk also enhances innate antimicrobial defense. Here we define the concentration of HA in human milk during the first 6 months postpartum. Importantly, HA isolated from milk has a biological function. Treatment of HT-29 colonic epithelial cells with human milk HA at physiologic concentrations results in time- and dose-dependent induction of the antimicrobial peptide human ?-defensin 2 and is abrogated by digestion of milk HA with a specific hyaluronidase. Milk HA induction of human ?-defensin 2 expression is also reduced in the presence of a CD44-blocking antibody and is associated with a specific increase in ERK1/2 phosphorylation, suggesting a role for the HA receptor CD44. Furthermore, oral administration of human milk-derived HA to adult, wild-type mice results in induction of the murine H? D2 ortholog in intestinal mucosa and is dependent upon both TLR4 and CD44 in vivo. Finally, treatment of cultured colonic epithelial cells with human milk HA enhances resistance to infection by the enteric pathogen Salmonella typhimurium. Together, our observations suggest that maternally provided HA stimulates protective antimicrobial defense in the newborn. PMID:23950179

Hill, David R.; Rho, Hyunjin K.; Kessler, Sean P.; Amin, Ripal; Homer, Craig R.; McDonald, Christine; Cowman, Mary K.; de la Motte, Carol A.

2013-01-01

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Vasoactive intestinal peptide signaling axis in human leukemia  

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Full Text Available The vasoactive intestinal peptide (VIP signaling axis constitutes a master “communication coordinator” between cells of the nervous and immune systems. To date, VIP and its two main receptors expressed in T lymphocytes, vasoactive intestinal peptide receptor (VPAC1 and VPAC2, mediate critical cellular functions regulating adaptive immunity, including arresting CD4 T cells in G1 of the cell cycle, protection from apoptosis and a potent chemotactic recruiter of T cells to the mucosa associated lymphoid compartment of the gastrointestinal tissues. Since the discovery of VIP in 1970, followed by the cloning of VPAC1 and VPAC2 in the early 1990s, this signaling axis has been associated with common human cancers, including leukemia. This review highlights the present day knowledge of the VIP ligand and its receptor expression profile in T cell leukemia and cell lines. Also, there will be a discussion describing how the anti-leukemic DNA binding transcription factor, Ikaros, regulates VIP receptor expression in primary human CD4 T lymphocytes and T cell lymphoblastic cell lines (e.g. Hut-78. Lastly, future goals will be mentioned that are expected to uncover the role of how the VIP signaling axis contributes to human leukemogenesis, and to establish whether the VIP receptor signature expressed by leukemic blasts can provide therapeutic and/or diagnostic information.

Glenn Paul Dorsam

2011-01-01

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Vasoactive intestinal peptide signaling axis in human leukemia.  

Science.gov (United States)

The vasoactive intestinal peptide (VIP) signaling axis constitutes a master "communication coordinator" between cells of the nervous and immune systems. To date, VIP and its two main receptors expressed in T lymphocytes, vasoactive intestinal peptide receptor (VPAC)1 and VPAC2, mediate critical cellular functions regulating adaptive immunity, including arresting CD4 T cells in G(1) of the cell cycle, protection from apoptosis and a potent chemotactic recruiter of T cells to the mucosa associated lymphoid compartment of the gastrointestinal tissues. Since the discovery of VIP in 1970, followed by the cloning of VPAC1 and VPAC2 in the early 1990s, this signaling axis has been associated with common human cancers, including leukemia. This review highlights the present day knowledge of the VIP ligand and its receptor expression profile in T cell leukemia and cell lines. Also, there will be a discussion describing how the anti-leukemic DNA binding transcription factor, Ikaros, regulates VIP receptor expression in primary human CD4 T lymphocytes and T cell lymphoblastic cell lines (e.g. Hut-78). Lastly, future goals will be mentioned that are expected to uncover the role of how the VIP signaling axis contributes to human leukemogenesis, and to establish whether the VIP receptor signature expressed by leukemic blasts can provide therapeutic and/or diagnostic information. PMID:21765981

Dorsam, Glenn Paul; Benton, Keith; Failing, Jarrett; Batra, Sandeep

2011-06-26

60

[Human intestinal parasitosis: role of Dientamoeba fragilis in human infections].  

Science.gov (United States)

The Authors report prevalences of intestinal parasitosis among home children and adults during 2002-2004, as in O&P as in acute or prolonged diarrhoea, with particular attention to the role of Dientamoeba fragilis, because often undervalued. Among 3139 subjects, 116 cases of dientamoebiasis (3.7%) and 62 of giardiasis (2.0%) were observed; not typical pathogenic protozoa were reported in 71 cases (2.3%); helminths were identified only in 8 cases (0.5%). Particularly, inside O&P group D. fragilis prevailed in 5.2% of cases (7.8% in adults and 0.5% in children) and G. duodenalis in 2.7% (3.5% and 1.3% respectively); inside acute diarrhoeas D. fragilis prevailed in 1.6% (3.9% and 0.3%) and G. duodenalis in 0.6% (1.3% and 0. 1%); inside prolonged diarrhoeas D. fragilis prevailed in 3.5 % (2.6% and 5.4%) and G. duodenalis in 3.9% (5.8% in adults and never in children). D. fragilis was more often observed among adults (6.3% of all) than among children (0.6%), like G. duodenalis (3.1% versus 0.6%). So, 107 strains of D. fragilis (92.2%) and 53 strains of G. duodenalis (85.5%) were identified in adults. D. fragilis was more frequent among females (24/39 cases, 61.5%, in the last year) while G. duodenalis was more frequent in males (13/23 cases, 56.5%). The Authors conclude underlining the importance of a permanent stain, as Giemsa stain, for a good and complete diagnosis of protozoal intestinal infections, particularly for D. fragilis. PMID:17405510

Crotti, D; D'Annibale, M L

2007-01-01

 
 
 
 
61

Anatomical study on The Arm Greater Yang Small Intestine Meridian Muscle in Human  

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This study was carried to identify the component of Small Intestine Meridian Muscle in human, dividing the regional muscle group into outer, middle, and inner layer. the inner part of body surface were opened widely to demonstrate muscles, nerve, blood vessels and the others, displaying the inner structure of Small Intestine Meridian Muscle. We obtained the results as follows; 1. Small Intestine Meridian Muscle is composed of the muscle, nerve and blood vessels. 2. In human anatomy, i...

Kyoung-sik, Park

2004-01-01

62

Mechanisms underlying modulation of monocarboxylate transporter 1 (MCT1) by somatostatin in human intestinal epithelial cells  

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Somatostatin (SST), an important neuropeptide of the gastrointestinal tract has been shown to stimulate sodium chloride absorption and inhibit chloride secretion in the intestine. However, the effects of SST on luminal butyrate absorption in the human intestine have not been investigated. Earlier studies from our group and others have shown that monocarboxylate transporter (MCT1) plays an important role in the transport of butyrate in the human intestine. The present studies were undertaken t...

Saksena, Seema; Theegala, Saritha; Bansal, Nikhil; Gill, Ravinder K.; Tyagi, Sangeeta; Alrefai, Waddah A.; Ramaswamy, Krishnamurthy; Dudeja, Pradeep K.

2009-01-01

63

Screening of exopolysaccharide-producing Lactobacillus and Bifidobacterium strains isolated from the human intestinal microbiota.  

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Using phenotypic approaches, we have detected that 17% of human intestinal Lactobacillus and Bifidobacterium strains could be exopolysaccharide (EPS) producers. However, PCR techniques showed that only 7% harbored genes related to the synthesis of heteropolysaccharides. This is the first work to screen the human intestinal ecosystem for the detection of EPS-producing strains. PMID:17483284

Ruas-Madiedo, Patricia; Moreno, José Antonio; Salazar, Nuria; Delgado, Susana; Mayo, Baltasar; Margolles, Abelardo; de Los Reyes-Gavilán, Clara G

2007-07-01

64

Impaired transit of chyme in chronic intestinal pseudoobstruction. Correction by cisapride  

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Chronic intestinal pseudoobstruction is a clinical syndrome whose pathophysiology, objective diagnosis, and treatment are poorly understood. We investigated 8 patients with this syndrome in whom intestinal dysmotility was established manometrically by two or more of the following criteria: abnormal configuration or propagation of interdigestive motor complexes, sustained incoordinate pressure activity, non-propagated bursts of phasic pressure activity, and failure of a solid-liquid meal to induce a fed pattern. To establish the functional impairment and region of the gut primarily affected by the disease, we quantified radio-scintigraphically the gastrointestinal transit of the solid (131I-fiber) and liquid (99 mTc-DTPA) components of a meal. Our techniques allowed us to quantify separately gastric emptying and pylorus-to-cecum transit. Furthermore, we evaluated the effects of a new prokinetic agent, cisapride. Gastric emptying times in pseudoobstruction were not significantly delayed; however, transit times through the small bowel (t1/2) were markedly prolonged (solids, 235 +/- 43 min (mean +/- SEM) vs. 138 +/- 25 controls, p less than 0.05; liquids, 310 +/- 67 vs. 181 +/- 28 controls, p = 0.07). Cisapride was effective in reducing the delayed intestinal transit time to within the normal range (delta solids = -115 +/- 25 min; delta liquids = -146 +/- 71 min; p less than 0.05 for both). These studies suggest that intestinal dysmotility in this group of patients with pseudoobstruction was associated with delayed small bowel transit of radiolabeled solid and liquid components of chyme. Cisapride can restore to normal the delayed transit, indicating that it may potentially correct the impaired propulsive activity in the small bowel of these patients.

Camilleri, M.; Brown, M.L.; Malagelada, J.R.

1986-09-01

65

Impaired transit of chyme in chronic intestinal pseudoobstruction. Correction by cisapride  

International Nuclear Information System (INIS)

Chronic intestinal pseudoobstruction is a clinical syndrome whose pathophysiology, objective diagnosis, and treatment are poorly understood. We investigated 8 patients with this syndrome in whom intestinal dysmotility was established manometrically by two or more of the following criteria: abnormal configuration or propagation of interdigestive motor complexes, sustained incoordinate pressure activity, non-propagated bursts of phasic pressure activity, and failure of a solid-liquid meal to induce a fed pattern. To establish the functional impairment and region of the gut primarily affected by the disease, we quantified radio-scintigraphically the gastrointestinal transit of the solid (131I-fiber) and liquid (99 mTc-DTPA) components of a meal. Our techniques allowed us to quantify separately gastric emptying and pylorus-to-cecum transit. Furthermore, we evaluated the effects of a new prokinetic agent, cisapride. Gastric emptying times in pseudoobstruction were not significantly delayed; however, transit times through the small bowel (t1/2) were markedly prolonged [solids, 235 +/- 43 min (mean +/- SEM) vs. 138 +/- 25 controls, p less than 0.05; liquids, 310 +/- 67 vs. 181 +/- 28 controls, p = 0.07]. Cisapride was effective in reducing the delayed intestinal transit time to within the normal range (delta solids = -115 +/- 25 min; delta liquids = -146 +/- 71 min; p less than 0.05 for both). These studies suggest that intestinal dysmotility in this group of patients with pseudoobstruction was associated with delayed small bowel transit of radiolabeled solid and liquid components of chyme. Cisapride can restore to normal the delayed transit, indicating that it may potentially correct the impaired propulsive activity in the small bowel of these patients

66

Release of 5-aminosalicylic acid from Pentasa during normal and accelerated intestinal transit time.  

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The influence of intestinal transit time on the release of 5-aminosalicylic acid (5-ASA) from a peroral, slow-release preparation (Pentasa) was studied at steady state in seven healthy volunteers. Daily dose was 1500 mg Pentasa, normal transit time (NTT) was 24 h (16-26 h) and accelerated transit time (ATT), caused by a laxative, was 5 h (4-9 h). Median total recovery (24 h, 5-ASA + acetyl-5-ASA) was 87% (61-129%) (NTT) and 81% (56-100%) (ATT), respectively, (P greater than 0.10). The total f...

Christensen, L. A.; Slot, O.; Sanchez, G.; Boserup, J.; Rasmussen, S. N.; Bondesen, S.; Hansen, S. H.; Hvidberg, E. F.

1987-01-01

67

Direct In Vivo Human Intestinal Permeability (Peff ) Determined with Different Clinical Perfusion and Intubation Methods.  

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Regional in vivo human intestinal effective permeability (Peff ) is calculated by measuring the disappearance rate of substances during intestinal perfusion. Peff is the most relevant parameter in the prediction of rate and extent of drug absorption from all parts of the intestine. Today, human intestinal perfusions are not performed on a routine basis in drug development. Therefore, it would be beneficial to increase the accuracy of the in vitro and in silico tools used to evaluate the intestinal Peff of novel drugs. This review compiles historical Peff data from 273 individual measurements of 80 substances from 61 studies performed in all parts of the human intestinal tract. These substances include: drugs, monosaccharaides, amino acids, dipeptides, vitamins, steroids, bile acids, ions, fatty acids, and water. The review also discusses the determination and prediction of Peff using in vitro and in silico methods such as quantitative structure-activity relationship, Caco-2, Ussing chamber, animal intestinal perfusion, and physiologically based pharmacokinetic (PBPK) modeling. Finally, we briefly outline how to acquire accurate human intestinal Peff data by deconvolution of plasma concentration-time profiles following regional intestinal bolus dosing. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. PMID:25410736

Dahlgren, David; Roos, Carl; Sjögren, Erik; Lennernäs, Hans

2014-11-19

68

Analysis of RNA transcripts for HLA class II genes in human small intestinal biopsies.  

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Studies of the expression of selected genes within the intestinal mucosa will provide important new information about physiologic pathological processes that effect mucosal growth, differentiation, and function. To study gene expression in the gut, we developed a method to obtain sufficient undegraded RNA from human endoscopic intestinal biopsy specimens for Northern and slot blot analysis. To verify the method, we examined the differential expression of HLA class II genes in small intestinal...

Volk, B. A.; Brenner, D. A.; Kagnoff, M. F.

1989-01-01

69

Microbial Eco-Physiology of the human intestinal tract: a flow cytometric approach  

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This thesis describes a multifaceted approach to further enhance our view of the complex human intestinal microbial ecosystem. This approach combines me advantages of flow cyrometry (FCM), a single cell and high-throughput technology, and molecular techniques that have proven themselves to be invaluabIe tools in studying the microbial diversity and structure of the intestinal microbiota. The ultimate aim was to relate the genetic biodiversity of the intestinal microbiota with their in situ ph...

Ben Amor, K.

2004-01-01

70

Human and simulated intestinal fluids as solvent systems to explore food effects on intestinal solubility and permeability.  

Science.gov (United States)

The mixed micelles and vesicles present in the intraluminal environment of the postprandial state exhibit suitable solubilizing capacities for lipophilic drugs. This increase in solubility, however, is accompanied by a decrease in the free fraction caused by micellar entrapment of these lipophilic compounds. In this study, both simulated and aspirated human intestinal fluids of fasted and fed state conditions were used to evaluate the influence of food on the intestinal disposition of a series of structurally related ?-blockers, with varying logP values. Using the in situ intestinal perfusion technique with mesenteric blood sampling in rats, it was demonstrated that fed state conditions significantly decreased the absorptive flux of the more lipophilic compounds metoprolol, propranolol and carvedilol, whereas the influence on the flux of the hydrophilic ?-blocker atenolol was limited. The solubility of BCS class II compound carvedilol was found to increase significantly in simulated and aspirated media of the fed state. Intestinal perfusions using intestinal media saturated with carvedilol, revealed a higher flux in the fasted state compared to the fed state, despite the higher solubility in the fed state. This study underscores the importance of addressing the complex nature of the behavior of compounds in the intraluminal environment in fasted and fed state conditions. Moreover, our data point out the value of studying the effect of food on both solubility and permeability using biorelevant experimental conditions. PMID:25063035

Stappaerts, Jef; Wuyts, Benjamin; Tack, Jan; Annaert, Pieter; Augustijns, Patrick

2014-10-15

71

Distribution of the IgG Fc Receptor, FcRn, in the Human Fetal Intestine  

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The intestinal Fc receptor, FcRn, functions in the maternofetal transfer of gamma globulin (IgG) in the neonatal rodent. In humans, most of this transfer is presumed to occur in utero via the placenta. Although the fetus swallows amniotic fluid that contains immunoglobulin, it is unknown whether this transfer also occurs via the fetal intestine. A human FcRn has been identified in the syncytiotrophoblast that mediates the maternofetal transfer of antibody. It has also been identified in human...

Shah, Uzma; Dickinson, Bonny L.; Blumberg, Richard S.; Simister, Neil E.; Lencer, Wayne I.; Walker, W. Allan

2003-01-01

72

Cell dedifferentiation and epithelial to mesenchymal transitions during intestinal regeneration in H. glaberrima  

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Full Text Available Abstract Background Determining the type and source of cells involved in regenerative processes has been one of the most important goals of researchers in the field of regeneration biology. We have previously used several cellular markers to characterize the cells involved in the regeneration of the intestine in the sea cucumber Holothuria glaberrima. Results We have now obtained a monoclonal antibody that labels the mesothelium; the outer layer of the gut wall composed of peritoneocytes and myocytes. Using this antibody we studied the role of this tissue layer in the early stages of intestinal regeneration. We have now shown that the mesothelial cells of the mesentery, specifically the muscle component, undergo dedifferentiation from very early on in the regeneration process. Cell proliferation, on the other hand, increases much later, and mainly takes place in the mesothelium or coelomic epithelium of the regenerating intestinal rudiment. Moreover, we have found that the formation of the intestinal rudiment involves a novel regenerative mechanism where epithelial cells ingress into the connective tissue and acquire mesenchymal phenotypes. Conclusions Our results strongly suggest that the dedifferentiating mesothelium provides the initial source of cells for the formation of the intestinal rudiment. At later stages, cell proliferation supplies additional cells necessary for the increase in size of the regenerate. Our data also shows that the mechanism of epithelial to mesenchymal transition provides many of the connective tissue cells found in the regenerating intestine. These results present some new and important information as to the cellular basis of organ regeneration and in particular to the process of regeneration of visceral organs.

Rivera-Cruz Angélica

2011-10-01

73

Formation and blood supply of the large intestine in human neonates  

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Full Text Available A study of the large intestine has been carried out on 24 specimens of human newborns. It has been established that the form and size of the neonates large intestine demonstrated a sidnificant individual variability. The hepatic and splenic flexures of the colon had different relations with the inferior border of the liver and spleen.

Haina N.I.

2008-01-01

74

A comparison of peripheral and central effects of clonidine on rat intestinal transit.  

Science.gov (United States)

This study was designed to examine the effects of centrally or peripherally administered clonidine on small intestinal transit (SIT) in rats with diarrhea. Adult, male rats weighing 200 to 250 grams were surgically implanted with a silicone catheter in the proximal small intestine. Some animals were additionally implanted with a cannula in the right lateral cerebroventricle. SIT was determined by measuring the progression of an intraduodenally administered radioactive marker (Na2CrO4, 0.5uCi) along the small intestine. In most experiments, the effects of clonidine or saline were determined in animals challenged with sodium ricinoleate (100 mg) intraduodenally, the active ingredient in castor oil except treatment with reserpine. Given subcutaneously (s.c.) clonidine significantly inhibited SIT at doses between 25 and 200 micrograms/kg. The effects of s.c. clonidine were antagonized by yohimbine, but not by reserpine or subdiaphragmatic truncal vagotomy. In contrast, given intracerebroventricularly (i.c.v.) clonidine produced a more long lasting effect at total doses greater than 20 micrograms. Intestinal antipropulsive effects of i.c.v. clonidine were blocked by yohimbine, but not by prazosin. Reserpine (s.c.) or 6-hydroxydopamine (i.c.v.) did not affect the actions of central clonidine. However, effects of i.c.v. clonidine were abolished after vagotomy. The results indicate that clonidine inhibits rat intestinal transit in similar total doses when given s.c. or i.c.v. Inhibition of SIT by clonidine results from alpha-2 adrenergic receptor activation. In the case of i.c.v. clonidine, the receptors appear to be located postsynaptically and the response is dependent upon intact vagal innervation. PMID:1362003

Tadano, T; Kisara, K; Stewart, J J

1992-11-01

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Characterization of intracellular pteroylpolyglutamate hydrolase (PPH) from human intestinal mucosa  

International Nuclear Information System (INIS)

There are two forms of pteroylpolyglutamate hydrolase (PPH) in the human intestinal mucosa, one in the brush border membrane and the other intracellular; brush border PPH is an exopeptidase with optimal activity at pH 6.5 and a requirement for zinc. The presence study characterized human intracellular PPH and compared its properties to those of brush border PPH. Intracellular PPH was purified 30-fold. The enzyme had a MW of 75,000 by gel filtration, was optimally active at pH 4.5, and had an isoelectric point at pH 8.0. In contrast to brush border PPH, intracellular PPH was unstable at increasing temperatures, was unaffected by dialysis against chelating agents and showed no requirement for Zn2+. Using PteGlu2[14C]Glu as substrate, they demonstrated a K/sub m/ of 1.2 ?M and increasing affinity for folates with longer glutamate chains. Intracellular PPH required the complete folic acid (PteGlu) moiety and a ?-glutamyl linkage for activity. Using ion exchange chromatography and an HPLC method to determine the hydrolytic products of the reaction, they found intracellular PPH could cleave both internal and terminal ?-glutamyl linkages, with PteGlu as an end product. After subcellular fractionation of the mucosa, PPH was found in the lysosomes. In summary, the distinct characteristics of brush border and intracellular PPH suggest that the two hydrolases serve different roles in folate metabolism

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Vasoactive intestinal peptide (VIP) induces malignant transformation of the human prostate epithelial cell line RWPE-1.  

Science.gov (United States)

The carcinogenic potential of vasoactive intestinal peptide (VIP) was analyzed in non-tumor human prostate epithelial cells (RWPE-1) and in vivo xenografts. VIP induced morphological changes and a migratory phenotype consistent with stimulation of expression/activity of metalloproteinases MMP-2 and MMP-9, decreased E-cadherin-mediated cell-cell adhesion, and increased cell motility. VIP increased cyclin D1 expression and cell proliferation that was blocked after VPAC(1)-receptor siRNA transfection. Similar effects were seen in RWPE-1 tumors developed by subcutaneous injection of VIP-treated cells in athymic nude mice. VIP acts as a cytokine in RWPE-1 cell transformation conceivably through epithelial-mesenchymal transition (EMT), reinforcing VIP role in prostate tumorigenesis. PMID:20709445

Fernández-Martínez, Ana B; Bajo, Ana M; Isabel Arenas, M; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J

2010-12-18

77

Effect of pregnancy on intestinal transit: comparison of results using radioactive and non-radioactive test meals  

International Nuclear Information System (INIS)

Studies were performed to determine the effect of pregnancy on both gastrointestinal transit and small intestinal transit. Gastrointestinal transit was examined by determining the leading edge of distribution within the small intestine of a charcoal marker placed directly into the stomach. Intestinal transit was evaluated by quantifying the distribution of a radiolabelled marker placed dirrectly into the duodenum. The distribution of the marker was determined (1) by calculating the slope of the distribution curve and (2) by calculating the geometric center of distribution of the radioisotope. In all studies the data from animals in either the second or third trimester of pregnancy were compared with the results obtained from non-pregnant females. The results confirm previous observations that gastrointestinal transit is reduced during the latter stages of pregnancy. This can be explained, at least in part, by a decreased intestinal transit. The data also suggest that analysis of the geometric center of distribution provides a more sensitive and reliable measure of intestinal transit than does analysis of the slope of the distribution curve

78

Small intestinal transit in patients with liver cirrhosis and portal hypertension: a descriptive study  

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Full Text Available Abstract Background Gastrointestinal dysmotility may be involved in the development of bacterial translocation and infection in patients with liver cirrhosis. The aim of the present study was to describe gastric, small intestinal and colorectal motility and transit in patients with liver cirrhosis and portal hypertension using a magnet-based Motility Tracking System (MTS-1 and standard radiopaque markers. Methods We included 15 patients with liver cirrhosis (8 Child-Pugh A, 6 Child-Pugh B, and 1 Child-Pugh C and portal hypertension (11 males, median age 54?years (range 38–73, median hepatic venous pressure gradient 18?mmHg (range 12–37, and 18 healthy controls (8 males, median age 58?years (range 34–64. The gastric emptying time and small intestinal motility were evaluated by MTS-1, and the total gastrointestinal transit time was assessed by radiopaque markers and abdominal radiographs. Results The velocity through the proximal small intestine was significantly higher in cirrhotic patients (median 1.27 metres (m/hour, range 0.82–2.68 than in the healthy controls (median 1.00?m/hour, range 0.46–1.88 (p?=?0.03. Likewise, the magnet travelled significantly longer in both fast (p?=?0.04 and slow movements (p?=?0.05 in the patient group. There was no significant difference in either gastric emptying time—23?minutes (range 5–131 in patients and 29?minutes (range 10.5–182 in healthy controls (p?=?0.43—or total gastrointestinal transit time—1.6?days (range 0.5–2.9 in patients and 2.0?days (range 1.0–3.9 in healthy controls (p?=?0.33. No correlation was observed between the hepatic venous pressure gradient and the velocity of the magnet through the small intestine. Conclusion Patients with liver cirrhosis and portal hypertension demonstrated faster-than-normal transit through the proximal small intestine. This may be due to an overactive bowel, as suggested by previous studies.

Karlsen Stine

2012-12-01

79

Vasoactive intestinal peptide binding autoantibodies in autoimmune humans and mice.  

Science.gov (United States)

Autoantibodies capable of binding the immunoregulatory neuropeptide vasoactive intestinal peptide (VIP) were detected in the sera of a mouse strain prone to autoimmune disease due to the lpr mutation (MRL/lpr). The autoantibodies were not present in control wildtype MRL/lpr mice, but they were readily detected in humans without autoimmune disease. The binding was due to low affinity VIP recognition. Increased VIP binding activity was evident in patients with systemic lupus erythematosus but not systemic sclerosis, Sjögren's syndrome (SS), rheumatoid arthritis or autoimmune thyroiditis. Recombinant VIP binding Fv clones (fragment variable; the variable domains of the light and heavy chains antibody subunits joined with a peptide linker) were isolated from a phage display library prepared from lupus patients. One Fv clone displaying VIP-selective binding and several clones displaying cross-reactivity with unrelated peptides were identified. Replacement mutations in the VIP-selective clone were preferentially localized in the regions known to make contacts with the antigen, i.e. the complementarity determining regions, suggesting that the selective binding activity is due to immunological maturation of the antibodies. Frequent occurrences of autoantibody responses to VIP indicate that immunological tolerance to this neuropeptide can be readily broken. The depletion of VIP by specific antibodies in autoimmune disease may interfere with VIP regulation of T cells and inflammatory cells and result in further amplification of autoreactive immunological responses. PMID:12535706

Bangale, Yogesh; Cavill, Dana; Gordon, Tom; Planque, Stephanie; Taguchi, Hiroaki; Bhatia, Gita; Nishiyama, Yasuhiro; Arnett, Frank; Paul, Sudhir

2002-12-01

80

The Mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract.  

Science.gov (United States)

A 16S rRNA-targeted probe, MUC-1437, was designed and validated in order to determine the presence and numbers of cells of Akkermansia muciniphila, a mucin degrader, in the human intestinal tract. As determined by fluorescent in situ hybridization, A. muciniphila accounted more than 1% of the total fecal cells and was shown to be a common bacterial component of the human intestinal tract. PMID:18083887

Derrien, Muriel; Collado, M Carmen; Ben-Amor, Kaouther; Salminen, Seppo; de Vos, Willem M

2008-03-01

 
 
 
 
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The mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract  

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A 16S rRNA-targeted probe, MUC-1437, was designed and validated in order to determine the presence and numbers of cells of Akkermansia muciniphila, a mucin degrader, in the human intestinal tract. As determined by fluorescent in situ hybridization, A. muciniphila accounted more than 1% of the total fecal cells and was shown to be a common bacterial component of the human intestinal tract.

Derrien, M. M. N.; Collado, M. C.; Ben-amor, K.; Salminen, S.; Vos, W. M.

2008-01-01

82

Effects of casoxin 4 on morphine inhibition of small animal intestinal contractility and gut transit in the mouse  

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Full Text Available Glen S Patten1,2, Richard J Head1, Mahinda Y Abeywardena1,21CSIRO Preventative Health National Research Flagship, Adelaide, Australia; 2CSIRO Food and Nutritional Sciences, Adelaide, AustraliaBackground and aims: Chronic opioid analgesia has the debilitating side-effect of constipation in human patients. The major aims of this study were to: 1 characterize the opioid-specific antagonism of morphine-induced inhibition of electrically driven contraction of the small intestine of mice, rats, and guinea pigs; and 2 test if the oral delivery of small milk-derived opioid antagonist peptides could block morphine-induced inhibition of intestinal transit in mice.Methods: Mouse, rat, and guinea pig intact ileal sections were electrically stimulated to contract and inhibited with morphine in vitro. Morphine inhibition was then blocked by opioid subtype antagonists in the mouse and guinea pig. Using a polymeric dye, Poly R-478, the opioid antagonists casoxin 4 and lactoferroxin A were tested orally for blocking activity of morphine inhibition of gut transit in vivo by single or double gavage techniques.Results: The guinea pig tissue was more sensitive to morphine inhibition compared with the mouse or the rat (IC50 [half maximal inhibitory concentration] values as nmol/L ± SEM were 34 ± 3, 230 ± 13, and 310 ± 14 respectively (P < 0.01. The inhibitory influence of opioid agonists (IC50 in electrically driven ileal mouse preparations were DADLE ([D-Ala2, D-Leu5]-enkephalin ? met-enkephalin ? dynorphin A ? DAMGO ([D-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin > morphine > morphiceptin as nmol/L 13.9, 17.3, 19.5, 23.3, 230, and 403 respectively. The mouse demonstrated predominantly ?- and ?-opioid receptor activity with a smaller µ-opioid receptor component. Both mouse and guinea pig tissue were sensitive to casoxin 4 antagonism of morphine inhibition of contraction. In contrast to naloxone, relatively high oral doses of the µ-opioid receptor antagonists, casoxin 4 and lactoferroxin A, applied before and after morphine injection were unable to antagonize morphine inhibition of gut transit.Conclusions: Casoxin 4 reverses morphine-induced inhibition of contraction in mice and guinea pigs in vitro but fails to influence morphine inhibition of mouse small intestinal transit by the oral route.Keywords: lactoferroxin A, µ-opioid receptor antagonist, opioid agonists

Glen S Patten

2011-02-01

83

Espiroquetosis intestinal humana: serie clínica y revisión de la literatura / Human intestinal spirochetosis: clinical series and literature review  

Scientific Electronic Library Online (English)

Full Text Available SciELO Chile | Language: Spanish Abstract in spanish Introducción: La espiroquetosis intestinal humana (EIH) se define como la colonización del intestino grueso por espiroquetas. Se asocia a diarrea crónica. Su incidencia y prevalencia van desde 0,4 a 12% Objetivo: Determinar la prevalencia de EIH en el Hospital Del Salvador, de Santiago, Chile, entre [...] los años 2003 y 2008, en pacientes con antecedentes clínicos de diarrea crónica y colonoscopia sin hallazgos patológicos, separados en dos grupos: pacientes con y sin antecedentes de infección por VIH. Material y Método: Evaluación morfológica retrospectiva de las biopsias endoscópicas de intestino grueso de los grupos seleccionados. Resultados: Se revisaron 115 biopsias, 98 correspondieron a pacientes sin infección por VIH y 17 a pacientes seropositivos para VIH. Se detectaron dos casos de espiroquetosis intestinal, ambos en pacientes sin infección por VIH, con una prevalencia de 1,7 %. Comentario: La prevalencia de EIH es similar a la publicada en países occidentales. Se requieren estudios poblacionales para determinar el real impacto epidemiológico en nuestro medio. Abstract in english Introduction: Human intestinal spirochetosis (HIE) is defined as colonization by spirochetes of the large intestine. Is associated with chronic diarrhea. The incidence and prevalence ranges from 0.4% to 12%. Objective: To determine the prevalence of HIE in the Salvador's Hospital, between 2003 and 2 [...] 008 in patients with a history of chronic diarrhea and without abnormalities in colonoscopy, in 2 separate groups: patients with and without a history of HIV infection. Material and Methods: Retrospective morphology evaluation of the large bowel endoscopic biopsies to the selected groups. Results: We reviewed 115 biopsies, 98 were from HIV-negative and 17 HIV from positive patients. Two cases of intestinal spirochetosis were detected, both HIV negative, with a prevalence of 1.7%. Comment: The prevalence of HIE is similar to that reported in Western countries. Population studies are needed to determine the real epidemiological impact in our environment.

Carlo, Lozano; Leonardo, Arellano; Pamela, Yaquich.

2012-08-01

84

Evolutionary alkaline transition in human cytochrome c.  

Science.gov (United States)

Conformational transitions in cytochrome c (cyt c) are being realized to be responsible for its multi-functions. Among a number of conformational transitions in cyt c, the alkaline transition has attracted much attention. The cDNA of human cyt c is cloned by RT-PCR and a high-effective expression system for human cyt c has been developed in this study. The equilibrium and kinetics of the alkaline transition of human cyt c have been systematically investigated for the first time, and compared with those of yeast and horse cyt c from an evolutionary perspective. The pK(a) value for the alkaline transition of human cyt c is apparently higher than that of yeast and horse. Kinetic studies suggest that it is increasingly difficult for the alkaline transition of cyt c from yeast, horse and human. Molecular modeling of human cyt c shows that the omega loop where the lysine residue is located apparently further away from heme in human cyt c than in yeast iso-1 and horse heart cyt c. These results regarding alkaline conformational transition provide valuable information for understanding the molecular basis for the biological multi-functions of cyt c. PMID:19593652

Ying, Tianlei; Zhong, Fangfang; Xie, Jin; Feng, Yanjiao; Wang, Zhong-Hua; Huang, Zhong-Xian; Tan, Xiangshi

2009-06-01

85

Chicory inulin does not increase stool weight or speed up intestinal transit time in healthy male subjects.  

Science.gov (United States)

Inulin is a non-digestible oligosaccharide classified as a prebiotic, a substrate that promotes the growth of certain beneficial microorganisms in the gut. We examined the effect of a 20 g day(-1) supplement of chicory inulin on stool weight, intestinal transit time, stool frequency and consistency, selected intestinal microorganisms and enzymes, fecal pH, short chain fatty acids and ammonia produced as by-products of bacterial fermentation. Twelve healthy male volunteers consumed a well-defined, controlled diet with and without a 20 g day(-1) supplement of chicory inulin (degree of polymerization (DP) ranging for 2-60), with each treatment lasting for 3 weeks in a randomized, double-blind crossover trial. Inulin was consumed in a low fat ice cream. No differences were found in flavor or appeal between the control and inulin-containing ice creams. Inulin consumption resulted in a significant increase in total anaerobes and Lactobacillus species and a significant decrease in ammonia levels and ?-glucuronidase activity. Flatulence increased significantly with the inulin treatment. No other significant differences were found in bowel function with the addition of inulin to the diet. Thus, inulin is easily incorporated into a food product and has no negative effects on food acceptability. Twenty grams of inulin was well tolerated, but had minimal effects on measures of laxation in healthy, human subjects. PMID:21773588

Slavin, Joanne; Feirtag, Joellen

2011-01-01

86

Zingerone regulates intestinal transit, attenuates behavioral and oxidative perturbations in irritable bowel disorder in rats.  

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Stress can lead to the manifestation of functional gastrointestinal disorders, the most prominent being irritable bowel disorder. The present study investigated the impact zingerone in ameliorating chronic water stress induced irritable bowel disorder, brain gut axis dysfunction and dysregulation of the intestinal barrier due to oxidative stress. Rats were randomly allocated to groups and subjected to chronic water stress for a period of 21 days for 1h and the fecal pellet output was measured. At the end of chronic stress, behavioral assessment for anxiety like behavior was recorded and plasma corticosterone levels were measured 60min after water stress. The colonic transit was determined, levels of oxidative and antioxidant biomarkers were measured in the colon homogenate. Myeloperoxidase activity was determined as an indirect index of neutrophil infiltration. Chronic water stress increased the rate of colonic transit, fecal output, induced behavioral changes, and decreased antioxidant levels. An increase in lipid peroxide levels, catalase and corticosterone was observed. Mast cell infiltration was evident in the stressed group. Zingerone significantly reduced colonic transit, fecal output, neutrophil infiltration, and lipid peroxide formation. The levels of catalase were not altered; however, a marginal increase in the levels of glutathione peroxidase was observed. Zingerone significantly enhanced the levels of superoxide dismutase, glutathione and decreased the levels of corticosterone. Zingerone produced marked improvement in stress induced irritable bowel disorder which could be attributed to the powerful antioxidant nature, direct effect on the intestinal smooth muscle and adaptogenic nature. PMID:24262066

Banji, David; Banji, Otilia J F; Pavani, Bandlapalli; Kranthi Kumar, Ch; Annamalai, A R

2014-03-15

87

Diet and the development of the human intestinal microbiome.  

Science.gov (United States)

The important role of the gut microbiome in maintaining human health has necessitated a better understanding of the temporal dynamics of intestinal microbial communities as well as the host and environmental factors driving these dynamics. Genetics, mode of birth, infant feeding patterns, antibiotic usage, sanitary living conditions and long term dietary habits contribute to shaping the composition of the gut microbiome. This review focuses primarily on diet, as it is one of the most pivotal factors in the development of the human gut microbiome from infancy to the elderly. The infant gut microbiota is characterized by a high degree of instability, only reaching a state similar to that of adults by 2-3 years of age; consistent with the establishment of a varied solid food diet. The diet-related factors influencing the development of the infant gut microbiome include whether the child is breast or formula-fed as well as how and when solid foods are introduced. In contrast to the infant gut, the adult gut microbiome is resilient to large shifts in community structure. Several studies have shown that dietary changes induce transient fluctuations in the adult microbiome, sometimes in as little as 24 h; however, the microbial community rapidly returns to its stable state. Current knowledge of how long-term dietary habits shape the gut microbiome is limited by the lack of long-term feeding studies coupled with temporal gut microbiota characterization. However, long-term weight loss studies have been shown to alter the ratio of the Bacteroidetes and Firmicutes, the two major bacterial phyla residing in the human gastrointestinal tract. With aging, diet-related factors such as malnutrition are associated with microbiome shifts, although the cause and effect relationship between these factors has not been established. Increased pharmaceutical usage is also more prevalent in the elderly and can contribute to reduced gut microbiota stability and diversity. Foods containing prebiotic oligosaccharide components that nurture beneficial commensals in the gut community and probiotic supplements are being explored as interventions to manipulate the gut microbiome, potentially improving health status. PMID:25295033

Voreades, Noah; Kozil, Anne; Weir, Tiffany L

2014-01-01

88

Vasoactive intestinal peptide (VIP) inhibits human renal cell carcinoma proliferation.  

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Clear renal cell carcinoma (cRCC) is an aggressive and fatal neoplasm. The present work was undertaken to investigate the antiproliferative potential of vasoactive intestinal peptide (VIP) exposure on non-tumoral (HK2) and tumoral (A498, cRCC) human proximal tubular epithelial cell lines. Reverse transcription and semiquantitative PCR was used at the VIP mRNA level whereas enzyme immunoanalysis was performed at the protein level. Both renal cell lines expressed VIP as well as VIP/pituitary adenylate cyclase-activating peptide (VPAC) receptors whereas only HK2 cells expressed formyl peptide receptor-like 1 (FPRL-1). Receptors were functional, as shown by VIP stimulation of adenylyl cyclase activity. Treatment with 0.1?M VIP (24h) inhibited proliferation of A498 but not HK2 cells as based on a reduction in the incorporation of [(3)H]-thymidine and BrdU (5'-Br-2'-deoxyuridine), PCNA (proliferating-cell nuclear antigen) expression and STAT3 (signal transducer and activator of transcription 3) expression and activation. VPAC(1)-receptor participation was established using JV-1-53 antagonist and siRNA transfection. Growth-inhibitory response to VIP was related to the cyclic adenosine monophosphate (cAMP)/exchange protein directly activated by cAMP (EPAC)/phosphoinositide 3-kinase (PI3-K) signaling systems as shown by studies on adenylate cyclase stimulation, and using the EPAC-specific compound 8CPT-2Me-cAMP and specific kinase inhibitors such as H89, wortmannin and PD98059. The efficacy of VIP on the prevention of tumor progression was confirmed in vivo using xenografted athymic mouse. These actions support a potential role of this peptide and its agonists in new therapies for cRCC. PMID:22728770

Vacas, Eva; Fernández-Martínez, Ana B; Bajo, Ana M; Sánchez-Chapado, Manuel; Schally, Andrew V; Prieto, Juan C; Carmena, María J

2012-10-01

89

Comparative proteomic analysis of cell lines and scrapings of the human intestinal epithelium  

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Full Text Available Abstract Background In vitro models are indispensable study objects in the fields of cell and molecular biology, with advantages such as accessibility, homogeneity of the cell population, reproducibility, and growth rate. The Caco-2 cell line, originating from a colon carcinoma, is a widely used in vitro model for small intestinal epithelium. Cancer cells have an altered metabolism, making it difficult to infer their representativity for the tissue from which they are derived. This study was designed to compare the protein expression pattern of Caco-2 cells with the patterns of intestinal epithelial cells from human small and large intestine. HT-29 intestinal cells, Hep G2 liver cells and TE 671 muscle cells were included too, the latter two as negative controls. Results Two-dimensional gel electrophoresis was performed on each tissue and cell line protein sample. Principal component and cluster analysis revealed that global expression of intestinal epithelial scrapings differed from that of intestinal epithelial cell lines. Since all cultured cell lines clustered together, this finding was ascribed to an adaptation of cells to culture conditions and their tumor origin, and responsible proteins were identified by mass spectrometry. When investigating the profiles of Caco-2 cells and small intestinal cells in detail, a considerable overlap was observed. Conclusion Numerous proteins showed a similar expression in Caco-2 cells, HT-29 cells, and both the intestinal scrapings, of which some appear to be characteristic to human intestinal epithelium in vivo. In addition, several biologically significant proteins are expressed at comparable levels in Caco-2 cells and small intestinal scrapings, indicating the usability of this in vitro model. Caco-2 cells, however, appear to over-express as well as under-express certain proteins, which needs to be considered by scientists using this cell line. Hence, care should be taken to prevent misinterpretation of in vitro obtained findings when translating them to the in vivo situation.

Renes Johan

2007-04-01

90

Effects of cisapride on gall bladder emptying, intestinal transit, and serum deoxycholate: a prospective, randomised, double blind, placebo controlled trial  

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BACKGROUND—Octreotide inhibits gall bladder emptying and prolongs intestinal transit. This leads to increases in the proportion of deoxycholic acid in, and cholesterol saturation of, gall bladder bile, factors that contribute to the pathogenesis of octreotide induced gall stones.?AIMS—To see if an intestinal prokinetic, cisapride, could overcome these adverse effects of octreotide and if so, be considered as a candidate prophylactic drug for preventing iatrogenic gall bladder stones.?...

Veysey, M.; Malcolm, P.; Mallet, A.; Jenkins, P.; Besser, G.; Murphy, G.; Dowling, R.

2001-01-01

91

The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates  

DEFF Research Database (Denmark)

The human gastrointestinal tract (GI tract) harbors a complex community of microbes. The microbiota composition varies between different locations in the GI tract, but most studies focus on the fecal microbiota, and that inhabiting the colonic mucosa. Consequently, little is known about the microbiota at other parts of the GI tract, which is especially true for the small intestine because of its limited accessibility. Here we deduce an ecological model of the microbiota composition and function in the small intestine, using complementing culture-independent approaches. Phylogenetic microarray analyses demonstrated that microbiota compositions that are typically found in effluent samples from ileostomists (subjects without a colon) can also be encountered in the small intestine of healthy individuals. Phylogenetic mapping of small intestinal metagenome of three different ileostomy effluent samples from a single individual indicated that Streptococcus sp., Escherichia coli, Clostridium sp. and high G+C organisms are most abundant in the small intestine. The compositions of these populations fluctuated in time and correlated to the short-chain fatty acids profiles that were determined in parallel. Comparative functional analysis with fecal metagenomes identified functions that are overrepresented in the small intestine, including simple carbohydrate transport phosphotransferase systems (PTS), central metabolism and biotin production. Moreover, metatranscriptome analysis supported high level in-situ expression of PTS and carbohydrate metabolic genes, especially those belonging to Streptococcus sp. Overall, our findings suggest that rapid uptake and fermentation of available carbohydrates contribute to maintaining the microbiota in the human small intestine.

Zoetendal, Erwin G; Raes, Jeroen

2012-01-01

92

Nucleotide and amino acid sequences of human intestinal alkaline phosphatase: close homology to placental alkaline phosphatase  

International Nuclear Information System (INIS)

A cDNA clone for human adult intestinal alkaline phosphatase (ALP) [orthophosphoric-monoester phosphohydrolase (alkaline optimum); EC 3.1.3.1] was isolated from a ?gt11 expression library. The cDNA insert of this clone is 2513 base pairs in length and contains an open reading frame that encodes a 528-amino acid polypeptide. This deduced polypeptide contains the first 40 amino acids of human intestinal ALP, as determined by direct protein sequencing. Intestinal ALP shows 86.5% amino acid identity to placental (type 1) ALP and 56.6% amino acid identity to liver/bone/kidney ALP. In the 3'-untranslated regions, intestinal and placental ALP cDNAs are 73.5% identical (excluding gaps). The evolution of this multigene enzyme family is discussed

93

Association between the ABO blood group and the human intestinal microbiota composition  

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Full Text Available Abstract Background The mucus layer covering the human intestinal epithelium forms a dynamic surface for host-microbial interactions. In addition to the environmental factors affecting the intestinal equilibrium, such as diet, it is well established that the microbiota composition is individually driven, but the host factors determining the composition have remained unresolved. Results In this study, we show that ABO blood group is involved in differences in relative proportion and overall profiles of intestinal microbiota. Specifically, the microbiota from the individuals harbouring the B antigen (secretor B and AB differed from the non-B antigen groups and also showed higher diversity of the Eubacterium rectale-Clostridium coccoides (EREC and Clostridium leptum (CLEPT -groups in comparison with other blood groups. Conclusions Our novel finding indicates that the ABO blood group is one of the genetically determined host factors modulating the composition of the human intestinal microbiota, thus enabling new applications in the field of personalized nutrition and medicine.

Mäkivuokko Harri

2012-06-01

94

Characterization of two cysteine proteases secreted by Blastocystis ST7, a human intestinal parasite.  

Science.gov (United States)

Blastocystis spp. are unicellular anaerobic intestinal parasites of both humans and animals and the most prevalent ones found in human stool samples. Their association with various gastrointestinal disorders raises the questions of its pathogenicity and of the molecular mechanisms involved. Since secreted proteases are well-known to be implicated in intestinal parasite virulence, we intended to determine whether Blastocystis spp. possess such pathogenic factors. In silico analysis of the Blastocystis subtype 7 (ST7) genome sequence highlighted 22 genes coding proteases which were predicted to be secreted. We characterized the proteolytic activities in the secretory products of Blastocystis ST7 using specific protease inhibitors. Two cysteine proteases, a cathepsin B and a legumain, were identified in the parasite culture supernatant by gelatin zymographic SDS-PAGE gel and MS/MS analysis. These proteases might act on intestinal cells and disturb gut function. This work provides serious molecular candidates to link Blastocystis spp. and intestinal disorders. PMID:22402106

Wawrzyniak, Ivan; Texier, Catherine; Poirier, Philippe; Viscogliosi, Eric; Tan, Kevin S W; Delbac, Frédéric; El Alaoui, Hicham

2012-09-01

95

New Isolation Technique to Study Apoptosis in Human Intestinal Epithelial Cells  

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Intestinal epithelial cells derive from stem cells at the base of the crypt and migrate along the crypt-lumen axis. Their life is terminated as they reach the luminal surface where they detach and are shed. Intestinal epithelial cells show evidence of apoptosis in the region of shedding, and cell death is thought to resemble a form of apoptosis called detachment-induced cell death, or anoikis. Human intestinal epithelial cells die rapidly in vitro due to loss of anchorage during isolation, ma...

Grossmann, Johannes; Maxson, Julie M.; Whitacre, Cecilia M.; Orosz, David E.; Berger, Nathan A.; Fiocchi, Claudio; Levine, Alan D.

1998-01-01

96

Pro-Inflammatory Flagellin Proteins of Prevalent Motile Commensal Bacteria Are Variably Abundant in the Intestinal Microbiome of Elderly Humans  

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Some Eubacterium and Roseburia species are among the most prevalent motile bacteria present in the intestinal microbiota of healthy adults. These flagellate species contribute “cell motility” category genes to the intestinal microbiome and flagellin proteins to the intestinal proteome. We reviewed and revised the annotation of motility genes in the genomes of six Eubacterium and Roseburia species that occur in the human intestinal microbiota and examined their respective locus organizatio...

Neville, B. Anne; Sheridan, Paul O.; Harris, Hugh M. B.; Coughlan, Simone; Flint, Harry J.; Duncan, Sylvia H.; Jeffery, Ian B.; Claesson, Marcus J.; Ross, R. Paul; Scott, Karen P.; O Toole, Paul W.

2013-01-01

97

The scintigraphic determination of small intestinal transit time in patients with irritable bowel syndrome  

International Nuclear Information System (INIS)

Diffuse disturbance in gastrointestinal motility may be present in patients with irritable bowel syndrome (IBS). To further investigate small intestinal motility in IBS patients small intestinal transit time (SITT) was determined and related to the symptom status. 11 female patients with IBS (mean age 29 years) were divided into those whose predominate symptom was diarrhea (N=6), and those with only constipation (N=5). All subjects ingested an isosmotic solution of lactulose (10 gm in 150cc of water) labeled with 99m-Tc-DTPA (Sn). The patient was studied supine under a 25 inch gamma camera with data collected at 1 frame per minute for 180 minutes or until activity appeared in the ascending colon. Regions of interest were selected over the cecum and ascending colon. The time of first appearance of radioactivity in the region of the cecum was taken as the small intestinal transit time. SITT in the 5 normal females was 98.7 +- 13 min (mean +- SEM). SITT in the IBS patients with diarrhea, 67.3 +- 7 min was significantly faster (p< 0.08). SITT in the constipated IBS patients, 126 +- 12 min, was slower than normals and significantly different from diarrhea patients (p< 0.001). These studies show that IBS patients with diarrhea have significantly faster SITT than normals while constipated IBS patients have significantly slower SITT than the diarrhea subgroup. Further, this study emphasizes the need to study the various symptomatic subgroups of IBs patients independently and indicates a possible role for abnormal SITT in the pathogenesis of IBS

98

Association between the ABO blood group and the human intestinal microbiota composition  

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Abstract Background The mucus layer covering the human intestinal epithelium forms a dynamic surface for host-microbial interactions. In addition to the environmental factors affecting the intestinal equilibrium, such as diet, it is well established that the microbiota composition is individually driven, but the host factors determining the composition have remained unresolved. Results In this study, we show that ABO blood group is involved in differences in rel...

Mäkivuokko Harri; Lahtinen Sampo J; Wacklin Pirjo; Tuovinen Elina; Tenkanen Heli; Nikkilä Janne; Björklund Marika; Aranko Kari; Ouwehand Arthur C; Mättö Jaana

2012-01-01

99

Cooperation between MEF2 and PPAR? in human intestinal ?,?-carotene 15,15'-monooxygenase gene expression  

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Abstract Background Vitamin A and its derivatives, the retinoids, are essential for normal embryonic development and maintenance of cell differentiation. ?, ?-carotene 15,15'-monooxygenase 1 (BCMO1) catalyzes the central cleavage of ?-carotene to all-trans retinal and is the key enzyme in the intestinal metabolism of carotenes to vitamin A. However, human and various rodent species show markedly different efficiencies in intestinal BCMO1-mediated carotene to retin...

Yan Bingfang; Tsai Shu-Whei; Gong Xiaoming; Rubin Lewis P

2006-01-01

100

Growth inhibition of Streptococcus mutans by cellular extracts of human intestinal lactic acid bacteria.  

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The in vitro growth of Streptococcus mutans was completely inhibited by water-soluble extracts from cells of various intestinal lactic acid bacteria identified as Streptococcus faecium, Streptococcus equinus, Lactobacillus fermentum, and Lactobacillus salivarius. The growth inhibition was dependent on the concentrations of the extracts. In contrast, the extracts did not inhibit the growth of the major indigenous intestinal lactic acid bacteria isolated from humans. These lactic acid bacteria ...

Ishihara, K.; Miyakawa, H.; Hasegawa, A.; Takazoe, I.; Kawai, Y.

