Rare small intestinal volvulus from entrapment in hepato-diaphragmatic adhesions in a 45-year-old lady.

PubMed

Olaoye, Iyiade Olatunde; Adesina, Micheal Dapo

2016-12-20

Small intestinal volvulus is rare in adults and rarely caused by string adhesions between the liver and the diaphragm. Similar adhesions were described in Fitz-Hugh-Curtis syndrome. We report a 45-year-old lady with small intestinal volvulus from entrapment of a loop in string adhesions between the liver and the diaphragm. Her plain radiographs showed a significant shadow of the trapped loop. Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author 2016.

[Effect of somatostatin-14 in simple mechanical obstruction of the small intestine].

PubMed

Jimenez-Garcia, A; Ahmad Araji, O; Balongo Garcia, R; Nogales Munoz, A; Salguero Villadiego, M; Cantillana Martinez, J

1994-02-01

In order to investigate the properties of somatostatin-14 we studied an experimental model of simple mechanical and closed loop occlusion. Forty-eight New Zealand rabbits were assigned randomly to three groups of 16: group C (controls) was operated and treated with saline solution (4 cc/Kg/h); group A was operated and initially treated with saline solution and an equal dose of somatostatin-14 (3.5 micrograms/Kg/h; and group B was operated and treated in the same manner as group A, but later, 8 hours after the laparotomy. The animals were sacrificed 24 hours later; intestinal secretion was quantified, blood and intestinal fluid chemistries were performed and specimens of the intestine were prepared for histological examination. Descriptive statistical analysis of the results was performed with the ANOVA, a semi-quantitative test and the covariance test. Somatostatin-14 produced an improvement in the volume of intestinal secretion in the treated groups compared with the control group. The results were statistically significant in group B treated after an 8-hour delay: closed loop (ml): 6.40 +/- 1.12, 2.50 +/- 0.94, 1.85 +/- 0.83 and simple mechanical occlusion (ml): 175 +/- 33.05, 89.50 +/- 9.27, 57.18 +/- 21.23, p < 0.01 for groups C, A and B C, A and B respectively. Net secretion of Cl and Na ions was also improved, p < 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

The synergistic necrohemorrhagic action of Clostridium perfringens perfringolysin and alpha toxin in the bovine intestine and against bovine endothelial cells

PubMed Central

2013-01-01

Bovine necrohemorrhagic enteritis is a major cause of mortality in veal calves. Clostridium perfringens is considered as the causative agent, but there has been controversy on the toxins responsible for the disease. Recently, it has been demonstrated that a variety of C. perfringens type A strains can induce necrohemorrhagic lesions in a calf intestinal loop assay. These results put forward alpha toxin and perfringolysin as potential causative toxins, since both are produced by all C. perfringens type A strains. The importance of perfringolysin in the pathogenesis of bovine necrohemorrhagic enteritis has not been studied before. Therefore, the objective of the current study was to evaluate the role of perfringolysin in the development of necrohemorrhagic enteritis lesions in calves and its synergism with alpha toxin. A perfringolysin-deficient mutant, an alpha toxin-deficient mutant and a perfringolysin alpha toxin double mutant were less able to induce necrosis in a calf intestinal loop assay as compared to the wild-type strain. Only complementation with both toxins could restore the activity to that of the wild-type. In addition, perfringolysin and alpha toxin had a synergistic cytotoxic effect on bovine endothelial cells. This endothelial cell damage potentially explains why capillary hemorrhages are an initial step in the development of bovine necrohemorrhagic enteritis. Taken together, our results show that perfringolysin acts synergistically with alpha toxin in the development of necrohemorrhagic enteritis in a calf intestinal loop model and we hypothesize that both toxins act by targeting the endothelial cells. PMID:23782465

Segmental-dependent permeability throughout the small intestine following oral drug administration: Single-pass vs. Doluisio approach to in-situ rat perfusion.

PubMed

Lozoya-Agullo, Isabel; Zur, Moran; Beig, Avital; Fine, Noa; Cohen, Yael; González-Álvarez, Marta; Merino-Sanjuán, Matilde; González-Álvarez, Isabel; Bermejo, Marival; Dahan, Arik

2016-12-30

Intestinal drug permeability is position dependent and pertains to a specific point along the intestinal membrane, and the resulted segmental-dependent permeability phenomenon has been recognized as a critical factor in the overall absorption of drug following oral administration. The aim of this research was to compare segmental-dependent permeability data obtained from two different rat intestinal perfusion approaches: the single-pass intestinal perfusion (SPIP) model and the closed-loop (Doluisio) rat perfusion method. The rat intestinal permeability of 12 model drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed) was assessed in three small intestinal regions: the upper jejunum, mid-small intestine, and the terminal ileum, using both the SPIP and the Doluisio experimental methods. Excellent correlation was evident between the two approaches, especially in the upper jejunum (R 2 =0.95). Significant regional-dependent permeability was found in half of drugs studied, illustrating the importance and relevance of segmental-dependent intestinal permeability. Despite the differences between the two methods, highly comparable results were obtained by both methods, especially in the medium-high P eff range. In conclusion, the SPIP and the Doluisio method are both equally useful in obtaining crucial segmental-dependent intestinal permeability data. Copyright © 2016 Elsevier B.V. All rights reserved.

Morphological and functional changes after benzalkonium chloride treatment of the small intestinal Thiry-Vella loop in rats.

PubMed

Móricz, K; Gyetvai, B; Bárdos, G

1998-08-01

The aim of this work was to study the effects of benzalkonium chloride (BAC) treatment on the small intestine and its functioning in rats surgically prepared with Thiry-Vella intestinal loop. The loops were treated with either BAC, which ablated much of the myenteric plexus and extrinsic innervation, or with physiological saline (SAL). In vivo drinking experiments were performed to examine the effect on fluid intake and behavioral indices of distending the loop with a balloon. Spontaneous motility and its changes induced by acetylcholine (ACh) and histamine (His) were studied on isolated stripes in vitro. Finally, samples from the loops were examined histologically. Though reduction of the cell number was less than expected and no differences of the thickness of the muscular layer between the two groups was observed, BAC treatment altered the pattern of spontaneous activity and also the sensitivity to ACh and His in isolated stripes. In vivo distension of the SAL-treated loops reduced fluid intake and produced signs of aversivity; these effects were absent in the BAC-treated group. Our results show that despite the differences in the degree of ablation from those obtained by others, BAC treatment can be used to study the mechanisms underlying the effects of the enteral stimuli on the behavior.

Humoral Immunity Provides Resident Intestinal Eosinophils Access to Luminal Antigen via Eosinophil-Expressed Low-Affinity Fcγ Receptors.

PubMed

Smith, Kalmia M; Rahman, Raiann S; Spencer, Lisa A

2016-11-01

Eosinophils are native to the healthy gastrointestinal tract and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g., food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct Ag engagement elicits eosinophil effector functions, including degranulation and Ag presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food Ags by a columnar epithelium might similarly engage food Ags. Using an intestinal ligated loop model in mice, in this study we determined that resident intestinal eosinophils acquire Ag from the lumen of Ag-sensitized but not naive mice in vivo. Ag acquisition was Ig-dependent; intestinal eosinophils were unable to acquire Ag in sensitized Ig-deficient mice, and passive immunization with immune serum or Ag-specific IgG was sufficient to enable intestinal eosinophils in otherwise naive mice to acquire Ag in vivo. Intestinal eosinophils expressed low-affinity IgG receptors, and the activating receptor FcγRIII was necessary for Ig-mediated acquisition of Ags by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food Ags in sensitized mice via FcγRIII Ag focusing and that they may therefore participate in Ag-driven secondary immune responses to oral Ags. Copyright © 2016 by The American Association of Immunologists, Inc.

Humoral immunity provides resident intestinal eosinophils access to luminal antigen via eosinophil-expressed low affinity Fc gamma receptors

PubMed Central

Smith, Kalmia M.; Rahman, Raiann S.; Spencer, Lisa A.