1985-01-01

 
 
 
 
101

Smoking cessation induces profound changes in the composition of the intestinal microbiota in humans  

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BACKGROUND: The human intestinal microbiota is a crucial factor in the pathogenesis of various diseases, such as metabolic syndrome or inflammatory bowel disease (IBD). Yet, knowledge about the role of environmental factors such as smoking (which is known to influence theses aforementioned disease states) on the complex microbial composition is sparse. We aimed to investigate the role of smoking cessation on intestinal microbial composition in 10 healthy smoking subjects undergoing controlled...

Biedermann, Luc; Zeitz, Jonas; Mwinyi, Jessica; Sutter-minder, Eveline; Rehman, Ateequr; Ott, Stephan J.; Steurer-stey, Claudia; Frei, Anja; Frei, Pascal; Scharl, Michael; Loessner, Martin J.; Vavricka, Stephan R.; Fried, Michael; Schreiber, Stefan; Schuppler, Markus

2013-01-01

102

Inhibition of gastric emptying and intestinal transit in anesthetized rats by a Tityus serrulatus scorpion toxin  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english The effects of a fraction (T1) of Tityus serrulatus scorpion venom prepared by gel filtration on gastric emptying and small intestinal transit were investigated in male Wistar rats. Fasted animals were anesthetized with urethane, submitted to tracheal intubation and right jugular vein cannulation. S [...] corpion toxin (250 µg/kg) or saline was injected iv and 1 h later a bolus of saline (1.0 ml/100 g) labeled with 99m technetium-phytate (10 MBq) was administered by gavage. After 15 min, animals were sacrificed and the radioactivity remaining in the stomach was determined. Intestinal transit was evaluated by instillation of a technetium-labeled saline bolus (1.0 ml) through a cannula previously implanted in the duodenum. After 60 min, the progression of the marker throughout 7 consecutive gut segments was estimated by the geometric center method. Gastric retention of the liquid test meal in rats injected with scorpion toxin (median: 88%; range: 52-95%) was significantly higher (P

L.E.A., Troncon; A.A., Santos; V.L., Garbacio; M., Secaf; A.V., Verceze; J.R., Cunha-Melo.

1053-10-01

103

Adhesion and absorption of Tc-99 labelled tracers for estimating the intestinal transit  

International Nuclear Information System (INIS)

Liquid, semisolid and solid markers are used to calculate esophageal transit, gastric emptying or intestinal transit. The purpose of this study was to prove in vivo stability and wall absorption. 41 Wistar rats were fed with sup(99m)Tc-DTPA (n=11), sup(99m)Tc-labeled chicken liver (n=11), sup(99m)Tc-Chelex (n=11) or sup(99m)Tc-pertechnetate (n=8). One to three hours later the animals were killed, the gut was dissected and rinsed with water. The water for rinsing, the activity of the intestinal wall and other organs were measured in a whole body counter. The calculated fractions (%) of intraluminal (1), wall-absorbed (W) and extraintestianl (E) activity in relation to total counts were: DPTA: (1) 89 +- 3.2, (W) 8 +- 2.1, (E) 2.3 +- 1.6. CHELEX: (1) 98.8 +- 0.6, (W) 0.9 +-0.4, (E) 0.3 +- 0.4. CHICKEN LIVER: (1) 96.9 +- 1.3, (W) 2.3 +- 1.1, (E) 0.8 +- 0.8. PERTECHNETATE: (1) 36.4 +- 12, (W) 9.5 +- 2.7, (E) 54.2 +- 13. The differences were significant between all groups (p<0.05). The most inert tracer is Chelex which, in contrast to chicken liver, is simple to handle and is different to liquid tracers in intraluminal kinetics. Clinical use is proposed. (Author)

104

Sildenafil delays the intestinal transit of a liquid meal in awake rats  

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Full Text Available SciELO Brazil | Language: English Abstract in english Sildenafil slows down the gastric emptying of a liquid test meal in awake rats and inhibits the contractility of intestinal tissue strips. We studied the acute effects of sildenafil on in vivo intestinal transit in rats. Fasted, male albino rats (180-220 g, N = 44) were treated (0.2 mL, iv) with sil [...] denafil (4 mg/kg) or vehicle (0.01 N HCl). Ten minutes later they were fed a liquid test meal (99m technetium-labeled saline) injected directly into the duodenum. Twenty, 30 or 40 min after feeding, the rats were killed and transit throughout the gastrointestinal tract was evaluated by progression of the radiotracer using the geometric center method. The effect of sildenafil on mean arterial pressure (MAP) was monitored in a separate group of rats (N = 14). Data (medians within interquartile ranges) were compared by the Mann-Whitney U-test. The location of the geometric center was significantly more distal in vehicle-treated than in sildenafil-treated rats at 20, 30, and 40 min after test meal instillation (3.3 (3.0-3.6) vs 2.9 (2.7-3.1); 3.8 (3.4-4.0) vs 2.9 (2.5-3.1), and 4.3 (3.9-4.5) vs 3.4 (3.2-3.7), respectively; P

J.R.V, Graça; G.M, Macedo; R.C, Palheta Jr; F. de A.A, Gondim; R.O, Nogueira; J.M, Correia; F.H, Rola; R.B, Oliveira; M.A.N, Souza; A.A, Santos.

2008-01-01

105

High taxonomic level fingerprint of the human intestinal microbiota by Ligase Detection Reaction - Universal Array approach  

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Full Text Available Abstract Background Affecting the core functional microbiome, peculiar high level taxonomic unbalances of the human intestinal microbiota have been recently associated with specific diseases, such as obesity, inflammatory bowel diseases, and intestinal inflammation. Results In order to specifically monitor microbiota unbalances that impact human physiology, here we develop and validate an original DNA-microarray (HTF-Microbi.Array for the high taxonomic level fingerprint of the human intestinal microbiota. Based on the Ligase Detection Reaction-Universal Array (LDR-UA approach, the HTF-Microbi.Array enables specific detection and approximate relative quantification of 16S rRNAs from 30 phylogenetically related groups of the human intestinal microbiota. The HTF-Microbi.Array was used in a pilot study of the faecal microbiota of eight young adults. Cluster analysis revealed the good reproducibility of the high level taxonomic microbiota fingerprint obtained for each of the subject. Conclusion The HTF-Microbi.Array is a fast and sensitive tool for the high taxonomic level fingerprint of the human intestinal microbiota in terms of presence/absence of the principal groups. Moreover, analysis of the relative fluorescence intensity for each probe pair of our LDR-UA platform can provide estimation of the relative abundance of the microbial target groups within each samples. Focusing the phylogenetic resolution at division, order and cluster levels, the HTF-Microbi.Array is blind with respect to the inter-individual variability at the species level.

Vitali Beatrice

2010-04-01

106

Expression and promoter analysis of SLC19A2 in the human intestine.  

Science.gov (United States)

The molecular mechanism and regulation of the intestinal uptake process of dietary thiamine is not well understood. Previous studies have established the involvement of a carrier-mediated system for thiamine uptake in the human intestine. Recently a human thiamine transporter, SLC19A2, was cloned from a number of human tissues. Little, however, is known about expression of the SLC19A2 message along the native human gastrointestinal tract, and no analysis of its promoter in intestinal tissue is available. Therefore, the current studies were aimed at investigating the expression of SLC19A2 in the human gastrointestinal tract and at analyzing the promoter of this potential intestinal thiamine transporter. First we cloned SLC19A2 cDNA from a human intestinal cell line (Caco-2) by reverse transcriptase-polymerase chain reaction, then used this cDNA as a probe in Northern blot analysis. SLC19A2 message was found to be expressed in all gastrointestinal tissues in the following order: liver>stomach>duodenum>jejunum>colon>cecum>rectum>ileum. SLC19A2 was also expressed at the protein level in Caco-2 cells and in native human small intestine by Western blot analysis. We also cloned the 5'-regulatory region of the SLC19A2 gene and confirmed activity of its promoter following transfection into intestinal epithelial Caco-2 cells. Furthermore, we identified the minimal promoter region required for basal activity of SLC19A2 in these cells which was found to be mainly encoded in a sequence between -356 and -36, and included multiple cis-regulatory elements. Transcription initiation sites of the SLC19A2 gene in intestinal epithelial Caco-2 cells were also identified by 5'-rapid amplification of cDNA ends. These results demonstrate that SLC19A2 is expressed in various regions of the human gastrointestinal tract. In addition, the results provide the first characterization of the SLC19A2 promoter. These findings raise the possibility that SLC19A2 may play a role in the normal intestinal thiamine absorption process. PMID:11997118

Reidling, Jack C; Subramanian, Veedamali S; Dudeja, Pradeep K; Said, Hamid M

2002-04-12

107

The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen-specific  

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Mucosal antibody responses play a major role in mediating homeostasis with the intestinal flora. It has been suggested that imbalance in the IgA+ and IgG+ intestinal B cell repertoire may be associated with the development of diseases such as inflammatory bowel disease. Despite this, little is known about the antibody specificity of human intestinal plasmablasts. Here, we have determined the reactivity profile of single isolated IgA+ and IgG+ plasmablasts from human terminal ileum using antib...

Benckert, Julia; Schmolka, Nina; Kreschel, Cornelia; Zoller, Markus Josef; Sturm, Andreas; Wiedenmann, Bertram; Wardemann, Hedda

2011-01-01

108

Effect of Ceftaroline on Normal Human Intestinal Microflora?  

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Ceftaroline is a new broad-spectrum cephalosporin being developed for the treatment of serious bacterial infections, including those caused by aerobic Gram-positive and Gram-negative bacteria. The purpose of the present study was to investigate the effect of administration of ceftaroline on the intestinal flora of healthy subjects. Twelve healthy subjects (6 males and 6 females), 20 to 41 years of age, received ceftaroline (600 mg) by intravenous infusion every 12 h (q12h) for 7 days. Plasma ...

Panagiotidis, Georgios; Ba?ckstro?m, Tobias; Asker-hagelberg, Charlotte; Jandourek, Alena; Weintraub, Andrej; Nord, Carl Erik

2010-01-01

109

Human Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells  

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Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. Here, using an endogenous LGR5-GFP reporter, we derived adult stem cells from hPSCs that gave rise to functional human intestinal tissue comprising all major...

Forster, Ryan; Chiba, Kunitoshi; Schaeffer, Lorian; Regalado, Samuel g; Lai, Christine s; Gao, Qing; Kiani, Samira; Farin, Henner f; Clevers, Hans; Cost, Gregory j; Chan, Andy; Rebar, Edward j; Urnov, Fyodor d; Gregory, Philip d; Pachter, Lior

2014-01-01

110

Isolation and identification of intestinal CYP3A inhibitors from cranberry (Vaccinium macrocarpon) using human intestinal microsomes.  

Science.gov (United States)

Cranberry juice is used routinely, especially among women and the elderly, to prevent and treat urinary tract infections. These individuals are likely to be taking medications concomitantly with cranberry juice, leading to concern about potential drug-dietary substance interactions, particularly in the intestine, which, along with the liver, is rich in expression of the prominent drug metabolizing enzyme, cytochrome P450 3A (CYP3A). Using a systematic in vitro-in vivo approach, a cranberry juice product was identified recently that elicited a pharmacokinetic interaction with the CYP3A probe substrate midazolam in 16 healthy volunteers. Relative to water, cranberry juice inhibited intestinal first-pass midazolam metabolism. In vitro studies were initiated to identify potential enteric CYP3A inhibitors from cranberry via a bioactivity-directed fractionation approach involving dried whole cranberry [Vaccinium macrocarpon Ait. (Ericaceae)], midazolam, and human intestinal microsomes (HIM). Three triterpenes (maslinic acid, corosolic acid, and ursolic acid) were isolated. The inhibitory potency (IC(50)) of maslinic acid, corosolic acid, and ursolic acid was 7.4, 8.8, and < 10 µM, respectively, using HIM as the enzyme source and 2.8, 4.3, and < 10 µM, respectively, using recombinant CYP3A4 as the enzyme source. These in vitro inhibitory potencies, which are within the range of those reported for two CYP3A inhibitory components in grapefruit juice, suggest that these triterpenes may have contributed to the midazolam-cranberry juice interaction observed in the clinical study. PMID:20717876

Kim, Eunkyung; Sy-Cordero, Arlene; Graf, Tyler N; Brantley, Scott J; Paine, Mary F; Oberlies, Nicholas H

2011-02-01

111

Cooperation between MEF2 and PPAR? in human intestinal ?,?-carotene 15,15'-monooxygenase gene expression  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Vitamin A and its derivatives, the retinoids, are essential for normal embryonic development and maintenance of cell differentiation. ?, ?-carotene 15,15'-monooxygenase 1 (BCMO1 catalyzes the central cleavage of ?-carotene to all-trans retinal and is the key enzyme in the intestinal metabolism of carotenes to vitamin A. However, human and various rodent species show markedly different efficiencies in intestinal BCMO1-mediated carotene to retinoid conversion. The aim of this study is to identify potentially human-specific regulatory control mechanisms of BCMO1 gene expression. Results We identified and functionally characterized the human BCMO1 promoter sequence and determined the transcriptional regulation of the BCMO1 gene in a BCMO1 expressing human intestinal cell line, TC-7. Several functional transcription factor-binding sites were identified in the human promoter that are absent in the mouse BCMO1 promoter. We demonstrate that the proximal promoter sequence, nt -190 to +35, confers basal transcriptional activity of the human BCMO1 gene. Site-directed mutagenesis of the myocyte enhancer factor 2 (MEF2 and peroxisome proliferator-activated receptor (PPAR binding elements resulted in decreased basal promoter activity. Mutation of both promoter elements abrogated the expression of intestinal cell BCMO1. Electrophoretic mobility shift and supershift assays and transcription factor co-expression in TC-7 cells showed MEF2C and PPAR? bind to their respective DNA elements and synergistically transactivate BCMO1 expression. Conclusion We demonstrate that human intestinal cell BCMO1 expression is dependent on the functional cooperation between PPAR? and MEF2 isoforms. The findings suggest that the interaction between MEF2 and PPAR factors may provide a molecular basis for interspecies differences in the transcriptional regulation of the BCMO1 gene.

Yan Bingfang

2006-02-01

112

Identification of the transcriptional response of human intestinal mucosa to Lactobacillus plantarum WCFS1 in vivo  

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Full Text Available Abstract Background There is limited knowledge on the extent and dynamics of the mucosal response to commensal and probiotic species in the human intestinal lumen. This study aimed to identify the acute, time-dependent responses of intestinal mucosa to commensal Lactobacillus plantarum WCFS1 in vivo in two placebo-controlled human intervention studies in healthy volunteers. Transcriptional changes in duodenal mucosa upon continuous intraduodenal infusion of L. plantarum WCFS1 for one- and six h, respectively, were studied using oro- and nasogastric intubations with dedicated orogastric catheters and tissue sampling by standard flexible gastroduodenoscopy. Results One- and six-h exposure of small intestinal mucosa to L. plantarum WCFS1 induced differential expression of 669 and 424 gene reporters, respectively. While short-term exposure to L. plantarum WCFS1 inhibited fatty acid metabolism and cell cycle progression, cells switched to a more proliferative phase after prolonged exposure with an overall expression profile characterized by upregulation of genes involved in lipid metabolism, cellular growth and development. Cell death and immune responses were triggered, but cell death-executing genes or inflammatory signals were not expressed. Proteome analysis showed differential expression of several proteins. Only the microsomal protein 'microsomal triglyceride transfer protein' was regulated on both the transcriptional and the protein level in all subjects. Conclusion Overall, this study showed that intestinal exposure to L. plantarum WCFS1 induced consistent, time-dependent transcriptional responses in healthy intestinal mucosa. This extensive exploration of the human response to L. plantarum WCFS1 could eventually provide molecular support for specific or probiotic activity of this strain or species, and exemplifies the strength of the applied technology to identify the potential bio-activity of microbes in the human intestine.

Kodde Andrea

2008-08-01

113

Glucose induces intestinal human UDP-glucuronosyltransferase (UGT) 1A1 to prevent neonatal hyperbilirubinemia.  

Science.gov (United States)

Inadequate calorie intake or starvation has been suggested as a cause of neonatal jaundice, which can further cause permanent brain damage, kernicterus. This study experimentally investigated whether additional glucose treatments induce the bilirubin-metabolizing enzyme--UDP-glucuronosyltransferase (UGT) 1A1--to prevent the onset of neonatal hyperbilirubinemia. Neonatal humanized UGT1 (hUGT1) mice physiologically develop jaundice. In this study, UGT1A1 expression levels were determined in the liver and small intestine of neonatal hUGT1 mice that were orally treated with glucose. In the hUGT1 mice, glucose induced UGT1A1 in the small intestine, while it did not affect the expression of UGT1A1 in the liver. UGT1A1 was also induced in the human intestinal Caco-2 cells when the cells were cultured in the presence of glucose. Luciferase assays demonstrated that not only the proximal region (-1300/-7) of the UGT1A1 promoter, but also distal region (-6500/-4050) were responsible for the induction of UGT1A1 in the intestinal cells. Adequate calorie intake would lead to the sufficient expression of UGT1A1 in the small intestine to reduce serum bilirubin levels. Supplemental treatment of newborns with glucose solution can be a convenient and efficient method to treat neonatal jaundice while allowing continuous breastfeeding. PMID:25209391

Aoshima, Naoya; Fujie, Yoshiko; Itoh, Tomoo; Tukey, Robert H; Fujiwara, Ryoichi

2014-01-01

114

[Expression of human intestinal trefoil factor in Pichia pastoris and its biological activity on intestinal epithelium in vitro].  

Science.gov (United States)

In order to produce relatively large amounts of recombinant human intestinal trefoil factor and assess its biological activity. The expression plasmid pPIC9-hITF containing AOX1 promotor and the sequences of secreting signal peptides was transformed into the yeast cells. Then through selection, positive transformants were cultivated in fermentation basal salts medium in a 5L fermenter to obtain large amount product with low cost. The secreted peptides were then purified by a combination of ionic exchange chromatography and molecular sieve. To verify the product, electrospray mass spectrometry analyses was used to determine the structure of rhITF and Western Blotting was performed to test the immunological activity. Furthermore, the biological activity of the peptide was examined by experiments from cell to tissue. The nucleotide sequence of rhITF was the same as expected. With a 5-L fermenter, 253mg of hITF was isolated at the purity of 96% from 3.5 L of yeast fermentation broth. The expression level for recombinant human ITF in this yeast system was 73.33mg/L. In our study, we provided a way to gain a production among milligram to gram of recombinant human ITF by the use of a yeast expression system. As human ITF are difficult to purify in any significant amount from tissue extraction, the way described may become a valuable tool in obtaining pure peptide for further studies of trefoil peptide function. PMID:18051859

Liu, Wei; Zheng, Hua-Bao; Zhong, Xue-Mei; Yang, Sheng; Xu, Chun-Di

2007-09-01

115

Evaluation by computerized morphometry of histopathological alterations of the colon wall in segments with and without intestinal transit in rats Avaliação por morfometria computadorizada das alterações histopatológicas da parede cólica em segmentos com e sem trânsito intestinal em ratos  

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PURPOSE: To evaluate histopathological alterations of the colon wall in segments with and without intestinal transit, by computer-assisted imaging, and to correlate these with the length of time diversion. METHODS: Thirty male Wistar rats were subjected to intestinal transit diversion by a proximal colostomy and distal mucosa fistula. The animals were divided into three experimental groups according to how long after the initial surgical procedure they were sacrificed: six, twelve and eightee...

Marcos Vieira de Sousa; Denise Gonçalves Priolli; Adriana Valim Portes; Izilda Aparecida Cardinalli; José Aires Pereira; Carlos Augusto Real Martinez

2008-01-01

116

Hyperplastic innervation of vasoactive intestinal peptide in human gallbladder with cholelithiasis  

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The vasoactive intestinal peptide (VIP) immunoreactive nerve fibres in the gallbladder from 14 human patients with cholelithiasis was examined by immunohistochemical method. In the chronic cholecystitis, hyperplastic VIP immunoreactive nerves were observed around the hypertrophied muscle bundles, Rokitansky Aschoff Sinus and in the mucosal layer. However, in the acute cholecystitis and gangrenous cholecystitis, reduction or disappearance of VIP nerve fibres...

Gonda, T.; Akiyoshi, H.; Ichihara, K.

1995-01-01

117

Human Rights and Transitional Societies: Contemporary Challenges  

DEFF Research Database (Denmark)

This paper will assess how alternative approaches to transitional justice have the potential for overcoming tensions in between human rights standards. A rule in international law prescribing that states have a duty to prosecute gross human rights violations has emerged. Accordingly, transitional societies are said to have an obligation to apply criminal justice in dealing with such past violations. In Rwanda, the transitional government decided to prosecute the perpetrators of the 1994 genocide. As a result of widespread participation in the genocide and a devastated legal sector, difficulties in respecting the rights of the accused arose. A group of paralegals known as the "Corps of Judicial Defenders" was thus relied upon as to provide legal assistance for genocide suspects, but also for civil parties. This paper describes the work of these paralegals relating to the transitional trials, and, more generally, asserts how Judicial Defenders may have contributed to justice in other ways in post conflict Rwanda. The author argues that an efficient transitional justice policy must take sufficiently into account the context of the society in question, and aim at establishing linkages between justice in transitions and justice in the long-term.

Hansen, Thomas Obel

2008-01-01

118

Transcriptomic profiling of intestinal epithelial cells in response to human, bovine and commercial bovine lactoferrins.  

Science.gov (United States)

Lactoferrin (Lf) is an iron-binding glycoprotein present in high concentration in human milk. It is a pleiotropic protein and involved in diverse bioactivities, such as stimulation of cell proliferation and immunomodulatory activities. Lf is partly resistant to proteolysis in the gastrointestinal tract. Thus, Lf may play important roles in intestinal development. Due to differences in amino acid sequences and isolation methods, Lfs from human and bovine milk as well as commercially available bovine Lf (CbLf) may differ functionally or exert their functions via various mechanisms. To provide a potential basis for further applications of CbLf, we compared effects of Lfs on intestinal transcriptomic profiling using an intestinal epithelial cell model, human intestinal epithelial crypt-like cells (HIEC). All Lfs significantly stimulated proliferation of HIEC and no significant differences were found among these three proteins. Microarray assays were used to investigate transcriptomic profiling of intestinal epithelial cells in response to Lfs. Selected genes were verified by RT-PCR with a high validation rate. Genes significantly regulated by hLf, bLf, and CbLf were 150, 395 and 453, respectively. Fifty-four genes were significantly regulated by both hLf and CbLf, whereas 129 genes were significantly modulated by bLf and CbLf. Although only a limited number of genes were regulated by all Lfs, the three Lfs positively influenced cellular development and immune functions based on pathway analysis using IPA (Ingenuity). Lfs stimulate cellular and intestinal development and immune functions via various signaling pathways, such as Wnt/?-catenin signaling, interferon signaling and IL-8 signaling. PMID:24831230

Jiang, Rulan; Lönnerdal, Bo

2014-10-01

119

Splitting the scotoperiod: effects on feeding behaviour, intestinal fill and digestive transit time in broiler chickens  

DEFF Research Database (Denmark)

1. The aim of this study was to evaluate how splitting the dark period (scotoperiod) affects feeding behaviour and associated intestinal measures in broilers. 2. Ross 308 broilers were reared to 37 d in groups given either a daily 8-h continuous scotoperiod (DARK 8) or an intermittent light schedule with two equally spaced 4-h scotoperiods (DARK 4þ4), which yielded the same total duration of darkness per 24 h. 3. Feeding behaviour was recorded weekly from 24-h video recordings of 24 groups each of 64 birds. Empty intestinal weights as well as their contents were measured weekly at 4 time points (n¼192). Digestive transit time was estimated on d 29 using a chromic oxide marker; production variables and the extent of foot pad dermatitis were also recorded. 4. In the 3 h prior to a scotoperiod, feeding activity increased in chickens from DARK 8 but not DARK 4þ4. This increase was reflected in a higher relative content of the crop in DARK 8 at this time. 5. Immediately following the scotoperiod, feeding activity peaked and, although the chickens in DARK 4þ4 expressed more feeding behaviour in the first 20 min after the scotoperiod, the chickens in DARK 8 had overall higher feeding activity across the day. However, DARK 4þ4 had a higher feed intake and weight gain. The occurrence and severity of foot pad dermatitis was similar between treatments. 6. In conclusion, broilers modify their feeding behaviour according to the prevailing light schedule. Eight consecutive hours of darkness reduced growth, but did not affect overall feed conversion efficiency, and did not appear to exacerbate hunger or foot pad dermatitis to any great extent.

Duve, Linda Rosager; Steenfeldt, Sanna

2011-01-01

120

Rotavirus Infection Induces Cytoskeleton Disorganization in Human Intestinal Epithelial Cells: Implication of an Increase in Intracellular Calcium Concentration  

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Rotavirus infection is the most common cause of severe infantile gastroenteritis worldwide. In vivo, rotavirus exhibits a marked tropism for the differentiated enterocytes of the intestinal epithelium. In vitro, differentiated and undifferentiated intestinal cells can be infected. We observed that rotavirus infection of the human intestinal epithelial Caco-2 cells induces cytoskeleton alterations as a function of cell differentiation. The vimentin network disorganization detected in undiffere...

Brunet, Jean-philippe; Jourdan, Nathalie; Cotte-laffitte, Jacqueline; Linxe, Catherine; Ge?niteau-legendre, Monique; Servin, Alain; Que?ro, Anne-marie

2000-01-01

 
 
 
 
121

PDX1 regulation of FABP1 and novel target genes in human intestinal epithelial Caco-2 cells  

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The transcription factor pancreatic and duodenal homeobox 1 (PDX1) plays an essential role in pancreatic development and in maintaining proper islet function via target gene regulation. Few intestinal PDX1 targets, however, have been described. We sought to define novel PDX1-regulated intestinal genes. Caco-2 human intestinal epithelial cells were engineered to overexpress PDX1 and gene expression profiles relative to control cells were assessed. Expression of 80 genes significantly increased...

Chen, Chin; Fang, Rixun; Chou, Lin-chiang; Lowe, Anson W.; Sibley, Eric

2012-01-01

122

Effect of liquiritin on human intestinal bacteria growth: metabolism and modulation.  

Science.gov (United States)

Licorice is one of the oldest and most frequently used prescribed traditional Chimese medicines. However, the route and metabolites of liquiritin by human intestinal microflora are not well understood and its metabolites may accumulate to exert physiological effects. Therefore, our objective was to screen the ability of the bacteria to metabolize liquiritin and assess the effect of this compound on the intestinal bacteria. Finally, six strains, comprising Bacteroides sp. 22 and sp.57, Veillonella sp. 31 and sp.48, Bacillus sp. 46 and Clostridium sp. 51, were isolated and their abilities to convert liquiritin studied. A total of five metabolites were identified using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry in human incubated solution. The results indicated that hydrolysis, hydrogenation, methylation, deoxygenation and acetylation were the major routes of metabolism of liquiritin. On the other hand, effect of liquiritin on different strains of intestinal bacteria growth was detected using an Emax precision microplate reader. Growth of certain pathogenic bacteria, such as Enterobacter, Enterococcus, Clostridium and Bacteroides, was significantly repressed by liquiritin, while growth of commensal probiotics such as Lactobacillus and Bifidobacterium was less severely affected. Our observation provided further evidence for the importance of intestinal bacteria in the metabolism, and the potential activity of liquiritin in human health and disease. PMID:24616071

Zhang, Wei; Jiang, Shu; Qian, Dawei; Shang, Er-xin; Duan, Jin-ao

2014-09-01

123

Interaction of Campylobacter spp. and human probiotics in chicken intestinal mucus.  

Science.gov (United States)

Campylobacter is the most common cause of bacterial food-borne diarrhoeal disease throughout the world. The principal risk of human contamination is handling and consumption of contaminated poultry meat. To colonize poultry, Campylobacter adheres to and persists in the mucus layer that covers the intestinal epithelium. Inhibiting adhesion to the mucus could prevent colonization of the intestine. The aim of this study was to investigate in vitro the protective effect of defined commercial human probiotic strains on the adhesion of Campylobacter spp. to chicken intestinal mucus, in a search for alternatives to antibiotics to control this food-borne pathogen. The probiotic strains Lactobacillus rhamnosus GG and Propionibacterium freudenreichii ssp. shermanii JS and a starter culture strain Lactococcus lactis ssp. lactis adhered well to chicken intestinal mucus and were able to reduce the binding of Campylobacter spp. when the mucus was colonized with the probiotic strain before contacting the pathogen. Human-intended probiotics could be useful as prophylactics in poultry feeding for controlling Campylobacter spp. colonization. PMID:22672405

Ganan, M; Martinez-Rodriguez, A J; Carrascosa, A V; Vesterlund, S; Salminen, S; Satokari, R

2013-03-01

124

Human-derived probiotic Lactobacillus reuteri strains differentially reduce intestinal inflammation.  

Science.gov (United States)

Lactobacillus reuteri (L. reuteri) is a probiotic that inhibits the severity of enteric infections and modulates the immune system. Human-derived L. reuteri strains DSM17938, ATCC PTA4659, ATCC PTA 5289, and ATCC PTA 6475 have demonstrated strain-specific immunomodulation in cultured monocytoid cells, but information about how these strains affect inflammation in intestinal epithelium is limited. We determined the effects of the four different L. reuteri strains on lipopolysaccharide (LPS)-induced inflammation in small intestinal epithelial cells and in the ileum of newborn rats. IPEC-J2 cells (derived from the jejunal epithelium of a neonatal piglet) and IEC-6 cells (derived from the rat crypt) were treated with L. reuteri. Newborn rat pups were gavaged cow milk formula supplemented with L. reuteri strains in the presence or absence of LPS. Protein and mRNA levels of cytokines and histological changes were measured. We demonstrate that even though one L. reuteri strain (DSM 17938) did not inhibit LPS-induced IL-8 production in cultured intestinal cells, all strains significantly reduced intestinal mucosal levels of KC/GRO (?IL-8) and IFN-? when newborn rat pups were fed formula containing LPS ± L. reuteri. Intestinal histological damage produced by LPS plus cow milk formula was also significantly reduced by all four strains. Cow milk formula feeding (without LPS) produced mild gut inflammation, evidenced by elevated mucosal IFN-? and IL-13 levels, a process that could be suppressed by strain 17938. Other cytokines and chemokines were variably affected by the different strains, and there was no toxic effect of L. reuteri on intestinal cells or mucosa. In conclusion, L. reuteri strains differentially modulate LPS-induced inflammation. Probiotic interactions with both epithelial and nonepithelial cells in vivo must be instrumental in modulating intrinsic anti-inflammatory effects in the intestine. We suggest that the terms anti- and proinflammatory be used only to describe the effects of a probiotic in the living host. PMID:20798357

Liu, Yuying; Fatheree, Nicole Y; Mangalat, Nisha; Rhoads, Jon Marc

2010-11-01

125

[Effects of NSAIDs and PGE1 analogue on the permeability of human small intestine].  

Science.gov (United States)

We studied permeability of human small intestine to clarify the following questions. 1) Does indomethacin increase intestinal permeability (IP)? 2) Does ornoprostil (PGE1 analogue) prevent the increased IP due to indomethacin? 3) Does acemetacin (pro-drug) increase IP? Eleven healthy volunteers were studied before and after ingestion of indomethacin, acemetacin, ornoprostil. After an overnight fast, they drank an isotonic solution containing 1.5 g rhamnose and 10.5 g lactulose. IP was estimated with lactulose/rhamnose percentage excretion in urine for 5 hours. An administration of indomethacin (75 mg) for one day increased IP significantly, and the coadministration of indomethacin and ornoprostil showed no significant change in IP compared with those of controls. Pro-drug administration did not increase IP. It is suggested that simultaneous administration of ornoprostil prevent the mucosal damage caused by indomethacin clinically, and that the mechanism of this increase IP is due to lack of mucosal prostaglandins on the small intestine. PMID:9277110

Nagase, K; Hiwatashi, N; Ito, K; Maekawa, H; Noguchi, M; Kinouchi, Y; Toyota, T

1997-07-01

126

Influence of Camembert consumption on the composition and metabolism of intestinal microbiota: a study in human microbiota-associated rats.  

Science.gov (United States)

The objective of the present study was to evaluate the consequence of Camembert consumption on the composition and metabolism of human intestinal microbiota. Camembert cheese was compared with milk fermented by yoghurt starters and Lactobacillus casei as a probiotic reference. The experimental model was the human microbiota-associated (HM) rat. HM rats were fed a basal diet (HMB group), a diet containing Camembert made from pasteurised milk (HMCp group) or a diet containing fermented milk (HMfm group). The level of micro-organisms from dairy products was measured in faeces using cultures on a specific medium and PCR-temporal temperature gradient gel electrophoresis. The metabolic characteristics of the caecal microbiota were also studied: SCFA, NH3, glycosidase and reductase activities, and bile acid degradations. The results showed that micro-organisms from cheese comprised 10(5)-10(8) bacteria/g faecal sample in the HMCp group. Lactobacillus species from fermented milk were detected in HMfm rats. Consumption of cheese and fermented milk led to similar changes in bacterial metabolism: a decrease in azoreductase activity and NH3 concentration and an increase in mucolytic activities. However, specific changes were observed: in HMCp rats, the proportion of ursodeoxycholic resulting from chenodeoxycholic epimerisation was higher; in HMfm rats, alpha and beta-galactosidases were higher than in other groups and both azoreductases and nitrate reductases were lower. The results show that, as for fermented milk, Camembert consumption did not greatly modify the microbiota profile or its major metabolic activities. Ingested micro-organisms were able to survive in part during intestinal transit. These dairy products exert a potentially beneficial influence on intestinal metabolism. PMID:15469646

Lay, Christophe; Sutren, Malène; Lepercq, Pascale; Juste, Catherine; Rigottier-Gois, Lionel; Lhoste, Evelyne; Lemée, Riwanon; Le Ruyet, Pascale; Doré, Joël; Andrieux, Claude

2004-09-01

127

Autoradiographic and enzyme histochemical studies of intestinal metaplasia in human stomach  

International Nuclear Information System (INIS)

The relationship between growth potency and alkaline phosphatase activity of intestinal metaplasia of human stomach was studied using enzyme histochemical and autoradiographic technique. Both alkaline phosphatase positive and negative glands were seen in the intestinal metaplasia. Two types of alkaline phosphatase positive glands were observed, one in which alkaline phosphatase positive cells were distributed from the lower part to the surface of the gland and the other in which alkaline phosphatase positive cells were localized only at the surface of the gland. 3H-Thymidine labelled cells in the former gland were localized only at the bottom but the labelled cells in the latter were distributed in the lower part of the gland. 3H-Thymidine labelled cells in alkaline phosphatase negative gland were distributed from the bottom to middle part of the gland. These results imply that the intestinal metaplasia in which cell proliferative zone was localized at the bottom of the gland showed alkaline phosphatase activity just like the activity in the small intestine, however the gland in which the cell proliferative zone was prolonged showed the alkaline phosphatase activity different from the small intestine. (author)

128

Comparative quantification of human intestinal bacteria based on cPCR and LDR/LCR  

Directory of Open Access Journals (Sweden)

Full Text Available AIM: To establish a multiple detection method based on comparative polymerase chain reaction (cPCR and ligase detection reaction (LDR/ligase chain reaction (LCR to quantify the intestinal bacterial components. METHODS: Comparative quantification of 16S rDNAs from different intestinal bacterial components was used to quantify multiple intestinal bacteria. The 16S rDNAs of different bacteria were amplified simultaneously by cPCR. The LDR/LCR was examined to actualize the genotyping and quantification. Two beneficial (Bifidobacterium, Lactobacillus and three conditionally pathogenic bacteria (Enterococcus, Enterobacterium and Eubacterium were used in this detection. With cloned standard bacterial 16S rDNAs, standard curves were prepared to validate the quantitative relations between the ratio of original concentrations of two templates and the ratio of the fluorescence signals of their final ligation products. The internal controls were added to monitor the whole detection flow. The quantity ratio between two bacteria was tested. RESULTS: cPCR and LDR revealed obvious linear correlations with standard DNAs, but cPCR and LCR did not. In the sample test, the distributions of the quantity ratio between each two bacterial species were obtained. There were significant differences among these distributions in the total samples. But these distributions of quantity ratio of each two bacteria remained stable among groups divided by age or sex. CONCLUSION: The detection method in this study can be used to conduct multiple intestinal bacteria genotyping and quantification, and to monitor the human intestinal health status as well.

Jun-Hua Xiao

2012-01-01

129

Human, rat and chicken small intestinal Na+ - Cl- -creatine transporter: functional, molecular characterization and localization.  

Science.gov (United States)

In spite of all the fascinating properties of oral creatine supplementation, the mechanism(s) mediating its intestinal absorption has(have) not been investigated. The purpose of this study was to characterize intestinal creatine transport. [(14)C] creatine uptake was measured in chicken enterocytes and rat ileum, and expression of the creatine transporter CRT was examined in human, rat and chicken small intestine by reverse transcription-polymerase chain reaction, Northern blot, in situ hybridization, immunoblotting and immunohistochemistry. Results show that enterocytes accumulate creatine against its concentration gradient. This accumulation was electrogenic, Na(+)- and Cl(-)-dependent, with a probable stoichiometry of 2 Na(+): 1 Cl(-): 1 creatine, and inhibited by ouabain and iodoacetic acid. The kinetic study revealed a K(m) for creatine of 29 microM. [(14)C] creatine uptake was efficiently antagonized by non-labelled creatine, guanidinopropionic acid and cyclocreatine. More distant structural analogues of creatine, such as GABA, choline, glycine, beta-alanine, taurine and betaine, had no effect on intestinal creatine uptake, indicating a high substrate specificity of the creatine transporter. Consistent with these functional data, messenger RNA for CRT was detected only in the cells lining the intestinal villus. The sequences of partial clones, and of the full-length cDNA clone, isolated from human and rat small intestine were identical to previously cloned CRT cDNAs. Immunological analysis revealed that CRT protein was mainly associated with the apical membrane of the enterocytes. This study reports for the first time that mammalian and avian enterocytes express CRT along the villus, where it mediates high-affinity, Na(+)- and Cl(-)-dependent, apical creatine uptake. PMID:12433955

Peral, M J; García-Delgado, M; Calonge, M L; Durán, J M; De La Horra, M C; Wallimann, T; Speer, O; Ilundáin, A

2002-11-15

130

Human, rat and chicken small intestinal Na+-Cl?-creatine transporter: functional, molecular characterization and localization  

Science.gov (United States)

In spite of all the fascinating properties of oral creatine supplementation, the mechanism(s) mediating its intestinal absorption has(have) not been investigated. The purpose of this study was to characterize intestinal creatine transport. [14C]Creatine uptake was measured in chicken enterocytes and rat ileum, and expression of the creatine transporter CRT was examined in human, rat and chicken small intestine by reverse transcription-polymerase chain reaction, Northern blot, in situ hybridization, immunoblotting and immunohistochemistry. Results show that enterocytes accumulate creatine against its concentration gradient. This accumulation was electrogenic, Na+- and Cl?-dependent, with a probable stoichiometry of 2 Na+: 1 Cl?: 1 creatine, and inhibited by ouabain and iodoacetic acid. The kinetic study revealed a Km for creatine of 29 ?m. [14C]Creatine uptake was efficiently antagonized by non-labelled creatine, guanidinopropionic acid and cyclocreatine. More distant structural analogues of creatine, such as GABA, choline, glycine, ?-alanine, taurine and betaine, had no effect on intestinal creatine uptake, indicating a high substrate specificity of the creatine transporter. Consistent with these functional data, messenger RNA for CRT was detected only in the cells lining the intestinal villus. The sequences of partial clones, and of the full-length cDNA clone, isolated from human and rat small intestine were identical to previously cloned CRT cDNAs. Immunological analysis revealed that CRT protein was mainly associated with the apical membrane of the enterocytes. This study reports for the first time that mammalian and avian enterocytes express CRT along the villus, where it mediates high-affinity, Na+- and Cl?-dependent, apical creatine uptake. PMID:12433955

Peral, M J; García-Delgado, M; Calonge, M L; Durán, J M; De La Horra, M C; Wallimann, T; Speer, O; Ilundáin, A A

2002-01-01

131

Decreased gastric emptying and gastrointestinal and intestinal transits of liquid after complete spinal cord transection in awake rats  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english We studied the effect of complete spinal cord transection (SCT) on gastric emptying (GE) and on gastrointestinal (GI) and intestinal transits of liquid in awake rats using the phenol red method. Male Wistar rats (N = 65) weighing 180-200 g were fasted for 24 h and complete SCT was performed between [...] C7 and T1 vertebrae after a careful midline dorsal incision. GE and GI and intestinal transits were measured 15 min, 6 h or 24 h after recovery from anesthesia. A test meal (0.5 mg/ml phenol red in 5% glucose solution) was administered intragastrically (1.5 ml) and the animals were sacrificed by an iv thiopental overdose 10 min later to evaluate GE and GI transit. For intestinal transit measurements, 1 ml of the test meal was administered into the proximal duodenum through a cannula inserted into a gastric fistula. GE was inhibited (P

F. de-A.A., Gondim; J.R.V., da-Graça; G.R., de-Oliveira; M.C.V., Rêgo; R.B.M., Gondim; F.H., Rola.

1998-12-01

132

Human small intestinal epithelial cells differentiated from adult intestinal stem cells as a novel system for predicting oral drug absorption in humans.  

Science.gov (United States)

Adult intestinal stem cells (ISCs) possess both a long-term proliferation ability and differentiation capability into enterocytes. As a novel in vitro system for the evaluation of drug absorption, we characterized a human small intestinal epithelial cell (HIEC) monolayer that differentiated from adult ISCs. Continuous proliferation/differentiation from ISCs consistently conferred the capability of maturation of enterocytes to HIECs over 25 passages. The morphologically matured HIEC monolayer consisted of polarized columnar epithelia with dense microvilli, tight junctions, and desmosomes 8 days after seeding onto culture inserts. Transepithelial electrical resistance across the monolayer was 9-fold lower in HIECs (98.9 ? × cm(2)) than in Caco-2 cells (900 ? × cm(2)), which indicated that the looseness of the tight junctions in the HIEC monolayer was similar to that in the human small intestine (approximately 40 ? × cm(2)). No significant differences were observed in the overall gene expression patterns of the major drug-metabolizing enzymes and transporters between the HIEC and Caco-2 cell monolayers. Furthermore, the functions of P-glycoprotein and breast cancer resistance protein in the HIEC monolayer were confirmed by the vectorial transport of marker substrates and their disappearance in the presence of specific inhibitors. The apparent drug permeability values of paracellularly transported compounds (fluorescein isothiocyanate-dextran 4000, atenolol, and terbutaline) and nucleoside transporter substrates (didanosine, ribavirin, and doxifluridine) in the HIEC monolayer were markedly higher than those of Caco-2 cells, whereas transcellularly transported drugs (pindolol and midazolam) were equally well permeated. In conclusion, the HIEC monolayer can serve as a novel and superior alternative to the conventional Caco-2 cell monolayer for predicting oral absorption in humans. PMID:25200868

Takenaka, Toru; Harada, Naomoto; Kuze, Jiro; Chiba, Masato; Iwao, Takahiro; Matsunaga, Tamihide

2014-11-01

133

Clostridium perfringens Enterotoxin Damages the Human Intestine In Vitro  

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In vitro, Clostridium perfringens enterotoxin (CPE) binds to human ileal epithelium and induces morphological damage concurrently with reduced short-circuit current, transepithelial resistance, and net water absorption. CPE also binds to the human colon in vitro but causes only slight morphological and transport changes that are not statistically significant.

Ferna?ndez Miyakawa, M. E.; Pistone Creydt, V.; Uzal, F. A.; Mcclane, B. A.; Ibarra, C.

2005-01-01

134

Expression and functional contribution of hTHTR-2 in thiamin absorption in human intestine.  

Science.gov (United States)

The aim of this study was to investigate expression and relative contribution of human thiamin transporter (hTHTR)-2 toward overall carrier-mediated thiamin uptake by human intestinal epithelial cells. Northern blot analysis showed that the message of the hTHTR-2 is expressed along the native human gastrointestinal tract with highest expression being in the proximal part of small intestine. hTHTR-2 protein was found, by Western blot analysis, to be expressed at the brush-border membrane (BBM), but not at the basolateral membrane, of native human enterocytes. This pattern of expression was confirmed in studies using a fusion protein of hTHTR-2 with the enhanced green fluorescent protein (hTHTR2-EGFP) expressed in living Caco-2 cells grown on filter. Pretreating Caco-2 cells (which also express the hTHTR-2 at RNA and protein levels) with hTHTR-2 gene-specific small interfering RNA (siRNA) led to a significant (P thiamin uptake. Similarly, pretreating Caco-2 cells with siRNA that specifically target hTHTR-1 (which is expressed in Caco-2 cells) also significantly (P thiamin uptake. When Caco-2 cells were pretreated with siRNAs against both hTHTR-2 and hTHTR-1 genes, an almost complete inhibition in carrier-mediated thiamin uptake was observed. These results show that the message of hTHTR-2 is expressed along the human gastrointestinal tract and that expression of its protein in intestinal epithelia is mainly localized to the apical BBM domain. In addition, results show that this transporter plays a significant role in carrier-mediated thiamin uptake in human intestine. PMID:14615284

Said, Hamid M; Balamurugan, Krishnaswamy; Subramanian, Veedamali S; Marchant, Jonathan S

2004-03-01

135

Similarity of hydrolyzing activity of human and rat small intestinal disaccharidases  

Directory of Open Access Journals (Sweden)

Full Text Available Tsuneyuki Oku¹, Kenichi Tanabe¹, Shigeharu Ogawa², Naoki Sadamori¹, Sadako Nakamura¹¹Graduate School of Human Health Science, University of Nagasaki, Siebold, Nagayo, Japan; ²Juzenkai Hospital, Kagomachi, Nagasaki, JapanBackground: The purpose of this study was to clarify whether it is possible to extrapolate results from studies of the hydrolyzing activity of disaccharidases from rats to humans.Materials and methods: We measured disaccharidase activity in humans and rats using identical preparation and assay methods, and investigated the similarity in hydrolyzing activity. Small intestinal samples without malignancy were donated by five patients who had undergone bladder tumor surgery, and homogenates were prepared to measure disaccharidase activity. Adult rat homogenates were prepared using small intestine.Results: Maltase activity was the highest among the five disaccharidases, followed by sucrase and then palatinase in humans and rats. Trehalase activity was slightly lower than that of palatinase in humans and was similar to that of sucrase in rats. Lactase activity was the lowest in humans, but was similar to that of palatinase in rats. Thus, the hydrolyzing activity of five disaccharidases was generally similar in humans and rats. The relative activity of sucrose and palatinase versus maltase was generally similar between humans and rats. The ratio of rat to human hydrolyzing activity of maltase, sucrase, and palatinase was 1.9–3.1, but this was not a significant difference. Leaf extract from Morus alba strongly inhibited the activity of maltase, sucrase, and palatinase, but not trehalase and lactase, and the degree of inhibition was similar in humans and rats. L-arabinose mildly inhibited sucrase activity, but hardly inhibited the activity of maltase, palatinase, trehalase and lactase in humans and rats. The digestibility of 1-kestose, galactosylsucrose, and panose by small intestinal enzymes was very similar between humans and rats.Conclusion: These results demonstrate that the digestibility of newly developed saccharide materials evaluated by rat small intestinal enzymes can substitute for evaluation using human enzymes.Keywords: disaccharidase, maltase, sucrase, trehalase, palatinase, digestibility

Oku T

2011-06-01

136

Effects of laxative and N-acetylcysteine on mucus accumulation, bacterial load, transit, and inflammation in the cystic fibrosis mouse small intestine.  

Science.gov (United States)

The accumulation of mucus in affected organs is characteristic of cystic fibrosis (CF). The CF mouse small intestine has dramatic mucus accumulation and exhibits slower interdigestive intestinal transit. These factors are proposed to play cooperative roles that foster small intestinal bacterial overgrowth (SIBO) and contribute to the innate immune response of the CF intestine. It was hypothesized that decreasing the mucus accumulation would reduce SIBO and might improve other aspects of the CF intestinal phenotype. To test this, solid chow-fed CF mice were treated with an osmotic laxative to improve gut hydration or liquid-fed mice were treated orally with N-acetylcysteine (NAC) to break mucin disulfide bonds. Treatment with laxative or NAC reduced mucus accumulation by 43% and 50%, respectively, as measured histologically as dilation of the intestinal crypts. Laxative and NAC also reduced bacterial overgrowth in the CF intestine by 92% and 63%, respectively. Treatment with laxative normalized small intestinal transit in CF mice, whereas NAC did not. The expression of innate immune response-related genes was significantly reduced in laxative-treated CF mice, whereas there was no significant effect in NAC-treated CF mice. In summary, laxative and NAC treatments of CF mice reduced mucus accumulation to a similar extent, but laxative was more effective than NAC at reducing bacterial load. Eradication of bacterial overgrowth by laxative treatment was associated with normalized intestinal transit and a reduction in the innate immune response. These results suggest that both mucus accumulation and slowed interdigestive small intestinal transit contribute to SIBO in the CF intestine. PMID:17615175

De Lisle, Robert C; Roach, Eileen; Jansson, Kyle

2007-09-01

137

Naturally occurring products of proglucagon 111-160 in the porcine and human small intestine  

DEFF Research Database (Denmark)

Recent studies have revealed that the glucagon gene is expressed in the mammalian intestine. Here it codes for "glicentin" (proglucagon 1-69) and a glucagon-like peptide, proglucagon 78-107, recently isolated from porcine intestine. We studied the fate of the remaining COOH-terminal part of proglucagon (proglucagon 111-160) using radioimmunoassays against proglucagon 111-123 and 126-160. Two peptides were isolated from acid ethanol extracts of porcine ileal mucosa and sequenced: one corresponding to proglucagon 126-158 and one probably corresponding to proglucagon 111-158. By comparing human and porcine proglucagon sequences, Ala117 is replaced by Thr, and Ile138, Ala144, Ile152 and Gln153 are replaced by Val, Thr, Leu, and His. By gel filtration and radioimmunoassay of intestinal extracts it was established that a large part of porcine and virtually all of human proglucagon are processed to release proglucagon 111-123 (designated spacer peptide 2), which, like proglucagon 126-158 must be considered a potential hormonal entity. By isocratic high pressure liquid chromatography human spacer peptide 2 was indistinguishable from synthetic proglucagon 111-122 amide, suggesting that this is the structure of the naturally occurring human peptide.

Buhl, T; Thim, L

1988-01-01

138

Hydrolysis of pyrethroids by human and rat tissues: Examination of intestinal, liver and serum carboxylesterases  

International Nuclear Information System (INIS)

Hydrolytic metabolism of pyrethroid insecticides in humans is one of the major catabolic pathways that clear these compounds from the body. Rodent models are often used to determine the disposition and clearance rates of these esterified compounds. In this study the distribution and activities of esterases that catalyze pyrethroid metabolism have been investigated in vitro using several human and rat tissues, including small intestine, liver and serum. The major esterase in human intestine is carboxylesterase 2 (hCE2). We found that the pyrethroid trans-permethrin is effectively hydrolyzed by a sample of pooled human intestinal microsomes (5 individuals), while deltamethrin and bioresmethrin are not. This result correlates well with the substrate specificity of recombinant hCE2 enzyme. In contrast, a sample of pooled rat intestinal microsomes (5 animals) hydrolyze trans-permethrin 4.5-fold slower than the sample of human intestinal microsomes. Furthermore, it is demonstrated that pooled samples of cytosol from human or rat liver are ? 2-fold less hydrolytically active (normalized per mg protein) than the corresponding microsomal fraction toward pyrethroid substrates; however, the cytosolic fractions do have significant amounts (? 40%) of the total esteratic activity. Moreover, a 6-fold interindividual variation in carboxylesterase 1 protein expression in human hepatic cytosols was observed. Human serum was shown to lack pyrethroid hydrolytic activity, but rat seruroid hydrolytic activity, but rat serum has hydrolytic activity that is attributed to a single CE isozyme. We purified the serum CE enzyme to homogeneity to determine its contribution to pyrethroid metabolism in the rat. Both trans-permethrin and bioresmethrin were effectively cleaved by this serum CE, but deltamethrin, esfenvalerate, alpha-cypermethrin and cis-permethrin were slowly hydrolyzed. Lastly, two model lipase enzymes were examined for their ability to hydrolyze pyrethroids. However, no hydrolysis products could be detected. Together, these results demonstrate that extrahepatic esterolytic metabolism of specific pyrethroids may be significant. Moreover, hepatic cytosolic and microsomal hydrolytic metabolism should each be considered during the development of pharmacokinetic models that predict the disposition of pyrethroids and other esterified compounds

139

Transit time of epithelial cells in the small intestines of germfree mice and ex-germfree mice associated with indigenous microorganisms.  

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Germfree mice housed in isolators under controlled environmental and nutritional conditions were associated with an intestinal microflora. These associated animals and germfree mice drawn from the same population were tested for the rate at which the epithelial cells transited from the crypts of Lieberkuhn to the tips of the villi in their small intestines. The method for estimating the rate of transit of epithelial cells involved the use of liquid scintillation counting to determine the amou...

Savage, D. C.; Siegel, J. E.; Snellen, J. E.; Whitt, D. D.

1981-01-01

140

Generation of L cells in mouse and human small intestine organoids.  

Science.gov (United States)

Upon a nutrient challenge, L cells produce glucagon-like peptide 1 (GLP-1), a powerful stimulant of insulin release. Strategies to augment endogenous GLP-1 production include promoting L-cell differentiation and increasing L-cell number. Here we present a novel in vitro platform to generate functional L cells from three-dimensional cultures of mouse and human intestinal crypts. We show that short-chain fatty acids selectively increase the number of L cells, resulting in an elevation of GLP-1 release. This is accompanied by the upregulation of transcription factors associated with the endocrine lineage of intestinal stem cell development. Thus, our platform allows us to study and modulate the development of L cells in mouse and human crypts as a potential basis for novel therapeutic strategies in patients with type 2 diabetes. PMID:24130334

Petersen, Natalia; Reimann, Frank; Bartfeld, Sina; Farin, Henner F; Ringnalda, Femke C; Vries, Robert G J; van den Brink, Stieneke; Clevers, Hans; Gribble, Fiona M; de Koning, Eelco J P

2014-02-01

 
 
 
 
141

Generation of L-cells in mouse and human small intestine organoids  

Science.gov (United States)

Upon a nutrient challenge, L-cells produce glucagon-like peptide 1 (GLP-1), a powerful stimulant of insulin release. Strategies to augment endogenous GLP-1 production include promoting L-cell differentiation and increasing L-cell number. Here we present a novel in vitro platform to generate functional L-cells from 3D cultures of mouse and human intestinal crypts. We show that short-chain fatty acids (SCFAs) selectively increase the number of L-cells resulting in an elevation of GLP-1 release. This is accompanied by up-regulation of transcription factors, associated with the endocrine lineage of intestinal stem cell development. Thus, our platform allows us to study and modulate the development of L-cells in mouse and human crypts as a potential basis for novel therapeutic strategies in type 2 diabetes. PMID:24130334

Petersen, Natalia; Reimann, Frank; Bartfeld, Sina; Farin, Henner F.; Ringnalda, Femke C.; Vries, Robert G. J.; van den Brink, Stieneke; Clevers, Hans; Gribble, Fiona M.; de Koning, Eelco J. P.

2015-01-01

142

Homology of the human intestinal Na+/glucose and Escherichia coli Na+/proline cotransporters.  

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Cotransport proteins are responsible for the active accumulation of organic substrates in cells. Na+ gradients provide the driving force for uptake of most substrates into eukaryotes and for a few substrates in some prokaryotes. We report here the cloning and sequencing of the human intestinal Na+/glucose cotransporter (SGLT1) and compare its structure with other cloned transporters. At the DNA level and the predicted amino acid and secondary structure levels, close homology is evident betwee...

Hediger, M. A.; Turk, E.; Wright, E. M.

1989-01-01

143

Use of Stable Isotopes To Measure the Metabolic Activity of the Human Intestinal Microbiota?  

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The human intestinal microbiota is a complex biological system comprising a vast repertoire of microbes with considerable metabolic activity relevant to both bacterial growth and host health. Greater strides have been made in the analysis of microbial diversity than in the measurement of functional activity, particularly in vivo. Stable isotope probing offers a new approach by coupling measurements of metabolic activity with microbial identification. Using a low-enrichment labeling strategy i...

Reichardt, Nicole; Barclay, Andrew R.; Weaver, Lawrence T.; Morrison, Douglas J.

2011-01-01

144

Angiotensin-converting enzyme (ACE) inhibitor transport in human intestinal epithelial (Caco-2) cells.  

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1. The role of proton-linked solute transport in the absorption of the angiotensin-converting enzyme (ACE) inhibitors captopril, enalapril maleate and lisinopril has been investigated in human intestinal epithelial (Caco-2) cell monolayers. 2. In Caco-2 cell monolayers the transepithelial apical-to-basal transport and intracellular accumulation (across the apical membrane) of the hydrolysis-resistant dipeptide, glycylsarcosine (Gly-Sar), were stimulated by acidification (pH 6.0) of the apical...

Thwaites, D. T.; Cavet, M.; Hirst, B. H.; Simmons, N. L.

1995-01-01

145

Interaction of Escherichia coli heat-stable enterotoxin B with cultured human intestinal epithelial cells.  

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Binding of Escherichia coli heat-stable enterotoxin B (STb) to the human intestinal epithelial cell lines T84 and HT29 and to polarized T84 cells was studied to define the initial interaction of this peptide toxin with target cells. Equilibrium and competitive binding isotherms showed that 125I-STb bound specifically to T84 and HT29 cells; however, the toxin-epithelial cell interactions could be characterized by low-affinity binding ( or...

Chao, K. L.; Dreyfus, L. A.

1997-01-01

146

Development and characterisation of T lymphocyte lines from human small intestinal biopsies.  

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T lymphocyte lines were developed from human small intestinal biopsies obtained at the time of gastroduodenoscopy. Lines were established as outgrowths from biopsy specimens in microculture using a combination of T cell mitogens, indomethacin, interleukin (IL-2) and autologous irradiated feeder cells. The predominant phenotype of T cells after six to 12 weeks in culture was CD2, CD3, and CD4 positive. Functionally, these T cell lines secreted IL-2 in response to stimulation with phytohemagglu...

Kelleher, D.; Kagnoff, M. F.

1989-01-01

147

Interaction of Macrolide Antibiotics with Intestinally Expressed Human and Rat Organic Anion-Transporting Polypeptides  

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The macrolide antibiotics azithromycin and clarithromycin are large molecular weight compounds that exhibit moderate to excellent oral bioavailability in preclinical species and humans. Previous concomitant dosing studies in rats using rifamycin SV, a general organic anion-transporting polypeptide (OATP) inhibitor, suggested that the high oral absorption of azithromycin and clarithromycin may be caused by facilitative uptake by intestinal Oatps. In this study, we used OATP/Oatp-expressing cel...

Lan, Tian; Rao, Anuradha; Haywood, Jamie; Davis, Charles B.; Han, Chao; Garver, Eric; Dawson, Paul A.

2009-01-01

148

Vasoactive intestinal peptide in the human pituitary gland and adenomas. An immunocytochemical study.  

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Recent evidence indicates that vasoactive intestinal peptide (VIP) may be involved in normal pituitary function. Immunocytochemistry was used to localize VIP in human biopsied pituitary adenomas and postmortem anterior pituitary glands. Paraffin sections were immunostained for VIP with the avidin-biotin-peroxidase technique. Strong VIP-like immunoreactivity (VIP-LI) was observed in 16 of 17 prolactinomas, 12 of 14 growth hormone-secreting tumors associated with acromegaly, four of 12 ACTH-sec...

Hsu, D. W.; Riskind, P. N.; Hedley-whyte, E. T.

1989-01-01

149

In Vitro Modulation of Human Intestinal Microbiota by Mannoligosaccharides Synthesized from Amorphophallus muelleri Glucomannan  

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The corms of Amorphophallus muelleri Blume contain a large amount of glucomannan, a kind of polysaccharide that are commonly consumed by people as gelly foods. In order to improve the beneficial properties of glucomannan, we previously have established the enzymatic process to produce the mannoligosaccharides from flour of glucomannan using microbial mannanase. The effects of mannoligosaccharides on the growth modulation of human intestinal microbiota were investigated in this study. A set of...

ACHMAD DINOTO; CORY CORAZON WATUMLAWAR; YOPI

2013-01-01

150

Expression of receptors for enterotoxigenic Escherichia coli during enterocytic differentiation of human polarized intestinal epithelial cells in culture.  

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To study the expression of human intestinal receptors for enterotoxigenic Escherichia coli (ETEC), the human polarized intestinal epithelial cell line Caco-2 in culture and several subpopulations of HT-29 cells in culture--parental (mainly undifferentiated) HT-29 cells (HT-29 Std), an enterocytelike subpopulation obtained by selection through glucose deprivation (HT-29 Glc-), and an enterocytelike subpopulation obtained by selection through glucose deprivation which maintains its differentiat...

Kerne?is, S.; Chauvie?re, G.; Darfeuille-michaud, A.; Aubel, D.; Coconnier, M. H.; Joly, B.; Servin, A. L.

1992-01-01

151

Prebiotic effects of almonds and almond skins on intestinal microbiota in healthy adult humans.  

Science.gov (United States)

Almonds and almond skins are rich in fiber and other components that have potential prebiotic properties. In this study we investigated the prebiotic effects of almond and almond skin intake in healthy humans. A total of 48 healthy adult volunteers consumed a daily dose of roasted almonds (56 g), almond skins (10 g), or commercial fructooligosaccharides (8 g) (as positive control) for 6 weeks. Fecal samples were collected at defined time points and analyzed for microbiota composition and selected indicators of microbial activity. Different strains of intestinal bacteria had varying degrees of growth sensitivity to almonds or almond skins. Significant increases in the populations of Bifidobacterium spp. and Lactobacillus spp. were observed in fecal samples as a consequence of almond or almond skin supplementation. However, the populations of Escherichia coli did not change significantly, while the growth of the pathogen Clostridum perfringens was significantly repressed. Modification of the intestinal microbiota composition induced changes in bacterial enzyme activities, specifically a significant increase in fecal ?-galactosidase activity and decreases in fecal ?-glucuronidase, nitroreductase and azoreductase activities. Our observations suggest that almond and almond skin ingestion may lead to an improvement in the intestinal microbiota profile and a modification of the intestinal bacterial activities, which would induce the promotion of health beneficial factors and the inhibition of harmful factors. Thus we believe that almonds and almond skins possess potential prebiotic properties. PMID:24315808

Liu, Zhibin; Lin, Xiuchun; Huang, Guangwei; Zhang, Wen; Rao, Pingfan; Ni, Li

2014-04-01

152

Protein abundance of clinically relevant multidrug transporters along the entire length of the human intestine.  

Science.gov (United States)

Intestinal transporters are crucial determinants in the oral absorption of many drugs. We therefore studied the mRNA expression (N = 33) and absolute protein content (N = 10) of clinically relevant transporters in healthy epithelium of the duodenum, the proximal and distal jejunum and ileum, and the ascending, transversal, descending, and sigmoidal colon of six organ donors (24-54 years). In the small intestine, the abundance of nearly all studied proteins ranged between 0.2 and 1.6 pmol/mg with the exception of those of OCT3 (ASBT were significantly more abundant in jejunum and ileum than in colon. In contrast to this, the level of expression of ABCC2, ABCC3, and OCT3 was found to be highest in colon. Site-dependent differences in the levels of gene and protein expression were observed for ABCB1 and ASBT. Significant correlations between mRNA and protein levels have been found for ABCG2, ASBT, OCT3, and PEPT1 in the small intestine. Our data provide further physiological pieces of the puzzle required to predict intestinal drug absorption in humans. PMID:25158075

Drozdzik, Marek; Gröer, Christian; Penski, Jette; Lapczuk, Joanna; Ostrowski, Marek; Lai, Yurong; Prasad, Bhagwat; Unadkat, Jashvant D; Siegmund, Werner; Oswald, Stefan

2014-10-01

153

Some food-associated mycotoxins as potential risk factors in humans predisposed to chronic intestinal inflammatory diseases.  

Science.gov (United States)

Mycotoxins are fungal metabolites able to affect the functions of numerous tissues and organs in animals and humans, including intestinal and immune systems. However, the potential link between exposure to some mycotoxins and human chronic intestinal inflammatory diseases, such as celiac and Crohn's diseases or ulcerative colitis, has not been investigated. Instead, several theories based on bacterial, immunological or neurological events have been elaborated to explain the etiology of these pathologies. Here we reviewed the literature on mycotoxin-induced intestinal dysfunctions and compared these perturbations to the impairments of intestinal functions typically observed in human chronic intestinal inflammatory diseases. Converging evidence based on various cellular and animal studies show that several mycotoxins induce intestinal alterations that are similar to those observed at the onset and during the progression of inflammatory bowel diseases. Although epidemiologic evidence is still required, existing data are sufficient to suspect a role of some food-associated mycotoxins in the induction and/or persistence of human chronic intestinal inflammatory diseases in genetically predisposed patients. PMID:20466014

Maresca, Marc; Fantini, Jacques

2010-09-01

154

C-ring cleavage of flavonoids by human intestinal bacteria.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Four hitherto undescribed Clostridium strains capable of cleaving the C ring of quercetin, kaempferol, and naringenin at C-3-C-4 were isolated from the fecal flora of humans. None of the strains cleaved catechin. C-ring fission occurred when the substrate was either in solution or in suspension. Mixed cultures of flavonoid-hydrolyzing bacteria, flavonoid-cleaving bacteria, and Escherichia coli, which was used to provide the anaerobic environment, rapidly metabolized rutin to 3,4-dihydroxyphen...

Winter, J.; Moore, L. H.; Dowell, V. R.; Bokkenheuser, V. D.

1989-01-01

155

Localisation of hyaluronan in the human intestinal wall.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

By using biotin labelled proteoglycan core protein and an avidin enzyme system, hyaluronan (hyaluronic acid) was visualised in specimens of human jejunum. Intense staining for hyaluronan was seen in the loose connective tissue of the villi and of lamina propria while the epithelial layer was unstained. The muscularis mucosae showed only faint staining. The accumulation of hyaluronan in the subepithelial layer of the jejunal mucosa indicates that the previously reported high jejunal secretion ...

Gerdin, B.; Ha?llgren, R.

1991-01-01

156

Effects of human fecal flora on intestinal morphology and mucosal immunity in human flora-associated piglet.  

Science.gov (United States)

Human flora-associated (HFA) piglet model was established to examine the effects of gut microbes from a different donor species on the intestinal morphology and mucosal immunity. Newborn germ-free piglets, obtained by caesarean section, were orally inoculated with a human and a porcine faecal suspension, and artificially fed to establish a HFA group (n = 7) and pig flora-associated (PFA) group (n = 7), respectively. All pigs were killed 6 weeks later. Tissue samples from duodenum, jejunum, ileum and colon were collected and studied by histochemistry and immunohistochemistry methods for intestinal morphological analyses and detection of immunocompetent cells. In summary, both groups of pigs performed well but HFA pigs had a somewhat better daily weight gain, and their jejunal villus height and crypt depth were significantly higher. In comparison with PFA pigs, the number of intraepithelial lymphocytes in jejunum was lower but the number of goblet cells containing neutral mucins was significantly increased in HFA pigs. No difference was observed in the number of mast cells. The areas of IgA producing cells and CD4(+) T cells in the jejunum and IgG producing cells in the small intestine were significantly higher in HFA pigs. However, the areas of MHC class II expressing cells were significantly increased in the duodenum and colon. Additionally, the amount of Bifidobacteria spp. was significantly higher in HFA pigs. This study confirms that the composition of gut microbes differentially affects the host intestinal mucosal immunity and suggests that commensal bacteria have great effects on intestinal health and development. PMID:19281534

Che, C; Pang, X; Hua, X; Zhang, B; Shen, J; Zhu, J; Wei, H; Sun, L; Chen, P; Cui, L; Zhao, L; Yang, Q

2009-03-01

157

Adhesion of enterotoxigenic Escherichia coli to human small intestinal enterocytes.  

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An improved enterocyte adhesion assay has been used to examine a collection of 44 strains of enterotoxigenic Escherichia coli (ETEC) for their ability to adhere to the brush border of isolated human duodenal enterocytes. Fourteen strains showed good adhesion; in each case the ability to adhere correlated with the production of colonization factor antigen I or II (CFA/I or CFA/II) fimbriae. CFA/II-positive producing coli surface antigens 1 and 3 (CS1 and CS3), coli surface antigens 2 and 3 (CS...

Knutton, S.; Lloyd, D. R.; Candy, D. C.; Mcneish, A. S.

1985-01-01

158

Enterocyte Shedding and Epithelial Lining Repair Following Ischemia of the Human Small Intestine Attenuate Inflammation  

Science.gov (United States)

Background Recently, we observed that small-intestinal ischemia and reperfusion was found to entail a rapid loss of apoptotic and necrotic cells. This study was conducted to investigate whether the observed shedding of ischemically damaged epithelial cells affects IR induced inflammation in the human small gut. Methods and Findings Using a newly developed IR model of the human small intestine, the inflammatory response was studied on cellular, protein and mRNA level. Thirty patients were consecutively included. Part of the jejunum was subjected to 30 minutes of ischemia and variable reperfusion periods (mean reperfusion time 120 (±11) minutes). Ethical approval and informed consent were obtained. Increased plasma intestinal fatty acid binding protein (I-FABP) levels indicated loss in epithelial cell integrity in response to ischemia and reperfusion (p<0.001 vs healthy). HIF-1? gene expression doubled (p?=?0.02) and C3 gene expression increased 4-fold (p?=?0.01) over the course of IR. Gut barrier failure, assessed as LPS concentration in small bowel venous effluent blood, was not observed (p?=?0.18). Additionally, mRNA expression of HO-1, IL-6, IL-8 did not alter. No increased expression of endothelial adhesion molecules, TNF? release, increased numbers of inflammatory cells (p?=?0.71) or complement activation, assessed as activated C3 (p?=?0.14), were detected in the reperfused tissue. Conclusions In the human small intestine, thirty minutes of ischemia followed by up to 4 hours of reperfusion, does not seem to lead to an explicit inflammatory response. This may be explained by a unique mechanism of shedding of damaged enterocytes, reported for the first time by our group. PMID:19753114

Matthijsen, Robert A.; Derikx, Joep P. M.; Kuipers, Dian; van Dam, Ronald M.; Dejong, Cornelis H. C.; Buurman, Wim A.

2009-01-01

159

Scintigraphic determination of small intestinal transit time of water in man  

International Nuclear Information System (INIS)

A method utilizing a lactulose solution to measure small intestinal transit time (SITT) has been previously reported. Lactulose is a non-absorbable sugar and is known to increase SITT. In order to determine the extent to which lactulose accelerates SITT, a group of 4 normal male volunteers were studied after the ingestion of 150cc of water to which 100 uCi of 111-In was added. To provide adequate caloric intake, as occurs physiologically, the water was drunk while ingesting a solid meal. The subject was then placed supine under a 15 inch gamma camera. Data were collected and stored in a computer at one frame every 3 minute for 240 minutes. If activity was not present in the cecal region by this time, the subject was allowed to move about for 15 minutes and then repositioned under the gamma camera. Data were first viewed in a movie format. Regions of interest were selected over the cecum and ascending colon. The time of first appearance of radioactivity in the region of the cecum was taken as the SITT. Each subject was studied on three separate occasions. The mean (+- SEM) SITT for each of the separate studies was 248 +- 58 min., 240 +- 47 min. and 232 +- 54 min. respectively (p?NS). Two previously studied groups of normal volunteers had a mean SITT of approximately 80 minutes. Water appears to have a significantly slower SITT when ingested with a solid meal when compared to lactulose. Clinically, the potential to use water as a test for SITT would not seem to be as attractive or practical as using lactulose as the test substance

160

Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells  

International Nuclear Information System (INIS)

Monolayers of a well differentiated human intestinal epithelial cell line, Caco-2, were used as a model to study passive drug absorption across the intestinal epithelium. Absorption rate constants (expressed as apparent permeability coefficients) were determined for 20 drugs and peptides with different structural properties. The permeability coefficients ranged from approximately 5 x 10- 8 to 5 x 10- 5 cm/s. A good correlation was obtained between data on oral absorption in humans and the results in the Caco-2 model. Drugs that are completely absorbed in humans had permeability coefficients greater than 1 x 10- 6 cm/s. Drugs that are absorbed to greater than 1% but less than 100% had permeability coefficients of 0.1-1.0 x 10- 6 cm/s while drugs and peptides that are absorbed to less than 1% had permeability coefficients of less than or equal to 1 x 10- 7 cm/s. The results indicate that Caco-2 monolayers can be used as a model for studies on intestinal drug absorption

 
 
 
 
161

Contribution of Listeria monocytogenes RecA to acid and bile survival and invasion of human intestinal Caco-2 cells.  

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The food-borne pathogen Listeria monocytogenes is able to colonize the human gastro-intestinal tract and subsequently cross the intestinal barrier. Thus, for L. monocytogenes to become virulent, it must survive the low pH of the stomach, high bile concentrations in the small intestine, and invade the epithelial cells. In this study, we show that RecA, which is an important factor in DNA repair and the activator of the SOS response, contributes to the resistance against acid and bile and to the ability of L. monocytogenes to adhere and invade human intestine epithelial cells. Activation of recA was shown with a promoter reporter after exposure to low pH and high bile concentrations and during adhesion and invasion of Caco-2 intestinal epithelial cells. Furthermore, an in-frame recA deletion mutant showed reduced survival after exposure to low pH and high bile concentrations. This mutant also showed a deficiency in adhesion and invasion of Caco-2 cells. These results suggest that RecA may contribute to the colonization of the human gastro-intestinal tract and crossing of the intestinal barrier. PMID:21273119

van der Veen, Stijn; Abee, Tjakko

2011-04-01

162

Subversion of human intestinal mucosa innate immunity by a Crohn's disease-associated E. coli.  

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Adherent-invasive Escherichia coli (AIEC), associated with Crohn's disease, are likely candidate contributory factors in the disease. However, signaling pathways involved in human intestinal mucosa innate host response to AIEC remain unknown. Here we use a 3D model of human intestinal mucosa explant culture to explore the effects of the AIEC strain LF82 on two innate immunity platforms, i.e., the inflammasome through evaluation of caspase-1 status, and NF?B signaling. We showed that LF82 bacteria enter and survive within a few intestinal epithelial cells and macrophages, without altering the mucosa overall architecture. Although 4-h infection with a Salmonella strain caused crypt disorganization, caspase-1 activation, and mature IL-18 production, LF82 bacteria were unable to activate caspase-1 and induce IL-18 production. In parallel, LF82 bacteria activated NF?B signaling in epithelial cells through I?B? phosphorylation, NF?Bp65 nuclear translocation, and TNF? secretion. In addition, NF?B activation was crucial for the maintenance of epithelial homeostasis upon LF82 infection. In conclusion, here we decipher at the whole-mucosa level the mechanisms of the LF82-induced subversion of innate immunity that, by maintaining host cell integrity, ensure intracellular bacteria survival.Mucosal Immunology advance online publication, 1 October 2014; doi:10.1038/mi.2014.89. PMID:25269707

Jarry, A; Crémet, L; Caroff, N; Bou-Hanna, C; Mussini, J M; Reynaud, A; Servin, A L; Mosnier, J F; Liévin-Le Moal, V; Laboisse, C L

2014-10-01

163

A Strategy for assessing potential drug-drug interactions of a concomitant agent against a drug absorbed via an intestinal transporter in humans.  

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A strategy for assessing potential drug-drug interactions (DDIs) based on a simulated intestinal concentration is described. The proposed prediction method was applied to the DDI assessment of luseogliflozin, a novel antidiabetic drug, against miglitol absorbed via the intestinal sodium-glucose cotransporter 1 (SGLT1). The method involves four steps: collection of physicochemical and pharmacokinetic parameters of luseogliflozin for use in a computer simulation; evaluation of the validity of these parameters by verifying the goodness of fit between simulated and observed plasma profiles; simulation of the intestinal luseogliflozin concentration-time profile using the Advanced Compartment Absorption and Transit (ACAT) model in a computer program and estimation of the time spent above a value 10-fold higher than the IC50 value (TAIC) for SGLT1; and evaluation of the DDI potential of luseogliflozin by considering the percentage of TAIC against the miglitol Tmax (time for Cmax) value (TAIC/Tmax). An initial attempt to prove the validity of this method was performed in rats. The resulting TAIC/Tmax in rats was 32%, suggesting a low DDI potential of luseogliflozin against miglitol absorption. The validity was then confirmed using an in vivo interaction study in rats. In humans, luseogliflozin was expected to have no DDI potential against miglitol absorption, since the TAIC/Tmax in humans was lower than that in rats. This prediction was proven, as expected, in a clinical interaction study. In conclusion, the present strategy based on a simulation of the intestinal concentration-time profile using dynamic modeling would be useful for assessing the clinical DDI potential of a concomitant agent against drugs absorbed via an intestinal transporter. PMID:25005603

Mizuno-Yasuhira, Akiko; Nakai, Yasuhiro; Gunji, Emi; Uchida, Saeko; Takahashi, Teisuke; Kinoshita, Kohnosuke; Jingu, Shigeji; Sakai, Soichi; Samukawa, Yoshishige; Yamaguchi, Jun-Ichi

2014-09-01

164

Intestinal Coccidia  

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Intestinal Coccidia are a subclass of Apicomplexa phylum. Eucoccidida are facultative heteroxenous, but some of them are monoxenous. They have sexual and asexual life cycle. Some coccidia are human pathogens, for example: Cryptosporidium: Cryptosporidiums has many species that are mammalian intestinal parasites.C. Parvum specie is a human pathogenic protozoa. Cryptosporidum has circle or ellipse shapes and nearly 4-6 mm. It is transmitted in warm seasons. Oocyst is obtained insexual life cycl...

Mj, Ggaravi

2007-01-01

165

Interaction of macrolide antibiotics with intestinally expressed human and rat organic anion-transporting polypeptides.  

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The macrolide antibiotics azithromycin and clarithromycin are large molecular weight compounds that exhibit moderate to excellent oral bioavailability in preclinical species and humans. Previous concomitant dosing studies in rats using rifamycin SV, a general organic anion-transporting polypeptide (OATP) inhibitor, suggested that the high oral absorption of azithromycin and clarithromycin may be caused by facilitative uptake by intestinal Oatps. In this study, we used OATP/Oatp-expressing cells to investigate the interaction of macrolides with rat Oatp1a5, human OATP1A2, and human/rat OATP2B1/Oatp2b1. These experiments showed that azithromycin and clarithromycin were potent inhibitors of rat Oatp1a5-mediated taurocholate uptake with apparent inhibitor constant (K(i)) values of 3.3 and 2.4 microM, respectively. The macrolides functioned as noncompetitive inhibitors but were not transport substrates for rat Oatp1a5, as assessed by direct uptake measurements of radiolabeled azithromycin and clarithromycin. cis-Inhibition and direct uptake studies further showed that azithromycin and clarithromycin were only very weak inhibitors and not substrates for human OATP1A2 and human/rat OATP2B1/Oatp2b1. In summary, these results indicate that the macrolides azithromycin and clarithromycin potently inhibit rat Oatp1a5 but do not significantly interact with OATP1A2 and OATP2B1/Oatp2b1. These intestinally expressed OATP/Oatp(s) are not responsible for the postulated facilitative uptake of azithromycin and clarithromycin, and alternative facilitative pathways must exist for their intestinal absorption. PMID:19741038

Lan, Tian; Rao, Anuradha; Haywood, Jamie; Davis, Charles B; Han, Chao; Garver, Eric; Dawson, Paul A

2009-12-01

166

Studies on the determination of extracellular galactosyltransferase in human intestinal tissue  

International Nuclear Information System (INIS)

The determination of extracellular galactosyl transferase (EC 2.4.1.38) activity in human intestinal tissue by assessment of the incorporation of label after incubation with UDP[3H]galactose was evaluated. Intestinal biopsy specimens were incubated with membrane-permeable L-[1-14C]fucose and non-permeable UDP-D-[6-3H]galactose (UDP[3H]Gal). Comparison of the amounts of 3H- and 14C-label incorporated into subcellular fractions showed uptake and incorporation of galactose formed by the hydrolysis of UDP[3H]Gal by brush-border enzymes. The results indicate that incorporation of galactose after incubation of the tissue with UDP[3H]Gal is not exclusively attributable to extracellular galactosyl transferase. (Auth.)

167

Culture media from hypoxia conditioned endothelial cells protect human intestinal cells from hypoxia/reoxygenation injury.  

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Remote ischemic preconditioning (RIPC) is a phenomenon, whereby short episodes of non-lethal ischemia to an organ or tissue exert protection against ischemia/reperfusion injury in a distant organ. However, there is still an apparent lack of knowledge concerning the RIPC-mediated mechanisms within the target organ and the released factors. Here we established a human cell culture model to investigate cellular and molecular effects of RIPC and to identify factors responsible for RIPC-mediated intestinal protection. Human umbilical vein cells (HUVEC) were exposed to repeated episodes of hypoxia (3 × 15 min) and conditioned culture media (CM) were collected after 24h. Human intestinal cells (CaCo-2) were cultured with or without CM and subjected to 90 min of hypoxia/reoxygenation injury. Reverse transcription-polymerase chain reaction, Western blotting, gelatin zymography, hydrogen peroxide measurements and lactate dehydrogenase (LDH) assays were performed. In HUVEC cultures hypoxic conditioning did not influence the profile of secreted proteins but led to an increased gelatinase activity (P<0.05) in CM. In CaCo-2 cultures 90 min of hypoxia/reoxygenation resulted in morphological signs of cell damage, increased LDH levels (P<0.001) and elevated levels of hydrogen peroxide (P<0.01). Incubation of CaCo-2 cells with CM reduced the hypoxia-induced signs of cell damage and LDH release (P<0.01) and abrogated the hypoxia-induced increase of hydrogen peroxide. These events were associated with an enhanced phosphorylation status of the prosurvival kinase Erk1/2 (P<0.05) but not Akt and STAT-5. Taken together, CM of hypoxia conditioned endothelial cells protect human intestinal cells from hypoxia/reoxygenation injury. The established culture model may help to unravel RIPC-mediated cellular events and to identify molecules released by RIPC. PMID:24394542

Hummitzsch, Lars; Zitta, Karina; Bein, Berthold; Steinfath, Markus; Albrecht, Martin

2014-03-10

168

Human intestinal parasites in non-biting synanthropic flies in Ogun State, Nigeria.  

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Filth-feeding and breeding, non-biting synanthropic flies have been incriminated in the dissemination of human enteropathogens in the environment. This study determined the species of non-biting synanthropic flies associated with four filthy sites in Ilishan, Ogun State, southwest Nigeria, and assessed their potentials for mechanical transmission of human intestinal parasites. 7190 flies identified as Musca domestica (33.94%), Chrysomya megacephala (26.01%), Musca sorbens (23.23%), Lucilia cuprina (8.76%), Calliphora vicina (4.59%), Sarcophaga sp. (2.78%) and Fannia scalaris (0.70%) were examined for human intestinal parasites by the formol-ether concentration and modified Ziehl-Neelsen techniques. Eggs of the following parasites: Ascaris lumbricoides (34.08%), Trichuris trichiura (25.87%), hookworms (20.45%), Taenia sp. (2.36%), Hymenolepis nana (1.11%), Enterobius vermicularis (0.56%), Strongyloides stercoralis (larvae; 3.89%) and cysts of Entamoeba histolytica/dispar (27.26%), Entamoeba coli (22.67%), Giardia lamblia (3.34%) and Cryptosporidium sp. (1.81%) were isolated from the body surfaces and or gut contents of 75.24% of 719 pooled fly batches. The helminths A. lumbricoides and T. trichiura and the protozoans, E. histolytica/dispar and E. coli were the dominant parasites detected, both on body surfaces and in the gut contents of flies. C. megacephala was the highest carrier of parasites (diversity and number). More parasites were isolated from the gut than from body surfaces (P < 0.05). Flies from soiled ground often carried more parasites than those from abattoir, garbage or open-air market. Synanthropic fly species identified in this study can be of potential epidemiological importance as mechanical transmitters of human intestinal parasites acquired naturally from filth and carried on their body surfaces and or in the gut, because of their vagility and feeding mechanisms. PMID:23290716

Adenusi, Adedotun Adesegun; Adewoga, Thomas O Sunday

2013-01-01

169

In Vitro Modulation of Human Intestinal Microbiota by Mannoligosaccharides Synthesized from Amorphophallus muelleri Glucomannan  

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Full Text Available The corms of Amorphophallus muelleri Blume contain a large amount of glucomannan, a kind of polysaccharide that are commonly consumed by people as gelly foods. In order to improve the beneficial properties of glucomannan, we previously have established the enzymatic process to produce the mannoligosaccharides from flour of glucomannan using microbial mannanase. The effects of mannoligosaccharides on the growth modulation of human intestinal microbiota were investigated in this study. A set of in vitro single batch culture experiment was conducted to study the effect of mannooligosaccharides on human-origin Lactobacillus fermentum AA0014 and Lactobacillus plantarum FU0811. A modified MRS medium containing 10% (w/v sucrose, glucomannan, and mannoligosaccharide was used instead of glucose as carbon source. The results showed the highest growth rate (0.13 h-1 with both L. fermentum AA0014 and L. plantarum FU0811 in the presence of mannooligosaccharides. We confirmed this result by a similar in vitro experiment using human fecal samples of six healthy adults as innocula and analyzed the microbial population by fluorescence in situ hybridization (FISH. Lactobacilli were proliferated higher in the presence of mannoligosaccharide than other carbon sources, yielding the microbial proportion as much of 10.9% of total microbiota. Overall, this study demonstrated the potential use of mannoligosaccharides synthesized from A. muelleri glucomannan as prebiotic candidate of modulating the beneficial human intestinal microbiota.

ACHMAD DINOTO

2013-11-01

170

Probiotic supplementation decreases intestinal transit time: Meta-analysis of randomized controlled trials  

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Full Text Available AIM: To determine the efficacy of probiotic supplementation on intestinal transit time (ITT and to identify factors that influence these outcomes. METHODS: A systematic review of randomized controlled trials (RCTs of probiotic supplementation that measured ITT in adults was conducted by searching MEDLINE and EMBASE using relevant key word combinations. Main search limits included RCTs of probiotic supplementation in healthy or constipated adults that measured ITT. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference (SMD of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses were conducted to examine the impact of moderator variables on ITT SMD. RESULTS: A total of 11 clinical trials with 13 treatment effects representing 464 subjects were included in this analysis. Probiotic supplementation was associated with decreased ITT in relation to controls, with an SMD of 0.40 (95%CI: 0.20-0.59, P < 0.001. Constipation (r2 = 39%, P = 0.01, higher mean age (r2 = 27%, P = 0.03, and higher percentage of female subjects (r2 = 23%, P < 0.05 were predictive of decreased ITT with probiotics in meta-regression. Subgroup analyses demonstrated statistically greater reductions in ITT with probiotics in subjects with vs without constipation and in older vs younger subjects [both SMD: 0.59 (95%CI: 0.39-0.79 vs 0.17 (95%CI: -0.08-0.42, P = 0.01]. Medium to large treatment effects were identified with Bifidobacterium Lactis (B. lactis HN019 (SMD: 0.72, 95%CI: 0.27-1.18, P < 0.01 and B. lactis DN-173 010 (SMD: 0.54, 95%CI: 0.15-0.94, P < 0.01 while other single strains and combination products yielded small treatment effects. CONCLUSION: Overall, short-term probiotic supplementation decreases ITT with consistently greater treatment effects identified in constipated or older adults and with certain probiotic strains.

Larry E Miller

2013-01-01

171

Rotavirus Infection Induces an Increase in Intracellular Calcium Concentration in Human Intestinal Epithelial Cells: Role in Microvillar Actin Alteration  

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Rotaviruses, which infect mature enterocytes of the small intestine, are recognized as the most important cause of viral gastroenteritis in young children. We have previously reported that rotavirus infection induces microvillar F-actin disassembly in human intestinal epithelial Caco-2 cells (N. Jourdan, J. P. Brunet, C. Sapin, A. Blais, J. Cotte-Laffitte, F. Forestier, A. M. Quero, G. Trugnan, and A. L. Servin, J. Virol. 72:7228–7236, 1998). In this study, to determine the mechanism respon...

Brunet, Jean-philippe; Cotte-laffitte, Jacqueline; Linxe, Catherine; Quero, Anne-marie; Ge?niteau-legendre, Monique; Servin, Alain

2000-01-01

172

Adaptive regulation of human intestinal thiamine uptake by extracellular substrate level: a role for THTR-2 transcriptional regulation  

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The intestinal thiamine uptake process is adaptively regulated by the level of vitamin in the diet, but the molecular mechanism involved is not fully understood. Here we used the human intestinal epithelial Caco-2 cells exposed to different levels of extracellular thiamine to delineate the molecular mechanism involved. Our results showed that maintaining Caco-2 cells in a thiamine-deficient medium resulted in a specific and significant increase of [3H]thiamine uptake compared with cell exposu...

Nabokina, Svetlana M.; Subramanian, Veedamali S.; Valle, Judith E.; Said, Hamid M.

2013-01-01

173

Poliovirus mutants excreted by a chronically infected hypogammaglobulinemic patient establish persistent infections in human intestinal cells  

International Nuclear Information System (INIS)

Immunodeficient patients whose gut is chronically infected by vaccine-derived poliovirus (VDPV) may excrete large amounts of virus for years. To investigate how poliovirus (PV) establishes chronic infections in the gut, we tested whether it is possible to establish persistent VDPV infections in human intestinal Caco-2 cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000) 3001], were used to infect both undifferentiated, dividing cells, and differentiated, polarized enterocytes. A VDPV mutant excreted 36 days postvaccination by the patient was lytic in both types of intestinal cell cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs excreted 136, 442, and 637 days postvaccination, established persistent infections both in undifferentiated cells and in enterocytes. Thus, viral determinants selected between day 36 and 136 conferred on VDPV mutants the capacity to infect intestinal cells persistently. The percentage of persistently VDPV-infected cultures was higher in enterocytes than in undifferentiated cells, implicating cellular determinants involved in the differentiation of enterocytes in persistent VDPV infections. The establishment of persistent infections in enterocytes was not due to poor replication of VDPVs in these cells, but was associated with reduced viral adsorption to the cell surface

174

Cellular and molecular mechanism study of declined intestinal transit function in the cholesterol gallstone formation process of the guinea pig.  

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The aim of this study was to investigate the cellular and molecular mechanisms of declined intestinal transit (IT) function in the cholesterol gallstone (CG) formation process. Forty guinea pigs were divided into an experimental group (EG) and a control group (CoG), and the reverse transcription-polymerase chain reaction (RT-PCR) was performed for the analysis of c-kit and stem cell factor (scf) mRNA expression in the small bowel. In addition, immunofluorescence staining and confocal laser microscopy were performed for the observation of the changes in the number of interstitial cells of Cajal (ICCs) in the terminal ileum of each group. RT-PCR showed that, compared with the CoG, the intestinal c-kit and scf mRNA expression levels in the EG were significantly decreased; the average positive area of ICCs in the ileum in the EG was also significantly reduced. During the diet-induced CG formation procedure, the c-kit and scf mRNA expression levels in the small intestine decreased and the number of ICCs decreased. Inhibition of the c-kit/scf pathway may be involved in the declined IT function during the CG formation process. PMID:25289052

Fan, Ying; Wu, Shuodong; Yin, Zhenhua; Fu, Bei-Bei

2014-11-01

175

An earthworm-like robotic endoscope system for human intestine: design, analysis, and experiment.  

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The existing endoscope brings too much discomfort to patients because its slim and rigid rod is difficult to pass through alpha, gamma loop of the human intestine. A robotic endoscope, as a novel solution, is expected to replace the current endoscope in clinic. A microrobotic endoscope based on wireless power supply was developed in this paper. This robot is mainly composed of a locomotion mechanism, a wireless power supply subsystem, and a communication subsystem. The locomotion mechanism is composed of three liner-driving cells connected with each other through a two-freedom universal joint. The wireless power supply subsystem is composed of a resonance transmit coil to transmit an alternating magnetic field, and a secondary coil to receive the power. Wireless communication system could transmit the image to the monitor, or send the control commands to the robot. The whole robot was packaged in the waterproof bellows. Activating the three driving cells under some rhythm, the robot could creep forward or backward as a worm. A mathematic model is built to express the energy coupling efficiency. Some experiments are performed to test the efficiency and the capability of energy transferring. The results show the wireless energy supply has enough power capacity. The velocity and the navigation ability in a pig intestine were measured in in vitro experiments. The results demonstrated this robot can navigate the intestine easily. In general, the wireless power supply and the wireless communication remove the need of a connecting wire and improve the motion flexibility. Meanwhile, the presented locomotion mechanism and principle have a high reliability and a good adaptability to the in vitro intestine. This research has laid a good foundation for the real application of the robotic endoscope in the future. PMID:19003537

Wang, Kundong; Yan, Guozheng; Ma, Guanying; Ye, Dongdong

2009-01-01

176

Regulation of Villin by Wnt5a and Ror2 in human intestinal cells  

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Full Text Available Regulation of expression of the intestinal epithelial actin-binding protein, villin, is poorly understood. The aim of this study was to determine whether Wnt5a stimulates Ror2 in intestinal epithelia caused transient increases in phospho-ERK1/2 (pERK1/2 and subsequently increased expression of villin transcript and protein. To demonstrate Wnt5a-Ror2 regulation of villin expression, we overexpressed wild-type, truncated, or mutant Ror2 constructs in HT-29 adenocarcinoma cells and nontransformed fetally-derived human intestinal epithelial cells, added conditioned media containing Wnt5a and measured changes in ERK1/2 phosphorylation, villin amplicons and protein expression by RT-PCR and Western blot techniques. Wnt5a addition caused a transient increase in pERK1/2, which was maximal at 10 min but extinguished by 30 min. Transient transfection with a siRNA duplex against Ror2 diminished Ror2 amplicons and protein and reduced the extent of pERK1/2 activation. Structure-function analysis revealed that the deletion of the cysteine-rich, kringle, or tyrosine kinase domain or substitution mutations of tyrosine residues in the intracellular Ser/Thr-1 region of Ror2 prevented the Wnt5a-stimulation of pERK1/2. Deletion of the intracellular proline and serine/threonine rich regions of Ror2 had no effect on Wnt5a-stimulation of pERK1/2. The increase in villin expression was blocked by pharmacological inhibition of MEK1 and casein kinase 1, but not by PKC and p38 inhibitors. Neither Wnt3a nor EGF addition caused increases in villin protein. Our findings suggest that Wnt5a/ Ror2 signaling can regulate villin expression in the intestine.

JacquelineKelly

2011-09-01

177

Intestinal parasite co-infection among pulmonary tuberculosis cases without human immunodeficiency virus infection in a rural county in China.  

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Epidemiologic studies of co-infection with tuberculosis (TB) and intestinal parasites in humans have not been extensively investigated in China. A cross-section study was conducted in a rural county of Henan Province, China. Pulmonary TB (PTB) case-patients receiving treatment for infection with Mycobacterium tuberculosis and healthy controls matched for geographic area, age, and sex were surveyed by using questionnaires. Fecal and blood specimens were collected for detection of intestinal parasites, routine blood examination, and infection with human immunodeficiency virus. The chi-square test was used for univariate analysis and multivariate logistic regression models were used to adjust for potential confounding factors. A total of 369 persons with PTB and 366 healthy controls were included; all participants were negative for human immunodeficiency virus. The overall prevalence of intestinal parasites in persons with PTB was 14.9%, including intestinal protozoa (7.9%) and helminthes (7.6%). The infection spectrum of intestinal parasites was Entamoeba spp. (1.4%), Blastocystis hominis (6.2%), Trichomonas hominis (0.3%), Clonorchis sinensis (0.3%), Ascaris lumbricoides (0.5%), Trichuris trichiura (2.2%), and hookworm (4.6%). The prevalence of intestinal parasites showed no significant difference between persons with PTB and healthy controls after adjusting for potential confounding factors. There was no factor that affected infection rates for intestinal parasites between the two groups. Infection with intestinal parasites of persons with PTB was associated with female sex (adjusted odds ratio [AOR] = 2.05, 95% confidence interval [CI] = 1.01-4.17), body mass index ? 19 (AOR = 3.02, 95% CI = 1.47-6.20), and anemia (AOR = 2.43, 95% CI = 1.17-5.03). Infection of healthy controls was only associated with an annual labor time in farmlands > 2 months (AOR = 4.50, 95% CI = 2.03-10.00). In addition, there was no significant trend between rates of infection with intestinal parasites and duration of receiving treatment for infection with M. tuberculosis in persons with PTB. The prevalence of intestinal parasites was not higher in persons with PTB, and there was no evidence that PTB increased susceptibility to intestinal parasites in this study. However, for patients with PTB, women and patients with comorbidities were more likely to be infected with intestinal parasites. PMID:24166044

Li, Xin-Xu; Chen, Jia-Xu; Wang, Li-Xia; Tian, Li-Guang; Zhang, Yu-Ping; Dong, Shuang-Pin; Hu, Xue-Guang; Liu, Jian; Wang, Feng-Feng; Wang, Yue; Yin, Xiao-Mei; He, Li-Jun; Yan, Qiu-Ye; Zhang, Hong-Wei; Xu, Bian-Li; Zhou, Xiao-Nong

2014-01-01

178

Transport of Aflatoxin M1 in Human Intestinal Caco-2/TC7 Cells  

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Aflatoxin M1 (AFM1) is a hydroxylated metabolite of aflatoxin B1 (AFB1). After it is formed, it is secreted in the milk of mammals. Despite the potential risk of human exposure to AFM1, data reported in literature on the metabolism, toxicity and bioavailability of this molecule are limited and out of date. The aim of the present research was to study the absorption profile of AFM1 and possible damage to tight junctions of the intestinal Caco-2/TC7 clone grown on microporous filter supports...

FrancescaCaloni

2012-01-01

179

Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium  

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The diversity of mucin-degrading bacteria in the human intestine was investigated by combining culture and 16S rRNA-dependent approaches. A dominant bacterium, strain MucT, was isolated by dilution to extinction of faeces in anaerobic medium containing gastric mucin as the sole carbon and nitrogen source. A pure culture was obtained using the anaerobic soft agar technique. Strain MucT was a Gram-negative, strictly anaerobic, non-motile, non-spore-forming, oval-shaped bacterium that could grow...

Derrien, M. M. N.; Vaughan, E. E.; Plugge, C. M.; Vos, W. M.

2004-01-01

180

Butyrate stimulates IL-32? expression in human intestinal epithelial cell lines  

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AIM: To investigate the effects of butyrate on interleukin (IL)-32? expression in epithelial cell lines.METHODS: The human intestinal epithelial cell lines HT-29, SW480, and T84 were used. Intracellular IL-32? was determined by Western blotting analyses. IL-32? mRNA expression was analyzed by real-time polymerase chain reaction.RESULTS: Acetate and propionate had no effects on IL-32? mRNA expression. Butyrate significantly enhanced IL-32? expression in all cell lines. Butyrate also up-re...

Ayako Kobori, Shigeki Bamba

2010-01-01

 
 
 
 
181

Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species.  

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Ellagitannin and ellagic acid metabolism to urolithins in the gut shows a large human interindividual variability and this has been associated with differences in the colon microbiota. In the present study we describe the isolation of one urolithin-producing strain from the human faeces of a healthy volunteer and the ellagic acid transformation to different urolithin metabolites by two species of intestinal bacteria. The isolate belongs to a new species described as Gordonibacter urolithinfaciens, sp. nov. The type strain of the Gordonibacter genus, Gordonibacter pamelaeae DSM 19378(T), was also demonstrated to produce urolithins. Both human intestinal bacteria grew similarly in the presence and absence of ellagic acid at 30 ?M concentration. Ellagic acid catabolism and urolithin formation occurred during the stationary phase of the growth of the bacteria under anaerobic conditions. The HPLC-MS analyses showed the sequential production of pentahydroxy-urolithin (urolithin M-5), tetrahydroxy-urolithin (urolithin M-6) and trihydroxy-urolithin (urolithin C), while dihydroxy-urolithins (urolithin A and isourolithin A), and monohydroxy-urolithin (urolithin B) were not produced in pure cultures. Consequently, either other bacteria from the gut or the physiological conditions found in vivo are necessary for completing metabolism until the final urolithins (dihydroxy and monohydroxy urolithins) are produced. This is the first time that the urolithin production capacity of pure strains has been demonstrated. The identification of the urolithin-producing bacteria is a relevant outcome as urolithin implication in health (cardiovascular protection, anti-inflammatory and anticarcinogenic properties) has been supported by different bioassays and urolithins can be used in the development of functional foods and nutraceuticals. This study represents an initial work that opens interesting possibilities of describing enzymatic activities involved in urolithin production that can help in understanding both the human interindividual differences in polyphenol metabolism, the microbial pathways involved, and the role of polyphenols in human health. The presence of urolithin producing bacteria can indirectly affect the health benefits of ellagitannin consumption. PMID:24909569

Selma, María V; Beltrán, David; García-Villalba, Rocío; Espín, Juan C; Tomás-Barberán, Francisco A

2014-08-01

182

Vasoactive intestinal peptide maintains the nonpathogenic profile of human th17-polarized cells.  

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The cytokine microenvironment modulates CD4 T cell differentiation causing the shift of naïve CD4 T cells into different cell subsets. This process is also regulated by modulators such as vasoactive intestinal peptide (VIP), a neuropeptide with known immunomodulatory properties on CD4 T cells that exert this action through specific receptors, vasoactive intestinal peptide receptor (VPAC)1 and VPAC2. Our results show that the pattern of VIP receptors expression ratio is modified during Th17 differentiation. In this report, we evaluate the capacity of VIP to modulate naïve human cells into Th17 cells in vitro by analyzing their functional phenotype. The presence of VIP maintains the nonpathogenic profile of Th17-polarized cells, increases the proliferation rate, and decreases their Th1 potential. VIP induces the upregulation of the STAT3 gene interaction with the VPAC1 receptor during the onset of Th17 differentiation. Moreover, RAR-related orphan receptor C (RORC), RAR-related orphan receptor A (RORA), and interleukin (IL)-17A genes are upregulated in the presence of VIP through interaction with VPAC1 and VPAC2 receptors. Interestingly, VIP induces the expression of the IL-23R gene through interaction with the VPAC2 receptor during the expansion phase. This is the first report that describes the differentiation of naïve human T cells to Th17-polarized cells in the presence of VIP and demonstrates how this differentiation regulates the expression of the VIP receptors. PMID:24805298

Jimeno, Rebeca; Leceta, Javier; Martínez, Carmen; Gutiérrez-Cañas, Irene; Carrión, Mar; Pérez-García, Selene; Garín, Marina; Mellado, Mario; Gomariz, Rosa P; Juarranz, Yasmina

2014-11-01

183

Expression of Tn, sialosyl-Tn and T antigens in human foetal large intestine  

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Full Text Available Tn, sialosyl-Tn and T antigens are simple mucintype carbohydrate antigens that may be expressed in human neoplasies due to alteration of the glycoprotein biosynthetic pathway. Utilising specific monoclonal antibodies (HB-Tn1, HB-STn1 and HB-T1, we have investigated the expression of these simple mucin-type carbohydrate antigens in large intestine of 8 human foetuses at early gestational age (9-10 weeks, obtained after therapeutic abortion. In all cases the expression of Tn antigen was mainly localised as a thin rim at the cell membrane and occasionally in the supranuclear region of epithelial cells, while sialosyl-Tn antigen was documented in some goblet cell vacuoles and occasionally in the cytoplasm of columnar cells. T antigen was not expressed in any case. These results indicate that Tn and sialosyl-Tn antigens are expressed as early as nine weeks of gestation, further supporting the notion that they may be considered as oncodevelopmental cancerassociated antigens in the large intestine.

G Barresi

2009-12-01

184

Effect of c-kit ligand, stem cell factor, on mediator release by human intestinal mast cells isolated from patients with inflammatory bowel disease and controls.  

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The regulation of mediator release in human intestinal mast cells is largely unknown. Apart from IgE receptor crosslinking no secretagogues have been described so far. This study examined the effect of two cytokines (c-kit ligand and interleukin 3) and other agonists on human intestinal mast cell function. Cells were isolated from surgery specimens of 47 patients undergoing intestinal resection because of tumours or inflammatory bowel disease. Cell suspensions contained 3.6% mast cells (mean ...

Bischoff, S. C.; Schwengberg, S.; Wordelmann, K.; Weimann, A.; Raab, R.; Manns, M. P.

1996-01-01

185

Tspan-1 interacts with the thiamine transporter-1 in human intestinal epithelial cells and modulates its stability  

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The human thiamine transporter-1 (hTHTR-1) contributes to intestinal thiamine uptake, and its function is regulated at both the transcriptional and posttranscriptional levels. Nothing, however, is known about the protein(s) that may interact with hTHTR-1 and affects its cell biology and physiology. We addressed this issue in the present investigation using a bacterial two-hybrid system to screen a human intestinal cDNA library with the complete coding sequence of hTHTR-1 as a bait. Our result...

Nabokina, Svetlana M.; Senthilkumar, Sundar Rajan; Said, Hamid M.

2011-01-01

186

Isolation and Identification of Intestinal CYP3A Inhibitors from Cranberry (Vaccinium macrocarpon) using Human Intestinal Microsomes  

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Cranberry juice is used routinely, especially among women and the elderly, to prevent and treat urinary tract infections. These individuals are likely to be taking medications concomitantly with cranberry juice, leading to concern about potential drug-dietary substance interactions, particularly in the intestine, which, along with the liver, is rich in expression of the prominent drug metabolizing enzyme, cytochrome P450 3A (CYP3A). Using a systematic in vitro-in vivo approach, a cranberry ju...