2016-01-01

Eosinophils are native to the healthy gastrointestinal tract, and are associated with inflammatory diseases likely triggered by exposure to food allergens (e.g. food allergies and eosinophilic gastrointestinal disorders). In models of allergic respiratory diseases and in vitro studies, direct antigen engagement elicits eosinophil effector functions including degranulation and antigen presentation. However, it was not known whether intestinal tissue eosinophils that are separated from luminal food antigens by a columnar epithelium might similarly engage food antigens. Using an intestinal ligated loop model in mice, here we determined that resident intestinal eosinophils acquire antigen from the lumen of antigen-sensitized but not naïve mice in vivo. Antigen acquisition was immunoglobulin-dependent; intestinal eosinophils were unable to acquire antigen in sensitized immunoglobulin-deficient mice, and passive immunization with immune serum or antigen-specific IgG was sufficient to enable intestinal eosinophils in otherwise naïve mice to acquire antigen in vivo. Intestinal eosinophils expressed low affinity IgG receptors, and the activating receptor FcγRIII was necessary for immunoglobulin-mediated acquisition of antigens by isolated intestinal eosinophils in vitro. Our combined data suggest that intestinal eosinophils acquire lumen-derived food antigens in sensitized mice via FcγRIII antigen focusing, and may therefore participate in antigen-driven secondary immune responses to oral antigens. PMID:27683752

Early immune response following Salmonella enterica subspecies enterica serovar Typhimurium infection in porcine jejunal gut loops

PubMed Central

Meurens, François; Berri, Mustapha; Auray, Gael; Melo, Sandrine; Levast, Benoît; Virlogeux-Payant, Isabelle; Chevaleyre, Claire; Gerdts, Volker; Salmon, Henri

2009-01-01

Salmonella enterica subspecies enterica serovar Typhimurium, commonly called S. Typhimurium, can cause intestinal infections in humans and various animal species such as swine. To analyze the host response to Salmonella infection in the pig we used an in vivo gut loop model, which allows the analysis of multiple immune responses within the same animal. Four jejunal gut-loops were each inoculated with 3×108 cfu of S. Typhimurium in 3 one-month-old piglets and mRNA expressions of various cytokines, chemokines, transcription factors, antimicrobial peptides, toll like and chemokine receptors were assessed by quantitative real-time PCR in the Peyer’s patch and the gut wall after 24 h. Several genes such as the newly cloned CCRL1/CCX-CKR were assessed for the first time in the pig at the mRNA level. Pro-inflammatory and T-helper type-1 (Th1) cytokine mRNA were expressed at higher levels in infected compared to non-infected control loops. Similarly, some B cell activation genes, NOD2 and toll like receptor 2 and 4 transcripts were more expressed in both tissues while TLR5 mRNA was down-regulated. Interestingly, CCL25 mRNA expression as well as the mRNA expressions of its receptors CCR9 and CCRL1 were decreased both in the Peyer’s patch and gut wall suggesting a potential Salmonella strategy to reduce lymphocyte homing to the intestine. In conclusion, these results provide insight into the porcine innate mucosal immune response to infection with entero-invasive microorganisms such as S. Typhimurium. In the future, this knowledge should help in the development of improved prophylactic and therapeutic approaches against porcine intestinal S. Typhimurium infections. PMID:18922229

Gastroschisis in the rat model is associated with a delayed maturation of intestinal pacemaker cells and smooth muscle cells.

PubMed

Midrio, P; Faussone-Pellegrini, M S; Vannucchi, M G; Flake, A W

2004-10-01

A pacemaker system is required for peristalsis generation. The interstitial cells of Cajal (ICC) are considered the intestinal pacemaker, and are identified by expression of the c-kit gene--encoded protein. Gastroschisis is characterized by a severe gastrointestinal dysmotility in newborns. In spite of this clinical picture, few studies have focused on smooth muscle cells (SMC) morphology and none on ICC. Therefore, their morphology has been studied in fetuses at term in the rat model of gastroschisis. At 18.5 day's gestation (E18.5), 10 rat fetuses were killed, 10 underwent surgical creation of gastroschisis, and 10 underwent manipulation only. The small intestine of the latter 2 groups was harvested at E21.5. Specimens were processed for H&E, c-kit and actin (alpha smooth muscle antibody [alpha-SMA]) immunohistochemistry, and transmission electron microscopy (TEM). In the controls, SMC were c-kit+ and alpha-SMA+, with labeling intensity increasing by age. At E21.5, some cells around the Auerbach's plexus were more intensely c-kit+, and differentiating ICC were seen under TEM at this level. Gastroschisis fetuses had no c-kit+ cells referable to ICC. In the more damaged loops, SMC were very faintly c-kit+ and alpha-SMA+. Under TEM, there were few differentiated SMC and no presumptive ICC. In the less-damaged loops, SMC were faintly c-kit+ and alpha-SMA+ and had ultrastructural features intermediate between those of E18.5 and E21.5 controls; ICC were very immature. ICC and SMC differentiation is delayed in gastroschisis with the most damaged loops showing the most incomplete picture. These findings might help in understanding the delayed onset of peristalsis and the variable time-course of the recover seen in babies affected by gastroschisis.