Kim, Eunkyung; Sy-cordero, Arlene; Graf, Tyler N.; Brantley, Scott J.; Paine, Mary F.; Oberlies, Nicholas H.

2011-01-01

187

Receptor-Mediated Transcytosis of Leptin through Human Intestinal Cells In Vitro  

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Full Text Available Gastric Leptin is absorbed by duodenal enterocytes and released on the basolateral side towards the bloodstream. We investigated in vitro some of the mechanisms of this transport. Caco-2/15 cells internalize leptin from the apical medium and release it through transcytosis in the basal medium in a time- temperature-dependent and saturable fashion. Leptin receptors are revealed on the apical brush-border membrane of the Caco-2 cells. RNA-mediated silencing of the receptor led to decreases in the uptake and basolateral release. Leptin in the basal medium was found bound to the soluble form of its receptor. An inhibitor of clathrin-dependent endocytosis (chlorpromazine decreased leptin uptake. Confocal immunocytochemistry and the use of brefeldin A and okadaic acid revealed the passage of leptin through the Golgi apparatus. We propose that leptin transcytosis by intestinal cells depends on its receptor, on clathrin-coated vesicles and transits through the Golgi apparatus.

Émile Levy

2010-01-01

188

Mapping of liver-enriched transcription factors in the human intestine  

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Full Text Available AIM: To investigate the gene expression pattern of hepatocyte nuclear factor 6 (HNF6 and other liver-enriched transcription factors in various segments of the human intestine to better understand the differentiation of the gut epithelium.METHODS: Samples of healthy duodenum and jejunum were obtained from patients with pancreatic cancer whereas ileum and colon was obtained from patients undergoing right or left hemicolectomy or (rectosigmoid or rectal resection. All surgical specimens were subjected to histopathology. Excised tissue was shock-frozen and analyzed for gene expression of liver-enriched transcription factors by semiquantitative reverse transcription polymerase chain and compared to the human colon carcinoma cell line Caco-2. Protein expression of major liver-enriched transcription factors was determined by Western blotting while the DNA binding of HNF6 was investigated by electromobility shift assays.RESULTS: The gene expression patterning of liver-enriched transcription factors differed in the various segments of the human intestine with HNF6 gene expression being most abundant in the duodenum (P < 0.05 whereas expression of the zinc finger protein GATA4 and of the HNF6 target gene ALDH3A1 was most abundant in the jejunum (P < 0.05. Likewise, expression of FOXA2 and the splice variants 2 and 4 of HNF4? were most abundantly expressed in the jejunum (P < 0.05. Essentially, expression of transcription factors declined from the duodenum towards the colon with the most abundant expression in the jejunum and less in the ileum. The expression of HNF6 and of genes targeted by this factor, i.e. neurogenin 3 (NGN3 was most abundant in the jejunum followed by the ileum and the colon while DNA binding activity of HNF4? and of NGN3 was confirmed by electromobility shift assays to an optimized probe. Furthermore, Western blotting provided evidence of the expression of several liver-enriched transcription factors in cultures of colon epithelial cells, albeit at different levels.CONCLUSION: We describe significant local and segmental differences in the expression of liver-enriched transcription factors in the human intestine which impact epithelial cell biology of the gut.

Frank Lehner, Ulf Kulik, Juergen Klempnauer,Juergen Borlak

2010-08-01

189

Utilização do método videolaparoscopico na reconstituição do trânsito intestinal após a operação de Hartmann The use of videolaparoscopic approach in the intestinal transit restoration after Hartmann's procedure  

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Full Text Available O objetivo é apresentar a padronização da técnica operatória e os resultados obtidos com a utilização do acesso videolaparoscópico na reconstituição do trânsito intestinal em pacientes previamente submetidos à operação de Hartmann por causas diversas. Foram analisados prospectivamente 32 pacientes, no período de dezembro de 1991 a junho de 1997, com distribuição semelhante com relação ao sexo e com idade média de 42,4 anos. Todos os pacientes foram submetidos ao mesmo preparo pré-operatório e à mesma técnica cirúrgica. Ocorreram três (9,3% complicações transoperatórias. Uma (3,1 % anastomose mecânica incompleta, necessitando de endossutura manual, uma (3,1 % laceração do reto com o grampeador mecânico e uma (3,1 % lesão da artéria epigástrica direita. Ocorreram ainda três (9,3% conversões, sendo uma (3,1 % devido à laceração do reto com o grampeador mecânico, outra (3.1 % pela invasão tumoral na pelve e outra (3,1 % pela presença de excessivas aderências intraperitoneais. O tempo operatório variou de 30 a 240 minutos, na média de 126,2 minutos (2,1 horas. A evolução clínica pós-operatória foi satisfatória. Nove (31,0% pacientes não referiram dor, enquanto 13 (44,8% a referiram em pequena intensidade, e apenas sete (24,0% queixaram-se de dor com maior intensidade. A dieta líquida via oral foi instituída no período médio de 1,6 dias, e a primeira evacuação ocorreu na média de 3,2 dias de pós-operatório. O período médio de hospitalização foi de 4,7 dias. Ocorreram complicações pós-operatórias em oito (27,5% pacientes. Duas (6,8% infecções da ferida do estoma, dois pacientes (6,8% com dor no ombro direito, uma (3,4% deiscência de anastomose, um (3,4% caso de peritonite por provável contaminação do material cirúrgico, uma coleção líquida pélvica e uma hérnia incisional. Em conclusão, a reconstituição do trânsito intestinal por videolaparoscopia apresentou-se segura e eficaz, podendo constituir-se no método cirúrgico de escolha, pois foi utilizada com sucesso em 90,6% dos pacientes.We present the operative technique and the results of the laparoscopic approach for Hartmann's colostomy reversal. Thirty two patients were prospectively analysed from december 1991 to june 1997. They presented a similar incidence regarding sex distribution, and a median age of 42.4 years old. Ali patients underwent the same preoperative preparation and operative technique. Three (9.3% intraoperative complications were observed: an uncompleted anastomosis (3.1%, requiring an endosuture, a rectal perforation by the mechanical stapler and a right epigastric artery lesion. There were convertion to open surgery in three (9.3% patients: one (3.1% due to rectal perforation by the mechanical staple1; one (3.1% for tumoral pelvic invasion and another because of excessive intra-peritoneal adhesions. Operative time varied from 30 to 240 minutes, with a mean time of 126;2 minutes. Nine (31.0% patients didn't present pain, while 13 (44.8% referred minimal pain and seven (24.0% complained severe pain. Oral liquid diet intake occurred within a mean time of 1.6 days and the first evacuation observed after a mean 3.2 postoperative days. Mean hospitalization time was 4.7 days. Postoperative complications occurred in eight (27.5% patients. Two (6.8% stoma wound infections, right shoulder pain in two (6.8% patients, one (3.4% anastomotic dehiscence, one peritonitis probably due to contaminationfrom surgical instruments, a liquid pelvic coliection and an incisional haernia. 1n conclusion, videolaparoscopic restoration of the intestinal transit demonstrated to be safe and effective. It could be the method of choice because of its success in 90.6 per cent of the patients.

Francisco Sérgio P. Regadas

2000-02-01

190

Human intestinal parasites in the past: new findings and a review  

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Full Text Available Almost all known human specific parasites have been found in ancient feces. A review of the paleoparasitological helminth and intestinal protozoa findings available in the literature is presented. We also report the new paleoparasitologic findings from the examination performed in samples collected in New and Old World archaeological sites. New finds of ancylostomid, Ascaris lumbricoides, Trichuris trichiura, Enterobius vermicularis, Trichostrongylus spp., Diphyllobothrium latum, Hymenolepis nana and Acantocephalan eggs are reported. According to the findings, it is probable that A. lumbricoides was originally a human parasite. Human ancylostomids, A. lumbricoides and T. trichiura, found in the New World in pre-Columbian times, have not been introduced into the Americas by land via Beringia. These parasites could not supported the cold climate of the region. Nomadic prehistoric humans that have crossed the Bering Land Bridge from Asia to the Americas in the last glaciation, probably during generations, would have lost these parasites, which life cycles need warm temperatures in the soil to be transmitted from host to host. Alternative routes are discussed for human parasite introduction into the Americas.

Marcelo Luiz Carvalho Gonçalves

2003-01-01

191

Human Capital Formation during Communism and Transition: Evidence from Bulgaria  

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Is it true that communist countries had well-developed human capital, or is it just a myth? What were human capital stocks at the beginning of transition to market economy? What happened to human capital formation during the transition? We attempt to answer these questions using evidence from Bulgaria. This is also a story about how a communist government had coped with labour market problems in a small closed economy. Unfortunately, during communism, there had been quite insufficient public ...

Simeonova-ganeva, Ralitsa

2005-01-01

192

Vitamin A metabolism in the human intestinal Caco-2 cell line  

International Nuclear Information System (INIS)

The human intestinal Caco-2 cell line, described as enterocyte-like in a number of studies, was examined for its ability to carry out the metabolism of vitamin A normally required in the absorptive process. Caco-2 cells contained cellular retinol-binding protein II, a protein which is abundant in human villus-associated enterocytes and may play an important role in the absorption of vitamin A. Microsomal preparations from Caco-2 cells contained retinal reductase, acyl-CoA-retinol acyltransferase (ARAT), and lecithin-retinol acyltransferase (LRAT) activites, which have previously been proposed to be involved in the metabolism of dietary vitamin A in the enterocyte. When intact Caco-2 cells were provided with ?-carotene, retinyl acetate, or retinyl acetate, or retinol, synthesis of retinyl palmitoleate, oleate, palmitate, and small amounts of stearate resulted. However, exogenous retinyl palmitate or stearate was not used by Caco-2 cells as a source of retinol for ester synthesis. While there was a disproportionate synthesis of monoenoic fatty acid esters of retinol in Caco-2 cells compared to the retinyl esters typically found in human chylomicrons or the esters normally synthesized in rat intestine, the pattern was consistent with the substantial amount of unsaturated fatty acids, particularly 18:1 and 16:1, found in the sn-1 position of Caco-2 microsomal phosphatidylcholine, the fatty acyl donor for LRAT. Both ARAT and LRAT have been proposed to be responsible for rave been proposed to be responsible for retinyl ester synthesis in the enterocyte. These data suggest the LRAT may be the physiologically important enzyme for the esterification of retinol in Caco-2 cells

193

Vitamin A metabolism in the human intestinal Caco-2 cell line  

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The human intestinal Caco-2 cell line, described as enterocyte-like in a number of studies, was examined for its ability to carry out the metabolism of vitamin A normally required in the absorptive process. Caco-2 cells contained cellular retinol-binding protein II, a protein which is abundant in human villus-associated enterocytes and may play an important role in the absorption of vitamin A. Microsomal preparations from Caco-2 cells contained retinal reductase, acyl-CoA-retinol acyltransferase (ARAT), and lecithin-retinol acyltransferase (LRAT) activites, which have previously been proposed to be involved in the metabolism of dietary vitamin A in the enterocyte. When intact Caco-2 cells were provided with {beta}-carotene, retinyl acetate, or retinyl acetate, or retinol, synthesis of retinyl palmitoleate, oleate, palmitate, and small amounts of stearate resulted. However, exogenous retinyl palmitate or stearate was not used by Caco-2 cells as a source of retinol for ester synthesis. While there was a disproportionate synthesis of monoenoic fatty acid esters of retinol in Caco-2 cells compared to the retinyl esters typically found in human chylomicrons or the esters normally synthesized in rat intestine, the pattern was consistent with the substantial amount of unsaturated fatty acids, particularly 18:1 and 16:1, found in the sn-1 position of Caco-2 microsomal phosphatidylcholine, the fatty acyl donor for LRAT. Both ARAT and LRAT have been proposed to be responsible for retinyl ester synthesis in the enterocyte. These data suggest the LRAT may be the physiologically important enzyme for the esterification of retinol in Caco-2 cells.

Quick, T.C.; Ong, D.E. (Vanderbilt Univ. School of Medicine, Nashville, TN (USA))

1990-12-01

194

Characterization of the transport of ?-methylaminoisobutyric acid by a human intestinal cell line (HT-29)  

International Nuclear Information System (INIS)

Under certain growth conditions, the human colon adenocarcinoma cell line HT-29 exhibits intestinal enterocyte-like properties. The differentiated cells possess a brush border with the enzyme markers (aminopeptidase and sucrase) normally associated with the intestine. To aid in the characterization of the transport properties of these cells, the uptake of a non-metabolizable amino acid analog, 14C-?-methylaminoisobutyric acid (MeAIB) as examined in the HT-29-Al subclone which possesses a brush border. The cells exhibited a time-dependent uptake of MeAIB which was concentrative and sodium-dependent. The pH optimum for uptake was about 7.8. Uptake was inhibited by low temperature, 1 mM ouabain, or 0.5 mM dinitrophenol. A 1 hr-preincubation of the cells in an isotonic KCl solution resulted in a decreased uptake rate, suggesting that a negative membrane potential is important for MeAIB uptake. The rate of 0.5 mM MeABIB uptake was inhibited by 40 to 90% by 5 mM of certain small neutral amino acids such as Ala, Ser, Pro, Gly, met but not by acidic or basic amino acids such as Asp, Glu, Arg or Lys. The uptake of MeAIB appears to be mediated by an amino acid transport carrier similar to the A-system described previously for Chinese hamster ovary cells

195

Kudoa septempunctata invasion increases the permeability of human intestinal epithelial monolayer.  

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Kudoa septempunctata is a myxosporean parasite of Paralichthys olivaceus (olive flounder) and causes a foodborne illness that affects more than 100 cases in Japan each year. We previously reported that the consumption of raw olive flounder meat containing a high concentration of K. septempunctata spores induces transient but severe diarrhea and emesis through an unknown mechanism. Here, we demonstrate that K. septempunctata sporoplasm plays an important role in mediating the toxicity of K. septempunctata. When K. septempunctata spores were inoculated in Caco-2 human intestinal cells, K. septempunctata sporoplasms were released from spores, and they invaded the cells. Electron microscopic observations revealed that the sporoplasm invasion severely damaged the Caco-2 cells. The inoculation of K. septempunctata spores eliminated the transepithelial electrical resistance (TER) across the cell monolayer. Inhibiting the invasion of the sporoplasms prevented the observed loss in cell layer integrity, as illustrated by the rapid elimination of the TER. These results suggest that the invasion by sporoplasms severely damaged individual intestinal cells, resulting in a loss of cell monolayer integrity. PMID:23373474

Ohnishi, Takahiro; Kikuchi, Yutaka; Furusawa, Hiroko; Kamata, Yoichi; Sugita-Konishi, Yoshiko

2013-02-01

196

Intestinal infections in humans in the Rocky Mountain region, United States.  

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To evaluate the seasonal prevalence of human intestinal parasites in the western states of Colorado, Utah, New Mexico, and Montana, fecal samples were examined as part of routine diagnostic testing from patients experiencing gastrointestinal discomfort in August (summer) 2006, January (winter), and April (spring) 2007. Parasite identification in positive samples was confirmed using light microscopy after wet mount and trichrome staining techniques. Seventy-eight of the 1,083 patients surveyed (7.2%) in August tested positive for at least 1 species of intestinal parasite. Forty-eight of 726 (6.6%) patients and 51 of 795 (6.4%) patients tested positive for at least 1 species in January and April, respectively. Blastocystis sp. was the most prevalent, followed by Giardia lamblia. Approximately 25% of the parasite occurrences were multiple infections involving fecal-oral transmitted species. Co-infections with Entamoeba spp. and Blastocystis sp. were common, suggesting a possible fecal-oral transmission for the latter parasite. Entamoeba spp. were more likely to co-occur than independently. Other species detected included Endolimax nana, Diphyllobothrium latum, Hymenolepis nana, Dientamoeba fragilis, and Iodamoeba butschlii. PMID:19807196

Church, Cynthia; Neill, Andrea; Schotthoefer, Anna M

2010-02-01

197

Molecular cloning and functional expression of a human intestinal lactoferrin receptor.  

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Lactoferrin (Lf), a major iron-binding protein in human milk, has been suggested to have multiple biological roles such as facilitating iron absorption, modulating the immune system, embryonic development, and cell proliferation. Our previous binding studies suggested the presence of a specific receptor for Lf (LfR) in the small intestine of newborn infants, which may facilitate iron absorption. We here report the cloning and the functional expression of the human intestinal LfR and the evidence of its involvement in iron metabolism. The entire coding region of the LfR cDNA was cloned by PCR based on amino acid sequences of the purified native LfR (nLfR). The recombinant LfR (rLfR) was then expressed in a baculovirus-insect cell system and purified by immobilized human Lf (hLf) affinity chromatography where binding of hLf to the rLfR was partially Ca(2+) dependent. The apparent molecular mass was 136 kDa under nonreducing conditions and 34 kDa under reducing conditions. 125I-hLf bound to the rLfR with an apparent K(d) of approximately 360 nM. These biochemical properties of the rLfR are similar to those of the nLfR. RT-PCR revealed that the gene was expressed at high levels in fetal small intestine and in adult heart and at lower levels in Caco-2 cells. PI-PLC treatment of Caco-2 cells indicated that the LfR is GPI anchored. In Caco-2 cells transfected with the LfR gene, 125I-hLf binding and 59Fe-hLf uptake were increased by 1.7 and 3.4 times, respectively, compared to those in mock-transfected cells. Our findings demonstrate the presence of a unique receptor-mediated mechanism for nutrient uptake by the newborn. PMID:11747454

Suzuki, Y A; Shin, K; Lönnerdal, B

2001-12-25

198

Evaluation of fasted and fed state simulated and human intestinal fluids as solvent system in the Ussing chambers model to explore food effects on intestinal permeability.  

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The Ussing chambers model is almost exclusively used in the presence of plain aqueous phosphate buffers as solvent system. In an attempt to further elucidate the effect of luminal ingredients and postprandial conditions on intestinal permeability, pooled fasted and fed state human intestinal fluids (FaHIFpool, FeHIFpool) were used. In addition, simulated intestinal fluids of both nutritional states (FaSSIF, FeSSIF) were evaluated as possible surrogate media for HIF. The use of FaHIFpool generated a broad range of Papp values for a series of 16 model drugs, ranging from 0.03×10(-6)cm/s (carvedilol) to 33.8×10(-6)cm/s (naproxen). A linear correlation was observed between Papp values using FaSSIF and FaHIFpool as solvent system (R=0.990), justifying the use of FaSSIF as surrogate medium for FaHIF in the Ussing chambers. In exclusion of the outlier carvedilol, a strong sigmoidal relationship was found between Papp and fahuman of 15 model drugs, illustrated by correlation coefficients of 0.961 and 0.936 for FaHIFpool and FaSSIF, respectively. When addressing food effects on intestinal permeability, the use of FeHIFpool resulted in a significantly lower Papp value for nine out of sixteen compounds compared to fasting conditions. FeSSIF as solvent system significantly overestimated Papp values in FeHIFpool. To conclude, the optimized Ussing chambers model using biorelevant media as apical solvent system holds great potential to investigate food effects in a more integrative approach, taking into account drug solubilisation, supersaturation and formulation effects. PMID:25510602

Wuyts, Benjamin; Riethorst, Danny; Brouwers, Joachim; Tack, Jan; Annaert, Pieter; Augustijns, Patrick

2015-01-30

199

Activation of intestinal human pregnane X receptor protects against azoxymethane/dextran sulfate sodium-induced colon cancer.  

Science.gov (United States)

The role of intestinal human pregnane X receptor (PXR) in colon cancer was determined through investigation of the chemopreventive role of rifaximin, a specific agonist of intestinal human PXR, toward azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colon cancer. Rifaximin treatment significantly decreased the number of colon tumors induced by AOM/DSS treatment in PXR-humanized mice, but not wild-type or Pxr-null mice. Additionally, rifaximin treatment markedly increased the survival rate of PXR-humanized mice, but not wild-type or Pxr-null mice. These data indicated a human PXR-dependent therapeutic chemoprevention of rifaximin toward AOM/DSS-induced colon cancer. Nuclear factor ?-light-chain-enhancer of activated B cells-mediated inflammatory signaling was upregulated in AOM/DSS-treated mice, and inhibited by rifaximin in PXR-humanized mice. Cell proliferation and apoptosis were also modulated by rifaximin treatment in the AOM/DSS model. In vitro cell-based assays further revealed that rifaximin regulated cell apoptosis and cell cycle in a human PXR-dependent manner. These results suggested that specific activation of intestinal human PXR exhibited a chemopreventive role toward AOM/DSS-induced colon cancer by mediating anti-inflammation, antiproliferation, and proapoptotic events. PMID:25277138

Cheng, Jie; Fang, Zhong-Ze; Nagaoka, Kenjiro; Okamoto, Minoru; Qu, Aijuan; Tanaka, Naoki; Kimura, Shioko; Gonzalez, Frank J

2014-12-01

200

Epidermal growth factor upregulates serotonin transporter in human intestinal epithelial cells via transcriptional mechanisms  

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Serotonin transporter (SERT) regulates extracellular availability of serotonin and is a potential pharmacological target for gastrointestinal disorders. A decrease in SERT has been implicated in intestinal inflammatory and diarrheal disorders. However, little is known regarding regulation of SERT in the intestine. Epidermal growth factor (EGF) is known to influence intestinal electrolyte and nutrient transport processes and has protective effects on intestinal mucosa. Whether EGF regulates SE...

Gill, Ravinder K.; Anbazhagan, Arivarasu Natarajan; Esmaili, Ali; Kumar, Anoop; Nazir, Saad; Malakooti, Jaleh; Alrefai, Waddah A.; Saksena, Seema

2011-01-01

 
 
 
 
201

Somatostatin, substance P and calcitonin gene-related peptide-positive intramural nerve structures of the human large intestine affected by carcinoma.  

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Full Text Available The aim of this study was to investigate the arrangement and chemical coding of enteric nerve structures in the human large intestine affected by cancer. Tissue samples comprising all layers of the intestinal wall were collected during surgery form both morphologically unchanged and pathologically altered segments of the intestine (n=15, and fixed by immersion in buffered paraformaldehyde solution. The cryostat sections were processed for double-labelling immunofluorescence to study the distribution of the intramural nerve structures (visualized with antibodies against protein gene-product 9.5 and their chemical coding using antibodies against somatostatin (SOM, substance P (SP and calcitonin gene-related peptide (CGRP. The microscopic observations revealed distinct morphological differences in the enteric nerve system structure between the region adjacent to the cancer invaded area and the intact part of the intestine. In general, infiltration of the cancer tissue resulted in the gradual (depending on the grade of invasion first decomposition and reduction to final partial or complete destruction and absence of the neuronal elements. A comparative analysis of immunohistochemically labeled sections (from the unchanged and pathologically altered areas revealed a statistically significant decrease in the number of CGRP-positive neurons and nerve fibres in both submucous and myenteric plexuses in the transitional zone between morphologically unchanged and cancer-invaded areas. In this zone, a decrease was also observed in the density of SP-positive nerve fibres in all intramural plexuses. Conversely, the investigations demonstrated statistically insignificant differences in number of SP- and SOM-positive neurons and a similar density of SOM-positive nerve fibres in the plexuses of the intact and pathologically changed areas. The differentiation between the potential adaptive changes in ENS or destruction of its elements by cancer invasion should be a subject of further investigations.

Jerzy Kaleczyc

2010-11-01

202

Acute induction of human IL-8 production by intestinal epithelium triggers neutrophil infiltration without mucosal injury  

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Aim: Neutrophil migration in the intestine depends on chemotaxis of neutrophils to CXC chemokines produced by epithelial cells. The goal of this project was to determine if acute induction of a CXC chemokine gradient originating from intestinal epithelial cells is sufficient to induce neutrophil influx into intact intestinal tissue.

Kucharzik, T.; Hudson, J. T.; Lu?gering, A.; Abbas, J. A.; Bettini, M.; Lake, J. G.; Evans, M. E.; Ziegler, T. R.; Merlin, D.; Madara, J. L.; Williams, I. R.

2005-01-01

203

[The efficacy of Plantago ovata as a regulator of intestinal transit. A double-blind study compared to placebo].  

Science.gov (United States)

The effect of Plantago ovata on patients with chronic constipation (CC) with or without irritable bowel syndrome (IBS) has been assessed by a double blind study comprising 20 patients with CC of which 10 had associated IBS. A clinical questionnaire, weight of feces and intestinal transit time measured with radiopaque markers were done. Patients were then randomly distributed, 10 receiving PO and 10 placebo. Similar tests were done after treatment one month later. All patients receiving PO had good results against only one in the placebo group. Frequency of stools increased from 2.5 +/- 1 vs 8 +/- 2.2 stools per week, p less than 0.001 for paired data). A decrease in consistency of stools was also observed in the treated group. Fecal weight and colonic transit time were not significantly modified in placebo patients, while weight increase was observed in the treated ones (124 +/- 71 vs 194 +/- 65, gr/d p less than 0.001 for paired data) as well as a decrease in transit time (48 +/- 15 vs 34 +/- 18 hours p less than 0.05 for paired data). No adverse effects were observed and particularly no flatulence as often seen in patients on bran. PMID:1520545

Tomás-Ridocci, M; Añón, R; Mínguez, M; Zaragoza, A; Ballester, J; Benages, A

1992-07-01

204

Intestinal parasitic infections and eosinophilia in an human immunedeficiency virus positive population in Honduras  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in english The occurrence of intestinal parasites, their regional distribution and their relations to eosinophilia were studied in 133 human immunodeficiency virus (HIV) positive individuals from Honduras. After signing an informed consent, participants answered a socio-demographic and risk factor questionnair [...] e, a complete physical examination, medical history, and a series of laboratory tests. All participants were HIV positive but not acquired immunodeficiency syndrome positive. Of them, 67% were co-infected with pathogen and non pathogen parasites. Overall occurrence of nematodes was: 44.3% for Trichuris trichiura, 24% for Ascaris lumbricoides, 12% for Hookworm and 7.5% for Strongyloides stercoralis. No cases of Giardia lamblia, acute amebiasis or cryptosporidiasis were diagnosed. Mean eosinophil percents for participants were consistently and significantly higher in infected than in non infected individuals: 22% for Hookworm vs 7.2% (p

Rina G, Kaminsky; Ramón J, Soto; Adriana, Campa; Marianna K, Baum.

2004-11-01

205

Isolation of cholesterol-lowering lactic acid bacteria from human intestine for probiotic use.  

Science.gov (United States)

Cholesterol-lowering effect of lactic acid bacteria (LAB: Streptococcus, Lactobacillus and Bifidobacterium) is well-known. Thus, we investigated LAB isolated from human intestine on the cholesterol-lowering effect in vitro. Seven Streptococcus (61.1%), 11 Lactobacillus (71.8%) and 7 Bifidobacterium (27.9%) were isolated as acid (pH 2.5 and 3.0) and bile (0.3% oxgall) tolerant strains. Streptococcus HJS-1, Lactobacillus HJL-37 and Bifidobacterium HJB-4 were finally selected as probiotic strains to use through the bile salt hydrolase (BSH) activity assay by using MRS media added taurodeoxycholic acid (TDCA) and the cholesterol-lowering test by using soluble cholesterol containing MRS broth. These studies suggested that the isolated LAB had an excellent hypocholesterolemic effect. PMID:15613825

Lim, Hyeong-Jun; Kim, So-Young; Lee, Wan-Kyu

2004-12-01

206

Absorption and transport of pachymic acid in the human intestinal cell line Caco-2 monolayers  

Directory of Open Access Journals (Sweden)

Full Text Available Objective: To study the absorption and transport of pachymic acid (PA isolated from the sclerotium of Poria cocos (Schw. Wolf. in human intestinal epithelium.Methods: By using Caco-2 (the human colonic adenocarcinoma cell lines cell monolayers as an intestinal epithelial cell model, the permeability of PA was studied from apical side (AP side to basolateral side (BL side or from BL side to AP side. The PA was measured by reversed-phase high performance liquid chromatography coupled with UV detector at maximum absorption wavelength of 210 nm. Transport parameters and apparent permeability coefficients (Papp were then calculated and compared with those of propranolol and atenolol, which were the transcellular transport markers for high and poor permeability respectively.Results: The Papp values of PA were (9.50±2.20 10?7 cm/s from AP side to BL side, and (11.30±5.90 10?7 cm/s from BL side to AP side, respectively. Under the condition of this experiment, the Papp values were 1.45×10?5 cm/s for propranolol and 4.22×10?7 cm/s for atenolol.Conclusion: PA is transported through the Caco-2 cell monolayer in a concentration-dependent manner and the transport was linear with time. The absorption in apical to basolateral direction and secretion in basolateral to apical direction were poor and their Papp values were comparable to atenolol. Besides passive diffusion of PA, ATP is partially involved in its transport

Yan ZHENG

2008-07-01

207

Transport of Aflatoxin M1 in Human Intestinal Caco-2/TC7 Cells  

Science.gov (United States)

Aflatoxin M1 (AFM1) is a hydroxylated metabolite of aflatoxin B1 (AFB1). After it is formed, it is secreted in the milk of mammals. Despite the potential risk of human exposure to AFM1, data reported in literature on the metabolism, toxicity, and bioavailability of this molecule are limited and out of date. The aim of the present research was to study the absorption profile of AFM1 and possible damage to tight junctions (TJ) of the intestinal Caco-2/TC7 clone grown on microporous filter supports. These inserts allowed for the separation of the apical and basolateral compartments which correspond to the in vivo lumen and the interstitial space/vascular systems of intestinal mucosa respectively. In this study, the Caco-2/TC7 cells were treated with different AFM1 concentrations (10–10,000?ng/kg) for short (40?min) and long periods of time (48?h). The AFM1 influx/efflux transport and effects on TJ were evaluated by measuring trans-epithelial electrical resistance and observing TJ protein (Zonula occludens-1 and occludin) localization. The results showed that: (i) when introduced to the apical and basolateral compartments, AFM1 was poorly absorbed by the Caco-2/TC7 cells but its transport across the cell monolayer occurred very quickly (Papp value of 105.10?±?7.98?cm/s?×?10?6). (ii) The integrity of TJ was not permanently compromised after exposure to the mycotoxin. Viability impairment or barrier damage did not occur either. The present results contribute to the evaluation of human risk exposure to AFM1, although the AFM1 transport mechanism need to be clarified. PMID:22701428

Caloni, Francesca; Cortinovis, Cristina; Pizzo, Fabiola; De Angelis, Isabella

2012-01-01

208

Innervation of enteric mast cells by primary spinal afferents in guinea pig and human small intestine.  

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Mast cells express the substance P (SP) neurokinin 1 receptor and the calcitonin gene-related peptide (CGRP) receptor in guinea pig and human small intestine. Enzyme-linked immunoassay showed that activation of intramural afferents by antidromic electrical stimulation or by capsaicin released SP and CGRP from human and guinea pig intestinal segments. Electrical stimulation of the afferents evoked slow excitatory postsynaptic potentials (EPSPs) in the enteric nervous system. The slow EPSPs were mediated by tachykinin neurokinin 1 and CGRP receptors. Capsaicin evoked slow EPSP-like responses that were suppressed by antagonists for protease-activated receptor 2. Afferent stimulation evoked slow EPSP-like excitation that was suppressed by mast cell-stabilizing drugs. Histamine and mast cell protease II were released by 1) exposure to SP or CGRP, 2) capsaicin, 3) compound 48/80, 4) elevation of mast cell Ca²? by ionophore A23187, and 5) antidromic electrical stimulation of afferents. The mast cell stabilizers cromolyn and doxantrazole suppressed release of protease II and histamine when evoked by SP, CGRP, capsaicin, A23187, electrical stimulation of afferents, or compound 48/80. Neural blockade by tetrodotoxin prevented mast cell protease II release in response to antidromic electrical stimulation of mesenteric afferents. The results support a hypothesis that afferent innervation of enteric mast cells releases histamine and mast cell protease II, both of which are known to act in a diffuse paracrine manner to influence the behavior of enteric nervous system neurons and to elevate the sensitivity of spinal afferent terminals. PMID:25147231

Wang, Guo-Du; Wang, Xi-Yu; Liu, Sumei; Qu, Meihua; Xia, Yun; Needleman, Bradley J; Mikami, Dean J; Wood, Jackie D

2014-10-01

209

Toxicity, genotoxicity and proinflammatory effects of amorphous nanosilica in the human intestinal Caco-2 cell line.  

Science.gov (United States)

Silica (SiO2) in its nanosized form is now used in food applications although the potential risks for human health need to be evaluated in further detail. In the current study, the uptake of 15 and 55nm colloidal SiO2 NPs in the human intestinal Caco-2 cell line was investigated by transmission electron microscopy. The ability of these NPs to induce cytotoxicity (XTT viability test), genotoxicity (?H2Ax and micronucleus assay), apoptosis (caspase 3), oxidative stress (oxidation of 2,7-dichlorodihydrofluorescein diacetate probe) and proinflammatory effects (interleukin IL-8 secretion) was evaluated. Quartz DQ12 was used as particle control. XTT and cytokinesis-block micronucleus assays revealed size- and concentration-dependent effects on cell death and chromosome damage following exposure to SiO2 nanoparticles, concomitantly with generation of reactive oxygen species (ROS), SiO2-15nm particles being the most potent. In the same way, an increased IL-8 secretion was only observed with SiO2-15nm at the highest tested dose (32?g/ml). TEM images showed that both NPs were localized within the cytoplasm but did not enter the nucleus. SiO2-15nm, and to a lower extent SiO2-55nm, exerted toxic effects in Caco-2 cells. The observed genotoxic effects of these NPs are likely to be mediated through oxidative stress rather than a direct interaction with the DNA. Altogether, our results indicate that exposure to SiO2 NPs may induce potential adverse effects on the intestinal epithelium in vivo. PMID:25448807

Tarantini, Adeline; Lanceleur, Rachelle; Mourot, Annick; Lavault, Marie-Thérèse; Casterou, Gérald; Jarry, Gérard; Hogeveen, Kevin; Fessard, Valérie

2015-03-01

210

EP Receptor Expression in Human Intestinal Epithelium and Localization Relative to the Stem Cell Zone of the Crypts  

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There is substantial evidence for PGE2 affecting intestinal epithelial proliferation. PGE2 is also reported to be involved in the regulation of growth and differentiation in adult stem cells, both effects mediated by binding to EP-receptors. We have used the Lgr5 as a marker to scrutinize EP-receptor and COX expression in human intestinal epithelial cells with focus on the stem cell area of the crypts. Normal tissue from ileum and colon, but also duodenal biopsies from patients with untreated...

Olsen Hult, Lene Th; Kleiveland, Charlotte R.; Fosnes, Kjetil; Jacobsen, Morten; Lea, Tor

2011-01-01

211

Sulfapyridine appearance in plasma after salicylazosulfapyridine. Another simple measure of intestinal transit  

International Nuclear Information System (INIS)

The appearance of sulfapyridine in plasma after oral administration of salicylazosulfapyridine (SASP) was evaluated as a method for defining arrival time in the cecum, an index of small bowel transit. After direct instillation of SASP and lactulose into the cecum, the appearances of their metabolites (sulfapyridine in plasma and hydrogen in breath) were rapid (1-10 min) and simultaneous. When a mixture of SASP and lactulose was taken by mouth, times of the respective signals varied among individuals from 40 to 180 min (n = 8) but were correlated within individuals. Salicylazosulfapyridine transit times from duodenum to cecum were also very similar to simultaneous measurements of transit by scintigraphic monitoring of technetium 99m. Timing of the sulfapyridine signal corresponded to the arrival of 5%-13% of technetium 99m DTPA in the cecum. Exemplifying the use of this new technique, simultaneous administration of lactulose into the stomach and SASP into the duodenum yielded consistently longer stomach-to-cecum than duodenum-to-cecum transits, attributable to the delay caused by gastric emptying. Therapeutic doses of morphine delayed small bowel transit of SASP. Transit of SASP offers a second marker technique for the cecal arrival of the head of a bolus; the approach may be useful as an inexpensive, noninvasive measurement of transit

212

Modulation of pathogen-induced CCL20 secretion from HT-29 human intestinal epithelial cells by commensal bacteria  

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Abstract Background Human intestinal epithelial cells (IECs) secrete the chemokine CCL20 in response to infection by various enteropathogenic bacteria or exposure to bacterial flagellin. CCL20 recruits immature dendritic cells and lymphocytes to target sites. Here we investigated IEC responses to various pathogenic and commensal bacteria as well as the modulatory effects of commensal bacteria on pathogen-induced CCL20 secretion. HT-29 human IECs were incubated with commensal ...

Sheil Barbara; Neill Shaun, O.; Mahony Jim, O.; Fanning Áine; Ryan Jude; O'Hara Ann M; Sibartie Shomik; Mahony Liam, O.; Shanahan Fergus

2009-01-01

213

Intestinal transit in healthy southern Indian subjects and in patients with tropical sprue.  

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Whole gut transit was measured in a group of 21 healthy volunteers and 21 patients with tropical sprue by radio-opaque marker technique, using mean transit time single (MTTS) and single stool transit (SST) method. Mean SST in controls was 25.8 (1.4) (SE) hours, which is considerably shorter than in controls in temperate zones. Mean SST (23.7 (0.6) h) correlated significantly with average MTTS (24.9 (1.6) h) (r = 0.88; p less than 0.001) confirming that SST is a valid method to measure intesti...

Jayanthi, V.; Chacko, A.; Gani, I. K.; Mathan, V. I.

1989-01-01

214

Differential modulation of human intestinal bifidobacterium populations after consumption of a wild blueberry (Vaccinium angustifolium) drink.  

Science.gov (United States)

Bifidobacteria are gaining increasing interest as health-promoting bacteria. Nonetheless, the genus comprises several species, which can exert different effects on human host. Previous studies showed that wild blueberry drink consumption could selectively increase intestinal bifidobacteria, suggesting an important role for the polyphenols and fiber present in wild blueberries. This study evaluated the modulation of the most common and abundant bifidobacterial taxonomic groups inhabiting the human gut in the same fecal samples. The analyses carried out showed that B. adolescentis, B. breve, B. catenulatum/pseudocatelulatum, and B. longum subsp. longum were always present in the group of subjects enrolled, whereas B. bifidum and B. longum subsp. infantis were not. Furthermore, it was found that the most predominant bifidobacterial species were B. longum subsp. longum and B. adolescentis. The results obtained revealed a high interindividual variability; however, a significant increase of B. longum subsp. infantis cell concentration was observed in the feces of volunteers after the wild blueberry drink treatment. This bifidobacterial group was shown to possess immunomodulatory abilities and to relieve symptoms and promote the regression of several gastrointestinal disorders. Thus, an increased cell concentration of B. longum subsp. infantis in the human gut could be considered of potential health benefit. In conclusion, wild blueberry consumption resulted in a specific bifidogenic effect that could positively affect certain populations of bifidobacteria with demonstrated health-promoting properties. PMID:23883473

Guglielmetti, Simone; Fracassetti, Daniela; Taverniti, Valentina; Del Bo', Cristian; Vendrame, Stefano; Klimis-Zacas, Dorothy; Arioli, Stefania; Riso, Patrizia; Porrini, Marisa

2013-08-28

215

A comparative analysis of the intestinal metagenomes present in guinea pigs (Cavia porcellus and humans (Homo sapiens  

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Full Text Available Abstract Background Guinea pig (Cavia porcellus is an important model for human intestinal research. We have characterized the faecal microbiota of 60 guinea pigs using Illumina shotgun metagenomics, and used this data to compile a gene catalogue of its prevalent microbiota. Subsequently, we compared the guinea pig microbiome to existing human gut metagenome data from the MetaHIT project. Results We found that the bacterial richness obtained for human samples was lower than for guinea pig samples. The intestinal microbiotas of both species were dominated by the two phyla Bacteroidetes and Firmicutes, but at genus level, the majority of identified genera (320 of 376 were differently abundant in the two hosts. For example, the guinea pig contained considerably more of the mucin-degrading Akkermansia, as well as of the methanogenic archaea Methanobrevibacter than found in humans. Most microbiome functional categories were less abundant in guinea pigs than in humans. Exceptions included functional categories possibly reflecting dehydration/rehydration stress in the guinea pig intestine. Finally, we showed that microbiological databases have serious anthropocentric biases, which impacts model organism research. Conclusions The results lay the foundation for future gastrointestinal research applying guinea pigs as models for humans.

Hildebrand Falk

2012-09-01

216

A comparative analysis of the intestinal metagenomes present in guinea pigs (Cavia porcellus) and humans (Homo sapiens)  

DEFF Research Database (Denmark)

Background: Guinea pig (Cavia porcellus) is an important model for human intestinal research. We have characterized the faecal microbiota of 60 guinea pigs using Illumina shotgun metagenomics, and used this data to compile a gene catalogue of its prevalent microbiota. Subsequently, we compared the guinea pig microbiome to existing human gut metagenome data from the MetaHIT project. Results: We found that the bacterial richness obtained for human samples was lower than for guinea pig samples. The intestinal microbiotas of both species were dominated by the two phyla Bacteroidetes and Firmicutes, but at genus level, the majority of identified genera (320 of 376) were differently abundant in the two hosts. For example, the guinea pig contained considerably more of the mucin-degrading Akkermansia, as well as of the methanogenic archaea Methanobrevibacter than found in humans. Most microbiome functional categories were less abundant in guinea pigs than in humans. Exceptions included functional categories possiblyreflecting dehydration/rehydration stress in the guinea pig intestine. Finally, we showed that microbiological databases have serious anthropocentric biases, which impacts model organism research. Conclusions: The results lay the foundation for future gastrointestinal research applying guinea pigs as models for humans.

Hildebrand, Falk; Ebersbach, Tine

2012-01-01

217

Accelerated intestinal glucose absorption in morbidly obese humans - relationship to glucose transporters, incretin hormones and glycaemia.  

Science.gov (United States)

Context: Intestinal glucose absorption is mediated by sodium dependent glucose transporter-1 (SGLT-1) and glucose transporter-2 (GLUT2), which are linked to sweet taste receptor (STR) signaling and incretin responses. Objective: This study aimed to examine intestinal glucose absorption in morbidly obese humans, and its relationship to the expression of STR and glucose transporters, glycaemia, and incretin responses. Design/Setting/Participants: 17 non-diabetic, morbidly obese subjects (BMI:48±4kg/m(2)) and 11 lean controls (BMI:25±1kg/m(2)) underwent endoscopic duodenal biopsies before and after a 30-min intraduodenal glucose infusion (30g glucose & 3g 3-O-methylglucose (3-OMG)). Main Outcome Measures: Blood glucose and plasma concentrations of 3-OMG, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, and glucagon were measured over 270min. Expression of duodenal SGLT-1, GLUT2 and STR was quantified by PCR. Results: The rise in plasma 3-OMG (P<0.001) and blood glucose (P<0.0001) were greater in obese than lean subjects. Plasma 3-OMG correlated directly with blood glucose (r=0.78, P<0.01). In response to intraduodenal glucose, plasma GIP (P<0.001), glucagon (P<0.001), and insulin (P<0.001) were higher, but GLP-1 (P<0.001) was less, in the obese compared to lean. Expression of SGLT-1 (P=0.035), but not GLUT2 or T1R2, was higher in the obese, and related to peak plasma 3-OMG (r=0.60, P=0.01), GIP (r=0.67, P=0.003) and insulin (r=0.58, P=0.02). Conclusions: In morbid obesity, proximal intestine glucose absorption is accelerated and related to increased SGLT-1 expression, leading to an incretin-glucagon profile promoting hyperinsulinemia and hyperglycemia. These findings are consistent with the concept that accelerated glucose absorption in the proximal gut underlies the foregut theory of obesity and type 2 diabetes. PMID:25423571

Nguyen, Nam Q; Debreceni, Tamara L; Bambrick, Jenna E; Chia, Bridgette; Wishart, Judith; Deane, Adam M; Rayner, Chris K; Horowitz, Michael; Young, Richard L

2014-11-25

218

E Durans Strain M4-5 Isolated From Human Colonic Flora Attenuates Intestinal Inflammation  

DEFF Research Database (Denmark)

PURPOSE: The aim of this study was to evaluate in vitro and in vivo effects of a unique high-butyrate-producing bacterial strain from human colonic flora, Enterococcus durans, in prevention and treatment of intestinal inflammation. METHODS: A compartmentalized Caco-2/leukocyte coculture model was used to examine the in vitro effects of E durans and its metabolite butyrate on basal and Escherichia coli–stimulated secretion of proinflammatory immune factors (IL-8, IL-6, and TNF-?) and the anti-inflammatory cytokine IL-10. A murine model of dextran sodium sulfate-induced colitis was used to examine in vivo effects of prevention and therapy with E durans on clinical, biochemical, and histologic parameters of inflammation. RESULTS: In the coculture model, treatment with E durans and with butyrate reduced basal as well as E coli stimulated secretion of IL-8, IL-6, and TNF-? and increased secretion of IL-10. In the in vivo murine model, preventive administration of E durans significantly ameliorated clinical disease activity index (weight loss, fecal bleeding, and stool consistency), reduced myeloperoxidase concentration in colon tissue extracts, improved histologic scores of colonic inflammation, and inhibited colonic transcription of proinflammatory immune factors. The effect of therapeutic treatment alone on these parameters was more moderate but still significant. CONCLUSIONS: We conclude that E durans strain M4 to 5 and its metabolic product butyrate induce significant anti-inflammatory effects, mediated by regulation of pro- and anti-inflammatory immune factors as well as preservation of intestine epithelial integrity, suggesting that this novel anti-inflammatory bacterium may be preferentially a useful prophylactic treatment to avoid inflammatory bowel disease.

Avram-Hananel, L.; Stock, J.

2010-01-01

219

Characterization of cadmium uptake in human intestinal crypt cells HIEC in relation to inorganic metal speciation.  

Science.gov (United States)

Cadmium (Cd) uptake was studied under inorganic exposure conditions in normal human intestinal crypt cells HIEC. The uptake time course of 0.3 microM Cd in a serum-free chloride medium was analyzed according to a first order equation with rapid initial (U0) and maximal (Umax) accumulation values of 14.1+/-1.4pmol/mgprotein and 41.4+/-2.0 pmol/mgprotein, respectively. The presence of a 300-fold excess of unlabeled Cd dramatically decreased tracer uptake, showing the involvement of specific mechanism(s) of transport. Our speciation studies revealed the preferential uptake of the free ion Cd2+, but also suggested that CdCln(2-n) species may contribute to Cd accumulation. Specific mechanisms of transport of very high and similar affinity (Km approximately 5 microM) have been characterized under both chloride and nitrate exposure conditions, but a two-fold higher capacity (Vmax) was estimated in the nitrate medium used to increase [Cd2+] over chlorocomplex formation. A clear inhibition of 109Cd uptake was observed at external acidic pH under both exposure media. An La-inhibitible 46% increase in 109Cd uptake was obtained in nominally Ca-free nitrate medium, whereas Zn provided additional inhibition. These results show different kinetic parameters for Cd uptake as a function of inorganic metal speciation. Cd2+ uptake would not involve the H+-coupled symport NRAMP2 but would be related instead to the Ca and/or Zn pathways. Because proliferative crypt cells play a critical role in the renewal process of the entire intestinal epithelium, studies on the impact of Cd on HIEC cell functions clearly deserve further investigation. PMID:16361035

Bergeron, Pierre-Michel; Jumarie, Catherine

2006-02-15

220

Utilização do método videolaparoscopico na reconstituição do trânsito intestinal após a operação de Hartmann / The use of videolaparoscopic approach in the intestinal transit restoration after Hartmann's procedure  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese O objetivo é apresentar a padronização da técnica operatória e os resultados obtidos com a utilização do acesso videolaparoscópico na reconstituição do trânsito intestinal em pacientes previamente submetidos à operação de Hartmann por causas diversas. Foram analisados prospectivamente 32 pacientes, [...] no período de dezembro de 1991 a junho de 1997, com distribuição semelhante com relação ao sexo e com idade média de 42,4 anos. Todos os pacientes foram submetidos ao mesmo preparo pré-operatório e à mesma técnica cirúrgica. Ocorreram três (9,3%) complicações transoperatórias. Uma (3,1 %) anastomose mecânica incompleta, necessitando de endossutura manual, uma (3,1 %) laceração do reto com o grampeador mecânico e uma (3,1 %) lesão da artéria epigástrica direita. Ocorreram ainda três (9,3%) conversões, sendo uma (3,1 %) devido à laceração do reto com o grampeador mecânico, outra (3.1 %) pela invasão tumoral na pelve e outra (3,1 %) pela presença de excessivas aderências intraperitoneais. O tempo operatório variou de 30 a 240 minutos, na média de 126,2 minutos (2,1 horas). A evolução clínica pós-operatória foi satisfatória. Nove (31,0%) pacientes não referiram dor, enquanto 13 (44,8%) a referiram em pequena intensidade, e apenas sete (24,0%) queixaram-se de dor com maior intensidade. A dieta líquida via oral foi instituída no período médio de 1,6 dias, e a primeira evacuação ocorreu na média de 3,2 dias de pós-operatório. O período médio de hospitalização foi de 4,7 dias. Ocorreram complicações pós-operatórias em oito (27,5%) pacientes. Duas (6,8%) infecções da ferida do estoma, dois pacientes (6,8%) com dor no ombro direito, uma (3,4%) deiscência de anastomose, um (3,4%) caso de peritonite por provável contaminação do material cirúrgico, uma coleção líquida pélvica e uma hérnia incisional. Em conclusão, a reconstituição do trânsito intestinal por videolaparoscopia apresentou-se segura e eficaz, podendo constituir-se no método cirúrgico de escolha, pois foi utilizada com sucesso em 90,6% dos pacientes. Abstract in english We present the operative technique and the results of the laparoscopic approach for Hartmann's colostomy reversal. Thirty two patients were prospectively analysed from december 1991 to june 1997. They presented a similar incidence regarding sex distribution, and a median age of 42.4 years old. Ali p [...] atients underwent the same preoperative preparation and operative technique. Three (9.3%) intraoperative complications were observed: an uncompleted anastomosis (3.1%), requiring an endosuture, a rectal perforation by the mechanical stapler and a right epigastric artery lesion. There were convertion to open surgery in three (9.3%) patients: one (3.1%) due to rectal perforation by the mechanical staple1; one (3.1%) for tumoral pelvic invasion and another because of excessive intra-peritoneal adhesions. Operative time varied from 30 to 240 minutes, with a mean time of 126;2 minutes. Nine (31.0%) patients didn't present pain, while 13 (44.8%) referred minimal pain and seven (24.0%) complained severe pain. Oral liquid diet intake occurred within a mean time of 1.6 days and the first evacuation observed after a mean 3.2 postoperative days. Mean hospitalization time was 4.7 days. Postoperative complications occurred in eight (27.5%) patients. Two (6.8%) stoma wound infections, right shoulder pain in two (6.8%) patients, one (3.4%) anastomotic dehiscence, one peritonitis probably due to contaminationfrom surgical instruments, a liquid pelvic coliection and an incisional haernia. 1n conclusion, videolaparoscopic restoration of the intestinal transit demonstrated to be safe and effective. It could be the method of choice because of its success in 90.6 per cent of the patients.

Francisco Sérgio P., Regadas; Sthela M. Murad, Regadas; Lusmar Veras, Rodrigues.

2000-02-01

 
 
 
 
221

Artículos originales Cultivo primario de queratinocitos humanos sembrados en submucosa intestinal porcina / Primary culture of human keratinocytes planted on pig’s intestine Submucosa  

Scientific Electronic Library Online (English)

Full Text Available SciELO Colombia | Language: Spanish Abstract in spanish En el campo de la regeneración de piel, la ingeniería de tejidos busca superar las limitaciones asociadas con el uso de autoinjertos inmediatos, dado que la elección de una región donante en el paciente, constituye un riesgo para el mismo, además de ser insuficiente cuando la lesión es extensa. Se h [...] a comprobado que el empleo de la submucosa del intestino delgado de cerdo (SIS) (por la sigla en inglés small intestinal submucosa), por su especial composición, como biomaterial de relleno para tratar lesiones, disminuye el dolor y la inflamación desde su primera aplicación y favorece la movilidad temprana de la región lesionada. Con el fin de determinar la utilidad de SIS, como sustituto epidérmico, en el presente estudio se desarrolló un protocolo para el cultivo primario de queratinocitos humanos, provenientes de prepucios infantiles, sobre una matriz de SIS como soporte. Se evaluó el potencial de adherencia y la capacidad de proliferación de queratinocitos sobre este sustrato. Abstract in english Tissue engineering, in the fields of skin regeneration, seeks to overcome the limitations associated with the use of immediate auto-grafts, since choosing the donor region of the patient constitutes a risk for the patient himself and is insufficient if the injury that has to be repaired is very larg [...] e. The use of the pig’s small intestine submucosa (SIS) has being proved as a filling biomaterial to treat injuries, because of its special composition, it lowers pain and inflammation since its first application and it favours early mobility to the wounded area. The present study developed a protocol for the primary culture of human keratinocytes from infant foreskins, and used small intestinal submucosa (SIS) like culture substrate. Cellular adherence potential and proliferation capability of the keratinocytes over this substrate was evaluated.