Intestinal volvulus with coagulative hepatic necrosis in a chicken.

PubMed

Haridy, Mohie; Goryo, Masanobu; Sasaki, Jun; Okada, Kosuke

2010-04-01

A 7-week-old SPF chicken inoculated at 4 weeks of age with chicken anemia virus was puffed up depressed and had ruffled feathers and a good body condition. Intestinal volvulus involving the jejunum and part of the duodenum forming two loops with one knob was observed. Microscopically, venous infarction of the obstructed loops, periportal and sublobular multifocal coagulative hepatic necrosis and granulomatous inflammation of the cecal tonsils were observed. Gram staining revealed no bacteria in hepatic tissue; however, gram-positive bacilli were detected in the necrotic debris in the intestinal lumen. Immunosuppression might have predisposed the chicken to intestinal and cecal tonsil infection that then progressed to volvulus. Loss of the mucosal barrier in infarction might allow bacterial toxins and vasoactive factors to escape into the systemic circulation (toxemia) and be responsible for the hepatic necrosis.

Endothelial binding of beta toxin to small intestinal mucosal endothelial cells in early stages of experimentally induced Clostridium perfringens type C enteritis in pigs.

PubMed

Schumacher, V L; Martel, A; Pasmans, F; Van Immerseel, F; Posthaus, H

2013-07-01

Beta toxin (CPB) is known to be an essential virulence factor in the development of lesions of Clostridium perfringens type C enteritis in different animal species. Its target cells and exact mechanism of toxicity have not yet been clearly defined. Here, we evaluate the suitability of a neonatal piglet jejunal loop model to investigate early lesions of C. perfringens type C enteritis. Immunohistochemically, CPB was detected at microvascular endothelial cells in intestinal villi during early and advanced stages of lesions induced by C. perfringens type C. This was first associated with capillary dilatation and subsequently with widespread hemorrhage in affected intestinal segments. CPB was, however, not demonstrated on intestinal epithelial cells. This indicates a tropism of CPB toward endothelial cells and suggests that CPB-induced endothelial damage plays an important role in the early stages of C. perfringens type C enteritis in pigs.

Synthesis of protein in intestinal cells exposed to cholera toxin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, J.W.; Berg, W.D. Jr.; Coppenhaver, D.H.

1987-11-01

The mechanism by which cyclic adenosine monophosphate (AMP), formed by intestinal epithelial cells in response to cholera toxin, ultimately results in alterations in water and electrolyte transport is poorly understood. Several studies have indicated that inhibitors of transcription or translation block much of the transport of ions and water in the intestine and edema formation in tissue elicited by cholera toxin. Data presented in this study confirmed the inhibitory effects of cycloheximide on cholera toxin-induced fluid accumulation in the rabbit intestinal loop model. Neither cycloheximide nor actinomycin D altered the amount of cyclic AMP that accumulated in intestinal cells andmore » Chinese hamster ovary cells exposed to cholera toxin. An increase in (/sup 3/H) leucine incorporation was readily demonstrable in intestinal epithelial cells from rabbits challenged with Vibrio cholerae. Similarly, intestinal epithelial cells incubated with cholera toxin for 4 hr synthesized substantially more protein than controls as determined by relative incorporation of (/sup 35/S) methionine. Most of the new protein synthesized in response to cholera toxin was membrane associated and of high molecular weight. The possible significance of the toxin-induced protein relative to cholera pathogenesis was discussed.« less

[Anisoperistaltic Roux-en-Y reconstruction: rare cause for recurrent cholangitis after hepatic jejunostomy].