Ángela Ximena, Amórtegui; Sandra Rocío, Ramírez.

2008-12-01

222

Role of metabolism by the human intestinal microflora in arbutin-induced cytotoxicity in HepG2 cell cultures.  

Science.gov (United States)

A possible role for metabolism by the human intestinal microflora in arbutin-induced cytotoxicity was investigated using human hepatoma HepG2 cells. When the cytotoxic effects of arbutin and hydroquinone (HQ), a deglycosylated metabolite of arbutin, were compared, HQ was more toxic than arbutin. Incubation of arbutin with a human fecal preparation could produce HQ. Following incubation of arbutin with a human fecal preparation for metabolic activation, the reaction mixture was filter-sterilized to test its toxic effects on HepG2 cells. The mixture induced cytotoxicity in HepG2 cells in a concentration-dependent manner. In addition, the mixture considerably inhibited expression of Bcl-2 together with an increase in Bax expression. Likewise, activation stimulated cleavage of caspase-3 and production of reactive oxygen species in HepG2 cell cultures. Furthermore, induction of apoptosis by the intestinal microflora reaction mixture was confirmed by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling assay. Taken together, these findings suggest that the human intestinal microflora is capable of metabolizing arbutin to HQ, which can induce apoptosis in mammalian cells. PMID:21889493

Khanal, Tilak; Kim, Hyung Gyun; Hwang, Yong Pil; Kong, Min Jeong; Kang, Mi Jeong; Yeo, Hee Kyung; Kim, Dong Hyun; Jeong, Tae Cheon; Jeong, Hye Gwang

2011-09-23

223

Perfil epidemiológico e morbimortalidade dos pacientes submetidos à reconstrução de trânsito intestinal: experiência de um centro secundário do nordeste Brasileiro / Epidemiologic profile and morbimortality of patients undergoing to intestinal transit reconstruction: experience of a secundary health service in Brazil northeast  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese Racional- A reconstrução do trânsito intestinal não está isenta de riscos cirúrgicos e apresenta taxas consideráveis de complicações pós-operatórias, sendo que a infecção continua a ser um dos maiores desafios existentes neste procedimento. Métodos- Foram analisados retrospectivamente 86 prontuários [...] de pacientes com colostomia ou ileostomia, através de fatores que tivessem impacto sobre a morbimortalidade após a reconstrução de trânsito intestinal, de janeiro de 2003 a abril de 2009. Resultados- Houve 20 mulheres e 60 homens, com idade média de 43 anos. A colostomia em alça (n: 34) e o trauma abdominal indicando colostomia ou ileostomia foram as condições mais frequentes. O intervalo médio entre a confecção do estoma e a reconstrução de trânsito intestinal foi 15,7 meses. O índice de morbidade foi 56,8%, sendo a infecção incisional a complicação mais comum (27.47%). A permanência hospitalar média foi 7,6 dias. Houve regressão linear positiva entre permanência hospitalar pós-operatória e a idade do paciente. Demonstrou-se associação estatisticamente significativa entre o prolongamento da permanência hospitalar e a ocorrência de complicações (p Abstract in english Background - The reconstruction of the intestinal tract is not surgical complications risk-free and is associated to postoperative complications high rates; furthermore, infection remains the hardest challenge in this procedure. Methods - Retrospectively, eighty-six patients with intestinal stomas w [...] ere analyzed through factors that impact on the morbimortality afterwards intestinal transit reconstruction, since January 2003 to April 2009. Results - Loop colostomy (n=34) and abdominal trauma implicating 38.2% of indications to colostomy or ileostomy were the most frequent conditions. The mean interval between stoma confection and intestinal transit reconstruction was 15.7 months. The morbidity frequency was 56.8% and incisional infection was its commonest complication (27.47%). The mean inpatient length of stay was 7.6 days. There was positive linear regression between post-operative inpatient length of stay and inpatient's age. Inpatient length of stay prolongation is associated to occurrence of complications (p

Jeany Borges e, Silva; Djalma Ribeiro, Costa; Francisco Julimar Correia de, Menezes; José Marconi, Tavares; Adryano Gonçalves, Marques; Rodrigo Dornfeld, Escalante.

2010-09-01

224

Digoxin inhibition of relaxation induced by prostacyclin and vasoactive intestinal polypeptide in small human placental arteries  

DEFF Research Database (Denmark)

Small chorionic plate arteries were obtained from human placentae following normal vaginal delivery. Tubal vascular preparations were dissected, mounted in organ baths, and their isometric tension was recorded. Digoxin (10(-6) M) caused a rise in basic tension, reaching a maximum of 17 per cent of contractions induced by potassium (124 mM) depolarization. Pretreatment with digoxin did not significantly influence the concentration-dependent contractile responses to 5-hydroxytryptamine and prostaglandin F2 alpha (PGF2 alpha). In preparations contracted with PGF2 alpha, cumulative addition of prostacyclin (PGI2) and vasoactive intestinal polypeptide (VIP) produced concentration dependent relaxations. Digoxin (10(-8) to 10(-6) M) inhibited and finally abolished these relaxant effects of PGI2 and VIP in a concentration-dependent fashion. Pretreatment by digoxin (10(-8) to 10(-6) M) diminished the relaxant effect of sodium nitroprusside, but the effect was less pronounced than that on PGI2- and VIP-induced relaxation. As PGI2 and VIP may be of importance for the maintenance of a low resistance of the fetal placental vascular bed, the finding that digoxin decreases the vasodilating effects of these agents might imply effects on placental resistance of cardiac glycosides when used in late human pregnancy.

Maigaard, S; Forman, Axel

1985-01-01

225

Molecular Paleoparasitological Hybridization Approach as Effective Tool for Diagnosing Human Intestinal Parasites from Scarce Archaeological Remains  

Science.gov (United States)

Paleoparasitology is the science that uses parasitological techniques for diagnosing parasitic diseases in the past. Advances in molecular biology brought new insights into this field allowing the study of archaeological material. However, due to technical limitations a proper diagnosis and confirmation of the presence of parasites is not always possible, especially in scarce and degraded archaeological remains. In this study, we developed a Molecular Paleoparasitological Hybridization (MPH) approach using ancient DNA (aDNA) hybridization to confirm and complement paleoparasitological diagnosis. Eight molecular targets from four helminth parasites were included: Ascaris sp., Trichuris trichiura, Enterobius vermicularis, and Strongyloides stercoralis. The MPH analysis using 18th century human remains from Praça XV cemetery (CPXV), Rio de Janeiro, Brazil, revealed for the first time the presence E. vermicularis aDNA (50%) in archaeological sites of Brazil. Besides, the results confirmed T. trichiura and Ascaris sp. infections. The prevalence of infection by Ascaris sp. and E. vermicularis increased considerably when MPH was applied. However, a lower aDNA detection of T. trichiura (40%) was observed when compared to the diagnosis by paleoparasitological analysis (70%). Therefore, based on these data, we suggest a combination of Paleoparasitological and MPH approaches to verify the real panorama of intestinal parasite infection in human archeological samples. PMID:25162694

Jaeger, Lauren Hubert; Iñiguez, Alena Mayo

2014-01-01

226

Molecular paleoparasitological hybridization approach as effective tool for diagnosing human intestinal parasites from scarce archaeological remains.  

Science.gov (United States)

Paleoparasitology is the science that uses parasitological techniques for diagnosing parasitic diseases in the past. Advances in molecular biology brought new insights into this field allowing the study of archaeological material. However, due to technical limitations a proper diagnosis and confirmation of the presence of parasites is not always possible, especially in scarce and degraded archaeological remains. In this study, we developed a Molecular Paleoparasitological Hybridization (MPH) approach using ancient DNA (aDNA) hybridization to confirm and complement paleoparasitological diagnosis. Eight molecular targets from four helminth parasites were included: Ascaris sp., Trichuris trichiura, Enterobius vermicularis, and Strongyloides stercoralis. The MPH analysis using 18th century human remains from Praça XV cemetery (CPXV), Rio de Janeiro, Brazil, revealed for the first time the presence E. vermicularis aDNA (50%) in archaeological sites of Brazil. Besides, the results confirmed T. trichiura and Ascaris sp. infections. The prevalence of infection by Ascaris sp. and E. vermicularis increased considerably when MPH was applied. However, a lower aDNA detection of T. trichiura (40%) was observed when compared to the diagnosis by paleoparasitological analysis (70%). Therefore, based on these data, we suggest a combination of Paleoparasitological and MPH approaches to verify the real panorama of intestinal parasite infection in human archeological samples. PMID:25162694

Jaeger, Lauren Hubert; Iñiguez, Alena Mayo

2014-01-01

227

Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects.  

Science.gov (United States)

It has been reported that the artificial sweetener, sucralose, stimulates glucose absorption in rodents by enhancing apical availability of the transporter GLUT2. We evaluated whether exposure of the proximal small intestine to sucralose affects glucose absorption and/or the glycaemic response to an intraduodenal (ID) glucose infusion in healthy human subjects. Ten healthy subjects were studied on two separate occasions in a single-blind, randomised order. Each subject received an ID infusion of sucralose (4 mM in 0.9% saline) or control (0.9% saline) at 4 ml/min for 150 min (T = - 30 to 120 min). After 30 min (T = 0), glucose (25 %) and its non-metabolised analogue, 3-O-methylglucose (3-OMG; 2.5 %), were co-infused intraduodenally (T = 0-120 min; 4.2 kJ/min (1 kcal/min)). Blood was sampled at frequent intervals. Blood glucose, plasma glucagon-like peptide-1 (GLP-1) and serum 3-OMG concentrations increased during ID glucose/3-OMG infusion (P OMG concentrations between sucralose and control infusions. In conclusion, sucralose does not appear to modify the rate of glucose absorption or the glycaemic or incretin response to ID glucose infusion when given acutely in healthy human subjects. PMID:20420761

Ma, Jing; Chang, Jessica; Checklin, Helen L; Young, Richard L; Jones, Karen L; Horowitz, Michael; Rayner, Christopher K

2010-09-01

228

In vitro glucuronidation of five rhubarb anthraquinones by intestinal and liver microsomes from humans and rats.  

Science.gov (United States)

Anthraquinones naturally distribute in many plants including rhubarb and have widespread applications throughout industry and medicine. Recent studies provided new insights in potential applications of these traditional laxative constituents. Glucuronidation was the main metabolic pathway of rhubarb anthraquinones in vivo. This study examined the activity and regioselectivity of glucuronidation of rhubarb anthraquinones (aloe-emodin, emodin, chrysophanol, physcion, rhein) in liver and intestinal microsomes from rats and humans, by comparing with the core structure danthron. All anthraquinones formed mono-glucuronides and, except for rhein, the conjugation sites of the main metabolites were unambiguously identified. Two minor glucuronides of emodin were first reported together with the dominant emodin-3-O-?-d-glucuronide. The substitution on the anthraquinone ring was crucial to the activity and regioselectivity of glucuronidation. In general, the activity was decreased greatly with a ?-COOH (rhein), while enhanced dramatically with a ?-OH (emodin). Glucuronidation showed an absolute preference towards ?-OH, followed by ?-OH and ?-alcoholic OH. The glucuronidation activity and regioselectivity also varied slightly with organs and species. All glucuronides of aloe-emodin, emodin, chrysophanol and physcion were formed by multiple human UGT isoforms with 1A9 being the most prominent in most cases. The UGT2B subfamily (2B7 and 2B15) only showed high activity towards a ?-OH. In conclusion, the substitution at the anthraquinone ring was crucial to the rate and preference of glucuronidation. The high glucuronidation activity of UGT1A9 towards anthraquinones highlighted potential drug interactions. PMID:24854283

Wu, Wenjin; Hu, Nan; Zhang, Qingwen; Li, Yaping; Li, Peng; Yan, Ru; Wang, Yitao

2014-08-01

229

Comparative quantification of human intestinal bacteria based on cPCR and LDR/LCR  

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AIM: To establish a multiple detection method based on comparative polymerase chain reaction (cPCR) and ligase detection reaction (LDR)/ligase chain reaction (LCR) to quantify the intestinal bacterial components. METHODS: Comparative quantification of 16S rDNAs from different intestinal bacterial components was used to quantify multiple intestinal bacteria. The 16S rDNAs of different bacteria were amplified simultaneously by cPCR. The LDR/LCR was examined to actualize the genotyping and quant...

Jun-Hua Xiao; Rui Huang; Zhen-Xian Xiao; Kai Li; Yu-Xun Zhou; Guo-Hao Gu; Zhou-Rui Tang

2012-01-01

230

Evaluation of physicochemical properties and intestinal permeability of six dietary polyphenols in human intestinal colon adenocarcinoma Caco-2 cells.  

Science.gov (United States)

Phenolic compounds are common ingredients in many dietary supplements and functional foods. However, data concerning physicochemical properties and permeability of polyphenols on the intestinal epithelial cells are scarce. The aims of this study were to determine the experimental partition coefficient (Log P), and parallel artificial membrane permeability assay (PAMPA), to characterize the bi-directional transport of six phenolic compounds viz. caffeic acid, chrysin, gallic acid, quercetin, resveratrol and rutin in Caco-2 cells. The experimental Log P values of six polyphenols were correlated (R (2) = 0.92) well with the calculated Log P values. The apparent permeability (P app) range of all polyphenols in PAMPA for the apical (AP) to basolateral (BL) was 1.18 ± 0.05 × 10(-6) to 5.90 ± 0.16 × 10(-6) cm/s. The apparent Caco-2 permeability (P app) range for the AP-BL was 0.96 ± 0.03 × 10(-6) to 3.80 ± 0.45 × 10(-6) cm/s. The efflux ratio of P app (BL ? AP) to P app (AP ? BL) for all phenolics was <2, suggesting greater permeability in the absorptive direction. Six compounds exhibited strong correlations between Log P and PAMPA/Caco-2 cell monolayer permeation data. Dietary six polyphenols were poorly absorbed through PAMPA and Caco-2 cells, and their transepithelial transports were mainly by passive diffusion. PMID:25351179

Rastogi, Himanshu; Jana, Snehasis

2014-10-29

231

Effect of absorbable and nonabsorbable sugars on intestinal calcium absorption in humans  

International Nuclear Information System (INIS)

The effects of glucose, galactose, and lactitol on intestinal calcium absorption and gastric emptying were studied in 9, 8, and 20 healthy subjects, respectively. Calcium absorption was measured by using a double-isotope technique and the kinetic parameters were obtained by a deconvolution method. The gastric emptying rate was determined with /sup 99m/Tc-diethylenetriaminepentaacetic acid and was expressed as the half-time of the emptying curve. Each subject was studied under two conditions: (a) with calcium alone and (b) with calcium plus sugar. Glucose and galactose increased the calcium mean transit time and improved the total fractional calcium absorption by 30% (p less than 0.02). Lactitol decreased the mean rate of absorption (p less than 0.001) and reduced the total fractional calcium absorption by 15% (p less than 0.001). The gastric emptying rate did not appear to influence directly the kinetic parameters of calcium absorption. These results show that both glucose and galactose exert the same stimulatory effect as lactose on calcium absorption in subjects with normal lactase whereas lactitol mimics the effects of lactose in lactase-deficient patients. Thus the absorbability of sugars determines their effect on calcium absorption

232

Novel resveratrol-based substrates for human hepatic, renal, and intestinal UDP-glucuronosyltransferases.  

Science.gov (United States)

Trans-Resveratrol (tRes) has been shown to have powerful antioxidant, anti-inflammatory, anticarcinogenic, and antiaging properties; however, its use as a therapeutic agent is limited by its rapid metabolism into its conjugated forms by UDP-glucuronosyltransferases (UGTs). The aim of the current study was to test the hypothesis that the limited bioavailability of tRes can be improved by modifying its structure to create analogs which would be glucuronidated at a lower rate than tRes itself. In this work, three synthetic stilbenoids, (E)-3-(3-hydroxy-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)acrylic acid (NI-12a), (E)-2,4-dimethoxy-6-(4-methoxystyryl)benzaldehyde oxime (NI-ST-05), and (E)-4-(3,5-dimethoxystyryl)-2,6-dinitrophenol (DNR-1), have been designed based on the structure of tRes and synthesized in our laboratory. UGTs recognize and glucuronidate tRes at each of the 3 hydroxyl groups attached to its aromatic rings. Therefore, each of the above compounds was designed with the majority of the hydroxyl groups blocked by methylation and the addition of other novel functional groups as part of a drug optimization program. The activities of recombinant human UGTs from the 1A and 2B families were examined for their capacity to metabolize these compounds. Glucuronide formation was identified using HPLC and verified by ?-glucuronidase hydrolysis and LC-MS/MS analysis. NI-12a was glucuronidated at both the -COOH and -OH functions, NI-ST-05 formed a novel N-O-glucuronide, and no product was observed for DNR-1. NI-12a is primarily metabolized by the hepatic and renal enzyme UGT1A9, whereas NI-ST-05 is primarily metabolized by an extrahepatic enzyme, UGT1A10, with apparent Km values of 240 and 6.2 ?M, respectively. The involvement of hepatic and intestinal UGTs in the metabolism of both compounds was further confirmed using a panel of human liver and intestinal microsomes, and high individual variation in activity was demonstrated between donors. In summary, these studies clearly establish that modified, tRes-based stilbenoids may be preferable alternatives to tRes itself due to increased bioavailability via altered conjugation. PMID:24571610

Greer, Aleksandra K; Madadi, Nikhil R; Bratton, Stacie M; Eddy, Sarah D; Mazerska, Zofia; Hendrickson, Howard P; Crooks, Peter A; Radominska-Pandya, Anna

2014-04-21

233

Specific binding of lactoferrin to Escherichia coli isolated from human intestinal infections  

International Nuclear Information System (INIS)

The degrees of human lactoferrin (HLf) and bovine lactoferrin (BLf) binding in 169 Escherichia coli strains isolated from human intestinal infections, and in an additional 68 strains isolated from healthy individuals, were examined in a 125I-labelled protein binding assay. The binding was expressed as a percentage calculated from the total labelled ligand added to bacteria. The HLf and BLf binding to E. coli was in the range 3.7 to 73.4% and 4.8 to 61.6%, respectively. Enterotoxigenic strains demonstrated a significantly higher HLf binding (median = 19%) than enteropathogenic, enteroinvasive, enterohaemorrhagic strains or normal intestinal E. coli isolates (medians 6 to 9). Enteropathogenic strains belonging to serotypes O44 and O127 demonstrated significantly higher HLf binding compared to O26, O55, O111, O119 and O126. No significant differences in the degree of HLf or BLf binding were found between aerobactin-producing and non-producing strains. The interaction was further characterized in a high Lf-binging EPEC strain, E34663 (serotype O127). The binding was stable in the pH range 4.0 to 7.5, did not dissociate in the presence of 2M NaCl or 2M urea, and reached saturation within two h. Unlabelled HLf and BLf displaced the 125I-HLf binding to E34663 in a dose-dependent manner. Apo- and iron-saturated forms of Lf demonstrated similar binding to E34663. Among various unlabelled subephithelial matrix proteins and carbohydrates tested (in 104eins and carbohydrates tested (in 104-fold excess) only fibronectin and fibrinogen caused a moderate inhibition of 125I-HLf binding. According to Scatchard plot analysis, 5,400 HLf-binding sites/cell, with an affinity constant (Ka) of 1.4 x 10-7 M, were estimated in strain E34663. These data establish the presence of a specific Lf-binding mechanism in E. coli. (au)

234

Specific binding of lactoferrin to Escherichia coli isolated from human intestinal infections  

Energy Technology Data Exchange (ETDEWEB)

The degrees of human lactoferrin (HLf) and bovine lactoferrin (BLf) binding in 169 Escherichia coli strains isolated from human intestinal infections, and in an additional 68 strains isolated from healthy individuals, were examined in a {sup 125}I-labelled protein binding assay. The binding was expressed as a percentage calculated from the total labelled ligand added to bacteria. The HLf and BLf binding to E. coli was in the range 3.7 to 73.4% and 4.8 to 61.6%, respectively. Enterotoxigenic strains demonstrated a significantly higher HLf binding (median = 19%) than enteropathogenic, enteroinvasive, enterohaemorrhagic strains or normal intestinal E. coli isolates (medians 6 to 9). Enteropathogenic strains belonging to serotypes O44 and O127 demonstrated significantly higher HLf binding compared to O26, O55, O111, O119 and O126. No significant differences in the degree of HLf or BLf binding were found between aerobactin-producing and non-producing strains. The interaction was further characterized in a high Lf-binging EPEC strain, E34663 (serotype O127). The binding was stable in the pH range 4.0 to 7.5, did not dissociate in the presence of 2M NaCl or 2M urea, and reached saturation within two h. Unlabelled HLf and BLf displaced the {sup 125}I-HLf binding to E34663 in a dose-dependent manner. Apo- and iron-saturated forms of Lf demonstrated similar binding to E34663. Among various unlabelled subephithelial matrix proteins and carbohydrates tested (in 10{sup 4}-fold excess) only fibronectin and fibrinogen caused a moderate inhibition of {sup 125}I-HLf binding. According to Scatchard plot analysis, 5,400 HLf-binding sites/cell, with an affinity constant (K{sub a}) of 1.4 x 10{sup -7} M, were estimated in strain E34663. These data establish the presence of a specific Lf-binding mechanism in E. coli. (au).

Naidu, S.S.; Erdei, J.; Forsgren, A.; Naidu, A.S. (Departments of Medical Microbiology, Malmoe General Hospital (Sweden)); Czirok, E.; Gado, I. (National Institute of Hygiene, Budapest (Hungary)); Kalfas, S. (School of Dentistry, University of Lund, Malmoe (Sweden)); Thoren, A. (Infectious Diseases, Malmoe General Hospital (Sweden))

1991-01-01

235

Mast cells modulate transport of CD23/IgE/antigen complex across human intestinal epithelial barrier  

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Full Text Available Background: Food allergy and chronic intestinal inflammation are common in western countries. The complex of antigen/IgE is taken up into the body from the gut lumen with the aid of epithelial cell-derived CD23 (low affinity IgE receptor II that plays an important role in the pathogenesis of intestinal allergy. This study aimed to elucidate the role of mast cell on modulation of antigen/IgE complex transport across intestinal epithelial barrier. Methods: Human intestinal epithelial cell line HT29 cell monolayer was used as a study platform. Transepithelial electric resistance (TER and permeability to ovalbumin (OVA were used as the markers of intestinal epithelial barrier function that were recorded in response to the stimulation of mast cell-derived chemical mediators. Results: Conditioned media from naïve mast cell line HMC-1 cells or monocyte cell line THP-1 cells significantly upregulated the expression of CD23 and increased the antigen transport across the epithelium. Treatment with stem cell factor (SCF, nerve growth factor (NGF, retinoic acid (RA or dimethyl sulphoxide (DMSO enhanced CD23 expression in HT29 cells. Conditioned media from SCF, NGF or RA-treated HMC-1 cells, and SCF, NGF, DMSO or RA-treated THP-1 cells enhanced immune complex transport via enhancing the expression of the CD23 in HT29 cells and the release of inflammatory mediator TNF-?. Nuclear factor kappa B inhibitor, tryptase and TNF-? inhibited the increase in CD23 in HT29 cells and prevents the enhancement of epithelial barrier permeability. Conclusions: Mast cells play an important role in modulating the intestinal CD23 expression and the transport of antigen/IgE/CD23 complex across epithelial barrier.

Ping-Chang Yang

2009-06-01

236

Cloning of a pig homologue of the human lactoferrin receptor: expression and localization during intestinal maturation in piglets.  

Science.gov (United States)

The presence of a small intestinal lactoferrin receptor (SI-LfR) has been suggested in the pig, but remains to be identified. LfR has been suggested to play a key role in the internalization of lactoferrin (Lf) and to facilitate absorption of iron bound to Lf. The aim of this study was to identify the pig SI-LfR cDNA, determine its mRNA and protein expression during different stages of intestinal development. The coding region of the pig LfR cDNA was cloned by PCR using conserved sequences among species. LfR mRNA expression and protein abundance were measured in proximal small intestine from piglets at 1 week (pre-weaning), 3 weeks (weaning) and 6 months (post-weaning) of age by quantitative real-time PCR (Q-PCR) and Western blot, respectively. Intestinal brush border membrane vesicles (BBMV) were also isolated to examine LfR abundance on the apical membrane. We determined the pig SI-LfR open reading frame (ORF) consists of 972 bp, resulting in a protein with a molecular mass approximately 135 kD and approximately 35 kD under non-reducing and reducing conditions, respectively. Using Q-PCR, we determined LfR expression significantly increased with age in the duodenum and reciprocally decreased in the jejunum. Intestinal LfR protein expression was maintained at all timepoints in the jejunum; however, in the duodenum LfR abundance reached maximum levels at 6 months. In BBMV fractions, LfR abundance significantly increased with age. Taken together our findings demonstrate the presence of a human SI-LfR homologue in pig, with mRNA and protein expression concomitantly regulated in the duodenum and inversely regulated in the jejunum. These findings suggest a mechanism by which pig Lf can be internalized in the intestine. PMID:17766154

Liao, Yalin; Lopez, Veronica; Shafizadeh, Tracy B; Halsted, Charles H; Lönnerdal, Bo

2007-11-01

237

Evaluation by computerized morphometry of histopathological alterations of the colon wall in segments with and without intestinal transit in rats Avaliação por morfometria computadorizada das alterações histopatológicas da parede cólica em segmentos com e sem trânsito intestinal em ratos  

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Full Text Available PURPOSE: To evaluate histopathological alterations of the colon wall in segments with and without intestinal transit, by computer-assisted imaging, and to correlate these with the length of time diversion. METHODS: Thirty male Wistar rats were subjected to intestinal transit diversion by a proximal colostomy and distal mucosa fistula. The animals were divided into three experimental groups according to how long after the initial surgical procedure they were sacrificed: six, twelve and eighteen weeks. Colon segments with and without transit were subjected to histopathological study. The variables colon crypt length, mucosal ulceration, muscle layer thickness of the muscularis mucosa, submucosa and muscularis propria, vascular congestion, number of caliciform cells, inflammatory grade and degree of inflammation, comparing the two colon segments in the different experimental groups were studied. Intestinal crypt length, muscle layer thickness of the mucosa, submucosa and muscularis propria and caliciform cells were measured by computer-assisted imaging method. Mean equality, variance analysis and correlation tests were used in the statistical analysis, and the significance level was set at 5%. RESULTS: Comparison between segments with and without transit showed that the latter presented reduced length of colon crypts and increased muscle layer thickness of the muscularis mucosa, submucosa and muscularis propria. There were greater quantities of ulceration of the mucosal and greater degree of inflammation with increasing time without transit. Mucosal ulceration, submucosal vascular congestion, increased thickness of the submucosal and muscularis propria layers, presence of caliciform cells, inflammatory infiltrate and inflammatory grade correlated significantly with the length of time without transit. CONCLUSIONS: Histological alterations occurred in all layers of the colon wall, in the segments without intestinal transit. Ulcerations in the intestinal mucosa, increased number of caliciform cells, greater vascular congestion of the submucosal layer and inflammatory reaction were related to increasing length of time without transit.OBJETIVO: Avaliar por método de imagem assistida por computador as alterações histopatológicas da parede cólica em segmentos providos e desprovidos de trânsito intestinal e relacioná-las ao tempo de exclusão. MÉTODOS: Trinta ratos Wistar machos foram submetidos à derivação do trânsito no cólon esquerdo por meio de colostomia proximal e fístula mucosa distal. Os animais foram divididos em três grupos experimentais segundo o sacrifício ter sido realizado seis, doze e dezoito semanas após o procedimento cirúrgico inicial. Segmentos dos cólons providos e desprovidos de trânsito foram submetidos a estudo histopatológico. Foram analisadas as variáveis: comprimento das criptas cólicas, ulceração na mucosa, espessura das camadas muscular da mucosa, submucosa e muscular própria, congestão vascular, número de células caliciformes e graduação inflamatória comparando os dois segmentos cólicos nos diferentes grupos experimentais. As variáveis, comprimento das criptas intestinais, espessura das camadas muscular da mucosa, submucosa e muscular própria foram mensuradas por método de imagem assistida por computador. Na análise estatística foram utilizados testes de igualdade de médias e medianas, análise de variância e correlação estabelecendo-se nível de significância de cinco por cento. RESULTADOS: A exclusão de trânsito mostrou-se associada à redução do comprimento das criptas cólicas, aumento da espessura das camadas muscular da mucosa, submucosa e muscular própria. Verificou-se maior quantidade de ulcerações na mucosa e maior grau de inflamação com o progredir do tempo de exclusão. Houve correlação significante entre as ulcerações da mucosa, congestão vascular da submucosa, aumento da espessura das camadas submucosa e muscular própria, presença de células caliciformes, infiltrado inflamatório, graduação inflamatória e o t

Marcos Vieira de Sousa

2008-10-01

238

Nuclear localization of vasoactive intestinal peptide (VIP) receptors in human breast cancer.  

Science.gov (United States)

Vasoactive intestinal peptide (VIP) and its receptors (VPACs) are involved in proliferation, survival, and differentiation in human breast cancer cells. Its mechanism of action is traditionally thought to be through specific plasma membrane receptors. There is compelling evidence for a novel intracrine mode of genomic regulation by G-protein-coupled receptors (GPCRs) that implies both endocytosis and nuclear translocation of peripheral GPCR and/or the activation of nuclear-located GPCRs by endogenously-produced, non-secreted ligands. Regarding to VPAC receptors, which are GPCRs, there is only a report suggesting them as a dynamic system for signaling from plasma membrane and nuclear membrane complex. In this study, we show that VPAC(1) receptor is localized in cell nuclear fraction whereas VPAC(2) receptor presents an extranuclear localization and its protein expression is lower than that of VPAC(1) receptor in human breast tissue samples. Both receptors as well as VIP are overexpressed in breast cancer as compared to non-tumor tissue. Moreover, we report the markedly nuclear localization of VPAC(1) receptors in estrogen-dependent (T47D) and independent (MDA-MB-468) human breast cancer cell lines. VPAC(1) receptors are functional in plasma membrane and nucleus as shown by VIP stimulation of cAMP production in both cell lines. In addition, VIP increases its own intracellular and extracellular levels, and could be involved in the regulation of VPAC(1)-receptor traffic from the plasma membrane to the nucleus. These results support new concepts on function and regulation of nuclear GPCRs which could have an impact on development of new therapeutic drugs. PMID:20691743

Valdehita, Ana; Bajo, Ana M; Fernández-Martínez, Ana B; Arenas, M Isabel; Vacas, Eva; Valenzuela, Pedro; Ruíz-Villaespesa, Antonio; Prieto, Juan C; Carmena, María J

2010-11-01

239

Adherence to and invasion of human intestinal cells by Arcobacter species and their virulence genotypes.  

Science.gov (United States)

The genus Arcobacter is composed of 17 species which have been isolated from various sources. Of particular interest are A. butzleri, A. cryaerophilus, and A. skirrowii, as these have been associated with human cases of diarrhea, the probable transmission routes being through the ingestion of contaminated drinking water and food. To date, only limited studies of virulence traits in this genus have been undertaken. The present study used 60 Arcobacter strains isolated from different sources, representing 16 of the 17 species of the genus, to investigate their ability to adhere to and invade the human intestinal cell line Caco-2. In addition, the presence of five putative virulence genes (ciaB, cadF, cj1349, hecA, and irgA) was screened for in these strains by PCR. All Arcobacter species except A. bivalviorum and Arcobacter sp. strain W63 adhered to Caco-2 cells, and most species (10/16) were invasive. The most invasive species were A. skirrowii, A. cryaerophilus, A. butzleri, and A. defluvii. All invasive strains were positive for ciaB (encoding a putative invasion protein). Other putative virulence genes were present in other species, i.e., A. butzleri (cadF, cj1349, irgA, and hecA), A. trophiarum (cj1349), A. ellisii (cj1349), and A. defluvii (irgA). No virulence genes were detected in strains which showed little or no invasion of Caco-2 cells. These results indicate that many Arcobacter species are potential pathogens of humans and animals. PMID:23770897

Levican, Arturo; Alkeskas, Aldukali; Günter, Claudia; Forsythe, Stephen J; Figueras, María José

2013-08-01

240

Conjugated linoleic acid enhances transepithelial calcium transport in human intestinal-like Caco-2 cells: An insight into molecular changes  

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Conjugated linoleic acid (CLA) has been shown to enhance paracellular and transcellular Ca transport across human intestinal-like Caco-2 cell monolayers. The mechanisms of action, however, are still unclear. Therefore, this study investigated the molecular mechanisms underlying CLA-induced stimulation of Ca transport by use of preliminary microarray data together with more detailed and comprehensive quantitative reverse transcriptase-PCR analysis. While molecular expression of junctional adhe...

Murphy, E. F.; Jewell, C.; Hooiveld, G. J. E. J.; Mu?ller, M. R.; Cashman, K. D.

2006-01-01

 
 
 
 
241

Novel Promoter and Alternate Transcription Start Site of the Human Serotonin Reuptake Transporter (SERT) in Intestinal Mucosa  

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Selective serotonin-reuptake inhibitors are therapies for psychological and bowel disorders, but produce adverse effects in the non-targeted system. To determine whether human SERT transcripts in the intestine are different from the brain, rapid amplification of cDNA ends, primer extension, and RT-PCR assays were used to evaluate SERT transcripts from each region. Potential slc6a4 gene promoter constructs were evaluated with a secreted alkaline phosphatase reporter assay. A novel transcript o...

Linden, David R.; White, Sheryl L.; Brooks, Elice M.; Mawe, Gary M.

2009-01-01

242

Microbiota/host crosstalk biomarkers: Regulatory response of human intestinal dendritic cells exposed to Lactobacillus extracellular encrypted peptide  

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The human gastrointestinal tract is exposed to a huge variety of microorganisms, either commensal or pathogenic; at this site, a balance between immunity and immune tolerance is required. Intestinal dendritic cells (DCs) control the mechanisms of immune response/tolerance in the gut. In this paper we have identified a peptide (STp) secreted by Lactobacillus plantarum, characterized by the abundance of serine and threonine residues within its sequence. STp is encoded in one of the main extrace...

Bernardo, David; Sa?nchez Garci?a, Borja; Al-hassi, Hafid O.; Mann, Elizabeth R.; Urdaci, Mari?a C.; Knight, Stella C.; Margolles Barros, Abelardo

2012-01-01

243

Effects of Human Immunodeficiency Virus Protease Inhibitors on the Intestinal Absorption of Tenofovir Disoproxil Fumarate In Vitro?  

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Human immunodeficiency virus protease inhibitors (PIs) modestly affect the plasma pharmacokinetics of tenofovir (TFV; ?15% to +37% change in exposure) following coadministration with the oral prodrug TFV disoproxil fumarate (TDF) by a previously undefined mechanism. TDF permeation was found to be reduced by the combined action of ester cleavage and efflux transport in vitro. Saturable TDF efflux observed in Caco-2 cells suggests that at pharmacologically relevant intestinal concentrations, ...

Tong, Leah; Phan, Truc K.; Robinson, Kelly L.; Babusis, Darius; Strab, Robert; Bhoopathy, Siddhartha; Hidalgo, Ismael J.; Rhodes, Gerald R.; Ray, Adrian S.

2007-01-01

244

For Application to Human Spaceflight and ISS Experiments: VESGEN Mapping of Microvascular Network Remodeling during Intestinal Inflammation  

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Challenges to long-duration space exploration and colonization in microgravity and cosmic radiation environments by humans include poorly understood risks for gastrointestinal function and cancer. Nonetheless, constant remodeling of the intestinal microvasculature is critical for tissue viability, healthy wound healing, and successful prevention or recovery from vascular-mediated inflammatory or ischemic diseases such as cancer. Currently no automated image analysis programs provide quantitat...

Parsons-wingerter, Patricia; Reinecker, Hans-christian

2012-01-01

245

Comparative Morphology of Minute Intestinal Fluke Eggs That Can Occur in Human Stools in the Republic of Korea  

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The egg morphology of minute intestinal flukes (MIF) that can occur as human infections in the Republic of Korea, i.e., Metagonimus yokogawai, M. miyatai, M. takahashii, Heterophyes nocens, Heterophyopsis continua, Stellantchasmus falcatus, Stictodora fuscata, Pygidiopsis summa, and Gymnophalloides seoi, was studied in comparison with Clonorchis sinensis. The adult worms were obtained from residents of endemic areas, and their intrauterine eggs were studied and measured using light microscopy...

Lee, Jin-joo; Jung, Bong-kwang; Lim, Hyemi; Lee, Mi Youn; Choi, Sung-yil; Shin, Eun-hee; Chai, Jong-yil

2012-01-01

246

Evaluation by computerized morphometry of histopathological alterations of the colon wall in segments with and without intestinal transit in rats / Avaliação por morfometria computadorizada das alterações histopatológicas da parede cólica em segmentos com e sem trânsito intestinal em ratos  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese OBJETIVO: Avaliar por método de imagem assistida por computador as alterações histopatológicas da parede cólica em segmentos providos e desprovidos de trânsito intestinal e relacioná-las ao tempo de exclusão. MÉTODOS: Trinta ratos Wistar machos foram submetidos à derivação do trânsito no cólon esque [...] rdo por meio de colostomia proximal e fístula mucosa distal. Os animais foram divididos em três grupos experimentais segundo o sacrifício ter sido realizado seis, doze e dezoito semanas após o procedimento cirúrgico inicial. Segmentos dos cólons providos e desprovidos de trânsito foram submetidos a estudo histopatológico. Foram analisadas as variáveis: comprimento das criptas cólicas, ulceração na mucosa, espessura das camadas muscular da mucosa, submucosa e muscular própria, congestão vascular, número de células caliciformes e graduação inflamatória comparando os dois segmentos cólicos nos diferentes grupos experimentais. As variáveis, comprimento das criptas intestinais, espessura das camadas muscular da mucosa, submucosa e muscular própria foram mensuradas por método de imagem assistida por computador. Na análise estatística foram utilizados testes de igualdade de médias e medianas, análise de variância e correlação estabelecendo-se nível de significância de cinco por cento. RESULTADOS: A exclusão de trânsito mostrou-se associada à redução do comprimento das criptas cólicas, aumento da espessura das camadas muscular da mucosa, submucosa e muscular própria. Verificou-se maior quantidade de ulcerações na mucosa e maior grau de inflamação com o progredir do tempo de exclusão. Houve correlação significante entre as ulcerações da mucosa, congestão vascular da submucosa, aumento da espessura das camadas submucosa e muscular própria, presença de células caliciformes, infiltrado inflamatório, graduação inflamatória e o tempo de exclusão de trânsito. CONCLUSÕES: Alterações histológicas ocorrem em todas as camadas da parede cólica, em segmentos sem trânsito intestinal. Ulcerações na mucosa intestinal, aumento no número de células caliciformes, maior congestão vascular na camada submucosa e reação inflamatória estavam relacionadas com o progredir do tempo de exclusão intestinal. Abstract in english PURPOSE: To evaluate histopathological alterations of the colon wall in segments with and without intestinal transit, by computer-assisted imaging, and to correlate these with the length of time diversion. METHODS: Thirty male Wistar rats were subjected to intestinal transit diversion by a proximal [...] colostomy and distal mucosa fistula. The animals were divided into three experimental groups according to how long after the initial surgical procedure they were sacrificed: six, twelve and eighteen weeks. Colon segments with and without transit were subjected to histopathological study. The variables colon crypt length, mucosal ulceration, muscle layer thickness of the muscularis mucosa, submucosa and muscularis propria, vascular congestion, number of caliciform cells, inflammatory grade and degree of inflammation, comparing the two colon segments in the different experimental groups were studied. Intestinal crypt length, muscle layer thickness of the mucosa, submucosa and muscularis propria and caliciform cells were measured by computer-assisted imaging method. Mean equality, variance analysis and correlation tests were used in the statistical analysis, and the significance level was set at 5%. RESULTS: Comparison between segments with and without transit showed that the latter presented reduced length of colon crypts and increased muscle layer thickness of the muscularis mucosa, submucosa and muscularis propria. There were greater quantities of ulceration of the mucosal and greater degree of inflammation with increasing time without transit. Mucosal ulceration, submucosal vascular congestion, increased thickness of the submucosal and muscularis propria layers, presence

Marcos Vieira de, Sousa; Denise Gonçalves, Priolli; Adriana Valim, Portes; Izilda Aparecida, Cardinalli; José Aires, Pereira; Carlos Augusto Real, Martinez.

2008-10-01

247

Arsenic Thiolation and the Role of Sulfate-Reducing Bacteria from the Human Intestinal Tract  

Science.gov (United States)

Background: Arsenic (As) toxicity is primarily based on its chemical speciation. Although inorganic and methylated As species are well characterized in terms of metabolism and formation in the human body, the origin of thiolated methylarsenicals is still unclear. Objectives: We sought to determine whether sulfate-reducing bacteria (SRB) from the human gut are actively involved in the thiolation of monomethylarsonic acid (MMAV). Methods: We incubated human fecal and colon microbiota in a batch incubator and in a dynamic gut simulator with a dose of 0.5 mg MMAV in the absence or presence of sodium molybdate, an SRB inhibitor. We monitored the conversion of MMAV into monomethyl monothioarsonate (MMMTAV) and other As species by high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry analysis. We monitored the sulfate-reducing activity of the SRB by measuring hydrogen sulfide (H2S) production. We used molecular analysis to determine the dominant species of SRB responsible for As thiolation. Results: In the absence of sodium molybdate, the SRB activity—primarily derived from Desulfovibrio desulfuricans (piger)—was specifically and proportionally correlated (p < 0.01) to MMAV conversion into MMMTAV. Inactivating the SRB with molybdate did not result in MMAV thiolation; however, we observed that the microbiota from a dynamic gut simulator were capable of demethylating 4% of the incubated MMAV into arsenous acid (iAsIII), the trivalent and more toxic form of arsenic acid (iAsV). Conclusion: We found that SRB of human gastrointestinal origin, through their ability to produce H2S, were necessary and sufficient to induce As thiolation. The toxicological consequences of this microbial As speciation change are not yet clear. However, given the efficient epithelial absorption of thiolated methylarsenicals, we conclude that the gut microbiome—and SRB activity in particular—should be incorporated into toxicokinetic analysis carried out after As exposure. Citation: DC.Rubin SS, Alava P, Zekker I, Du Laing G, Van de Wiele T. 2014. Arsenic thiolation and the role of sulfate-reducing bacteria from the human intestinal tract. Environ Health Perspect 122:817–822;?http://dx.doi.org/10.1289/ehp.1307759 PMID:24833621

Alava, Pradeep; Zekker, Ivar; Du Laing, Gijs

2014-01-01

248

Purification and characterization of 7 beta-hydroxysteroid dehydrogenase from Ruminococcus sp. of human intestine.  

Science.gov (United States)

7 beta-Hydroxysteroid dehydrogenase (7 beta-HSD) was produced by Ruminococcus sp. PO1-3 obtained from among human intestinal bacteria. The enzyme was purified from a crude extract by ammonium sulfate fractionation, and Butyl-Toyopearl 650M, Sephadex G-150, Matrex Red A and Octyl-Sepharose chromatographies. The purified enzyme was obtained as a single band on polyacrylamide gel electrophoresis with enzyme activity staining and as one band corresponding to a molecular weight of 30,000 on SDS-polyacrylamide gel electrophoresis. On gel filtration, its apparent molecular weight was estimated to be 60,000. The enzyme had a sulfhydryl group(s) in its active site. Substrate specificity studies revealed that the enzyme showed absolute specificity for the beta-configuration of a hydroxyl group at the 7 position of bile acids, and required NADP+ and NADPH as cosubstrates. The Km values for ursodeoxycholic acid, 7-k etolithocholic acid, NADP+, and NADPH were 5.0, 8.5, 7.7, and 24 microM, respectively. PMID:3480890

Akao, T; Akao, T; Kobashi, K

1987-09-01

249

Heparin induces the expression of specific matrix proteins by human intestinal smooth muscle cells  

International Nuclear Information System (INIS)

Human intestinal smooth muscle (HISM) cells have recently been identified as the major cell type responsible for stricture formation in Crohn's disease. Heparin, a sulfated glycosaminoglycan, has been shown to be a key modulator of vascular smooth muscle cell (VSMC) growth both in vivo and in vitro and to affect the phenotypic expression of proteins made by VSMC. Heparin has also been shown to effect the growth of HISM cells and in this report the authors demonstrate that heparin also has very specific effects on proteins released by HISM cells in vitro. Examination of the proteins in the culture medium of heparin-treated HISM cells observed at 3 time points following sparse plating and proliferation revealed an increase in 35S-methionine-labeled 200, 37, and 35 kd proteins. A transient effect on a 48 kd protein was observed in substrate-attached material left on the culture dish after the cells were removed with EGTA. No effects on intracellular labeled proteins could be demonstrated. The protein phenotype of HISM cells exposed to heparin appears very similar to that observed in VSMC. The release of specific proteins following exposure to heparin does not appear to be species specific. This response to heparin may reflect a significant influence of this glycosaminoglycan on the phenotypic expression of these cells

250

Modulation of Chromatin Remodelling Induced by the Freshwater Cyanotoxin Cylindrospermopsin in Human Intestinal Caco-2 Cells  

Science.gov (United States)

Cylindrospermopsin (CYN) is a cyanotoxin that has been recognised as an emerging potential public health risk. Although CYN toxicity has been demonstrated, the mechanisms involved have not been fully characterised. To identify some key pathways related to this toxicity, we studied the transcriptomic profile of human intestinal Caco-2 cells exposed to a sub-toxic concentration of CYN (1.6 µM for 24hrs) using a non-targeted approach. CYN was shown to modulate different biological functions which were related to growth arrest (with down-regulation of cdkn1a and uhrf1 genes), and DNA recombination and repair (with up-regulation of aptx and pms2 genes). Our main results reported an increased expression of some histone-modifying enzymes (histone acetyl and methyltransferases MYST1, KAT5 and EHMT2) involved in chromatin remodelling, which is essential for initiating transcription. We also detected greater levels of acetylated histone H2A (Lys5) and dimethylated histone H3 (Lys4), two products of these enzymes. In conclusion, CYN overexpressed proteins involved in DNA damage repair and transcription, including modifications of nucleosomal histones. Our results highlighted some new cell processes induced by CYN. PMID:24921660

Huguet, Antoine; Hatton, Aurélie; Villot, Romain; Quenault, Hélène; Blanchard, Yannick; Fessard, Valérie

2014-01-01

251

Butyrate stimulates IL-32? expression in human intestinal epithelial cell lines  

Directory of Open Access Journals (Sweden)

Full Text Available AIM: To investigate the effects of butyrate on interleukin (IL-32? expression in epithelial cell lines.METHODS: The human intestinal epithelial cell lines HT-29, SW480, and T84 were used. Intracellular IL-32? was determined by Western blotting analyses. IL-32? mRNA expression was analyzed by real-time polymerase chain reaction.RESULTS: Acetate and propionate had no effects on IL-32? mRNA expression. Butyrate significantly enhanced IL-32? expression in all cell lines. Butyrate also up-regulated IL-1?-induced IL-32? mRNA expression. Butyrate did not modulate the activation of phosphatidylinositol 3-kinase (PI3K, a mediator of IL-32? expression. Like butyrate, trichostatin A, a histone deacetylase inhibitor, also enhanced IL-1?-induced IL-32? mRNA expression.CONCLUSION: Butyrate stimulated IL-32? expression in epithelial cell lines. An epigenetic mechanism, such as histone hyperacetylation, might be involved in the action of butyrate on IL-32? expression.

Ayako Kobori, Shigeki Bamba, Hirotsugu Imaeda, Hiromitsu Ban, Tomoyuki Tsujikawa, Yasuharu Saito, Yoshihide Fujiyama, Akira Andoh

2010-05-01

252

The prediction of human intestinal absorption based on the molecular structure.  

Science.gov (United States)

Human Intestinal Absorption (HIA) has been modeled many times by using classification models. However, regression models are scarce. Here, Artificial Neural Networks (ANNs) are implemented for this purpose. A dataset of structurally diverse chemicals with their respective experimental HIA were used to design robust, true predictive and widespread applicable ANN models. An input variables pool was made up of structural invariants calculated by using either Dragon or our software Desmol 1. The selection of best variables was performed following three steps using the entire dataset of molecules. Firstly, variables poorly correlated with the experimental data were eliminated. Secondly, input variable selection was performed by stepwise multilinear regression. Thirdly, correlation matrix in the set of selected variables was then obtained to eliminate those variables strongly intercorrelated. Backpropagation ANNs were trained for these variables finally selected as inputs, and HIA as output. The training and selection procedure to find robust models consisted of randomly partitioning the dataset into three sets: training set, with 50% of the population, test set with 25%, and validation set with the other 25%. With each partitioning, diverse numbers of hidden nodes were assayed to optimize the performance in the prediction for the three sets. Models with r(2) greater than 0.6 for the three sets were considered as robust. A randomization test following all these steps was performed, and the poor results obtained confirm the validity of the method presented in this paper to predict HIA for datasets of structurally diverse organic compounds. PMID:24909422

de Julian-Ortiz, J Vicente; Zanni, Riccardo; Galvez-Llompart, Maria; Garcia-Domenech, Ramon

2014-01-01

253

Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation.  

Science.gov (United States)

The C-type lectin-like receptor CD161, which has recently been described to promote T cell expansion, is expressed on a discrete subset of human CD4 T cells. The function of such cells, however, has remained elusive. We now demonstrate that CD161(+) CD4 T cells comprise a circulating and gut-resident T helper 17 (Th17) cell population. During Crohn's disease (CD), these CD161(+) cells display an activated Th17 phenotype, as indicated by increased expression of interleukin (IL)-17, IL-22, and IL-23 receptor. CD161(+) CD4 T cells from CD patients readily produce IL-17 and interferon gamma upon stimulation with IL-23, whereas, in healthy subjects, priming by additional inflammatory stimuli such as IL-1beta was required to enable IL-23-induced cytokine release. Circulating CD161(+) Th17 cells are imprinted for gut homing, as indicated by high levels of CC chemokine receptor 6 and integrin beta7 expression. Supporting their colitogenic phenotype, CD161(+) Th17 cells were found in increased numbers in the inflammatory infiltrate of CD lesions and induced expression of inflammatory mediators by intestinal cells. Our data identify CD161(+) CD4 T cells as a resting Th17 pool that can be activated by IL-23 and mediate destructive tissue inflammation. PMID:19273624

Kleinschek, Melanie A; Boniface, Katia; Sadekova, Svetlana; Grein, Jeff; Murphy, Erin E; Turner, Scott P; Raskin, Lisa; Desai, Bela; Faubion, William A; de Waal Malefyt, Rene; Pierce, Robert H; McClanahan, Terrill; Kastelein, Robert A

2009-03-16

254

Modulation of chromatin remodelling induced by the freshwater cyanotoxin cylindrospermopsin in human intestinal caco-2 cells.  

Science.gov (United States)

Cylindrospermopsin (CYN) is a cyanotoxin that has been recognised as an emerging potential public health risk. Although CYN toxicity has been demonstrated, the mechanisms involved have not been fully characterised. To identify some key pathways related to this toxicity, we studied the transcriptomic profile of human intestinal Caco-2 cells exposed to a sub-toxic concentration of CYN (1.6 µM for 24hrs) using a non-targeted approach. CYN was shown to modulate different biological functions which were related to growth arrest (with down-regulation of cdkn1a and uhrf1 genes), and DNA recombination and repair (with up-regulation of aptx and pms2 genes). Our main results reported an increased expression of some histone-modifying enzymes (histone acetyl and methyltransferases MYST1, KAT5 and EHMT2) involved in chromatin remodelling, which is essential for initiating transcription. We also detected greater levels of acetylated histone H2A (Lys5) and dimethylated histone H3 (Lys4), two products of these enzymes. In conclusion, CYN overexpressed proteins involved in DNA damage repair and transcription, including modifications of nucleosomal histones. Our results highlighted some new cell processes induced by CYN. PMID:24921660

Huguet, Antoine; Hatton, Aurélie; Villot, Romain; Quenault, Hélène; Blanchard, Yannick; Fessard, Valérie

2014-01-01

255

Human intestinal epithelial cells produce proinflammatory cytokines in response to infection in a SCID mouse-human intestinal xenograft model of amebiasis.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The protozoan parasite Entamoeba histolytica causes amebic dysentery and amebic liver abscess, diseases associated with significant morbidity and mortality worldwide. E. histolytica infection appears to involve the initial attachment of amebic trophozoites to intestinal epithelial cells, followed by lysis of these cells and subsequent invasion into the submucosa. A recent in vitro study (L. Eckmann, S. L. Reed, J. R. Smith, and M. F. Kagnoff, J. Clin. Invest. 96:1269-1279, 1995) demonstrated ...