PubMed

Böhm, S A; Beckurts, K T; Landwehr, P; Hölscher, A H

1999-07-01

Stenosis of the hepatico-intestinal anastomosis after hepaticojejunostomy is a common cause for recurrent cholangitis. In the following report a patient's history of recurrent cholangitis after hepaticojejunostomy performed because of bile duct injury is presented. Preoperative imaging revealed a stricture of the hepatico-intestinal anastomosis and a massive dilatation of the Roux-en-Y loop, so that a draining disorder was assumed. Laparotomy showed an anisoperistaltic Roux-en-Y loop. When assessing the differential diagnosis of recurrent cholangitis after hepaticojejunostomy, anisoperistaltic reconstruction should be considered.

Toll-like receptors and intestinal defence: molecular basis and therapeutic implications.

PubMed

Cario, Elke

2003-07-07

Toll-like receptors (TLRs) play a principle role in distinct pathogen recognition and in the initiation of innate immune responses of the intestinal mucosa. Activated innate immunity interconnects downstream with adaptive immunity in complex feedback regulatory loops. Intestinal disease might result from inappropriate activation of the mucosal immune system driven by TLRs in response to normal luminal flora.

Exploring new technologies to facilitate laparoscopic surgery: creating intestinal anastomoses without sutures or staples, using a radio-frequency-energy-driven bipolar fusion device.

PubMed

Smulders, J F; de Hingh, I H J T; Stavast, J; Jackimowicz, J J

2007-11-01

Intestinal anastomotic healing requires apposition of the collagen containing submucosal layers of the opposing intestinal walls, which is traditionally achieved by staples or sutures. Recently, a feedback-controlled bipolar sealing system (LigaSure) has been successfully introduced to seal and transect vessels. Since this technology depends on fusion of collagen fibres which are abundantly present in the intestinal wall, the possibility to create intestinal anastomoses using this technology was investigated in the present study. For this purpose a new-generation radiofrequency (RF) generator and a prototype of the Ligasure Anastomotic Device (LAD) have been developed. The generator incorporates a closed loop control system which monitors tissue fusion, compares it with a mathematical model of ideal fusion based on the density and compliance of intestinal tissue and adjusts energy output accordingly. In total 8 anastomoses were created in a porcine model (4 pigs, 2 anastomoses each) and healing was assessed by macroscopic and histological examination. All seals were macroscopic intact both immediate after creation and at sacrifice at the 7th postoperative day. Between operations, pigs appeared healthy and had normal intestinal passage. Histological examination of the anastomoses revealed undisturbed healing with granulation tissue, newly synthesised collagen in the submucosa and re-epithelialization at the borders of the seals. These results confirm the feasibility to create experimental intestinal anastomoses using LigaSure technology. This may be an important step towards the development of new laparoscopic equipment combining dissecting and reconstructive properties within one single instrument.

Pylorus preserving loop duodeno-enterostomy with sleeve gastrectomy - preliminary results

PubMed Central

2014-01-01

Background Bariatric operations mostly combine a restrictive gastric component with a rerouting of the intestinal passage. The pylorus can thereby be alternatively preserved or excluded. With the aim of performing a “pylorus-preserving gastric bypass”, we present early results of a proximal postpyloric loop duodeno-jejunostomy associated with a sleeve gastrectomy (LSG) compared to results of a parallel, but distal LSG with a loop duodeno-ileostomy as a two-step procedure. Methods 16 patients underwent either a two-step LSG with a distal loop duodeno-ileostomy (DIOS) as revisional bariatric surgery or a combined single step operation with a proximal duodeno-jejunostomy (DJOS). Total small intestinal length was determined to account for inter-individual differences. Results Mean operative time for the second-step of the DIOS operation was 121 min and 147 min for the combined DJOS operation. The overall intestinal length was 750.8 cm (range 600-900 cm) with a bypassed limb length of 235.7 cm in DJOS patients. The mean length of the common channel in DIOS patients measured 245.6 cm. Overall excess weight loss (%EWL) of the two-step DIOS procedure came to 38.31% and 49.60%, DJOS patients experienced an %EWL of 19.75% and 46.53% at 1 and 6 months, resp. No complication related to the duodeno-enterostomy occurred. Conclusions Loop duodeno-enterosomies with sleeve gastrectomy can be safely performed and may open new alternatives in bariatric surgery with the possibility for inter-individual adaptation. PMID:24725654

Targeting Nuclear Receptors to Treat Fibrostenotic Crohn’s Disease

DTIC Science & Technology

2017-08-01

feedback loop . 15. SUBJECT TERMS Crohn’s disease, intestinal smooth muscle, intestinal fibroblasts, NR4A1, 6-MP, Cytosporone B, proliferation, inflammation...whether the exaggerated tissue remodelling observed in our studies reflects a hyper -fibrotic response, versus a hyper -inflammatory phenotype

Intestinal absorption of dideoxynucleosides: characterization using a multiloop in situ technique.