Seydel, K. B.; Li, E.; Swanson, P. E.; Stanley, S. L.

1997-01-01

256

Intestine Transplant  

Science.gov (United States)

... Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Intestine Transplant Although it is possible for a living donor to donate an intestine segment, most intestine transplants involve a whole organ from a deceased donor. ...

257

Ets Transcription Factors Control Epithelial Maturation and Transit and Crypt-Villus Morphogenesis in the Mammalian Intestine  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Members of the Ets transcription factor family are widely expressed in both the developing and mature mammalian intestine, but their biological functions remain primarily uncharacterized. We used a dominant repressor transgene approach to probe the function of epithelial Ets factors in the homeostasis of the crypt-villus unit, the functional unit of the small intestine. We show that targeted expression in small intestinal epithelium of a fusion protein composed of the Engrailed repressor doma...

Jedlicka, Paul; Sui, Xiaomei; Sussel, Lori; Gutierrez-hartmann, Arthur

2009-01-01

258

Lipoteichoic acid from Lactobacillus plantarum inhibits Pam2CSK4-induced IL-8 production in human intestinal epithelial cells.  

Science.gov (United States)

Lactobacilli are probiotic bacteria that are considered to be beneficial in the gastrointestinal tract of humans. Although lactobacilli are well known to alleviate intestinal inflammation, the molecular basis of this phenomenon is poorly understood. In this study, we investigated the effect of Lactobacillus plantarum lipoteichoic acid (Lp.LTA), which is a major cell wall component of this species, on the production of interleukin (IL)-8 in human intestinal epithelial Caco-2 cells. Treatment with Pam2CSK4, a synthetic lipopeptide that is known to mimic Gram-positive bacterial lipoproteins as an important virulence factor, significantly induced IL-8 expression in Caco-2 cells. However, neither heat-inactivated L. plantarum nor L. plantarum peptidoglycan inhibited Pam2CSK4-induced IL-8 mRNA expression. In addition, both a deacylated form and a dealanylated form of Lp.LTA failed to inhibit Pam2CSK4-induced IL-8 expression, indicating that the lipid and D-alanine moieties are critical for Lp.LTA-mediated inhibition. Moreover, Lp.LTA inhibited Pam2CSK4-induced activation of p38 kinase, JNK, and NF-?B transcription factor by suppressing toll-like receptor 2 activation. Collectively, these results suggest that Lp.LTA exerts anti-inflammatory effects on human intestinal epithelial cells by blocking IL-8 production. PMID:25481370

Noh, Su Young; Kang, Seok-Seong; Yun, Cheol-Heui; Han, Seung Hyun

2015-03-01

259

The human neonatal small intestine has the potential for arginine synthesis; developmental changes in the expression of arginine-synthesizing and -catabolizing enzymes  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background Milk contains too little arginine for normal growth, but its precursors proline and glutamine are abundant; the small intestine of rodents and piglets produces arginine from proline during the suckling period; and parenterally fed premature human neonates frequently suffer from hypoargininemia. These findings raise the question whether the neonatal human small intestine also expresses the enzymes that enable the synthesis of arginine from proline and/or gl...

Ruijter Jan M; Lm, Vermeulen Jacqueline; van Dijk Paul; van Ginneken Christa J; Sankaranarayanan Selvakumari; Köhler Eleonore S; Lamers Wouter H; Bruder Elisabeth

2008-01-01

260

PDX1 regulation of FABP1 and novel target genes in human intestinal epithelial Caco-2 cells.  

Science.gov (United States)

The transcription factor pancreatic and duodenal homeobox 1 (PDX1) plays an essential role in pancreatic development and in maintaining proper islet function via target gene regulation. Few intestinal PDX1 targets, however, have been described. We sought to define novel PDX1-regulated intestinal genes. Caco-2 human intestinal epithelial cells were engineered to overexpress PDX1 and gene expression profiles relative to control cells were assessed. Expression of 80 genes significantly increased while that of 49 genes significantly decreased more than 4-fold following PDX1 overexpression in differentiated Caco-2 cells. Analysis of the differentially regulated genes with known functional annotations revealed genes encoding transcription factors, growth factors, kinases, digestive glycosidases, nutrient transporters, nutrient binding proteins, and structural components. The gene for fatty acid binding protein 1, liver, FABP1, is repressed by PDX1 in Caco-2 cells. PDX1 overexpression in Caco-2 cells also results in repression of promoter activity driven by the 0.6kb FABP1 promoter. PDX1 regulation of promoter activity is consistent with the decrease in FABP1 RNA abundance resulting from PDX1 overexpression and identifies FABP1 as a candidate PDX1 target. PDX1 repression of FABP1, LCT, and SI suggests a role for PDX1 in patterning anterior intestinal development. PMID:22640736

Chen, Chin; Fang, Rixun; Chou, Lin-Chiang; Lowe, Anson W; Sibley, Eric

2012-06-22

 
 
 
 
261

Correlation between human papillomavirus infection and bladder transitional cell carcinoma  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background To determine the association of human papillomavirus infection (HPV) and transitional cell carcinoma (TCC). Methods Using polymerase chain reaction, fifty-nine bladder tissue specimens of patients with transitional cell carcinoma of bladder compared with 20 bladder samples of cases with non-neoplastic disorders. Results Male to female ratio was similar in the two groups (50/9 vs. 16/4, P = 0.62). Mean age was 67 ± 10.8...

Smm, Moghaddam Hosseini; Hajimohammadmehdiarbab A; Barghi, MR; Kazemi B

2005-01-01

262

HUMAN CARE FACING TRANSITION TO MATERNAL ROLE: PUERPERAL EXPERIENCES  

Digital Repository Infrastructure Vision for European Research (DRIVER)

It is a study on the changes the transition to maternal role brings about in the puerperal period. Itobjectified to uncover how the puerperal mother experiences transition to maternal role while care is delivered; toset up new methodological ways to implement new human care models privileging role change. It?s a qualitativestudy trailing a methodological research-care trajectory. Thirteen puerperal, several-aged primíparas were interviewed.The instrument used was a semi-structured interview...

Juliana Athayde; Karen Fabiana Pereira; Marialda Martins; Ivete Palmira Sanson Zagonel

2003-01-01

263

Conversion of 5-fluorocytosine to 5-fluorouracil by human intestinal microflora  

International Nuclear Information System (INIS)

5-Fluorocytosine (FC) is used to treat systemic fungal infections in man. Its clinical effectiveness has been limited by hematologic toxicity which may be secondary to the formation of 5-fluorouracil (FU). It is unclear how FU is formed since human cells lack cytosine deaminase. The present study examined if intestinal microflora (IMF) could convert FC to FU in man. An in vitro semicontinuous culture system was inoculated with human feces and maintained with sterile nutrient suspension. The microbial community was assessed for cell count and anaerobes as well as formation of volatile fatty acids and CH4. The system approximated that believed to occur in vivo. The study was initiated with addition of purified [6-14C]-FC. Unlabelled FC was then added to the system daily for 2 weeks following which [6-14C]-FC was again added. Following each addition of [6-14C]-FC, samples were removed at 2,4,8,24,48,72, and 96 hr. Utilizing HPLC, FC and FU could be separated with quantitation of radioactivity in each peak. Following the initial dose, no detectable FU was observed during the first 8 hr, but after 24 hr increasing levels were detected (9.42 ?g FU/ml after 4 days). Following chronic administration of FC, increased levles of FU were noted without an 8 hr lag time in the production of FU (31.86 ?g FU/ml after 4 days). In summary, these studies demonstrate that IMF can convert FC to FU possibly accounting for toxicity observed following administration of FC

264

Structural diversity and specific distribution of O-glycans in normal human mucins along the intestinal tract.  

Science.gov (United States)

Purified human mucins from different parts of the intestinal tract (ileum, cecum, transverse and sigmoid colon and rectum) were isolated from two individuals with blood group ALe(b) (A-Lewis(b)). After alkaline borohydride treatment the released oligosaccharides were structurally characterized by nano-ESI Q-TOF MS/MS (electrospray ionization quadrupole time-of-flight tandem MS) without prior fractionation or derivatization. More than 100 different oligosaccharides, with up to ten monosaccharide residues, were identified using this technique. Oligosaccharides based on core 3 structures, GlcNAc(beta1-3)GalNAc (where GlcNAc is N-acetyl-D-glucosamine and GalNAc is N-acetylgalactosamine), were widely distributed in human intestinal mucins. Core 5 structures, GalNAc(alpha1-3)GalNAc, were also recovered in all fractions. Moreover, a comparison of the oligosaccharide repertoire, with respect to size, diversity and expression of glycans and terminal epitopes, showed a high level of mucin-specific glycosylation: highly fucosylated glycans, found specifically in the small intestine, were mainly based on core 4 structures, GlcNAc-(beta1-3)[GlcNAc(beta1-6)]GalNAc, whereas the sulpho-Le(X) determinant carrying core 2 glycans, Gal(beta1-3)[GlcNAc(beta1-6)]-GalNAc (where Gal is galactose), was recovered mainly in the distal colon. Blood group H and A antigenic determinants were present exclusively in the ileum and cecum, whereas blood group Sd(a)/Cad related epitopes, GalNAc(beta1-4)[NeuAc(alpha2-3)]Gal (where NeuAc is N-acetylneuraminate), were found to increase along the length of the colon. Our findings suggest that mucins create an enormous repertoire of potential binding sites for micro-organisms that could explain the regio-specific colonization of bacteria in the human intestinal tract. PMID:15361072

Robbe, Catherine; Capon, Calliope; Coddeville, Bernadette; Michalski, Jean-Claude

2004-12-01

265

Human population growth and the demographic transition  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The world and most regions and countries are experiencing unprecedentedly rapid demographic change. The most obvious example of this change is the huge expansion of human numbers: four billion have been added since 1950. Projections for the next half century expect a highly divergent world, with stagnation or potential decline in parts of the developed world and continued rapid growth in the least developed regions. Other demographic processes are also undergoing extraordinary change: women's...

Bongaarts, John

2009-01-01

266

D-cycloserine uses an active transport mechanism in the human intestinal cell line Caco 2.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In a previous study we have shown that cultured epithelial cell lines can be used to measure the transepithelial passage of antimicrobial agents across the intestine and to obtain information on the mechanisms of transport utilized and predict the bioavailability of the antimicrobial agents after oral administration. In particular, among the drugs investigated, D-cycloserine had been shown to be transported in a polarized manner only in the intestinal cells. In the present work, further chara...

Ranaldi, G.; Islam, K.; Sambuy, Y.

1994-01-01

267

For Application to Human Spaceflight and ISS Experiments: VESGEN Mapping of Microvascular Network Remodeling during Intestinal Inflammation.  

Science.gov (United States)

Challenges to long-duration space exploration and colonization in microgravity and cosmic radiation environments by humans include poorly understood risks for gastrointestinal function and cancer. Nonetheless, constant remodeling of the intestinal microvasculature is critical for tissue viability, healthy wound healing, and successful prevention or recovery from vascular-mediated inflammatory or ischemic diseases such as cancer. Currently no automated image analysis programs provide quantitative assessments of the complex structure of the mucosal vascular system that are necessary for tracking disease development and tissue recovery. Increasing abnormalities to the microvascular network geometry were therefore mapped with VESsel GENeration Analysis (VESGEN) software from 3D tissue reconstructions of developing intestinal inflammation in a dextran sulfate sodium (DSS) mouse model. By several VESGEN parameters and a novel vascular network linking analysis, inflammation strongly disrupted the regular, lattice-like geometry that defines the normal microvascular network, correlating positively with the increased recruitment of dendritic cells during mucosal defense responses. PMID:25143705

Parsons-Wingerter, Patricia; Reinecker, Hans-Christian

2012-10-01

268

Reduced expression of aquaporins in human intestinal mucosa in early stage inflammatory bowel disease  

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Full Text Available Petr Ricanek,1,2 Lisa K Lunde,3 Stephan A Frye,1 Mari Støen,1 Ståle Nygård,4 Jens P Morth,5,6 Andreas Rydning,2 Morten H Vatn,7,8 Mahmood Amiry-Moghaddam,3 Tone Tønjum,1,9 1Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, 2Department of Gastroenterology, Akershus University Hospital, Lørenskog and Campus Ahus, Institute of Clinical Medicine, University of Oslo, Lørenskog, 3Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, 4Bioinformatics Core Facility, Institute for Medical Informatics, Oslo University Hospital and University of Oslo, 5Centre for Molecular Medicine, Nordic EMBL Partnership, University of Oslo, 6Institute for Experimental Research, Oslo University Hospital (Ullevaal, Oslo, 7EpiGen Institute, Campus Ahus, Institute of Clinical Medicine, University of Oslo, Lørenskog, 8Section of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, 9Department of Microbiology, University of Oslo, Oslo, Norway Objectives: The aim of this study was to investigate the relationship between aquaporin (AQP water channel expression and the pathological features of early untreated inflammatory bowel disease (IBD in humans. Methods: Patients suspected to have IBD on the basis of predefined symptoms, including abdominal pain, diarrhea, and/or blood in stool for more than 10 days, were examined at the local hospital. Colonoscopy with biopsies was performed and blood samples were taken. Patients who did not meet the diagnostic criteria for IBD and who displayed no evidence of infection or other pathology in the gut were included as symptomatic non-IBD controls. AQP1, 3, 4, 5, 7, 8, and 9 messenger RNA (mRNA levels were quantified in biopsies from the distal ileum and colon by quantitative real-time polymerase chain reaction. Protein expression of selected AQPs was assessed by confocal microscopy. Through multiple alignments of the deduced amino acid sequences, the putative three-dimensional structures of AQP1, 3, 7, and 8 were modeled. Results: AQP1, 3, 7, and 8 mRNAs were detected in all parts of the intestinal mucosa. Notably, AQP1 and AQP3 mRNA levels were reduced in the ileum of patients with Crohn's disease, and AQP7 and AQP8 mRNA levels were reduced in the ileum and the colon of patients with ulcerative colitis. Immunofluorescence confocal microscopy showed localization of AQP3, 7, and 8 at the mucosal epithelium, whereas the expression of AQP1 was mainly confined to the endothelial cells and erythrocytes. The reduction in the level of AQP3, 7, and 8 mRNA was confirmed by immunofluorescence, which also indicated a reduction of apical immunolabeling for AQP8 in the colonic surface epithelium and crypts of the IBD samples. This could indicate loss of epithelial polarity in IBD, leading to disrupted barrier function. Conclusion: AQPs 1 and 8 and the aquaglyceroporins AQPs 3 and 7 are the AQPs predominantly expressed in the lower intestinal tract of humans. Their expression is significantly reduced in patients with IBD, and they are differentially expressed in specific bowel segments in patients with Crohn's disease and ulcerative colitis. The data present a link between gut inflammation and water/solute homeostasis, suggesting that AQPs may play a significant role in IBD pathophysiology. Keywords: inflammatory bowel disease, Crohn's disease, ulcerative colitis, aquaporins, aquaglyceroporins

Ricanek P

2015-01-01

269

Regulation of apical transporter of L-DOPA in human intestinal Caco-2 cells.  

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The present study examined the nature of the apical inward L-3,4-dihydroxyphenylalanine (L-DOPA) transporter in human intestinal epithelial Caco-2 cells, and whether protein kinases modulate the activity of this transporter. The apical inward transfer of L-DOPA was promoted through an energy-dependent and sodium-insensitive transporter (Km=33 microM; Vmax=2932 pmol/mg protein/6 min). This transporter was insensitive to N-(methylamino)-isobutyric acid, but competitively inhibited by 2-aminobicyclo(2,2,1)-heptane-2-carboxylic acid (BCH; IC50=83 microM). The organic cation inhibitor decynium 24 failed to affect the accumulation of L-DOPA, whereas the organic anion inhibitor 4,4'-diisothiocynatostilbene-2,2'-disulphonic acid (DIDS) competitively inhibited L-DOPA uptake (IC50=83 microM). However, the apical-to-basal and basal-to-apical transepithelial transport and the cell accumulation of [3H]-PAH was close to that of [14C]-sorbitol and insensitive to DIDS (300 microM). Modulators of protein kinase A (PKA) [cyclic adenosine monophosphate (cAMP), forskolin, H-89 and cholera toxin], protein kinase G (PKG) [cyclic guanosine monophosphate (GMP), zaprinast, LY 83583 and sodium nitroprusside] and protein kinase C (PKC) (phorbol 12,13-dibutirate and chelerythrine) failed to affect the accumulation of L-DOPA. The Ca2+/calmodulin inhibitors calmidazolium and trifluoperazine inhibited L-DOPA uptake (IC50s of 53 and 252 microM, respectively), but the rise of intracellular Ca2+ by A23187 (1 microM) and thapsigargin (1 microM) played no role on L-DOPA uptake. It is concluded that Caco-2 cells take up L-DOPA over the apical cell border through the sodium-independent and pH-sensitive L-type amino acid transporter. PMID:12028130

Fraga, S; Sampaio-Maia, B; Serrão, M P; Soares-da-Silva, P

2002-06-01

270

Antioxidant activity of vasoactive intestinal peptide in HK2 human renal cells.  

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Oxidative stress is a major mediator of tissue and cell injuries. The injury in chronic nephrotic syndrome, acute renal failure, myeloma kidney injury and other kidney diseases is initiated by oxidative stress. We have previously demonstrated that vasoactive intestinal peptide (VIP) acts as an antiproliferative agent in renal cancer cells. This study was designed to evaluate the renoprotective activity of VIP against H(2)O(2)-induced oxidative damage in a proximal tubule kidney cell line (human, non-tumor, HK2 cells) in order to investigate the potential usefulness of this peptide in the treatment of oxidative-stress related kidney diseases. HK2 cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Propidium iodide was used to identify cells undergoing apoptosis. Western blotting was performed with anti-Bcl-2, anti-Bax and anti-formyl peptide receptor (low-affinity variant FPRL-1) monoclonal antibodies whereas 2,7-dichlorofluorescein diacetate was used for measurement of levels of intracellular reactive oxygen species (ROS). HK2 cells were injured with H(2)O(2) in order to induce apoptosis: the effect was time- and dose-dependent. VIP increased the levels of the antiapoptotic protein Bcl-2 and decreased those of the proapoptotic protein Bax. VIP decreased the intracellular ROS levels reached by H(2)O(2)-induced oxidative stress. VIP effect on ROS levels involved FPLR-1 but not VPAC(1,2) receptors as evidenced by the use of the respective antagonists WRW4 and JV-1-53. Thus, VIP protects HK2 cells from apoptosis by increasing Bcl-2 levels and this effect is initiated through FPLR1 receptor. In conclusion, VIP might exert a renoprotective effect by the suppression of oxidative stress. PMID:23000305

Vacas, Eva; Bajo, Ana M; Schally, Andrew V; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J

2012-12-01

271

Characterization of two distinct modes of drug binding to human intestinal fatty acid binding protein.  

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The aqueous cytoplasm of cells poses a potentially significant barrier for many lipophilic drugs to reach their sites of action. Fatty acid binding proteins (FABPs) bind to poorly water-soluble fatty acids (FAs) and lipophilic compounds and facilitate their intracellular transport. Several structures of FA in complex with FABPs have been described, but data describing the binding sites of other lipophilic ligands including drugs are limited. Here the environmentally sensitive fluorophores, 1-anilinonapthalene 8-sulfonic acid (ANS), and 11-dansylamino undecanoic acid (DAUDA) were used to investigate drug binding to human intestinal FABP (hIFABP). Most drugs that bound hIFABP were able to displace both ANS and DAUDA. A notable exception was ketorolac, a non-steroidal anti-inflammatory drug that bound to hIFABP and displaced DAUDA but failed to displace ANS. Isothermal titration calorimetry revealed that for the majority of ligands including FA, ANS, and DAUDA, binding to hIFABP was exothermic. In contrast, ketorolac binding to hIFABP was endothermic and entropy-driven. The X-ray crystal structure of DAUDA-hIFABP revealed a FA-like binding mode where the carboxylate of DAUDA formed a network of hydrogen bonds with residues at the bottom of the binding cavity and the dansyl group interacted with residues in the portal region. In contrast, NMR chemical shift perturbation (CSP) data suggested that ANS bound only toward the bottom of the hIFABP cavity, whereas ketorolac occupied only the portal region. The CSP data further suggested that ANS and ketorolac were able to bind simultaneously to hIFABP, consistent with the lack of displacement of ANS observed by fluorescence and supported by a model of the ternary complex. The NMR solution structure of the ketorolac-hIFABP complex therefore describes a newly characterized, hydrophobic ligand binding site in the portal region of hIFABP. PMID:25144524

Patil, Rahul; Laguerre, Aisha; Wielens, Jerome; Headey, Stephen J; Williams, Martin L; Hughes, Maria L R; Mohanty, Biswaranjan; Porter, Christopher J H; Scanlon, Martin J

2014-11-21

272

Human intestinal absorption of imidacloprid with Caco-2 cells as enterocyte model  

International Nuclear Information System (INIS)

In order to assess the risk to mammals of a chronic exposure to imidacloprid (IMI), we investigated its absorption with the human intestinal Caco-2 cell line. Measurements of transepithelial transport revealed an apparent permeability coefficient of 21.6 x 10-6 ± 3.2 x 10-6 cm/s reflecting a 100% absorption. The comparison of apical to basal (A-B) and basal to apical (B-A) transports showed that the monolayer presents a basal to apical polarized transport. Studies of apical uptake demonstrated that the transport was concentration-dependent and not saturable from 5 to 200 ?M. Arrhenius plot analysis revealed two apparent activation energies, Ea(4-12deg.C) = 63.8 kJ/mol and Ea(12-37deg. C) 18.2 kJ/mol, suggesting two temperature-dependent processes. IMI uptake was equivalent when it was performed at pH 6.0 or 7.4. Depletion of Na+ from the transport buffer did not affect the uptake, indicating that a sodium-dependent transporter was not involved. Decrease of uptake with sodium-azide or after cell surface trypsin (Ti) treatment suggested the involvement of a trypsin-sensitive ATP-dependent transporter. Investigations on apical efflux demonstrated that initial velocities paralleled the increase of loading concentrations. A cell surface trypsin treatment did not affect the apical efflux. The lack of effect when the efflux was performed against an IMI concentration gradient suggested that an enerntration gradient suggested that an energy-dependent transporter was involved. However, the inhibition of P-glycoproteins (P-gp) and multidrug resistance-associated proteins (MRP) by taxol, vincristine, and daunorubicine had no effect on IMI intracellular accumulation suggesting the involvement of transporters distinct from classical ATP binding cassette transport (ABC-transport) systems. All results suggest that IMI is strongly absorbed in vivo by inward and outward active transporters

273

Production of enterodiol from defatted flaxseeds through biotransformation by human intestinal bacteria  

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Full Text Available Abstract Background The effects of enterolignans, e.g., enterodiol (END and particularly its oxidation product, enterolactone (ENL, on prevention of hormone-dependent diseases, such as osteoporosis, cardiovascular diseases, hyperlipemia, breast cancer, colon cancer, prostate cancer and menopausal syndrome, have attracted much attention. To date, the main way to obtain END and ENL is chemical synthesis, which is expensive and inevitably leads to environmental pollution. To explore a more economic and eco-friendly production method, we explored biotransformation of enterolignans from precursors contained in defatted flaxseeds by human intestinal bacteria. Results We cultured fecal specimens from healthy young adults in media containing defatted flaxseeds and detected END from the culture supernatant. Following selection through successive subcultures of the fecal microbiota with defatted flaxseeds as the only carbon source, we obtained a bacterial consortium, designated as END-49, which contained the smallest number of bacterial types still capable of metabolizing defatted flaxseeds to produce END. Based on analysis with pulsed field gel electrophoresis, END-49 was found to consist of five genomically distinct bacterial lineages, designated Group I-V, with Group I strains dominating the culture. None of the individual Group I-V strains produced END, demonstrating that the biotransformation of substrates in defatted flaxseeds into END is a joint work by different members of the END-49 bacterial consortium. Interestingly, Group I strains produced secoisolariciresinol, an important intermediate of END production; 16S rRNA analysis of one Group I strain established its close relatedness with Klebsiella. Genomic analysis is under way to identify all members in END-49 involved in the biotransformation and the actual pathway leading to END-production. Conclusion Biotransformation is a very economic, efficient and environmentally friendly way of mass-producing enterodiol from defatted flaxseeds.

Ma Miao

2010-04-01

274

PKQuest: measurement of intestinal absorption and first pass metabolism – application to human ethanol pharmacokinetics  

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Full Text Available Abstract Background PKQuest, a new physiologically based pharmacokinetic (PBPK program, is applied to human ethanol data. The classical definition of first pass metabolism (FPM based on the differences in the area under the curve (AUC for identical intravenous and oral doses is invalid if the metabolism is non-linear (e.g. ethanol. Uncertainties in the measurement of FPM have led to controversy about the magnitude of gastric alcohol metabolism. PKQuest implements a new, rigorous definition of FPM based on finding the equivalent intravenous input function that would produce a blood time course identical to that observed for the oral intake. This input function equals the peripheral availability (PA and the FPM is defined by: FPM = Total oral dose – PA. PKQuest also provides a quantitative measurement of the time course of intestinal absorption. Methods PKQuest was applied to previously published ethanol pharmacokinetic data. Results The rate of ethanol absorption is primarily limited by the rate of gastric emptying. For oral ethanol with a meal: absorption is slow (? 3 hours and the fractional PKQuest FPM was 36% (0.15 gm/Kg dose and 7% (0.3 gm/Kg. In contrast, fasting oral ethanol absorption is fast (? 50 minutes and FPM is small. Conclusions The standard AUC and one compartment methods significantly overestimate the FPM. Gastric ethanol metabolism is not significant. Ingestion of a coincident meal with the ethanol can reduce the peak blood level by about 4 fold at low doses. PKQuest and all the examples are freely available on the web at http://www.pkquest.com.

Levitt David G

2002-08-01

275

Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium.  

Science.gov (United States)

The diversity of mucin-degrading bacteria in the human intestine was investigated by combining culture and 16S rRNA-dependent approaches. A dominant bacterium, strain MucT, was isolated by dilution to extinction of faeces in anaerobic medium containing gastric mucin as the sole carbon and nitrogen source. A pure culture was obtained using the anaerobic soft agar technique. Strain MucT was a Gram-negative, strictly anaerobic, non-motile, non-spore-forming, oval-shaped bacterium that could grow singly and in pairs. When grown on mucin medium, cells produced a capsule and were found to aggregate. Strain MucT could grow on a limited number of sugars, including N-acetylglucosamine, N-acetylgalactosamine and glucose, but only when a protein source was provided and with a lower growth rate and final density than on mucin. The G + C content of DNA from strain MucT was 47.6 mol%. 16S rRNA gene sequence analysis revealed that the isolate was part of the division Verrucomicrobia. The closest described relative of strain MucT was Verrucomicrobium spinosum (92 % sequence similarity). Remarkably, the 16S rRNA gene sequence of strain MucT showed 99 % similarity to three uncultured colonic bacteria. According to the data obtained in this work, strain MucT represents a novel bacterium belonging to a new genus in subdivision 1 of the Verrucomicrobia; the name Akkermansia muciniphila gen. nov., sp. nov. is proposed; the type strain is MucT (= ATCC BAA-835T = CIP 107961T). PMID:15388697

Derrien, Muriel; Vaughan, Elaine E; Plugge, Caroline M; de Vos, Willem M

2004-09-01

276

Anatomical study on The Arm Greater Yang Small Intestine Meridian Muscle in Human  

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Full Text Available This study was carried to identify the component of Small Intestine Meridian Muscle in human, dividing the regional muscle group into outer, middle, and inner layer. the inner part of body surface were opened widely to demonstrate muscles, nerve, blood vessels and the others, displaying the inner structure of Small Intestine Meridian Muscle. We obtained the results as follows; 1. Small Intestine Meridian Muscle is composed of the muscle, nerve and blood vessels. 2. In human anatomy, it is present the difference between a term of nerve or blood vessels which control the muscle of Meridian Muscle and those which pass near by Meridian Muscle. 3. The inner composition of meridian muscle in human arm is as follows ; 1 Muscle ; Abd. digiti minimi muscle(SI-2, 3, 4, pisometacarpal lig.(SI-4, ext. retinaculum. ext. carpi ulnaris m. tendon.(SI-5, 6, ulnar collateral lig.(SI-5, ext. digiti minimi m. tendon(SI-6, ext. carpi ulnaris(SI-7, triceps brachii(SI-9, teres major(SI-9, deltoid(SI-10, infraspinatus(SI-10, 11, trapezius(Sl-12, 13, 14, 15, supraspinatus(SI-12, 13, lesser rhomboid(SI-14, erector spinae(SI-14, 15, levator scapular(SI-15, sternocleidomastoid(SI-16, 17, splenius capitis(SI-16, semispinalis capitis(SI-16, digasuicus(SI-17, zygomaticus major(Il-18, masseter(SI-18, auriculoris anterior(SI-19 2 Nerve ; Dorsal branch of ulnar nerve(SI-1, 2, 3, 4, 5, 6, br. of mod. antebrachial cutaneous n.(SI-6, 7, br. of post. antebrachial cutaneous n.(SI-6,7, br. of radial n.(SI-7, ulnar n.(SI-8, br. of axillary n.(SI-9, radial n.(SI-9, subscapular n. br.(SI-9, cutaneous n. br. from C7, 8(SI-10, 14, suprascapular n.(SI-10, 11, 12, 13, intercostal n. br. from T2(SI-11, lat. supraclavicular n. br.(SI-12, intercostal n. br. from C8, T1(SI-12, accessory n. br.(SI-12, 13, 14, 15, 16, 17, intercostal n. br. from T1,2(SI-13, dorsal scapular n.(SI-14, 15, cutaneous n. br. from C6, C7(SI-15, transverse cervical n.(SI-16, lesser occipital n. & great auricular n. from cervical plexus(SI-16, cervical n. from C2,3(SI-16, fascial n. br.(SI-17, great auricular n. br.(SI-17, cervical n. br. from C2(SI-17, vagus n.(SI-17,hypoglossal n.(SI-17, glossopharyngeal n.(SI-17, sympathetic trunk(SI-17, zygomatic br. of fascial n.(SI-18, maxillary n. br.(SI-18, auriculotemporal n.(SI-19, temporal br. of fascial n.(SI-19 3 Blood vessels ; Dorsal digital vein.(SI-1, dorsal br. of proper palmar digital artery(SI-1, br. of dorsal metacarpal a. & v.(SI-2, 3, 4, dorsal carpal br. of ulnar a.(SI-4, 5, post. interosseous a. br.(SI-6,7, post. ulnar recurrent a.(SI-8, circuirflex scapular a.(SI-9, 11 , post. circumflex humeral a. br.(SI-10, suprascapular a.(SI-10, 11, 12, 13, first intercostal a. br.(SI-12, 14, transverse cervical a. br.(SI-12,13,14,15, second intercostal a. br.(SI-13, dorsal scapular a. br.(SI-13, 14, 15, ext. jugular v.(SI-16, 17, occipital a. br.(SI-16, Ext. jugular v. br.(SI-17, post. auricular a.(SI-17, int. jugular v.(SI-17, int. carotid a.(SI-17, transverse fascial a. & v.(SI-18,maxillary a. br.(SI-18, superficial temporal a. & v.(SI-19.

Kyoung-Sik, Park

2004-06-01

277

Utility of in vitro systems and preclinical data for the prediction of human intestinal first-pass metabolism during drug discovery and preclinical development.  

Science.gov (United States)

A growing awareness of the risks associated with extensive intestinal metabolism has triggered an interest in developing robust methods for its quantitative assessment. This study explored the utility of intestinal S9 fractions, human liver microsomes, and recombinant cytochromes P450 to quantify CYP3A-mediated intestinal extraction in humans for a selection of marketed drugs that are predominantly metabolized by CYP3A4. A simple competing rates model is used to estimate the fraction of drug escaping gut wall metabolism (fg) from in vitro intrinsic clearance in humans. The fg values extrapolated from the three in vitro systems used in this study, together with literature-derived fg from human intestinal microsomes, were validated against fg extracted from human in vivo pharmacokinetic (PK) profiles using a generic whole-body physiologically-based pharmacokinetic (PBPK) model. The utility of the rat as a model for human CYP3A-mediated intestinal metabolism was also evaluated. Human fg from PBPK compares well with that from the grapefruit juice method, justifying its use for the evaluation of human in vitro systems. Predictive performance of all human in vitro systems was comparable [root mean square error (RMSE) = 0.22-0.27; n = 10]. Rat fg derived from in vivo PK profiles using PBPK has the lowest RMSE (0.19; n = 11) for the prediction of human fg for the selected compounds, most of which have a fraction absorbed close to 1. On the basis of these evaluations, the combined use of fg from human in vitro systems and rats is recommended for the estimation of CYP3A4-mediated intestinal metabolism in lead optimization and preclinical development phases. PMID:23918667

Karlsson, Fredrik H; Bouchene, Salim; Hilgendorf, Constanze; Dolgos, Hugues; Peters, Sheila Annie

2013-12-01

278

Dipeptide model prodrugs for the intestinal oligopeptide transporter. Affinity for and transport via hPepT1 in the human intestinal Caco-2 cell line  

DEFF Research Database (Denmark)

The human intestinal di/tri-peptide carrier, hPepT1, has been suggested as a drug delivery target via increasing the intestinal transport of low permeability compounds by designing peptidomimetic prodrugs. Model ester prodrugs using the stabilized dipeptides D-Glu-Ala and D-Asp-Ala as pro-moieties for benzyl alcohol have been shown to maintain affinity for hPepT1. The primary aim of the present study was to investigate if modifications of the benzyl alcohol model drug influence the corresponding D-Glu-Ala and D-Asp-Ala model prodrugs' affinity for hPepT1 in Caco-2 cells. A second aim was to investigate the transepithelial transport and hydrolysis parameters for D-Asp(BnO)-Ala and D-Glu(BnO)-Ala across Caco-2 cell monolayers. In the present study, all investigated D-Asp-Ala and D-Glu-Ala model prodrugs retained various degrees of affinity for hPepT1 in Caco-2 cells. These affinities are used to establish a QSAR of our benzyl alcohol modified model prodrugs, aided at elucidating the observed differences in model prodrug affinity for hPepT1; additionally, these data suggest that the hydrophobicity of the side-chain model drug is the major determinant in the compounds affinity for hPepT1. Transepithelial transport studies performed using Caco-2 cells of D-Asp(BnO)-Ala and D-Glu(BnO)-Ala showed that the K(m) for transepithelial transport was not significantly different for the two compounds. The maximal transport rate of the carrier-mediated flux component does not differ between the two model prodrugs either. The transepithelial transport of D-Asp(BnO)-Ala and D-Glu(BnO)-Ala follows simple kinetics, and the release of benzyl alcohol is pH-dependent, but unaffected by 1 mM of the esterase inhibitor Paraoxon in 80% human plasma and Caco-2 cell homogenate.

Nielsen, C U; Andersen, R

2001-01-01

279

Adherence to and invasion of human intestinal epithelial cells by Campylobacter jejuni and Campylobacter coli isolates from retail meat products.  

Science.gov (United States)

The abilities of 34 Campylobacter jejuni and 9 Campylobacter coli isolates recovered from retail meats to adhere to and invade human intestinal epithelial T84 cells were examined and compared with those of a well-characterized human clinical strain, C. jejuni 81-176, to better assess the pathogenic potential of these meat isolates. The meat isolates exhibited a wide range of adherence and invasion abilities; a few of the isolates adhered to and invaded T84 cells almost as well as did C. jejuni 81-176. There was a significant correlation between the adherence ability and the invasion ability of the Campylobacter isolates. The presence of eight putative virulence genes in these Campylobacter isolates that are potentially responsible for adherence and invasion or that encode cytolethal distending toxin was determined using PCR. All Campylobacter isolates possessed flaA, cadF, pldA, cdtA, cdtB, and cdtC, and most (91%) also contained the ciaB gene. However, the virB11 gene, carried by virulence plasmid pVir, was absent in almost all the Campylobacter isolates. Our findings indicated that C. jejuni and C. coli present in retail meat were diverse in their ability to adhere to and invade human intestinal epithelial cells and that the putative virulence genes were widespread among the Campylobacter isolates. Thus, despite of the presence of the putative virulence genes, only some but not all Campylobacter strains isolated from retail meat can effectively invade human intestinal epithelial cells in vitro. PMID:16629018

Zheng, Jie; Meng, Jianghong; Zhao, Shaohua; Singh, Ruby; Song, Wenxia

2006-04-01

280

Solubilization of the active vasoactive intestinal peptide receptor from human colonic adenocarcinoma cells.  

Science.gov (United States)

The non-ionic detergent n-octyl-beta-D-glucopyranoside was used to solubilize the VIP (vasoactive intestinal peptide) receptor from human colonic adenocarcinoma cell line HT29-D4. The binding of monoiodinated 125I-VIP to the solubilized receptor was specific, time-dependent, and reversible. Scatchard analysis of data obtained from competitive displacement of monoiodinated 125I-VIP by native VIP suggested the presence of two classes of VIP binding sites with Kd values of 0.32 and 46.7 nM. The binding capacities of these two classes were 1.7 x 10(10) and 30.2 x 10(10) sites/mg of proteins, respectively. The solubilized receptor retained the specificity of the human VIP receptor towards the peptides of the VIP/secretin/glucagon family. The order of potency in inhibiting monoiodinated 125I-VIP binding was VIP (IC50 = 1.0 x 10(-9) M) much greater than peptide histidine methionine amide (IC50 = 10(-7) M) greater than growth hormone-releasing factor (IC50 = 3 x 10(-7) M) greater than secretin (IC50 greater than 10(-6) M); glucagon had no effect on VIP binding. The reducing agent dithiothreitol inhibited in a dose-dependent manner the binding of 125I-VIP. Covalent cross-linking experiments between the solubilized receptor and 125I-VIP showed that after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography two major and one minor polypeptides of Mr 67,000, 72,000, and 83,000 were specifically labeled. When analyzed by gel filtration, the n-octyl-beta-D-glucopyranoside-solubilized 125I-VIP-receptor complex was resolved into two major peaks with molecular mass in the range of 60-70 and 270-300 kDa. Thus, the soluble form of the VIP receptor was probably a multimeric complex in which disulfide bonds may play an important role to hold the receptor in an active configuration. PMID:2846575

el Battari, A; Martin, J M; Luis, J; Pouzol, O; Secchi, J; Marvaldi, J; Pichon, J

1988-11-25

 
 
 
 
281

Transcriptional response of HT-29 intestinal epithelial cells to human and bovine milk oligosaccharides.  

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Human milk oligosaccharides (HMO) have been shown to interact directly with immune cells. However, large quantities of HMO are required for intervention or clinical studies, but these are unavailable in most cases. In this respect, bovine milk is potentially an excellent source of commercially viable analogues of these unique molecules. In the present study, we compared the transcriptional response of colonic epithelial cells (HT-29) to the entire pool of HMO and bovine colostrum oligosaccharides (BCO) to determine whether the oligosaccharides from bovine milk had effects on gene expression that were similar to those of their human counterparts. Gene set enrichment analysis of the transcriptional data revealed that there were a number of similar biological processes that may be influenced by both treatments including a response to stimulus, signalling, locomotion, and multicellular, developmental and immune system processes. For a more detailed insight into the effects of milk oligosaccharides, the effect on the expression of immune system-associated glycogenes was chosen as a case study when performing validation studies. Glycogenes in the current context are genes that are directly or indirectly regulated in the presence of glycans and/or glycoconjugates. RT-PCR analysis revealed that HMO and BCO influenced the expression of cytokines (IL-1?, IL-8, colony-stimulating factor 2 (granulocyte-macrophage) (GM-CSF2), IL-17C and platelet factor 4 (PF4)), chemokines (chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-X-C motif) ligand 3 (CXCL3), chemokine (C-C motif) ligand 20 (CCL20), chemokine (C-X-C motif) ligand 2 (CXCL2), chemokine (C-X-C motif) ligand 6 (CXCL6), chemokine (C-C motif) ligand 5 (CCL5), chemokine (C-X3-C motif) ligand 1 (CX3CL1) and CXCL2) and cell surface receptors (interferon ? receptor 1 (IFNGR1), intercellular adhesion molecule-1 (ICAM-1), intercellular adhesion molecule-2 (ICAM-2) and IL-10 receptor ? (IL10RA)). The present study suggests that milk oligosaccharides contribute to the development and maturation of the intestinal immune response and that bovine milk may be an attractive commercially viable source of oligosaccharides for such applications. PMID:23710626

Lane, Jonathan A; O'Callaghan, John; Carrington, Stephen D; Hickey, Rita M

2013-12-01

282

Persistence and Toxin Production by Clostridium difficile within Human Intestinal Organoids Result in Disruption of Epithelial Paracellular Barrier Function.  

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Clostridium difficile is the leading cause of infectious nosocomial diarrhea. The pathogenesis of C. difficile infection (CDI) results from the interactions between the pathogen, intestinal epithelium, host immune system, and gastrointestinal microbiota. Previous studies of the host-pathogen interaction in CDI have utilized either simple cell monolayers or in vivo models. While much has been learned by utilizing these approaches, little is known about the direct interaction of the bacterium with a complex host epithelium. Here, we asked if human intestinal organoids (HIOs), which are derived from pluripotent stem cells and demonstrate small intestinal morphology and physiology, could be used to study the pathogenesis of the obligate anaerobe C. difficile. Vegetative C. difficile, microinjected into the lumen of HIOs, persisted in a viable state for up to 12 h. Upon colonization with C. difficile VPI 10463, the HIO epithelium is markedly disrupted, resulting in the loss of paracellular barrier function. Since similar effects were not observed when HIOs were colonized with the nontoxigenic C. difficile strain F200, we directly tested the role of toxin using TcdA and TcdB purified from VPI 10463. We show that the injection of TcdA replicates the disruption of the epithelial barrier function and structure observed in HIOs colonized with viable C. difficile. PMID:25312952

Leslie, Jhansi L; Huang, Sha; Opp, Judith S; Nagy, Melinda S; Kobayashi, Masayuki; Young, Vincent B; Spence, Jason R

2015-01-01

283

Mechanism of conjugated linoleic acid and vaccenic acid formation in human faecal suspensions and pure cultures of intestinal bacteria.  

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Faecal bacteria from four human donors and six species of human intestinal bacteria known to metabolize linoleic acid (LA) were incubated with LA in deuterium oxide-enriched medium to investigate the mechanisms of conjugated linoleic acid (CLA) and vaccenic acid (VA) formation. The main CLA products in faecal suspensions, rumenic acid (cis-9,trans-11-CLA; RA) and trans-9,trans-11-CLA, were labelled at C-13, as were other 9,11 geometric isomers. Traces of trans-10,cis-12-CLA formed were labelled to a much lower extent. In pure culture, Bifidobacterium breve NCFB 2258 formed labelled RA and trans-9,trans-11-CLA, while Butyrivibrio fibrisolvens 16.4, Roseburia hominis A2-183T, Roseburia inulinivorans A2-192T and Ruminococcus obeum-like strain A2-162 converted LA to VA, labelled in a manner indicating that VA was formed via C-13-labelled RA. Propionibacterium freudenreichii subsp. shermanii DSM 4902T, a possible probiotic, formed mainly RA with smaller amounts of trans-10,cis-12-CLA and trans-9,trans-11-CLA, labelled the same as in the mixed microbiota. Ricinoleic acid (12-OH-cis-9-18 : 1) did not form CLA in the mixed microbiota, in contrast to CLA formation described for Lactobacillus plantarum. These results were similar to those reported for the mixed microbiota of the rumen. Thus, although the bacterial genera and species responsible for biohydrogenation in the rumen and the human intestine differ, and a second route of RA formation via a 10-OH-18 : 1 is present in the intestine, the overall labelling patterns of different CLA isomers formation are common to both gut ecosystems. A hydrogen-abstraction enzymic mechanism is proposed that may explain the role of a 10-OH-18 : 1 intermediate in 9,11-CLA formation in pure and mixed cultures. PMID:19118369

McIntosh, Freda M; Shingfield, Kevin J; Devillard, Estelle; Russell, Wendy R; Wallace, R John

2009-01-01

284

Human Intestinal Epithelial Cells Express Interleukin-10 through Toll-Like Receptor 4-Mediated Epithelial-Macrophage Crosstalk.  

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In the intestine, interaction between epithelial cells and macrophages (M?s) create a unique immunoregulatory microenvironment necessary to maintain local immune and tissue homeostasis. Human intestinal epithelial cells (IECs) have been shown to express interleukin (IL)-10, which keeps epithelial integrity. We have demonstrated that bacterial signaling through Toll-like receptor (TLR) 4 induces 15-deoxy-?-12,14-prostaglandin J2 (15d-PGJ2) synthesis in intestinal M?s by cyclooxygenase (Cox)-2 expression. Here, we show that TLR4 signaling generates crosstalk between IECs and M?s that enhances IL-10 expression in IECs. Direct stimulation of TLR4 leads to the expression of IL-10 in IECs, while the presence of M?s in a Transwell system induces another peak in IL-10 expression in IECs at a later time point. The second peak of the IL-10 expression is two times greater than the first peak. This late induction of IL-10 depends on the nuclear receptor peroxisome proliferator-activated receptor (PPAR) ? that is accumulated in IECs by TLR4-mediated inhibition of the ubiquitin-proteasomal pathway. TLR4 signaling in M?s in turn synthesizes 15d-PGJ2 through p38 and ERK activation and Cox-2 induction, which activates PPAR? in IECs. These results suggest that TLR4 signaling maintains IL-10 production in IECs by generating epithelial-M?s crosstalk, which is an important mechanism in the maintenance of intestinal homeostasis mediated through host-bacterial interactions. © 2014 S. Karger AG, Basel. PMID:25171731

Hyun, Jinhee; Romero, Laura; Riveron, Reldy; Flores, Claudia; Kanagavelu, Saravana; Chung, Kristina D; Alonso, Ana; Sotolongo, John; Ruiz, Jose; Manukyan, Armine; Chun, Sally; Singh, Gaurav; Salas, Pedro; Targan, Stephan R; Fukata, Masayuki

2015-01-01

285

The polymorphism at codon 54 of the FABP2 gene increases fat absorption in human intestinal explants.  

Science.gov (United States)

Based on titration microcalorimetry and Caco-2 cell line transfection studies, it has been suggested that the A54T of the FABP2 gene plays a significant role in the assimilation of dietary fatty acids. However, reports were divergent with regard to the in vivo interaction between this polymorphism and postprandial lipemia. We therefore determined the influence of this intestinal fatty acid-binding protein polymorphism on intestinal fat transport using the human jejunal organ culture model, thus avoiding the interference of various circulating factors capable of metabolizing in vivo postprandial lipids. Analysis of DNA samples from 32 fetal intestines revealed 22 homozygotes for the wild-type Ala-54/Ala-54 genotype (0.83) and 10 heterozygotes for the polymorphic Thr-54/Ala-54 genotype (0.17). The Thr-encoding allele was associated with increased secretion of newly esterified triglycerides, augmented de novo apolipoprotein B synthesis, and elevated chylomicron output. On the other hand, no alterations were found in very low density lipoprotein and high density lipoprotein production, apolipoprotein A-I biogenesis, or microsomal triglyceride transfer protein mass and activity. Similarly, the alanine to threonine substitution at residue 54 did not result in changes in brush border hydrolytic activities (sucrase, glucoamylase, lactase, and alkaline phosphatase) or in glucose uptake or oxidation. Our data clearly document that the A54T polymorphism of FABP2 specifically influences small intestinal lipid absorption without modifying glucose uptake or metabolism. It is proposed that, in the absence of confounding factors such as environmental and genetic variables, the FABP2 polymorphism has an important effect on postprandial lipids in vivo, potentially influencing plasma levels of lipids and atherogenesis. PMID:11487582

Levy, E; Ménard, D; Delvin, E; Stan, S; Mitchell, G; Lambert, M; Ziv, E; Feoli-Fonseca, J C; Seidman, E

2001-10-26

286

Pro-inflammatory flagellin proteins of prevalent motile commensal bacteria are variably abundant in the intestinal microbiome of elderly humans.  

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Some Eubacterium and Roseburia species are among the most prevalent motile bacteria present in the intestinal microbiota of healthy adults. These flagellate species contribute "cell motility" category genes to the intestinal microbiome and flagellin proteins to the intestinal proteome. We reviewed and revised the annotation of motility genes in the genomes of six Eubacterium and Roseburia species that occur in the human intestinal microbiota and examined their respective locus organization by comparative genomics. Motility gene order was generally conserved across these loci. Five of these species harbored multiple genes for predicted flagellins. Flagellin proteins were isolated from R. inulinivorans strain A2-194 and from E. rectale strains A1-86 and M104/1. The amino-termini sequences of the R. inulinivorans and E. rectale A1-86 proteins were almost identical. These protein preparations stimulated secretion of interleukin-8 (IL-8) from human intestinal epithelial cell lines, suggesting that these flagellins were pro-inflammatory. Flagellins from the other four species were predicted to be pro-inflammatory on the basis of alignment to the consensus sequence of pro-inflammatory flagellins from the ?- and ?- proteobacteria. Many fliC genes were deduced to be under the control of ?(28). The relative abundance of the target Eubacterium and Roseburia species varied across shotgun metagenomes from 27 elderly individuals. Genes involved in the flagellum biogenesis pathways of these species were variably abundant in these metagenomes, suggesting that the current depth of coverage used for metagenomic sequencing (3.13-4.79 Gb total sequence in our study) insufficiently captures the functional diversity of genomes present at low (?1%) relative abundance. E. rectale and R. inulinivorans thus appear to synthesize complex flagella composed of flagellin proteins that stimulate IL-8 production. A greater depth of sequencing, improved evenness of sequencing and improved metagenome assembly from short reads will be required to facilitate in silico analyses of complete complex biochemical pathways for low-abundance target species from shotgun metagenomes. PMID:23935906

Neville, B Anne; Sheridan, Paul O; Harris, Hugh M B; Coughlan, Simone; Flint, Harry J; Duncan, Sylvia H; Jeffery, Ian B; Claesson, Marcus J; Ross, R Paul; Scott, Karen P; O'Toole, Paul W

2013-01-01

287

Intestinal Coccidia  

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Full Text Available Intestinal Coccidia are a subclass of Apicomplexa phylum. Eucoccidida are facultative heteroxenous, but some of them are monoxenous. They have sexual and asexual life cycle. Some coccidia are human pathogens, for example: Cryptosporidium: Cryptosporidiums has many species that are mammalian intestinal parasites.C. Parvum specie is a human pathogenic protozoa. Cryptosporidum has circle or ellipse shapes and nearly 4-6 mm. It is transmitted in warm seasons. Oocyst is obtained insexual life cycle that has 20% thin layer and 80% thick layer. Oocyst with thick layer is able to live a long time in nature. They are the third or forth of gastroentritis disease that have digestive disorder like anorexia, nausea, persistent diarrhoea, malabsorption and leanness. The disease forms choronic and acute stages and it is able to kill the immunodeficiency cases. Sometimes it has HIV symptoms similar to pneumonia and respiratory track infection. Laboratory diagnosis is based on Oocyst finding in stool exam and that shitter floatation and Cr (KOH2 are the best methods. Modified zyh-lnelson and fleocroum are the best staining methods too. This parasite is transmitted by zoonotic and Antroponotic origin. Molecular studies have shown two Genotypes (I&II. Genotype I is aquatic and II is zoonotic. The prevalence rate is 3% in infants and 10% in calves. Cyclospora: This parasite is novel and is bigger than cryptosporidium.It isn't known a clear life cycle but is transmitted by water, vegetables and fruits as raspberries. and mulberries. Human is a specific host. When a parasite is in the intestine it causes inflammatory reaction in Entrocyte.The patient shows watery diarrhoea with nausea, vomitting, pain, Stomach cramp, anorexia, malabsorption and cachexia. The disease period is 3 monthes in immunodeficiency cases but it is selflimited in normal cases. Autofluorescence characteristic is differential diagnosis, prevalence rate of disease is unknown. Isospora: This intestinal parasite is in most parts of the world. Sometimes it is noun traveller diarrhea Syndrom. The egg shapes of Oocyst are disporic tetrazoic. It is transmitted by vegetables and fruits. Trophozoite pass through schizogony step and repeats it several times. In the end of the cycle gametogony is done and the sexual forms will be repelled the human intestine. Symptoms are persistent diarrhoea, epigastric pain, headache, fever, vomitting and leanness, especially when physiologic disorder condition is seen in patient or they are in traveling. Misdiagnosis is a problem in laboratories but floatation method with zinc sulfate or sugar syrup is recommended. Sarcocystis: Sporocyst of S.hominis and S. suihominis is in the human feces, and the cyst form is in pig and cow muscles. It founds in tha tongue, pharynx and oesophagus muscles of habitant buffalo in Iran. Because of the large size of the cyst (1cm, it is seen with naked eyes and the risk of human infection is rare. If human eats raw or uncooked cow and pig meat, he will be infected with it. Sexual cycle is in the human body and sporocyst is repelled by the intestine. The disease may or may not have any symptoms. The symptoms are diarrhoea, stomach cramp, jejenuom and ileum necrosis. Diagnosis is based on concentrated floatation. The prevalence rate is too much in domestic animals.

MJ Ggaravi

2007-06-01

288

Formation of delta 2- and delta 3-cholenoic acids from bile acid 3-sulfates by a human intestinal Fusobacterium strain.  

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We isolated two strains of an unnamed Fusobacterium species from human intestinal microflora, which stereospecifically transformed bile acid 3-sulfates into C-3-unsubstituted, ring A-unsaturated bile acids. Both 3 alpha- and 3 beta-sulfates of 5 beta-bile acids were metabolized to delta 3-5 beta-cholenoic acids; 3 beta-sulfates of 5 alpha-bile acids were converted into a mixture of delta 2-5 alpha-bile acids and 3 alpha-hydroxy-5 alpha-bile acids, whereas 3 alpha-sulfates of 5 alpha-bile acid...

Robben, J.; Janssen, G.; Merckx, R.; Eyssen, H.

1989-01-01

289

Tspan-1 interacts with the thiamine transporter-1 in human intestinal epithelial cells and modulates its stability.  

Science.gov (United States)

The human thiamine transporter-1 (hTHTR-1) contributes to intestinal thiamine uptake, and its function is regulated at both the transcriptional and posttranscriptional levels. Nothing, however, is known about the protein(s) that may interact with hTHTR-1 and affects its cell biology and physiology. We addressed this issue in the present investigation using a bacterial two-hybrid system to screen a human intestinal cDNA library with the complete coding sequence of hTHTR-1 as a bait. Our results showed that a member of the tetraspanin family of proteins, Tspan-1, interacts with hTHTR-1. Coimmunoprecipitation and glutathione S-transferase (GST)-pulldown assays confirmed the existence of such an interaction between hTspan-1 and hTHTR-1 in human intestinal epithelial Caco-2 cells. Furthermore, live cell confocal imaging demonstrated that hTspan-1 and hTHTR-1 colocalize in human intestinal epithelial HuTu-80 cells. The importance of the interaction between hTspan-1 and hTHTR-1 for cell biology of the thiamine transporter was examined in HuTu-80 cells stably expressing hTHTR-1. Coexpression of hTspan-1 in these cells led to a significant decrease in the rate of degradation of hTHTR-1 compared with cells expressing the hTHTR-1 alone; in fact the half-life of the hTHTR-1 protein was twice longer in the former cell type compared with the latter cell type (12 h vs. 6 h, respectively). This finding was also confirmed at the functional level when a significantly higher thiamine uptake was observed in cycloheximide-treated (6 h) cells expressing hTHTR-1 together with hTspan-1 compared with those expressing hTHTR-1 alone. These studies demonstrate for the first time that Tspan-1 is an interacting partner with hTHTR-1 and that this interaction affects hTHTR-1 stability. PMID:21836059

Nabokina, Svetlana M; Senthilkumar, Sundar Rajan; Said, Hamid M

2011-11-01

290

MUC3 human intestinal mucin. Analysis of gene structure, the carboxyl terminus, and a novel upstream repetitive region  

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MUC3 is a large mucin glycoprotein expressed by the human intestine and gall bladder. In this manuscript, we present details of the deduced protein structure of MUC3. The MUC3 carboxyl-terminal domain is 617 residues in length, including 511 residues of a non-repetitive mucin-like domain (27% Thr, 22% Ser, and 11% Pro) and a 106-residue Cys-rich domain with homology to the epidermal growth factor (EGF)-like structural motifs found in many proteins. The region of MUC3 located upstream of the p...

Gum Jr, J. R.; Ho, J. J. L.; Hicks, J. W.; Roberton, A. M.; Kim, Y. S.; Pratt, W. S.; Hill, A. S.; Vinall, L. E.; Swallow, D. M.

1997-01-01

291

Transcriptional regulation of the human Na+/H+ exchanger NHE3 by serotonin in intestinal epithelial cells  

International Nuclear Information System (INIS)

Serotonin (5-HT) decreases NHE2 and NHE3 activities under acute conditions in human intestinal epithelial cells. Here, we have investigated the effects of 5-HT on expression of the human NHE3 gene and the mechanisms underlying its transcriptional regulation in differentiated C2BBe1 cells. Treatment of the human intestinal epithelial cell line, C2BBe1, with 5-HT (20 ?M) resulted in a significant decrease in NHE3 mRNA and protein expression. In transient transfection studies, 5-HT repressed the NHE3 promoter activity by ?55%. The repression of the NHE3 promoter activity in response to 5-HT was accompanied by reduced DNA-binding activity of transcription factors Sp1 and Sp3 to the NHE3 promoter without alteration in their nuclear levels. Pharmacological inhibitors of protein kinase C reversed the inhibitory effect of 5-HT on the promoter activity. Our data indicate that 5-HT suppresses the transcriptional activity of the NHE3 promoter and this effect may be mediated by PKC? and modulation of DNA-binding affinities of Sp1 and Sp3.

292

Polarized secretion of newly synthesized lipoproteins by the Caco-2 human intestinal cell line  

International Nuclear Information System (INIS)

Lipoprotein secretion by Caco-2 cells, a human intestinal cell line, was studied in cells grown on inserts containing a Millipore filter (0.45 micron), separating secretory products from the apical and basolateral membranes into separate chambers. Under these conditions, as observed by electron microscopy, the cells formed a monolayer of columnar epithelial cells with microvilli on the apical surface and tight junctions between cells. The electrical resistances of the cell monolayers were 250-500 ohms/cm2. Both 14C-labeled lipids and 35S-labeled proteins were used to assess lipoprotein secretion. After a 24-hr incubation with [14C]oleic acid, 60-80% of the secreted triglyceride (TG) was in the basolateral chamber; 40% of the TG was present in the d less than 1.006 g/ml (chylomicron + VLDL) fraction and 50% in the 1.006 less than d less than 1.063 g/ml (LDL) fraction. After a 4-hr incubation with [35S]methionine, apolipoproteins were found to be major secretory products with 75-100% secreted to the basolateral chamber. Apolipoproteins B-100, B-48, E, A-I, A-IV, and C-III were identified by immunoprecipitation. The d less than 1.006 g/ml fraction was found to contain all of the major apolipoproteins, while the LDL fraction contained primarily apoB-100 and apoE; the HDL (1.063 less than d less than 1.21 g/ml) fraction principally contained apoA-I and apoA-IV. Mn-heparin precipitated all of the [35S]methionine-labeled of the [35S]methionine-labeled apoB-100 and B-48 and a majority of the other apolipoproteins, and 80% of the [14C]oleic acid-labeled triglyceride, but only 15% of the phospholipid, demonstrating that Caco-2 cells secrete triglyceride-rich lipoproteins containing apoB

293

Intestinal Cancer  

Science.gov (United States)

... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...

294

HUMAN CARE FACING TRANSITION TO MATERNAL ROLE: PUERPERAL EXPERIENCES  

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Full Text Available It is a study on the changes the transition to maternal role brings about in the puerperal period. Itobjectified to uncover how the puerperal mother experiences transition to maternal role while care is delivered; toset up new methodological ways to implement new human care models privileging role change. It?s a qualitativestudy trailing a methodological research-care trajectory. Thirteen puerperal, several-aged primíparas were interviewed.The instrument used was a semi-structured interview in the clinic. Analysis was effected by informationreading and re-reading. To become the analysis process more accurate reaching depth in understanding, meaningunits were structured through intellectual exercise. Three categories take up the apprehended. Point out the needfor nurses to be alert for the signs of transition, stressing supportive professional help facing the multiple possibilitiesof being.

Juliana Athayde

2003-12-01

295

Antimicrobial activity of Phyllanthus amarus on some human intestinal facultatively anaerobic flora  

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Full Text Available Background: Phyllanthus amarus is an economic plant grown in West Africa that has antimicrobial properties. Aim: We investigated antimicrobial activity of aqueous extract of Phyllanthus amarus against some intestinal flora that are facultative anaerobes. Methods: The leaves were washed thoroughly in clean water, and rinsed in sterile distilled water, allowed to dry at room temperature for several days. It was oven dried at 45OC for about an hour until considered brittle enough to bleed. Final dilutions used were 500 mg/ml, 400 mg/ml, 300 mg/ml, 250 mg/ml and 200 mg/ml. Six intestinal organisms were isolated and identified: K. pneumoniae, P. aeruginosa, S. aureus, E. coli. P. mirabilis and E. faecalis. Both agar diffusion and broth dilution methods were used to assay antimicrobial activity against the organisms. Results: The result indicated that the growth of the organisms were inhibited at 50 mg/ml of aqueous extract by agar diffusion and broth dilution methods but varied at lower concentration. Phyllanthus amarus showed bacteriostatic action at this concentration because sub-culture yielded growth except on plate of K. pneumoniae. Consumption of cold or hot aqueous herbal preparations can alter microbial balance. The implication of ingestion of cold or hot aqueous herbal preparations against the normal intestinal flora was discussed. Conclusion: P. amarus possesses significant antimicrobial activity against normal intestinal flora.

Babatunde S.K

2014-03-01

296

Mouse gastric tumor models with prostaglandin E2 pathway activation show similar gene expression profiles to intestinal-type human gastric cancer  

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Full Text Available Abstract Background Gastric cancers are generally classified into better differentiated intestinal-type tumor and poorly differentiated diffuse-type one according to Lauren's histological categorization. Although induction of prostaglandin E2 pathway promotes gastric tumors in mice in cooperation with deregulated Wnt or BMP signalings, it has remained unresolved whether the gastric tumor mouse models recapitulate either of human gastric cancer type. This study assessed the similarity in expression profiling between gastric tumors of transgenic mice and various tissues of human cancers to find best-fit human tumors for the transgenic mice models. Results Global expression profiling initially found gastric tumors from COX-2/mPGES-1 (C2mE-related transgenic mice (K19-C2mE, K19-Wnt1/C2mE, and K19-Nog/C2mE resembled gastric cancers among the several tissues of human cancers including colon, breast, lung and gastric tumors. Next, classification of the C2mE-related transgenic mice by a gene signature to distinguish human intestinal- and diffuse-type tumors showed C2mE-related transgenic mice were more similar to intestinal-type compared with diffuse one. We finally revealed that induction of Wnt pathway cooperating with the prostaglandin E2 pathway in mice (K19-Wnt1/C2mE mice further reproduce features of human gastric intestinal-type tumors. Conclusion We demonstrated that C2mE-related transgenic mice show significant similarity to intestinal-type gastric cancer when analyzed by global expression profiling. These results suggest that the C2mE-related transgenic mice, especially K19-Wnt1/C2mE mice, serve as a best-fit model to study molecular mechanism underlying the tumorigenesis of human gastric intestinal-type cancers.

Oshima Masanobu

2009-12-01

297

Adaptive regulation of human intestinal thiamine uptake by extracellular substrate level: a role for THTR-2 transcriptional regulation.  

Science.gov (United States)

The intestinal thiamine uptake process is adaptively regulated by the level of vitamin in the diet, but the molecular mechanism involved is not fully understood. Here we used the human intestinal epithelial Caco-2 cells exposed to different levels of extracellular thiamine to delineate the molecular mechanism involved. Our results showed that maintaining Caco-2 cells in a thiamine-deficient medium resulted in a specific and significant increase of [3H]thiamine uptake compared with cell exposure to a high level of thiamine (1 mM). This adaptive regulation was also associated with a higher level of mRNA expression of thiamine transporter-2 (THTR-2), but not thiamine transporter-1 (THTR-1), in the deficient condition and a higher level of promoter activity of gene encoding THTR-2 (SLC19A3). Using 5'-truncated promoter-luciferase constructs, we identified the thiamine level-responsive region in the SLC19A3 promoter to be between -77 and -29 (using transcriptional start site as +1). By means of mutational analysis, a key role for a stimulating protein-1 (SP1)/guanosine cytidine box in mediating the effect of extracellular thiamine level on SLC19A3 promoter was established. Furthermore, extracellular level of thiamine was found to affect SP1 protein expression and binding pattern to the thiamine level-responsive region of SLC19A3 promoter in Caco-2 cells as shown by Western blotting and electrophoretic mobility shift assay analysis, respectively. These studies demonstrate that the human intestinal thiamine uptake is adaptively regulated by the extracellular substrate level via transcriptional regulation of the THTR-2 system, and report that SP1 transcriptional factor is involved in this regulation. PMID:23989004

Nabokina, Svetlana M; Subramanian, Veedamali S; Valle, Judith E; Said, Hamid M

2013-10-15

298

Absorção intestinal de D-xilose em crianças infectadas pelo vírus da imunodeficiência humana Intestinal absorption of D-xilose in children infected with the human immunodeficiency virus  

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Objetivos - Avaliar a absorção intestinal em crianças de 18 meses a 14 anos infectadas pelo HIV, atendidas em uma unidade de ambulatório e verificar se existe associação entre má absorção, diarréia, estado nutricional, alteração imunológica, parasitas entéricos clássicos e Cryptosporidium. Metodologia - A absorção intestinal foi investigada utilizando-se a medida da D-xilose sérica. Amostras fecais foram colhidas para a pesquisa de pátogenos entéricos clássicos e Cryptosp...

Perin, Nilza Medeiros; Pires, Maria Marlene Souza; Nassar, Si?lvia Modesto

2001-01-01

299

Fate and effect of ingested Bacillus cereus spores and vegetative cells in the intestinal tract of human-flora-associated rats  

DEFF Research Database (Denmark)

The fate and effect of Bacillus cereus F4433/73R in the intestine of human-flora-associated rats was studied using bacteriological culturing techniques and PCR-denaturing gradient gel electrophoresis in combination with cell assays and immunoassays for detection of enterotoxins. In faecal samples from animals receiving vegetative cells, only few B. cereus cells were detected. Spores survived the gastric barrier well, and were in some cases detected up to 2 weeks after ingestion. Selective growing revealed no major changes in the intestinal flora during passage of B. cereus. However, denaturing gradient gel electrophoresis analysis with universal 16S rRNA gene primers revealed significant changes in the intestinal microbiota of animals dosed with spores. Vero cell assays and a commercial kit (BCET-RPLA) did not reveal any enterotoxin production from B. cereus F4433/73R in the intestinal tract.

Wilcks, Andrea; Hansen, Bjarne Munk

2006-01-01

300

Multiple forms of human intestinal alkaline phosphatase: chemical and enzymatic properties, and circulating clearances of the fast- and slow-moving enzymes  

International Nuclear Information System (INIS)

Two forms of alkaline phosphatase orthophosphoric monoester phosphohydrolase (alkaline optimum, EC 3.1.3.1) have been purified from human small intestine by column chromatography on DEAE-cellulose and tyraminyl derivative affinity gel, and by preparative disc gel electrophoresis. Intestinal phosphatases were electrophoretically separated into two components, fast- and slow-moving enzymes, with apparent molecular weights of 140000 and 168000 and with subunit weights of 68000 and 80000, respectively. Organ distribution of injected 125I-labelled enzymes indicates that the desialylated hepatic enzyme was selectively distributed in liver, while the degalactosylated intestinal enzyme was incorporated into liver, lymph fluid, and small intestine. These results suggest that the pathway of circulating clearance of alkaline phosphatase has several routes. (Auth.)

 
 
 
 
301

Monensin inhibits canonical Wnt signaling in human colorectal cancer cells and suppresses tumor growth in multiple intestinal neoplasia mice.  

Science.gov (United States)

The Wnt signaling pathway is required during embryonic development and for the maintenance of homeostasis in adult tissues. However, aberrant activation of the pathway is implicated in a number of human disorders, including cancer of the gastrointestinal tract, breast, liver, melanoma, and hematologic malignancies. In this study, we identified monensin, a polyether ionophore antibiotic, as a potent inhibitor of Wnt signaling. The inhibitory effect of monensin on the Wnt/?-catenin signaling cascade was observed in mammalian cells stimulated with Wnt ligands, glycogen synthase kinase-3 inhibitors, and in cells transfected with ?-catenin expression constructs. Furthermore, monensin suppressed the Wnt-dependent tail fin regeneration in zebrafish and Wnt- or ?-catenin-induced formation of secondary body axis in Xenopus embryos. In Wnt3a-activated HEK293 cells, monensin blocked the phoshorylation of Wnt coreceptor low-density lipoprotein receptor related protein 6 and promoted its degradation. In human colorectal carcinoma cells displaying deregulated Wnt signaling, monensin reduced the intracellular levels of ?-catenin. The reduction attenuated the expression of Wnt signaling target genes such as cyclin D1 and SP5 and decreased the cell proliferation rate. In multiple intestinal neoplasia (Min) mice, daily administration of monensin suppressed progression of the intestinal tumors without any sign of toxicity on normal mucosa. Our data suggest monensin as a prospective anticancer drug for therapy of neoplasia with deregulated Wnt signaling. PMID:24552772

Tumova, Lucie; Pombinho, Antonio R; Vojtechova, Martina; Stancikova, Jitka; Gradl, Dietmar; Krausova, Michaela; Sloncova, Eva; Horazna, Monika; Kriz, Vitezslav; Machonova, Olga; Jindrich, Jindrich; Zdrahal, Zbynek; Bartunek, Petr; Korinek, Vladimir

2014-04-01

302

Cytotoxicity of carboxylic acid functionalized single wall carbon nanotubes on the human intestinal cell line Caco-2.  

Science.gov (United States)

The unique properties of carbon nanotubes (CNTs) have been explored for their use in biomedical sciences and in biotechnological fields; however, their possible toxic effects are of concern. The sources of human exposure to nanomaterials include inhalation, ingestion, dermal contact and injection. The pulmonary and dermal effects of CNTs in vitro have been previously studied with contradictory results, but data on intestinal cells are scarce. The aim of this study was to evaluate the cytotoxicity of single wall CNTs functionalized with carboxylic acid on differentiated and non-differentiated Caco-2 cells, derived from a human intestinal adenocarcinoma. Biomarkers assessed were neutral red uptake (NR), protein content (PT), a tetrazolium salt (MTS) metabolization, LDH leakage (LDH) and cell viability by means of the trypan blue exclusion test (TBET). Moreover, a morphological study was performed. Cells were exposed to concentrations between 5 and 1,000 microg/ml CNTs and toxic effects were studied after 24h of exposure. NR and MTS results showed a concentration-dependent trend with an inhibitory response from 100 microg/ml CNT, together with an increase in LDH leakage. TBET resulted in an 80% reduction at higher concentrations, and finally PT was only modified at higher concentrations. Overall, results indicated cytotoxic effects on the Caco-2 cells with differentiated cultures showing a higher sensitivity. Thus, a hazard assessment of CNTs is necessary as the nanotechnology industry grows, and more nanoscale wastes are released into the environment. PMID:19591917

Jos, Angeles; Pichardo, Silvia; Puerto, María; Sánchez, Elena; Grilo, Antonio; Cameán, Ana M

2009-12-01

303

Cholinergic signaling inhibits oxalate transport by human intestinal T84 cells  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Urolithiasis remains a very common disease in Western countries. Seventy to eighty percent of kidney stones are composed of calcium oxalate, and minor changes in urinary oxalate affect stone risk. Intestinal oxalate secretion mediated by anion exchanger SLC26A6 plays a major constitutive role in limiting net absorption of ingested oxalate, thereby preventing hyperoxaluria and calcium oxalate urolithiasis. Using the relatively selective PKC-? inhibitor rottlerin, we had previously found that ...

Hassan, Hatim A.; Cheng, Ming; Aronson, Peter S.

2011-01-01

304

Inhibition of the NF-?B Pathway in Human Intestinal Epithelial Cells by Commensal Streptococcus salivarius ? †  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Streptococcus salivarius exhibited an anti-inflammatory effect on intestinal epithelial cells (IECs) and monocytes. Strains were screened using a reporter clone, HT-29/kB-luc-E, induced by tumor necrosis factor alpha (TNF-?). Supernatant from each strain downregulated NF-?B activation. The two most efficient strains produced an active metabolite (<3 kDa) which was able to downregulate the secretion of the proinflammatory chemokine interleukin-8 (IL-8).

Kaci, Ghalia; Lakhdari, Omar; Dore?, Joe?l; Ehrlich, S. Dusko; Renault, Pierre; Blottie?re, Herve? M.; Delorme, Christine

2011-01-01

305

Vasoactive intestinal peptide inhibits human small-cell lung cancer proliferation in vitro and in vivo  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Small-cell lung carcinoma (SCLC) is an aggressive, rapidly growing and metastasizing, and highly fatal neoplasm. We report that vasoactive intestinal peptide inhibits the proliferation of SCLC cells in culture and dramatically suppresses the growth of SCLC tumor-cell implants in athymic nude mice. In both cases, the inhibition was mediated apparently by a cAMP-dependent mechanism, because the inhibition was enhanced by the adenylate cyclase activator forskolin and the phosphodiesterase inhibi...

Maruno, Kaname; Absood, Afaf; Said, Sami I.

1998-01-01

306

Human intestinal P-glycoprotein activity estimated by the model substrate digoxin  

DEFF Research Database (Denmark)

P-glycoprotein (Pgp) plays a part in the intestinal uptake of xenobiotics and has been associated with susceptibility to ulcerative colitis. The aim of this study was to examine Pgp activity in relation to age, gender, medical treatment (rifampicin or ketoconazole) and the multidrug resistance (MDR1) gene single nucleotide polymorphisms (SNPs) G2677T and C3435T using the model drug digoxin.

Larsen, U L; Hyldahl Olesen, L

2007-01-01

307

Adherence of Probiotic Bacteria to Human Intestinal Mucus in Healthy Infants and during Rotavirus Infection  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The concentration of fecal mucin and the adhesion of specific probiotics and their combinations in the intestinal mucus of infants during and after rotavirus diarrhea and in healthy children were determined. Mucus was prepared from fecal samples from 20 infants during and after rotavirus diarrhea and from 10 healthy age-matched children. Mucin concentration was determined, and the adhesion of five probiotics—Lactobacillus rhamnosus GG, Lactobacillus casei Shirota, Lactobacillus paracasei F1...

Juntunen, M.; Kirjavainen, P. V.; Ouwehand, A. C.; Salminen, S. J.; Isolauri, E.

2001-01-01

308

Expression and function of the lipocalin-2 (24p3/NGAL) receptor in rodent and human intestinal epithelia  

DEFF Research Database (Denmark)

The lipocalin 2//NGAL/24p3 receptor (NGAL-R/24p3-R) is expressed in rodent distal nephron where it mediates protein endocytosis. The mechanisms of apical endocytosis and transcytosis of proteins and peptides in the intestine are poorly understood. In the present study, the expression and localization of rodent 24p3-R (r24p3-R) and human NGAL-R (hNGAL-R) was investigated in intestinal segments by immunofluorescence and confocal laser scanning microscopy, immunohistochemistry and immunoblotting. r24p3-R/hNGAL-R was also studied in human Caco-2 BBE cells and CHO cells transiently transfected with r24p3-R by immunofluorescence microscopy, RT-PCR and immunoblotting of plasma membrane enriched vesicles (PM). To assay function, endocytosis/transcytosis of putative ligands phytochelatin (PC?), metallothionein (MT) and transferrin (Tf) was assayed by measuring internalization of fluorescence-labelled ligands in Caco-2 BBE cells grown on plastic or as monolayers on Transwell inserts. The binding affinity of Alexa 488-PC? to colon-like Caco-2 BBE PM was quantified by microscale thermophoresis (MST). r24p3-R/hNGAL-R expression was detected apically in all intestinal segments but showed the highest expression in ileum and colon. Colon-like, but not duodenum-like, Caco-2 BBE cells expressed hNGAL-R on their surface. Colon-like Caco-2 BBE cells or r24p3-R transfected CHO cells internalized fluorescence-labelled PC? or MT with half-maximal saturation at submicromolar concentrations. Uptake of PC? and MT (0.7 µM) by Caco-2 BBE cells was partially blocked by hNGAL (500 pM) and an EC?? of 18.6 ± 12.2 nM was determined for binding of Alexa 488-PC? to PM vesicles by MST. Transwell experiments showed rapid (0.5-2 h) apical uptake and basolateral delivery of fluorescent PC?/MT/Tf (0.7 µM). Apical uptake of ligands was significantly blocked by 500 pM hNGAL. hNGAL-R dependent uptake was more prominent with MT but transcytosis efficiency was reduced compared to PC? and Tf. Hence, r24p3-R/hNGAL-R may represent a high-affinity multi-ligand receptor for apical internalization and transcytosis of intact proteins/peptides by the lower intestine.

Langelueddecke, Christian; Roussa, Eleni

2013-01-01

309

Substrate specificity of carboxylesterase isozymes and their contribution to hydrolase activity in human liver and small intestine.  

Science.gov (United States)

Hydrolase activity from human liver and small intestine microsomes was compared with that of recombinant human carboxylesterases, hCE-1 and hCE-2. Although both hCE-1 and hCE-2 are present in human liver, the dominant component was found to be hCE-1, whereas the hydrolase activity of the human small intestine was found to be predominantly hCE-2. hCE-2 has a limited ability to hydrolyze large acyl compound substrates. Interestingly, propranolol derivatives, good substrates for hCE-2, were easily hydrolyzed by substitution of the methyl group on the 2-position of the acyl moiety, but were barely hydrolyzed when the methyl group was substituted on the 3-position. These findings suggest that hCE-2 does not easily form acylated intermediates because of conformational interference in its active site. In contrast, hCE-1 could hydrolyze a variety of substrates. The hydrolytic activity of hCE-2 increased with increasing alcohol chain length in benzoic acid derivative substrates, whereas hCE-1 preferentially catalyzed the hydrolysis of substrates with short alcohol chains. Kinetic data showed that the determining factor for the rate of hydrolysis of p-aminobenzoic acid esters was V(max) for hCE-1 and K(m) for hCE-2. Furthermore, the addition of hydrophobic alcohols to the reaction mixture with p-aminobenzoic acid propyl ester induced high and low levels of transesterification by hCE-1 and hCE-2, respectively. When considering the substrate specificities of hCE-1, it is necessary to consider the transesterification ability of hCE-1, in addition to the binding structure of the substrate in the active site of the enzyme. PMID:16837570

Imai, Teruko; Taketani, Megumi; Shii, Mayumi; Hosokawa, Masakiyo; Chiba, Kan

2006-10-01

310

Anti inflammatory and anti angiogenic effect of black raspberry extract on human esophageal and intestinal microvascular endothelial cells.  

Science.gov (United States)

Polyphenolic compounds (anthocyanins, flavonoid glycosides) in berries prevent the initiation, promotion, and progression of carcinogenesis in rat's digestive tract and esophagus, in part, via anti-inflammatory pathways. Angiogenesis has been implicated in the pathogenesis of chronic inflammation and tumorigenesis. In this study, we investigated the anti-inflammatory and anti-angiogenic effects of black raspberry extract (BRE) on two organ specific primary human intestinal microvascular endothelial cells, (HIMEC) and human esophageal microvascular endothelial cells (HEMEC), isolated from surgically resected human intestinal and donor discarded esophagus, respectively. HEMEC and HIMEC were stimulated with TNF-?/IL-1? with or without BRE. The anti-inflammatory effects of BRE were assessed based upon COX-2, ICAM-1 and VCAM-1 gene and protein expression, PGE2 production, NF?B p65 subunit nuclear translocation as well as endothelial cell-leukocyte adhesion. The anti-angiogenic effects of BRE were assessed on cell migration, proliferation and tube formation following VEGF stimulation as well as on activation of Akt, MAPK and JNK signaling pathways. BRE inhibited TNF-?/IL-1?-induced NF?B p65 nuclear translocation, PGE2 production, up-regulation of COX-2, ICAM-1 and VCAM-1 gene and protein expression and leukocyte binding in HEMEC but not in HIMEC. BRE attenuated VEGF-induced cell migration, proliferation and tube formation in both HEMEC and HIMEC. The anti-angiogenic effect of BRE is mediated by inhibition of Akt, MAPK and JNK phosphorylations. BRE exerted differential anti-inflammatory effects between HEMEC and HIMEC following TNF-?/IL-1? activation whereas demonstrated similar anti-angiogenic effects following VEGF stimulation in both cell lines. These findings may provide more insight into the anti-tumorigenic capacities of BRE in human disease and cancer. PMID:25446010

Medda, Rituparna; Lyros, Orestis; Schmidt, Jamie L; Jovanovic, Nebojsa; Nie, Linghui; Link, Benjamin J; Otterson, Mary F; Stoner, Gary D; Shaker, Reza; Rafiee, Parvaneh

2015-01-01

311

Immunomodulatory effect of a wild blueberry anthocyanin-rich extract in human Caco-2 intestinal cells.  

Science.gov (United States)

Intestinal inflammation is a natural process crucial for the maintenance of gut functioning. However, abnormal or prolonged inflammatory responses may lead to the onset of chronic degenerative diseases, typically treated by means of pharmacological interventions. Dietary strategies for the prevention of inflammation are a safer alternative to pharmacotherapy. Anthocyanins and other polyphenols have been documented to display anti-inflammatory activity. In the present study, three bioactive fractions (anthocyanin, phenolic, and water-soluble fractions) were extracted from a wild blueberry powder. The Caco-2 intestinal model was used to test the immunomodulatory effect of the above fractions. Only the anthocyanin-rich fraction reduced the activation of NF-?B, induced by IL-1? in intestinal epithelial Caco-2 cells. Specifically, concentrations of 50 and 100 ?g mL(-1) decreased NF-?B activation by 68.9 and 85.2%, respectively (p ? 0.05). These preliminary results provide further support for the role of food bioactives as potential dietary anti-inflammatory agents. PMID:25075866

Taverniti, Valentina; Fracassetti, Daniela; Del Bo', Cristian; Lanti, Claudia; Minuzzo, Mario; Klimis-Zacas, Dorothy; Riso, Patrizia; Guglielmetti, Simone

2014-08-20

312

Fourier-transform infrared spectroscopy of human cancerous and normal intestine  

Science.gov (United States)

FTIR employs a unique approach to optical diagnosis of tissue pathology based on the characteristic molecular vibrational spectra of the tissue. The architectural changes in the cellular and sub-cellular levels developing in abnormal tissue, including a majority of cancer forms, manifest themselves in different optical signatures, which can be detected in IR spectroscopy. The molecular vibrational modes, which are responsible for IR absorption spectra, are characteristic of the biochemistry of the cells and their sub-cellular components. The biological systems we have studied include adenocarcinoma and normal colonic tissues obtained from the department of pathology at Soroka Medical Center. Our method is based on microscopic IR study of thin tissue specimens and a direct comparison with normal histopathological analysis, which serves as a 'gold' reference. Several unique differences between normal and cancerous intestinal specimens have been observed. The cancerous intestine has weaker absorption strength over a wide region, which includes several significant vibrational bands. The results from microscopic IR absorption spectra from intestinal tissues have also been compared with other biological tissue samples.

Mordechai, Shaul; Salman, Ahmad O.; Argov, Shmuel; Cohen, Beny; Erukhimovitch, Vitaly; Goldstein, Jed; Chaims, Orna; Hammody, Ziad

2000-05-01

313

Analytically monitored digestion of silver nanoparticles and their toxicity on human intestinal cells.  

Science.gov (United States)

Orally ingested nanoparticles may overcome the gastrointestinal barrier, reach the circulatory system, be distributed in the organism and cause adverse health effects. However, ingested nanoparticles have to pass through different physicochemical environments, which may alter their properties before they reach the intestinal cells. In this study, silver nanoparticles are characterised physicochemically during the course of artificial digestion to simulate the biochemical processes occurring during digestion. Their cytotoxicity on intestinal cells was investigated using the Caco-2 cell model. Using field-flow fractionation combined with dynamic light scattering and small-angle X-ray scattering, the authors found that particles only partially aggregate as a result of the digestive process. Cell viabilities were determined by means of CellTiter-Blue® assay, 4',6-diamidino-2-phenylindole-staining and real-time impedance. These measurements reveal small differences between digested and undigested particles (1-100 µg/ml or 1-69 particles/cell). The findings suggest that silver nanoparticles may indeed overcome the gastrointestinal juices in their particulate form without forming large quantities of aggregates. Consequently, the authors presume that the particles can reach the intestinal epithelial cells after ingestion with only a slight reduction in their cytotoxic potential. The study indicates that it is important to determine the impact of body fluids on the nanoparticles of interest to provide a reliable interpretation of their nano-specific cytotoxicity testing in vivo and in vitro. PMID:23763544

Böhmert, Linda; Girod, Matthias; Hansen, Ulf; Maul, Ronald; Knappe, Patrick; Niemann, Birgit; Weidner, Steffen M; Thünemann, Andreas F; Lampen, Alfonso

2014-09-01

314

Polarity of fatty acid uptake and metabolism in a human intestinal cell line (CACO-2)  

International Nuclear Information System (INIS)

Free fatty acids (ffa) can enter the intestinal cell via the apical (AP) or basolateral (BL) membrane. The authors are using the Caco-2 intestinal cell line to examine the polarity of ffa uptake and metabolism in the enterocyte. Cells are grown on permeable polycarbonate Transwell filters in order to obtain access to both AP and BL compartments. Differentiated Caco-2 cells form tight polarized monolayers which express small intestine-specific enzymes and are impermeable to the fluid phase marker Lucifer Yellow. Submicellar concentrations of 3H-palmitic acid (2uM) were added to AP or BL sides of Caco-2 monolayers at 37 degrees C and cells were incubated for various times between 2 and 120 minutes. Total AP and BL uptake is similar; however, when relative membrane surface areas are accounted for, AP uptake is about 2-fold higher. The metabolism of AP and BL ffa is not significantly different: triacylglycerol and phosphatidylcholine account for most of the metabolites (32±4 and 24±2% respectively at 5 minutes). Little ffa oxidation is observed. Preincubation with albumin-bound 2-monoolein (100uM) and palmitate (50uM) increases the level of TG metabolites. The results suggest that in this cell line the uptake of AP ffa may be greater than BL ffa, but that AP (dietary) ffa and BL (plasma) ffa are metabolized similarly

315

A comparative analysis of the intestinal metagenomes present in guinea pigs (Cavia porcellus) and humans (Homo sapiens)  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract Background Guinea pig (Cavia porcellus) is an important model for human intestinal research. We have characterized the faecal microbiota of 60 guinea pigs using Illumina shotgun metagenomics, and used this data to compile a gene catalogue of its prevalent microbiota. Subsequently, we compared the guinea pig microbiome to existing human gut metagenome data from the MetaHIT project. Results We found that the bacterial richness obtained for human ...

Hildebrand Falk; Ebersbach Tine; Nielsen Henrik; Li Xiaoping; Sonne Si; Bertalan Marcelo; Dimitrov Peter; Madsen Lise; Qin Junjie; Wang Jun; Raes Jeroen; Kristiansen Karsten; Licht Tine

2012-01-01

316

Analysis of the human intestinal epithelial cell transcriptional response to Lactobacillus acidophilus, Lactobacillus salivarius, Bifidobacterium lactis and Escherichia coli  

DEFF Research Database (Denmark)

The complex microbial population residing in the human gastrointestinal tract consists of commensal, potential pathogenic and beneficial species, which are probably perceived differently by the host and consequently could be expected to trigger specific transcriptional responses. Here, we provide a comparative analysis of the global in vitro transcriptional response of human intestinal epithelial cells to Lactobacillus acidophilus NCFM™, Lactobacillus salivarius Ls-33, Bifidobacterium animalis subsp. lactis 420, and enterohaemorrhagic Escherichia coli O157:H7 (EHEC). Interestingly, L. salivarius Ls-33 DCE-induced changes were overall more similar to those of B. lactis 420 than to L. acidophilus NCFM™, which is consistent with previously observed in vivo immunomodulation properties. In the gene ontology and pathway analyses both specific and unspecific changes were observed. Common to all was the regulation of apoptosis and adipogenesis, and lipid-metabolism related regulation by the probiotics. Specific changes such as regulation of cell-cell adhesion by B. lactis 420, superoxide metabolism by L. salivarius Ls-33, and regulation of MAPK pathway by L. acidophilus NCFM™ were noted. Furthermore, fundamental differences were observed between the pathogenic and probiotic treatments in the Toll-like receptor pathway, especially for adapter molecules with a lowered level of transcriptional activation of MyD88, TRIF, IRAK1 and TRAF6 by probiotics compared to EHEC. The results in this study provide insights into the relationship between probiotics and human intestinal epithelial cells, notably with regard to strain-specific responses, and highlight the differences between transcriptional responses to pathogenic and probiotic bacteria.

Putaala, H; Barrangou, R

2010-01-01

317

Hes1 promotes the IL-22-mediated antimicrobial response by enhancing STAT3-dependent transcription in human intestinal epithelial cells  

Energy Technology Data Exchange (ETDEWEB)

Highlights: •Hes1 enhances IL-22-STAT3 signaling in human intestinal epithelial cells. •Hes1 enhances REG family gene induction by IL-22-STAT3 signaling. •Protein level of Hes1 restricts the response to IL-22. •Present regulation of a cytokine signal represents a new mode of Hes1 function. -- Abstract: Notch signaling plays an essential role in the proliferation and differentiation of intestinal epithelial cells (IECs). We have previously shown that Notch signaling is up-regulated in the inflamed mucosa of ulcerative colitis (UC) and thereby plays an indispensable role in tissue regeneration. Here we show that in addition to Notch signaling, STAT3 signaling is highly activated in the inflamed mucosa of UC. Forced expression of the Notch target gene Hes1 dramatically enhanced the IL-22-mediated STAT3-dependent transcription in human IECs. This enhancement of STAT3-dependent transcription was achieved by the extended phosphorylation of STAT3 by Hes1. Microarray analysis revealed that Hes1-mediated enhancement of IL-22-STAT3 signaling significantly increased the induction of genes encoding antimicrobial peptides, such as REG1A, REG3A and REG3G, in human IECs. Conversely, the reduction of Hes1 protein levels with a ?-secretase inhibitor significantly down-regulated the induction of those genes in IECs, resulting in a markedly poor response to IL-22. Our present findings identify a new role for the molecular function of Hes1 in which the protein can interact with cytokine signals and regulate the immune response of IECs.

Murano, Tatsuro [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan); Okamoto, Ryuichi, E-mail: rokamoto.gast@tmd.ac.jp [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan); Department of Advanced GI Therapeutics, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan); Ito, Go; Nakata, Toru; Hibiya, Shuji; Shimizu, Hiromichi; Fujii, Satoru; Kano, Yoshihito; Mizutani, Tomohiro; Yui, Shiro; Akiyama-Morio, Junko; Nemoto, Yasuhiro [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan); Tsuchiya, Kiichiro; Nakamura, Tetsuya [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan); Department of Advanced GI Therapeutics, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan); Watanabe, Mamoru [Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University, Tokyo (Japan)

2014-01-17

318

A Human Breast Cell Model of Preinvasive to Invasive Transition  

Science.gov (United States)

A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from preinvasive to invasive phenotype as it may occur “spontaneously” in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted basement membrane cultures. These cells remained noninvasive; however, unlike their nonmalignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including squamous and basal characteristics, with invasive cells exhibiting features of higher-grade tumors. To find functionally significant changes in transition from preinvasive to invasive phenotype, we performed attribute profile clustering analysis on the list of genes differentially expressed between preinvasive and invasive cells. We found integral membrane proteins, transcription factors, kinases, transport molecules, and chemokines to be highly represented. In addition, expression of matrix metalloproteinases MMP9, MMP13, MMP15, and MMP17 was up-regulated in the invasive cells. Using small interfering RNA–based approaches, we found these MMPs to be required for the invasive phenotype. This model provides a new tool for dissection of mechanisms by which preinvasive breast cells could acquire invasiveness in a metaplastic context. PMID:18316601

Rizki, Aylin; Weaver, Valerie M.; Lee, Sun-Young; Rozenberg, Gabriela I.; Chin, Koei; Myers, Connie A.; Bascom, Jamie L.; Mott, Joni D.; Semeiks, Jeremy R.; Grate, Leslie R.; Mian, I. Saira; Borowsky, Alexander D.; Jensen, Roy A.; Idowu, Michael O.; Chen, Fanqing; Chen, David J.; Petersen, Ole W.; Gray, Joe W.; Bissell, Mina J.

2009-01-01

319

The effect of probiotic strains on the microbiota of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME).  

Science.gov (United States)

The aim of the present work was to study five potential probiotic strains (Lactobacillus plantarum, two strains of L. paracasei subsp. paracasei, L. rhamnosus and Bifidobacterium sp.) comparatively in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) in vitro model, and to evaluate this model as a tool in the screening and selection of probiotic bacteria. The impact of the strains on the composition of microbiota and its metabolic activities (production of lactic acid and short-chain fatty acids) was studied. Changes in composition of the microbiota become apparent as a result of probiotic treatment. A marked, but temporary, increase was noted in the number of lactic acid bacteria and bifidobacteria. The profiles of D(-) and L(+) isomers of lactic acid detected in the SHIME after addition of probiotic strains corresponded well to those that are produced in pure culture conditions. The numbers of enterobacteriaceae decreased markedly and those of clostridia detectably during the intervention, while the enterococci tended to increase after the treatment. This pattern was similar in the reactors representing both the small and large intestine in the model. The changes in short-chain fatty acids were small, and no definite trend was observed. PMID:10050686

Alander, M; De Smet, I; Nollet, L; Verstraete, W; von Wright, A; Mattila-Sandholm, T

1999-01-12

320

The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4?  

International Nuclear Information System (INIS)

The cytosolic human intestinal fatty acid binding protein (hFABP2) is proposed to be involved in intestinal absorption of long-chain fatty acids. The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4? (HNF-4?), involved in regulation of genes of fatty acid metabolism and differentiation. Electromobility shift assays demonstrated that HNF-4? binds at position -324 to -336 within the hFABP2 promoter. Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4? by about 50%. Thus, binding element at position -336/-324 essentially determines the transcriptional activity of promoter and may be important in control of hFABP2 expression by dietary lipids and differentiation. Studying genotype interactions of hFABP2 and HNF-4?, that are both candidate genes for diabetes type 2, may be a powerful approach

 
 
 
 
321

Absorção intestinal de D-xilose em crianças infectadas pelo vírus da imunodeficiência humana / Intestinal absorption of D-xilose in children infected with the human immunodeficiency virus  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese Objetivos - Avaliar a absorção intestinal em crianças de 18 meses a 14 anos infectadas pelo HIV, atendidas em uma unidade de ambulatório e verificar se existe associação entre má absorção, diarréia, estado nutricional, alteração imunológica, parasitas entéricos clássicos e Cryptosporidium. Metodolog [...] ia - A absorção intestinal foi investigada utilizando-se a medida da D-xilose sérica. Amostras fecais foram colhidas para a pesquisa de pátogenos entéricos clássicos e Cryptosporidium. O tamanho da amostra foi calculado considerando a prevalência de 30% com precisão de 5% de alteração na absorção da D-xilose em crianças infectadas pelo HIV. Os procedimentos estatísticos utilizados foram: medidas descritivas, análise de correspondência múltipla e regressão logística. Resultados - Das 104 crianças estudadas, somente 8 (7,7%) apresentaram o teste da D-xilose alterado e 33 (31,73%) foram positivas para Cryptosporidium. A análise de correspondência múltipla aplicada aos dados encontrados sugeriu a associação entre o teste da D-xilose alterado e a presença de Cryptosporidium. Não se encontrou associação entre o teste alterado e diarréia, estado nutricional, alteração imunológica e parasistas entéricos clássicos. Conclusões - A má absorção intestinal avaliada pelo teste da D-xilose foi infreqüente nas crianças HIV positivas estudadas. O comprometimento intestinal, quando presente, parece estar relacionado com a presença de Cryptosporidium, porém não com diarréia, estado nutricional, alteração imunológica e parasistas entéricos clássicos. Abstract in english Aim - To evaluate the intestinal absorption in HIV-infected children children 14 months to 14 years and to investigate its relationship to diarrhea, nutritional status, immune dysfunction, classical enteric parasites and Cryptosporidium. Methods - Intestinal absorption was investigated by measuring [...] serum D-xylose. Fecal samples were investigated for classical pathogens and Cryptosporidium. The sample size was calculated considering a 30% prevalence of altered D-xylose absorption in HIV-infected children with a 5% accuracy. Statistical procedures used were: descriptive measurements, multiple correspondence analysis and logistic regression. Results - D-xylose absorption was altered in only 8 out of 104 (7,7%) and Cryptosporidium was positive in 33 out of 104 (31,73%) HIV-infected children. The multiple correspondence analysis suggested an association between an altered D-xylose test and Cryptosporidium. D-xylose malabsorption was not associated with diarrhea, nutritional status, immune disfunction and classic enteric parasites. Conclusions - Intestinal malabsorption evaluated through the D-xylose test was an uncommon finding in HIV-infected children. Intestinal dysfunction when present seems to be related to Cryptosporidium, but not to diarrhea, nutritional status, immune disfunction and classic enteric parasites.

Nilza Medeiros, PERIN; Maria Marlene de Souza, PIRES; Sílvia Modesto, NASSAR.

2001-10-01

322

Transition State Analogues of Plasmodium falciparum and Human Orotate Phosphoribosyltransferases*  

Science.gov (United States)

The survival and proliferation of Plasmodium falciparum parasites and human cancer cells require de novo pyrimidine synthesis to supply RNA and DNA precursors. Orotate phosphoribosyltransferase (OPRT) is an indispensible component in this metabolic pathway and is a target for antimalarials and antitumor drugs. P. falciparum (Pf) and Homo sapiens (Hs) OPRTs are characterized by highly dissociative transition states with ribocation character. On the basis of the geometrical and electrostatic features of the PfOPRT and HsOPRT transition states, analogues were designed, synthesized, and tested as inhibitors. Iminoribitol mimics of the ribocation transition state in linkage to pyrimidine mimics using methylene or ethylene linkers gave dissociation constants (Kd) as low as 80 nm. Inhibitors with pyrrolidine groups as ribocation mimics displayed slightly weaker binding affinities for OPRTs. Interestingly, p-nitrophenyl riboside 5?-phosphate bound to OPRTs with Kd values near 40 nm. Analogues designed with a C5-pyrimidine carbon–carbon bond to ribocation mimics gave Kd values in the range of 80–500 nm. Acyclic inhibitors with achiral serinol groups as the ribocation mimics also displayed nanomolar inhibition against OPRTs. In comparison with the nucleoside derivatives, inhibition constants of their corresponding 5?-phosphorylated transition state analogues are largely unchanged, an unusual property for a nucleotide-binding site. In silico docking of the best inhibitor into the HsOPRT active site supported an extensive hydrogen bond network associated with the tight binding affinity. These OPRT transition state analogues identify crucial components of potent inhibitors targeting OPRT enzymes. Despite their tight binding to the targets, the inhibitors did not kill cultured P. falciparum. PMID:24158442

Zhang, Yong; Evans, Gary B.; Clinch, Keith; Crump, Douglas R.; Harris, Lawrence D.; Fröhlich, Richard F. G.; Tyler, Peter C.; Hazleton, Keith Z.; Cassera, María B.; Schramm, Vern L.

2013-01-01

323

Structural Stability of Human Fibroblast Growth Factor-1 Is Essential for Protective Effects Against Radiation-Induced Intestinal Damage  

International Nuclear Information System (INIS)

Purpose: Human fibroblast growth factor-1 (FGF1) has radioprotective effects on the intestine, although its structural instability limits its potential for practical use. Several stable FGF1 mutants were created increasing stability in the order, wild-type FGF1, single mutants (Q40P, S47I, and H93G), Q40P/S47I, and Q40P/S47I/H93G. This study evaluated the contribution of the structural stability of FGF1 to its radioprotective effect. Methods and Materials: Each FGF1 mutant was administered intraperitoneally to BALB/c mice in the absence of heparin 24 h before or after total body irradiation (TBI) with ?-rays at 8-12 Gy. Several radioprotective effects were examined in the jejunum. Results: Q40P/S47I/H93G could activate all subtypes of FGF receptors in vitro much more strongly than the wild-type without endogenous or exogenous heparin. Preirradiation treatment with Q40P/S47I/H93G significantly increased crypt survival more than wild-type FGF1 after TBI at 10 or 12 Gy, and postirradiation treatment with Q40P/S47I/H93G was effective in promoting crypt survival after TBI at 10, 11, or 12 Gy. In addition, crypt cell proliferation, crypt depth, and epithelial differentiation were significantly promoted by postirradiation treatment with Q40P/S47I/H93G. The level of stability of FGF1 mutants correlated with their mitogenic activities in vitro in the absence of heparin; however, preirradiation treatment with the mutants increased the crypt number to almost the same level as Qrypt number to almost the same level as Q40P/S47I/H93G. When given 24 h after TBI at 10 Gy, all FGF1 mutants increased crypt survival more than wild-type FGF1, and Q40P/S47I/H93G had the strongest mitogenic effects in intestinal epithelial cells after radiation damage. Moreover, Q40P/S47I/H93G prolonged mouse survival after TBI because of the repair of intestinal damage. Conclusion: These findings suggest that the structural stability of FGF1 can contribute to the enhancement of protective effects against radiation-induced intestinal damage. Therefore, Q40P/S47I/H93G is pharmacologically one of the most promising candidates for clinical applications for radiation-induced gastrointestinal syndrome.

324

Structural Stability of Human Fibroblast Growth Factor-1 Is Essential for Protective Effects Against Radiation-Induced Intestinal Damage  

Energy Technology Data Exchange (ETDEWEB)

Purpose: Human fibroblast growth factor-1 (FGF1) has radioprotective effects on the intestine, although its structural instability limits its potential for practical use. Several stable FGF1 mutants were created increasing stability in the order, wild-type FGF1, single mutants (Q40P, S47I, and H93G), Q40P/S47I, and Q40P/S47I/H93G. This study evaluated the contribution of the structural stability of FGF1 to its radioprotective effect. Methods and Materials: Each FGF1 mutant was administered intraperitoneally to BALB/c mice in the absence of heparin 24 h before or after total body irradiation (TBI) with {gamma}-rays at 8-12 Gy. Several radioprotective effects were examined in the jejunum. Results: Q40P/S47I/H93G could activate all subtypes of FGF receptors in vitro much more strongly than the wild-type without endogenous or exogenous heparin. Preirradiation treatment with Q40P/S47I/H93G significantly increased crypt survival more than wild-type FGF1 after TBI at 10 or 12 Gy, and postirradiation treatment with Q40P/S47I/H93G was effective in promoting crypt survival after TBI at 10, 11, or 12 Gy. In addition, crypt cell proliferation, crypt depth, and epithelial differentiation were significantly promoted by postirradiation treatment with Q40P/S47I/H93G. The level of stability of FGF1 mutants correlated with their mitogenic activities in vitro in the absence of heparin; however, preirradiation treatment with the mutants increased the crypt number to almost the same level as Q40P/S47I/H93G. When given 24 h after TBI at 10 Gy, all FGF1 mutants increased crypt survival more than wild-type FGF1, and Q40P/S47I/H93G had the strongest mitogenic effects in intestinal epithelial cells after radiation damage. Moreover, Q40P/S47I/H93G prolonged mouse survival after TBI because of the repair of intestinal damage. Conclusion: These findings suggest that the structural stability of FGF1 can contribute to the enhancement of protective effects against radiation-induced intestinal damage. Therefore, Q40P/S47I/H93G is pharmacologically one of the most promising candidates for clinical applications for radiation-induced gastrointestinal syndrome.

Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Umeda, Sachiko [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Yasuda, Takeshi [Department of Radiation Emergency Medicine, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba (Japan); Asada, Masahiro; Motomura, Kaori; Suzuki, Masashi [Signaling Molecules Research Laboratory, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki (Japan); Zakrzewska, Malgorzata [Faculty of Biotechnology, University of Wroclaw (Poland); Imamura, Toru [Signaling Molecules Research Laboratory, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki (Japan); Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan)

2013-02-01

325

Geometrical guidance and trapping transition of human sperm cells  

CERN Document Server

The guidance of human sperm cells under confinement in quasi 2D microchambers is investigated using a purely physical method to control their distribution. Transport property measurements and simulations are performed with dilute sperm populations, for which effects of geometrical guidance and concentration are studied in detail. In particular, a trapping transition at convex angular wall features is identified and analyzed. We also show that highly efficient microratchets can be fabricated by using curved asymmetric obstacles to take advantage of the spermatozoa specific swimming strategy.

Guidobaldi, A; Berdakin, I; Moshchalkov, V V; Condat, C A; Marconi, V I; Giojalas, L; Silhanek, A V

2014-01-01

326

Intestinal absorption of human insulin in pigs using delivery systems based on superporous hydrogel polymers.  