PubMed

Mirchandani, H L; Chien, Y W

1995-01-01

The intestinal absorption of dideoxynucleosides was studied in rabbits, using a closed-loop mesenteric-sampling in situ technique developed in this laboratory, and the kinetic profiles were characterized. Each of the dideoxynucleosides exhibited different dependence on the intestinal regions studied: 3'-azido-2',3'-dideoxythymidine was best absorbed from the ileum, while 2',3'-dideoxyinosine and 2',3'-dideoxycytidine were preferentially absorbed from the jejunum. The results were validated by the mass-balance approach; the percent of drug retained in the intestinal lumen and that degraded at the intestinal pH, by colonic flora, in the intestinal tissue, and in plasma were assessed.

Study on the release of fenofibrate nanosuspension in vitro and its correlation with in situ intestinal and in vivo absorption kinetics in rats.

PubMed

Xu, Yuanlong; Wang, Yonglu; Li, Xue Ming; Huang, Qinqin; Chen, Wei; Liu, Ran; Chen, BaoAn; Wei, Ping

2014-07-01

As an oral delivery carrier for poorly water soluble drugs, the nanosuspension was prepared by melt emulsification method combined with high-pressure homogenization. The objective of this study was to clarify the absorption mechanism in rats of fenofibrate nanosuspension using the model of in situ gut perfusion. The release rate of drug from nanosuspension was fast which about 70% of the drug would be released within 5 minutes. The absorption of fenofibrate nanosuspension in the gastrointestinal (GI) tract was studied by the in situ closed loop method in rats. It was found that the absorption process in intestine was first-process with passive diffusion mechanism, and the whole intestine was the major segment for the drug absorption. Additionally, GI absorption in situ studies indicated that the fenofibrate nanosuspension had great success in regard to enhancement of intestinal absorption compared to the fenofibrate suspension of coarse powder. The pharmacokinetic characteristics were studied in rats after oral administration of fenofibrate nanosuspension or suspension at the dosage of 27 mg/kg. The plasma concentration-time curve was fitted to the one-compartment model. The correlation between in vitro dissolution (P), in situ intestinal absorption (F) and in vivo absorption (Fa) in rats was investigated with the results as follows: Fa = 6.2061P-456.38(r = 0.9559), F = 3.6911P-2.2169(r = 0.970), F = 0.5095P + 44.189(r = 0.9609). The highest level A could be obtained from the in vitro--in vivo correlation (IVIVC) between dissolution percentage and intestinal absorption of the fenofibrate nanosuspension in rats. Consequently, the in situ intestinal perfusion model could be used to predict the in vivo pharmacokinetic characteristics in rats.

Studies on different iron source absorption by in situ ligated intestinal loops of broilers.

PubMed

Jia, Y F; Jiang, M M; Sun, J; Shi, R B; Liu, D S

2015-02-01

The objective of this study was to investigate the iron source absorption in the small intestine of broiler. In situ ligated intestinal loops of 70 birds were poured into one of seven solutions, including inorganic iron (FeSO4, Fe2(SO4)3), organic Fe glycine chelate (Fe-Gly(II), Fe-Gly(III)), the mixtures (FeSO4 with glycine (Fe+Gly(II)), Fe2(SO4)3 with glycine (Fe+Gly(III)), and no Fe source (control). The total volume of 3-mL solution (containing 1 mg of elemental Fe) was injected into intestinal loops, and then 120-min incubation was performed. Compared with inorganic iron groups, in which higher FeSO4 absorption than Fe2(SO4)3 was observed, supplementation with organic Fe glycine chelate significantly increased the Fe concentration in the duodenum and jejunum (P < 0.05), however, decreased DMT1 and DcytB messenger RNA (mRNA) levels (P < 0.05). Organic Fe glycine chelate (Fe-Gly(II), Fe-Gly(III)) increased serum iron concentration (SI), compared with inorganic 3 valence iron groups (Fe2(SO4)3 and Fe+Gly(III)) (P < 0.05); moreover, lower TIBC value was observed for the chelate (P < 0.05); however, mixture of inorganic iron and glycine did not have a positive role at DMT1 and DcytB mRNA levels, SI and Fe concentrations in the small intestine. Those results indicated that the absorption of organic Fe glycine chelate was more effective than that of inorganic Fe, and the orders of iron absorption in the small intestine were: Fe-Gly(II), Fe-Gly(III) > FeSO4, Fe+Gly(II) > Fe2(SO4)3, Fe+Gly(III). Additionally, the simple mixture of inorganic iron and glycine could not increase Fe absorption, and the duodenum was the main site of Fe absorption in the intestines of broilers and the ileum absorbed iron rarely.