Science.gov (United States)

In this in vivo study, novel delivery systems based on superporous hydrogel (SPH) and SPH composite (SPHC) polymers were used to improve the intestinal absorption of insulin in healthy pigs. Six female pigs of approximately 35 kg body weight were used. A cannula was inserted into the jugular vein for blood sampling and a silicone fistula in the duodenum for administration of gelatin capsules containing the delivery systems or insulin solutions. The delivery systems consisted of two components, (1) conveyor system made of SPH and SPHC; (2) core containing insulin. The core was inserted either into the conveyor system (core inside, c.i.) or attached to the surface of conveyor system (core outside, c.o.). The following intestinal formulations were investigated: c.i., c.o. and intraduodenal (i.d.) administration of insulin solutions. Subcutaneous (s.c.) injection of insulin was also investigated for reasons of comparison. Blood samples were taken and analyzed for insulin and glucose concentrations. Relative bioavalibility values of 1.3+/-0.4 and 1.9+/-0.7% were achieved for c.o. and c.i. administrations, respectively. The bioavalibility for i.d. administration of insulin solution was 0.5+/-0.2%. These results indicate that the absorption of insulin was slightly increased using SPH/SPHC-based delivery systems. Furthermore, a large variability was observed, probably due to physiological and metabolic changes during the experiments. Blood glucose levels were slightly decreased after the c.o. and c.i administrations, whereas these levels did not decrease after i.d. administration of insulin solutions. In conclusion, SPH/SPHC-based delivery systems are able to enhance the intestinal absorption of insulin and are, therefore, considered as promising systems for peroral peptide drug delivery. However, insulin delivery from these delivery systems under in vivo have to be improved. PMID:12429484

Dorkoosh, F A; Verhoef, J C; Borchard, G; Rafiee-Tehrani, M; Verheijden, J H M; Junginger, H E

2002-10-24

327

Heparin modulates human intestinal smooth muscle (HISM) cell proliferation and matrix production  

International Nuclear Information System (INIS)

(HISM) cell proliferation and collagen production may play a role in the pathogenesis of intestinal stricture in Crohn's disease. The present studies were performed to evaluate the effects of heparin, a known modulator of vascular smooth muscle cells, on HISM cell proliferation and collagen production. Heparin (100 ?g/ml) was added daily to HISM cell cultures for cell proliferation studies and for 24 hours at various time points during culture for collagen synthesis studies. Collagen synthesis was determined by the uptake of 3H proline into collagenase-sensitive protein. Heparin completely inhibited cell proliferation for 7 days, after which cell numbers increased but at a slower rate than controls. Cells released from heparin inhibition demonstrated catch-up growth to control levels. Collagen production was significantly inhibited by 24 hours exposure to heparin but only at those times during culture when collagen synthesis was maximal (8 to 12 days). Non-collagen protein synthesis was inhibited by heparin at all time points during culture. Heparin through its modulation of HISM cells may play an important role in the control of the extracellular matrix of the intestinal wall

328

Differentially expressed genes related with injury of human intestinal epithelium cell by ?-ray  

International Nuclear Information System (INIS)

In order to isolate differentially expressed genes of intestinal epithelium cell related with ? radiation, by using HIEC cell line in vitro culture as research target, the cell line was irradiated by 8 Gy of ? ray and was continued to culture for 24 h as radiation group, the cell line without ? radiation was as control group. The authors isolated the differentially expressed genes between radiation group and control group by mRNA differential display. The authors obtained 101 fragments of differentially expressed genes, 31 of which were new expressed genes from radiation group, 29 of which were over expressed genes which was higher expressed in radiation group than in control group, 41 of which were no expression in radiation group and expression in control group, 31 of which were from the group of D-T11G as anchored primer, 59 of which were from the group of D-T11A as anchored primer, 32 of which were from the group of D-T11C as anchored primer. In summary, the authors obtained 101 fragments of differentially expressed genes related with ? radiation, 31 among them may be closely correlated with radiation damage to intestinal

329

A method for high purity intestinal epithelial cell culture from adult human and murine tissues for the investigation of innate immune function.  

Science.gov (United States)

Intestinal epithelial cells (IECs) serve as an important physiologic barrier between environmental antigens and the host intestinal immune system. Thus, IECs serve as a first line of defense and may act as sentinel cells during inflammatory insults. Despite recent renewed interest in IEC contributions to host immune function, the study of primary IEC has been hindered by lack of a robust culture technique, particularly for small intestinal and adult tissues. Here, a novel adaptation for culture of primary IEC is described for human duodenal organ donor tissue as well as duodenum and colon of adult mice. These epithelial cell cultures display characteristic phenotypes and are of high purity. In addition, the innate immune function of human primary IEC, specifically with regard to Toll-like receptor (TLR) expression and microbial ligand responsiveness, is contrasted with a commonly used intestinal epithelial cell line (HT-29). Specifically, TLR expression at the mRNA level and production of cytokine (IFN? and TNF?) in response to TLR agonist stimulation is assessed. Differential expression of TLRs as well as innate immune responses to ligand stimulation is observed in human-derived cultures compared to that of HT-29. Thus, use of this adapted method to culture primary epithelial cells from adult human donors and from adult mice will allow for more appropriate studies of IECs as innate immune effectors. PMID:25193428

Graves, Christina L; Harden, Scott W; LaPato, Melissa; Nelson, Michael; Amador, Byron; Sorenson, Heather; Frazier, Charles J; Wallet, Shannon M

2014-12-01

330

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry for rapid analysis of the metabolites of morroniside produced by human intestinal bacteria.  

Science.gov (United States)

Morroniside, the most abundant iridoid glycoside in the valuable traditional Chinese medicine Fructus Corni, exhibits various pharmacological activities and biological effects. Intestinal flora plays an important role in the metabolism of drug compounds, which might lead to the variation of ethnopharmacological profile of the medicine. However, little is known of the interactions of the morroniside with human intestinal bacteria. In this study, different pure bacteria were isolated from human feces and their capability to convert morroniside were investigated. The metabolites of morroniside were analyzed by ultra high performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) technique using Metabolynx™ software. Parent compound and three metabolites were detected and tentatively identified based on the characteristics of their protonated ions. The parent is proposed to be metabolized by three main metabolic pathways including deglycosylation, dehydroxylation and methylation. Morroniside was firstly metabolized to its aglycone (M1), and then was further converted to dehydroxylated aglycone (M2) and methylated aglycone (M3). This is the first report of the metabolism of morroniside by human intestinal bacteria. These metabolites might influence the biological activities of morroniside in vivo, which could affect the clinical effects of medicines. Thus, the study on the metabolism of morroniside by human intestinal bacteria is very helpful to unravel how traditional medicines work. PMID:25482010

Zhao, Min; Du, Leyue; Tao, Jinhua; Qian, Dawei; Guo, Jianming; Jiang, Shu; Shang, Er-Xin; Duan, Jin-Ao; Wu, Chen

2015-01-22

331

Enhanced uptake and transport of (+)-catechin and (-)-epigallocatechin gallate in niosomal formulation by human intestinal Caco-2 cells.  

Science.gov (United States)

The aim of this study was to evaluate (+)-catechin and (-)-epigallocatechin gallate (EGCG) cellular uptake and transport across human intestinal Caco-2 cell monolayer in both the absence and presence of niosomal carrier in variable conditions. The effect of free drugs and drug-loaded niosomes on the growth of Caco-2 cells was studied. The effects of time, temperature, and concentration on drug cellular uptake in the absence or presence of its niosomal delivery systems were investigated. The intestinal epithelial membrane transport of the drug-loaded niosomes was examined using the monolayer of the human Caco-2 cells. The kinetics of transport, and the effect of temperature, adenosine triphosphate inhibitor, permeability glycoprotein inhibitor, multidrug resistance-associated protein 2 inhibitor, and the absorption enhancer on transport mechanism were investigated. It was found that the uptake of catechin, EGCG, and their niosomes by Caco-2 cells was 1.22 ± 0.16, 0.90 ± 0.14, 3.25 ± 0.37, and 1.92 ± 0.22 ?g/mg protein, respectively (n=3). The apparent permeability coefficient values of catechin, EGCG, and their niosomes were 1.68 ± 0.16, 0.88 ± 0.09, 2.39 ± 0.31, and 1.42 ± 0.24 cm/second (n=3) at 37°C, respectively. The transport was temperature- and energy-dependent. The inhibitors of permeability glycoprotein and multidrug resistance-associated protein 2 and the absorption enhancer significantly enhanced the uptake amount. Compared with the free drugs, niosomal formulation significantly enhanced drug absorption. Additionally, drug-loaded niosomes exhibited stronger stability and lower toxicity. These findings showed that the oral absorption of tea flavonoids could be improved by using the novel drug delivery systems. PMID:24855353

Song, Qinxin; Li, Danhui; Zhou, Yongzhi; Yang, Jie; Yang, Wanqi; Zhou, Guohua; Wen, Jingyuan

2014-01-01

332

Metabolism of Rutin and Poncirin by Human Intestinal Microbiota and Cloning of Their Metabolizing ?-L-Rhamnosidase from Bifidobacterium dentium.  

Science.gov (United States)

To understand the metabolism of flavonoid rhamnoglycosides by human intestinal microbiota, we measured the metabolic activity of rutin and poncirin (distributed in many functional foods and herbal medicine) by 100 human stool specimens. The average ?-Lrhamnosidase activities on the p-nitrophenyl-?-L-rhamnopyranoside, rutin, and poncirin subtrates were 0.10 ± 0.07, 0.25 ± 0.08, and 0.15 ± 0.09 pmol/min/mg, respectively. To investigate the enzymatic properties, ?-L-rhamnosidase-producing bacteria were isolated from the specimens, and the ?-L-rhamnosidase gene was cloned from a selected organism, Bifidobacterium dentium, and expressed in E. coli. The cloned ?-L-rhamnosidase gene contained a 2,673 bp sequcence encoding 890 amino acid residues. The cloned gene was expressed using the pET 26b(+) vector in E. coli BL21, and the expressed enzyme was purified using Ni(2+)-NTA and Q-HP column chromatography. The specific activity of the purified ?-L-rhamnosidase was 23.3 ?mol/min/mg. Of the tested natural product constituents, the cloned ?-L-rhamnosidase hydrolyzed rutin most potently, followed by poncirin, naringin, and ginsenoside Re. However, it was unable to hydrolyze quercitrin. This is the first report describing the cloning, expression, and characterization of ?-L-rhamnosidase, a flavonoid rhamnoglycosidemetabolizing enzyme, from bifidobacteria. Based on these findings, the ?-L-rhamnosidase of intestinal bacteria such as B. dentium seem to be more effective in hydrolyzing (1-->6) bonds than (1-->2) bonds of rhamnoglycosides, and may play an important role in the metabolism and pharmacological effect of rhamnoglycosides. PMID:25179902

Bang, Seo-Hyeon; Hyun, Yang-Jin; Shim, Juwon; Hong, Sung-Woon; Kim, Dong-Hyun

2015-01-28

333

Vasoactive intestinal polypeptide and peptide histidine methionine. Presence in human follicular fluid and effects on DNA synthesis and steroid secretion in cultured human granulosa/lutein cells  

DEFF Research Database (Denmark)

Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) originate from the same precursor molecule, prepro VIP. In the present study we examined the concentrations of VIP and PHM in human follicular fluid and their effects on cultured human granulosa/lutein cells. Follicular fluid and cells were obtained from patients undergoing in-vitro fertilization for tubal infertility. The concentrations of VIP and PHM in pre-ovulatory human follicular fluid were measured radioimmunochemically. Granulosa/lutein cells isolated from follicular fluid were cultured under serum-free conditions with VIP and PHM in varying concentrations (0.1, 10, 1000 nmol/l). [3H]Thymidine incorporation in the cells and oestradiol as well as progesterone concentrations in the culture medium were measured. The mean (+/- SEM) concentrations of VIP and PHM were 6.8 +/- 0.1 and 7.7 +/- 0.8 pmol/l, respectively. VIP at a concentration of 10 nmol/l caused a significant increase in [3H]thymidine incorporation, and at 1000 nmol/l a significant increase in oestradiol secretion was observed. VIP had no effect on progesterone secretion. PHM at the concentrations tested did not influence any of the activities. We conclude that VIP and PHM are present in human preovulatory follicular fluid and that VIP stimulates DNA synthesis and oestradiol secretion in cultured human granulosa/lutein cells. This indicates that VIP and perhaps PHM participate in the local nervous regulation of human ovarian function.

Gräs, S; Ovesen, Per Glud

1994-01-01

334

Amebiasis intestinal / Intestinal amebiasis  

Scientific Electronic Library Online (English)

Full Text Available SciELO Colombia | Language: Spanish Abstract in spanish Entamoeba histolytica es el patógeno intestinal más frecuente en nuestro medio -después de Giardia lamblia-, una de las principales causas de diarrea en menores de cinco años y la cuarta causa de muerte en el mundo debida a infección por protozoarios. Posee mecanismos patogénicos complejos que le pe [...] rmiten invadir la mucosa intestinal y causar colitis amebiana. El examen microscópico es el método más usado para su identificación pero la existencia de dos especies morfológicamente iguales, una patógena ( E. histolytica) y una no patógena ( Entamoeba dispar), ha llevado al desarrollo de otros métodos de diagnóstico. El acceso al agua potable y los servicios sanitarios adecuados, un tratamiento médico oportuno y el desarrollo de una vacuna, son los ejes para disminuir la incidencia y mortalidad de esta entidad. Abstract in english Entamoeba histolytica is the most frequent intestinal pathogen seen in our country, after Giardia lamblia, being one of the main causes of diarrhea in children younger than five years of age, and the fourth leading cause of death due to infection for protozoa in the world. It possesses complex patho [...] genic mechanisms that allow it to invade the intestinal mucosa, causing amoebic colitis. Microscopy is the most used method for its identification, but the existence of two species morphologically identical, the pathogen one ( E. histolytica), and the non pathogen one ( E. dispar), have taken to the development of other methods of diagnosis. The access to drinkable water and appropriate sanitary services, an opportune medical treatment, and the development of a vaccine are the axes to diminish the incidence and mortality of this entity.

JULIO CÉSAR, GÓMEZ; JORGE ALBERTO, CORTÉS; SONIA ISABEL, CUERVO; MYRIAM CONSUELO, LÓPEZ.

2007-03-01

335

Endometriosis intestinal / Intestinal endometriosis  

Scientific Electronic Library Online (English)

Full Text Available SciELO Spain | Language: Spanish Abstract in spanish La endometriosis es un trastorno ginecológico crónico, benigno y frecuente entre las mujeres en edad fértil, estimándose que existe algún grado de endometriosis hasta en el 15% de las mujeres premenopáusicas, asociándose a historia de infertilidad, antecedente de cesárea, dismenorrea y anormalidad e [...] n el sangrado uterino. Se cree que es debida al ascenso por las trompas de Falopio de contenido menstrual (menstruación retrógrada). En la afectación intestinal, el colon es el segmento más frecuentemente afectado, sobre todo a nivel rectosigmodeo. La clínica de presentación es inespecífica, siendo lo más frecuente el dolor abdominal y/o pélvico de tipo cólico que coincide o se exacerba con la menstruación. El diagnóstico diferencial incluye la enfermedad inflamatoria intestinal, diverticulitis, colitis isquémica y procesos neoplásicos, siendo el diagnóstico definitivo anatomopatológico. En cuanto al tratamiento, éste dependerá de la clínica y de la edad de la paciente, así como de sus deseos de embarazo. Abstract in english Endometriosis is a chronic, benign gynaecological disorder that is frequent in women of a child-bearing age. It is estimated that there is some degree of endometriosis in as many as 15% of pre-menopausal women, associated with a history of infertility, caesarean antecedents, dysmenorrhoea and abnorm [...] ality in uterine bleeding. It is believed to be due to the rise of menstrual contents through the Fallopian tubes (retrograde menstruation). In the intestinal affectation, the colon is the segment most frequently affected, above all at the rectosigmoidal level. The clinical features are unspecific, with abdominal pain the most frequent and/or pelvic pain of a cholic type that coincides with, or is exacerbated by, menstruation. Differential diagnosis includes intestinal inflammatory disease, diverticulitis, ischemic colitis and neoplastic processes, with the definitive diagnosis being anatomopathological. With respect to treatment, this will depend on the clinical features and the age of the patient, as well as her wishes with regard to pregnancy.

C.I., González; M., Cires; F.J., Jiménez; T., Rubio.

2008-08-01

336

The human neonatal small intestine has the potential for arginine synthesis; developmental changes in the expression of arginine-synthesizing and -catabolizing enzymes  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Milk contains too little arginine for normal growth, but its precursors proline and glutamine are abundant; the small intestine of rodents and piglets produces arginine from proline during the suckling period; and parenterally fed premature human neonates frequently suffer from hypoargininemia. These findings raise the question whether the neonatal human small intestine also expresses the enzymes that enable the synthesis of arginine from proline and/or glutamine. Carbamoylphosphate synthetase (CPS, ornithine aminotransferase (OAT, argininosuccinate synthetase (ASS, arginase-1 (ARG1, arginase-2 (ARG2, and nitric-oxide synthase (NOS were visualized by semiquantitative immunohistochemistry in 89 small-intestinal specimens. Results Between 23 weeks of gestation and 3 years after birth, CPS- and ASS-protein content in enterocytes was high and then declined to reach adult levels at 5 years. OAT levels declined more gradually, whereas ARG-1 was not expressed. ARG-2 expression increased neonatally to adult levels. Neurons in the enteric plexus strongly expressed ASS, OAT, NOS1 and ARG2, while varicose nerve fibers in the circular layer of the muscularis propria stained for ASS and NOS1 only. The endothelium of small arterioles expressed ASS and NOS3, while their smooth-muscle layer expressed OAT and ARG2. Conclusion The human small intestine acquires the potential to produce arginine well before fetuses become viable outside the uterus. The perinatal human intestine therefore resembles that of rodents and pigs. Enteral ASS behaves as a typical suckling enzyme because its expression all but disappears in the putative weaning period of human infants.

Ruijter Jan M

2008-11-01

337

Interaction of CpG-Oligodeoxynucleotides with Toll Like Receptor 9 Induces Apoptosis and Modulates Metaloproteinase-2 Activity in Human Intestinal Epithelium  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Recent reports have indicated different effects of immunostimulatory sequences containing CpG-Oligodeoxynucleotides (ODN) on various immune cells. However, the exact role of CpG-ODN in the human gut is unclear. In the present study, we assessed potential effects of CpG-ODN on non lymphoid cell (intestinal epithelial cell line HT-29) on a dose-response and time-course basis. Intestinal epithelial cell line HT-29 was treated with CpG-ODN (CpG 2006) and lipopolysaccharide (LPS) at 5, 10, 25, 50 ...

Reza Falak; Nastaran Aalizadeh; Farshid Saadat; Farnaz Safavifar; Shahnaz Hosseinzadeh; Mohammad Reza Khorramizadeh; Zohre Jadali; Mohammad Pezeshki

2007-01-01

338

Localizations of Na(+)-D-glucose cotransporters SGLT1 and SGLT2 in human kidney and of SGLT1 in human small intestine, liver, lung, and heart.  

Science.gov (United States)

Novel affinity-purified antibodies against human SGLT1 (hSGLT1) and SGLT2 (hSGLT2) were used to localize hSGLT2 in human kidney and hSGLT1 in human kidney, small intestine, liver, lung, and heart. The renal locations of both transporters largely resembled those in rats and mice; hSGLT2 and SGLT1 were localized to the brush border membrane (BBM) of proximal tubule S1/S2 and S3 segments, respectively. Different to rodents, the renal expression of hSGLT1 was absent in thick ascending limb of Henle (TALH) and macula densa, and the expression of both hSGLTs was sex-independent. In small intestinal enterocytes, hSGLT1 was localized to the BBM and subapical vesicles. Performing double labeling with glucagon-like peptide 1 (GLP-1) or glucose-dependent insulinotropic peptide (GIP), hSGLT1 was localized to GLP-1-secreting L cells and GIP-secreting K cells as has been shown in mice. In liver, hSGLT1 was localized to biliary duct cells as has been shown in rats. In lung, hSGLT1 was localized to alveolar epithelial type 2 cells and to bronchiolar Clara cells. Expression of hSGLT1 in Clara cells was verified by double labeling with the Clara cell secretory protein CC10. Double labeling of human heart with aquaporin 1 immunolocalized the hSGLT1 protein in heart capillaries rather than in previously assumed myocyte sarcolemma. The newly identified locations of hSGLT1 implicate several extra renal functions of this transporter, such as fluid absorption in the lung, energy supply to Clara cells, regulation of enteroendocrine cells secretion, and release of glucose from heart capillaries. These functions may be blocked by reversible SGLT1 inhibitors which are under development. PMID:25304002

Vrhovac, Ivana; Balen Eror, Daniela; Klessen, Dirk; Burger, Christa; Breljak, Davorka; Kraus, Ognjen; Radovi?, Nikola; Jadrijevi?, Stipe; Aleksic, Ivan; Walles, Thorsten; Sauvant, Christoph; Saboli?, Ivan; Koepsell, Hermann

2014-10-11

339

?-helix to ?-hairpin transition of human amylin monomer  

Science.gov (United States)

The human islet amylin polypeptide is produced along with insulin by pancreatic islets. Under some circumstances, amylin can aggregate to form amyloid fibrils, whose presence in pancreatic cells is a common pathological feature of Type II diabetes. A growing body of evidence indicates that small, early stage aggregates of amylin are cytotoxic. A better understanding of the early stages of the amylin aggregation process and, in particular, of the nucleation events leading to fibril growth could help identify therapeutic strategies. Recent studies have shown that, in dilute solution, human amylin can adopt an ?-helical conformation, a ?-hairpin conformation, or an unstructured coil conformation. While such states have comparable free energies, the ?-hairpin state exhibits a large propensity towards aggregation. In this work, we present a detailed computational analysis of the folding pathways that arise between the various conformational states of human amylin in water. A free energy surface for amylin in explicit water is first constructed by resorting to advanced sampling techniques. Extensive transition path sampling simulations are then employed to identify the preferred folding mechanisms between distinct minima on that surface. Our results reveal that the ?-helical conformer of amylin undergoes a transformation into the ?-hairpin monomer through one of two mechanisms. In the first, misfolding begins through formation of specific contacts near the turn region, and proceeds via a zipping mechanism. In the second, misfolding occurs through an unstructured coil intermediate. The transition states for these processes are identified. Taken together, the findings presented in this work suggest that the inter-conversion of amylin between an ?-helix and a ?-hairpin is an activated process and could constitute the nucleation event for fibril growth.

Singh, Sadanand; Chiu, Chi-cheng; Reddy, Allam S.; de Pablo, Juan J.

2013-04-01

340

Effect of Clostridium difficile toxin A on human intestinal epithelial cells: induction of interleukin 8 production and apoptosis after cell detachment.  

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Clostridium difficile is the aetiological agent of pseudomembranous colitis, and animal studies suggest the essential role of secreted toxin A in inducing disease. This study examined the biological responses to toxin A by human intestinal epithelial cells. Confluent monolayers of Caco2, HT29, and T84 cells and primary epithelial cells in organ cultures of human colonic biopsy specimens and after detachment with EDTA were studied. Interleukin 8 was assayed using enzyme linked immunosorbent as...

Mahida, Y. R.; Makh, S.; Hyde, S.; Gray, T.; Borriello, S. P.

1996-01-01

 
 
 
 
341

[Immunologic reactivity and status of the intestinal viral flora of humans in pressurized chambers].  

Science.gov (United States)

Immunity status and intestinal viral flora were studied in 5 experiments with long-term exposure of 26 male subjects in pressurized chamber. In two experiments with congenital microclimate and gaseous environment cellular and humoral indices of immunity did not deviate from the physiological norm. None of 14 subjects in these experiments was identified as a virus-carrier. In three experiments with hard environmental conditions (elevated concentrations of ammonia and carbon dioxide) viruses were isolated from 8 out of 12 subjects. Activation of viral flora mainly occurred on a background of impaired immunologic reactivity. In two experiments carriage of virus was asymptomatic; in the third experiment with the rise of ammonia up to 7 mg/m3 two subjects developed clinic signs that could have been engendered by enteric viruses, the Coxsackie B strain specifically. PMID:11816403

Antropova, E N; Rykova, M P; Meshkov, D O; Kazantseva, V A

2000-01-01

342

Moderate consumption of red wine can modulate human intestinal inflammatory response.  

Science.gov (United States)

In this study, 24 immune markers were analyzed in feces from healthy volunteers (n = 34) before and after consumption of a red wine (12% ethanol, 1758 mg/L total polyphenols) for 4 weeks. Analysis of the data permitted the differentiation of a six-volunteer subgroup showing unusually high basal values of cytokines. For this subgroup, consumption of wine significantly (P wine consumption for the rest of the volunteers. Additionally, significant and negative correlations among cytokines IFN-?, IL-8, and IL-6 and the total fecal content of phenolic metabolites were found for the high-cytokines-values subgroup, before wine intake. This study shows, for the first time, that moderate consumption of red wine could modulate inflammatory intestinal response in vivo. PMID:25263395

Muñoz-González, Irene; Espinosa-Martos, Irene; Rodríguez, Juan M; Jiménez-Girón, Ana; Martín-Álvarez, Pedro J; Bartolomé, Begoña; Moreno-Arribas, M Victoria

2014-10-29

343

Intestinal obstruction  

Science.gov (United States)

... narcotics Mechanical causes of intestinal obstruction may include: Adhesions or scar tissue that forms after surgery Foreign ... in the intestine Infection Jaundice (yellowing of the skin and eyes) If the obstruction blocks the blood ...

344

Actin reorganization is involved in vasoactive intestinal peptide induced human mast cells priming to fraktalkine-induced chemotaxis  

Directory of Open Access Journals (Sweden)

Full Text Available Amr E El-ShazlyDepartment of Oto-Rhino-Laryngology and Head and Neck Surgery, Liege University Hospital (Centre hospitalier Universaitaire-C.H.U., Liege, BelgiumAbstract: We recently reported a novel neuro-immuno co-operation between vasoactive intestinal peptide (VIP and fraktalkine (FKN in recruiting human mast cells to the asthmatic airway that provided a classical example of priming effect on mast cells migratory function, but the role of the F-actin in human mast cell chemotaxis’ priming is poorly defined. Therefore the aim of this study was to further investigate the biophysical role of the cytoskeletal element; the F-actin, intracellular reorganization and its polymerization in mast cell priming of chemotaxis function. In the present communication it is shown by immunofluoresence confocal microscopy analysis that physical F-actin intracellular reorganization in a membrane bound manner on uman mast cell is involved in VIP-induced priming of human mast cell chemotaxis against FKN. The F-actin reorganization was calcium independent and without modifi cation of its contents as assessed by fluorescence-activated cell scanning analysis. These results identify a novel role for the biophysical association of F-actin in the crosstalk between neuro-inflammatory mediators and mast cells and may be an important target for therapeutic modalities in allergic inflammation.Keywords: mast cells, chemotaxis, neuroimmuno-axis, F-actin intracellular reorganization, VIP, priming

Amr E El-Shazly

2008-08-01

345

The prevalence and diversity of intestinal parasitic infections in humans and domestic animals in a rural Cambodian village  

DEFF Research Database (Denmark)

In Cambodia, intestinal parasitic infections are prevalent in humans and particularly in children. Yet, information on potentially zoonotic parasites in animal reservoir hosts is lacking. In May 2012, faecal samples from 218 humans, 94 dogs and 76 pigs were collected from 67 households in Dong village, Preah Vihear province, Cambodia. Faecal samples were examined microscopically using sodium nitrate and zinc sulphate flotation methods, the Baermann method, Koga Agar plate culture, formalin-ether concentration technique and Kato Katz technique. PCR was used to confirm hookworm, Ascaris spp., Giardia spp. and Blastocystis spp. Major gastrointestinal parasitic infections found in humans included hookworms (63.3%), Entamoeba spp. (27.1%) and Strongyloides stercoralis (24.3%). In dogs, hookworm (80.8%), Spirometra spp. (21.3%) and Strongyloides spp. (14.9%) were most commonly detected and in pigs Isospora suis (75.0%), Oesophagostomum spp. (73.7%) and Entamoeba spp. (31.6%) were found. Eleven parasite species weredetected in dogs (eight helminths and three protozoa), seven of which have zoonotic potential, including hookworm, Strongyloides spp., Trichuris spp., Toxocara canis, Echinostoma spp., Giardia duodenalis and Entamoeba spp. Five of the parasite species detected in pigs also have zoonotic potential, including Ascaris spp., Trichuris spp., Capillaria spp., Balantidium coli and Entamoeba spp. Further molecular epidemiological studies will aid characterisation of parasite species and genotypes and allow further insight into the potential for zoonotic cross transmission of parasites in this community.

Schär, Fabian; Inpankaew, Tawin

2014-01-01

346

Adhesion of marine cryptic Escherichia isolates to human intestinal epithelial cells.  

Science.gov (United States)

Five distinct cryptic lineages (clades I-V) have recently been recognized in the Escherichia genus. The five clades encompass strains that are phenotypically and taxonomically indistinguishable from Escherichia coli sensu stricto; however, scant data are available on their ecology, virulence and pathogenic properties. In this study 20 cryptic E. coli strains isolated from marine sediments were investigated to gain insights into their virulence characteristics and genetic traits. The ability to adhere to intestinal cells was highest among clade V strains, which also harbored the genes involved in gut colonization as well as the genes (pduC and eut operon) typically found in environmentally adapted E. coli strains. The pduC gene was significantly associated with clade V. Multilocus sequence typing of three representative clade V isolates revealed new sequence types (STs) and showed that the strains shared two allelic loci (adk 51 and recA 37). Our findings suggest that cryptic Escherichia lineages are common in coastal marine sediments and that this habitat may be suitable for their growth and persistence outside the host. On the other hand, detection in clade V strains of a gene repertoire and adhesion properties similar to those of intestinal pathogenic strains could indicate their potential virulence. It could be argued that there is a dual nature of cryptic clade V strains, where the ability to survive and persist in a secondary habitat does not involve the loss of the host-associated lifestyle. Clade V could be a group of closely related, environmentally adapted E. coli strains. PMID:25216085

Vignaroli, Carla; Sante, Laura Di; Magi, Gloria; Luna, Gian Marco; Di Cesare, Andrea; Pasquaroli, Sonia; Facinelli, Bruna; Biavasco, Francesca

2015-02-01

347

Rapid appraisal of human intestinal helminth infections among schoolchildren in Osh oblast, Kyrgyzstan.  

Science.gov (United States)

A population-representative lot quality assurance sampling (LQAS) survey was conducted in 2009 to determine the prevalence of intestinal helminth infections among schoolchildren across Osh oblast, Kyrgyzstan. The diagnostic approach consisted of duplicate Kato-Katz thick smears from a single stool sample and an adhesive tape test. A questionnaire was administered to identify risk factors for infections. A total of 1262 schoolchildren aged 6-15 years were recruited; 41% of them harboured at least one of the eight identified helminth species. The two most prevalent helminths were Ascaris lumbricoides (23.1%) and Enterobius vermicularis (19.3%). Lower prevalences were found for Hymenolepis nana (4.4%), Fasciola hepatica (1.9%) and Dicrocoelium dendriticum (1.8%). Washing raw vegetables was a protective factor with regard to A. lumbricoides infection (odds ratio (OR)=0.69, p=0.022); tap water was borderline protective (OR=0.56, p=0.057). Children of the richest families were at a lower risk of E. vermicularis infection than the poorest ones (OR=0.41, p=0.011). Sharing the bed with more than one person was a risk factor for E. vermicularis infection (OR=2.0, p=0.002). The results call for targeted interventions against intestinal helminths in Osh oblast. In a first stage, annual deworming of schoolchildren and other high-risk groups with albendazole or mebendazole should be implemented, and reliable diagnosis and additional anthelminthic drugs should be made available. Subsequently, transmission control including locally-adapted health education, improved water supply and adequate sanitation should become the central features. PMID:20615381

Steinmann, Peter; Usubalieva, Jumagul; Imanalieva, Cholpon; Minbaeva, Gulnara; Stefiuk, Kayte; Jeandron, Aurelie; Utzinger, Jürg

2010-12-01

348

Associations between the human intestinal microbiota, Lactobacillus rhamnosus GG and serum lipids indicated by integrated analysis of high-throughput profiling data  

Directory of Open Access Journals (Sweden)

Full Text Available Accumulating evidence indicates that the intestinal microbiota regulates our physiology and metabolism. Bacteria marketed as probiotics confer health benefits that may arise from their ability to affect the microbiota. Here high-throughput screening of the intestinal microbiota was carried out and integrated with serum lipidomic profiling data to study the impact of probiotic intervention on the intestinal ecosystem, and to explore the associations between the intestinal bacteria and serum lipids. We performed a comprehensive intestinal microbiota analysis using a phylogenetic microarray before and after Lactobacillus rhamnosus GG intervention. While a specific increase in the L. rhamnosus-related bacteria was observed during the intervention, no other changes in the composition or stability of the microbiota were detected. After the intervention, lactobacilli returned to their initial levels. As previously reported, also the serum lipid profiles remained unaltered during the intervention. Based on a high-resolution microbiota analysis, intake of L. rhamnosus GG did not modify the composition of the intestinal ecosystem in healthy adults, indicating that probiotics confer their health effects by other mechanisms. The most prevailing association between the gut microbiota and lipid profiles was a strong positive correlation between uncultured phylotypes of Ruminococcus gnavus-group and polyunsaturated serum triglycerides of dietary origin. Moreover, a positive correlation was detected between serum cholesterol and Collinsella (Coriobacteriaceae. These associations identified with the spectrometric lipidome profiling were corroborated by enzymatically determined cholesterol and triglyceride levels. Actinomycetaceae correlated negatively with triglycerides of highly unsaturated fatty acids while a set of Proteobacteria showed negative correlation with ether phosphatidylcholines. Our results suggest that several members of the Firmicutes, Actinobacteria and Proteobacteria may be involved in the metabolism of dietary and endogenous lipids, and provide a scientific rationale for further human studies to explore the role of intestinal microbes in host lipid metabolism.

Leo Lahti

2013-02-01

349

Testing of the Small Intestine (Intestinal Dysmotility)  

Science.gov (United States)

... Personal Stories Who We Are Contact Us Donate Testing of the Small Intestine Small Intestinal dysmotility Small ... Large Intestine Disorders of the Pelvic Floor Motility Testing Esophagus Stomach Small Intestine Large Intestine Anorectal and ...

350

1,25-Dihydroxyvitamin D3 increases the expression of the CaT1 epithelial calcium channel in the Caco-2 human intestinal cell line  

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Full Text Available Abstract Background The active hormonal form of vitamin D (1,25-dihydroxyvitamin D is the primary regulator of intestinal calcium absorption efficiency. In vitamin D deficiency, intestinal calcium absorption is low leading to an increased risk of developing negative calcium balance and bone loss. 1,25-dihydroxyvitamin D has been shown to stimulate calcium absorption in experimental animals and in human subjects. However, the molecular details of calcium transport across the enterocyte are not fully defined. Recently, two novel epithelial calcium channels (CaT1/ECaC2 and ECaC1/CaT2 have been cloned and suggested to be important in regulating intestinal calcium absorption. However, to date neither gene has been shown to be regulated by vitamin D status. We have previously shown that 1,25-dihydroxyvitamin stimulates transcellular calcium transport in Caco-2 cells, a human intestinal cell line. Results In the current study, we have demonstrated that Caco-2 cells express low but detectable levels of CaT1 mRNA in the absence of 1,25-dihydroxyvitamin D treatment. CaT1 mRNA expression is rapidly up regulated (4-fold increase at 4 h and 10-fold at 24 h by treatment with 1,25-dihydroxyvitamin D (10-7 moles/L. Moreover, the increase in CaT1 mRNA expression preceded by several hours the vitamin D induction of calbindin D9K, a putative cytosolic calcium transport protein. Conclusion These observations are the first to demonstrate regulation of CaT1 expression by vitamin D and are consistent with a new model of intestinal calcium absorption wherein vitamin D-mediated changes in brush border membrane CaT1 levels could be the primary gatekeeper regulating homeostatic modulation of intestinal calcium absorption efficiency.

Taparia Shveta

2001-08-01

351

Intestinal spirochetosis  

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Full Text Available The intestinal spirochetosis (IS is a histologically defined by the presence of spirochetal microorganisms connected to the apical cell membrane of the colorectal epithelium. The disease is caused by a heterogeneous group of bacteria. In humans, Brachyspira aalborgi and Brachyspira pilosicoli are prevalent. The incidence ranges from 1% in developed countries to 34% in poorer areas. It affects 62.5% of colonized areas, as well as men who have intercourse with men (MSM and those with the human immunodeficiency virus (HIV infected. Clinical significance of such colonization is still not clear. Most infected people are asymptomatic. At the presence of gastrointestinal symptoms, treatment with metronidazole is effective. Due to unknown reasons, MSM and HIV-positive men are more likely to be symptomatic. Treponema pallidum infection must be excluded, since this agent may cause serious and permanent complications, and because the treatment is different.A espiroquetose intestinal está definida histologicamente como a presença de micro-organismos da família spirochetaceae ligadas ao ápice das células do epitélio cólico. A doença pode ser provocada por um grupo heterogêneo de bactérias. Em humanos, a Brachyspira aalborgi e a Brachyspira pilosicoli predominam. A incidência varia desde 1%, nos países desenvolvidos, até 34% nas áreas mais pobres, atingindo taxas de colonização de 62,5%, em homens que fazem sexo com homens (HSH e vírus da imunodeficiência humana (HIV positivo. O significado clínico dessa colonização ainda é incerto e a maioria dos infectados permanece assintomática. Quando há sintomas gastrointestinais, o tratamento com metronidazol é efetivo. Por razões desconhecidas, HSH positivos para o HIV, apresentam mais infestação sintomática. A infecção pelo Treponema pallidum dever ser excluída, pois os tratamentos são diferentes e as complicações por essa última são mais graves e definitivas.

Luis Roberto Manzione Nadal

2011-12-01

352

Intestinal spirochetosis  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese A espiroquetose intestinal está definida histologicamente como a presença de micro-organismos da família spirochetaceae ligadas ao ápice das células do epitélio cólico. A doença pode ser provocada por um grupo heterogêneo de bactérias. Em humanos, a Brachyspira aalborgi e a Brachyspira pilosicoli pr [...] edominam. A incidência varia desde 1%, nos países desenvolvidos, até 34% nas áreas mais pobres, atingindo taxas de colonização de 62,5%, em homens que fazem sexo com homens (HSH) e vírus da imunodeficiência humana (HIV) positivo. O significado clínico dessa colonização ainda é incerto e a maioria dos infectados permanece assintomática. Quando há sintomas gastrointestinais, o tratamento com metronidazol é efetivo. Por razões desconhecidas, HSH positivos para o HIV, apresentam mais infestação sintomática. A infecção pelo Treponema pallidum dever ser excluída, pois os tratamentos são diferentes e as complicações por essa última são mais graves e definitivas. Abstract in english The intestinal spirochetosis (IS) is a histologically defined by the presence of spirochetal microorganisms connected to the apical cell membrane of the colorectal epithelium. The disease is caused by a heterogeneous group of bacteria. In humans, Brachyspira aalborgi and Brachyspira pilosicoli are p [...] revalent. The incidence ranges from 1% in developed countries to 34% in poorer areas. It affects 62.5% of colonized areas, as well as men who have intercourse with men (MSM) and those with the human immunodeficiency virus (HIV) infected. Clinical significance of such colonization is still not clear. Most infected people are asymptomatic. At the presence of gastrointestinal symptoms, treatment with metronidazole is effective. Due to unknown reasons, MSM and HIV-positive men are more likely to be symptomatic. Treponema pallidum infection must be excluded, since this agent may cause serious and permanent complications, and because the treatment is different.

Luis Roberto Manzione, Nadal; Sidney Roberto, Nadal.

2011-12-01

353

Impact of probiotic drugs, based on Enterobacter faecium autostrains, on human intestinal microflora in confined habitat  

Science.gov (United States)

The aim of research: Investigation of influence of probiotic drugs based on autostrains of Enter-obacter faecium, selected from the crew in long term isolation experiment in confined habitat. It is known that during long-term presence in confined habitat the risk of infectious diseases increases. One of the main infectious risk occurs during first 20 days of isolation as a result of exchange of strains and stress-mediated disbacterioses. Therefore it is necessary to evaluate activities of probiotics to avoid this risk. Furthermore, in case of super long term autonomous flight there should be possibilities of application of autochthonous microflora strains as pro-biotics to strengthen colonial resistance of crews. Materials and methods: In the experiment there were used probiotic drugs based on autostrains of E. faecium, selected from the crew before the experiment. Probiotic drugs were consumed during 30 days since the beginning of the experiment with the break of consumption between 10th to 19th day. Results: Comparing the state of intestinal microflora of the crew on the baseline and 14th day of experiment re-vealed remarkable changes of microflora: the increasing of concentration of bifidobacteria and E. faecium (approximately 10 times), elimination of hemolytic streptococcus, yeasts, reduction of the rate of S.aureus, hemolytic gramnegative non-fermenting rods, lactobacilli and normal E.coli. On the 45th day of isolation, 15 days after finishing of auto-strains administration, there fere signs of restoration of disbacteriosis: the quantitative decreasing lactobacilli, bifidobacteria and normal E.coli, increasing of the rate of S.aureus, hemolytic gramnegative nonfermentive rods. Conclusion: Thus we managed to avoid risk of pathogenicity potential growth in first 2 decades of isolation. Application of probiotic, based on the autostrains of E. faecium leads to insignificant changes of concentration of lactobacteries, bifidobacteries, normal E. coli and to pronounced reduction of concentration of . hemolytic streptococcus, yeasts, S.aureus, hemolytic gramnegative nonfermentive rods. This results give an opportunity to use this drug to prevent the violations in intestine microflora in altered habitat conditions.

Viacheslav, Ilyin; Batov, Alexey; Usanova, Nonna

354

Invariant natural killer T cells developing in the human fetus accumulate and mature in the small intestine.  

Science.gov (United States)

Invariant natural killer T (iNKT) cells are CD1d-restricted immunoregulatory lymphocytes that share characteristics of both the innate and adaptive immune systems. Although it has been reported that iNKT cells are present in the human fetal thymus, it is currently unknown how they distribute, differentiate, and function in fetal peripheral lymphoid and non-lymphoid organs. Here, we show that functional human fetal iNKT cells develop and differentiate in a tissue-specific manner during the second trimester. Fetal iNKT cells accumulated in the small intestine, where they gained a mature phenotype and mounted robust interferon (IFN)-? responses. In contrast, iNKT cells in the spleen and mesenteric lymph nodes were less frequently detected, less differentiated, mounted poor IFN-? responses, but proliferated vigorously upon stimulation with ?-galactosylceramide. These data demonstrate that fetal iNKT cells can differentiate and acquire potent effector functions in utero before the establishment of the commensal microflora. PMID:24646938

Loh, L; Ivarsson, M A; Michaëlsson, J; Sandberg, J K; Nixon, D F

2014-09-01

355

Absorption of black currant anthocyanins by monolayers of human intestinal epithelial Caco-2 cells mounted in ussing type chambers.  

Science.gov (United States)

Anthocyanins (ACNs) have been reported to have multiple biological properties imparting benefits to human health. Their role in human nutrition, however, needs to be related to biokinetic data, such as bioavailability. The purpose of the present study was to focus on the potential absorption of black currant ( Ribes nigrum L.) ACNs. Caco-2 monolayers were used as an in vitro model of the absorptive intestinal epithelium. For absorption studies, Caco-2 cells grown on permeable filters were mounted into Ussing type chambers. The monolayer integrity was monitored by measuring the transepithelial electrical resistance (TEER). Luminal to serosal transport of ACNs was examined by comparing ACN disappearance from the luminal solution of Ussing chambers not containing any inserts (control chambers) with that of Ussing chambers containing inserts. ACNs (C total ACN approximately 180 microM) were not detected in any serosal solution. However, it was shown that ACNs disappeared from the luminal side, not due to ACN degradation processes but rather--at least in part--due to physiological actions of the cells. The luminal net disappearance of ACNs was calculated (max(t20 min) approximately 11% for total ACNs) and labeled as "absorption efficiency". This apical transport might occur to a much larger extent than the further translocation across the basolateral membrane. Thus, cell metabolism and translocation across the basolateral membrane may be the key determinants of ACN absorption and bioavailability. PMID:18540609

Steinert, Robert E; Ditscheid, Bianka; Netzel, Michael; Jahreis, Gerhard

2008-07-01

356

Quantitation of human MAO A and B in liver, intestine and placenta: Reassessment of activity  

International Nuclear Information System (INIS)

Monoamine oxidases (MAO) oxidize a variety of exogenous and endogenous amines including neurotransmitters such as serotonin, dopamine and norepinephrine as well as the potent dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). The two forms of MAO (A and B) differ in molecular weight and inhibitor selectivity, and are differentially expressed in the nervous system and many other tissues. Although some substrates are preferentially oxidized by one form of MAO, substrates that can be oxidized by only one MAO form have not been reported. How well each MAO oxidizes various substrates has not been thoroughly characterized because of difficulties in separating and quantitating MAO A and B active sites. By immunoblotting SDS-polyacrylamide gels of mitochondrial extracts with monoclonal antibodies specific for each form of MAO, MAO B protein was detected in intestine and placenta, tissues that have been reported to contain MAO A activity. An improved procedure was developed for quantitating the ratio and amounts of MAO A and B active sites, using the ligand [3H]-pargyline to label MAO and specific monoclonal antibodies to separate MAO A from B. Data from liver, placenta and platelets were used to re-evaluate the molecular activity of both MAO A and B for six commonly studied substrates

357

Perfil epidemiológico e morbimortalidade dos pacientes submetidos à reconstrução de trânsito intestinal: experiência de um centro secundário do Nordeste Brasileiro / Epidemiologic profile and morbimortality of patients undergoing reconstruction intestinal transit: experience of a secundary health service in the Northeast of Brazil  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese RACIONAL: A reconstrução do trânsito intestinal não está isenta de riscos cirúrgicos e apresenta taxas consideráveis de complicações pós-operatórias, sendo que a infecção continua a ser um dos maiores desafios existentes neste procedimento. OBJETIVO: Perfil epidemiológico e morbimortalidade dos paci [...] entes submetidos à reconstrução de trânsito intestinal. MÉTODOS: Foram analisados retrospectivamente 86 prontuários de pacientes com colostomia ou ileostomia, através de fatores que tivessem impacto sobre a morbimortalidade após a reconstrução de trânsito intestinal, de janeiro de 2003 a abril de 2009. RESULTADOS: Houve 20 mulheres e 60 homens, com idade média de 43 anos. A colostomia em alça (n=34) e o trauma abdominal indicando colostomia ou ileostomia foram as condições mais frequentes. O intervalo médio entre a confecção do estoma e a reconstrução de trânsito intestinal foi 15,7 meses. O índice de morbidade foi 56,8%, sendo a infecção incisional a complicação mais comum (27.47%). A permanência hospitalar média foi 7,6 dias. Houve regressão linear positiva entre permanência hospitalar pós-operatória e a idade do paciente. Demonstrou-se associação estatisticamente significativa entre o prolongamento da permanência hospitalar e a ocorrência de complicações (p Abstract in english BACKGROUND: The reconstruction of the intestinal tract is not surgical complications risk-free and is associated to postoperative complications high rates; furthermore, infection remains the hardest challenge in this procedure. AIM: Epidemiological profile and mortality and morbidity in patients und [...] ergoing reconstruction of intestinal transit. METHODS: Retrospectively, 86 patients with intestinal stomas were analyzed through factors that impact on the morbimortality afterwards intestinal transit reconstruction, since January 2003 to April 2009. RESULTS: Loop colostomy (n=34) and abdominal trauma implicating 38.2% of indications to colostomy or ileostomy, were the most frequent conditions. The mean interval between stoma confection and intestinal transit reconstruction was 15.7 months. The morbidity frequency was 56.8% and incisional infection was its commonest complication (27.47%). The mean inpatient length of stay was 7.6 days. There was positive linear regression between post-operative inpatient length of stay and inpatient's age. Inpatient length of stay prolongation is associated to occurrence of complications (p

Jeany Borges e, Silva; Djalma Ribeiro, Costa; Francisco Julimar Correia de, Menezes; José Marconi, Tavares; Adryano Gonçalves, Marques; Rodrigo Dornfeld, Escalante.

2010-09-01

358

Identification of a new fimbrial structure in enterotoxigenic Escherichia coli (ETEC) serotype O148:H28 which adheres to human intestinal mucosa: a potentially new human ETEC colonization factor.  

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Three important fimbrial colonization factor antigens (CFAs) designated CFA/I, CFA/II, and E8775 were identified originally in some human enterotoxigenic Escherichia coli (ETEC) strains because of their mannose-resistant hemagglutination properties. To identify CFA, in strains lacking mannose-resistant hemagglutination properties we exploited the ability of human ETEC strains to adhere to human proximal small intestinal mucosa. ETEC strain B7A (O148:H28) was selected for study because it belo...

Knutton, S.; Lloyd, D. R.; Mcneish, A. S.

1987-01-01

359

Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Studies in embryonic development have guided successful efforts to direct the differentiation of human embryonic and induced pluripotent stem cells (PSCs) into specific organ cell types in vitro 1,2. For example, human PSCs have been differentiated into monolayer cultures of liver hepatocytes and pancreatic endocrine cells3–6 that have therapeutic efficacy in animal models of liver disease 7,8 and diabetes 9 respectively. However the generation of complex three-dimensional organ tissues ...

Spence, Jason R.; Mayhew, Christopher N.; Rankin, Scott A.; Kuhar, Matthew; Vallance, Jefferson E.; Tolle, Kathryn; Hoskins, Elizabeth E.; Kalinichenko, Vladimir V.; Wells, Susanne I.; Zorn, Aaron M.; Shroyer, Noah F.; Wells, James M.

2011-01-01

360

Intestinal absorption of vitamins.  

Science.gov (United States)

This article provides an overview of advances in understanding the cellular and molecular mechanisms and regulation of intestinal absorption processes of vitamins. The vitamins covered are the water-soluble vitamins folic acid, cobalamin (vitamin B12), biotin, pantothenic acid, and thiamine (vitamin B1) and the lipid-soluble vitamin A. For folate, significant advances have been made in regard to i) digestion of dietary folate polyglutamates to folate monoglutamates by the cloning of the responsible enzyme; ii) identification of the cDNA responsible for the intestinal folate transporter; iii) delineation of intracellular mechanisms that regulate small intestinal folate uptake; and iv) identification and characterization of a specific, pH-dependent, carrier-mediated system for folate uptake at the luminal (apical) membrane of human colonocytes. Studies on cobalamine have focused on cellular and molecular characterization of the intrinsic factor and its receptor. Studies on biotin transport in the small intestine have shown that the uptake process is shared by another water-soluble vitamin, pantothenic acid. Furthermore, a Na-dependent, carrier-mediated biotin uptake system that is also shared with pantothenic acid has been identified at the apical membrane of human colonocytes. This carrier is believed to be responsible for the absorption of the bacterially synthesized biotin and pantothenic acid in the large intestine. Also, preliminary studies have reported the cloning of a biotin transporter from the small intestine. As for thiamine intestinal transport, a study has shown thiamine uptake by small intestinal biopsy specimens to be via a carrier-mediated, Na-independent mechanism, which appears to be up-regulated in thiamine deficiency. Studies on vitamin A intestinal absorption have shown the existence of a receptor-mediated mechanism for the uptake of retinol bound to retinol-binding protein in the small intestine of suckling rats. Another study has shown that retinoic acid increases the mRNA level of the cellular retinol binding protein II and the rate of retinol uptake by Caco-2 intestinal epithelial cells. The study suggested that retinoids may play a role in the regulation of vitamin A intestinal absorption. PMID:17023940

Said, H M; Kumar, C

1999-03-01

 
 
 
 
361

Small intestinal bacterial overgrowth syndrome  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Human intestinal microbiota create a complex polymicrobial ecology. This is characterised by its high population density, wide diversity and complexity of interaction. Any dysbalance of this complex intestinal microbiome, both qualitative and quantitative, might have serious health consequence for a macro-organism, including small intestinal bacterial overgrowth syndrome (SIBO). SIBO is defined as an increase in the number and/or alteration in the type of bacteria in the upper gastrointestina...

Jan Bures, Jiri Cyrany

2010-01-01

362

Enhanced uptake and transport of (+-catechin and (--epigallocatechin gallate in niosomal formulation by human intestinal Caco-2 cells  

Directory of Open Access Journals (Sweden)

Full Text Available Qinxin Song,1–3 Danhui Li,3 Yongzhi Zhou,3 Jie Yang,1 Wanqi Yang,1 Guohua Zhou,2 Jingyuan Wen31Key Laboratory of Drug Qual