Ultrasonographic evaluation of abdominal distension in 52 camels (Camelus dromedarius).

PubMed

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Buczinski, Sébastien

2012-08-01

The purpose of this study was to assess the diagnostic value of ultrasonography in the evaluation of abdominal distension in 52 camels (Camelus dromedarius). The conditions included trypanosomiasis (n=35), intestinal obstruction (n=12) and ruptured urinary bladder (n=5). Fifteen clinically normal camels were included as controls. Transabdominal and transrectal ultrasonography was carried out on all camels. In animals with trypanosomiasis, ultrasonographic findings included accumulation of massive amounts of hypoechoic abdominal fluids where liver, intestine, kidney, spleen and urinary bladder were imaged floating. Except in two cases of bile duct calcification and one of hepatic abscessation, no detectable abnormal sonographic lesions were detected while imaging the hepatic and renal parenchyma, and the heart and its valves and major blood vessels. In camels with intestinal obstruction, ultrasonographic findings included distended intestinal loops with markedly reduced or absent motility. In one camel, the intestinal lumen contained localised hyperechoic material that was consistent with a foreign body. Hypoechoic fluid with or without fibrin was seen between intestinal loops. In camels with ruptured urinary bladder, ultrasonographic findings included collapsed and perforated bladder, echogenic blood clots within the urinary bladder and peritoneal cavity, increased thickness of the bladder wall, floating intestines in hypoechogenic fluid and echogenic calculi within the urethra. Ultrasonography was considered a useful tool for the evaluation of dromedary camels with abdominal distension. Copyright © 2011 Elsevier Ltd. All rights reserved.

IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions.

PubMed

Monticelli, Laurel A; Osborne, Lisa C; Noti, Mario; Tran, Sara V; Zaiss, Dietmar M W; Artis, David

2015-08-25

The barrier surfaces of the skin, lung, and intestine are constantly exposed to environmental stimuli that can result in inflammation and tissue damage. Interleukin (IL)-33-dependent group 2 innate lymphoid cells (ILC2s) are enriched at barrier surfaces and have been implicated in promoting inflammation; however, the mechanisms underlying the tissue-protective roles of IL-33 or ILC2s at surfaces such as the intestine remain poorly defined. Here we demonstrate that, following activation with IL-33, expression of the growth factor amphiregulin (AREG) is a dominant functional signature of gut-associated ILC2s. In the context of a murine model of intestinal damage and inflammation, the frequency and number of AREG-expressing ILC2s increases following intestinal injury and genetic disruption of the endogenous AREG-epidermal growth factor receptor (EGFR) pathway exacerbated disease. Administration of exogenous AREG limited intestinal inflammation and decreased disease severity in both lymphocyte-sufficient and lymphocyte-deficient mice, revealing a previously unrecognized innate immune mechanism of intestinal tissue protection. Furthermore, treatment with IL-33 or transfer of ILC2s ameliorated intestinal disease severity in an AREG-dependent manner. Collectively, these data reveal a critical feedback loop in which cytokine cues from damaged epithelia activate innate immune cells to express growth factors essential for ILC-dependent restoration of epithelial barrier function and maintenance of tissue homeostasis.

Evaluation of in vivo and in vitro biological activity of a Vibrio cholerae 01 hemolysin.

PubMed

Arellano Galindo, José; Rodriquez Angeles, María Guadalupe; Guadarrama, Norma Valázquez; Esteban, Enrique Santos; Cerezo, Silvia Giono

2007-01-01

To evaluate the hemolysin effect by ileal loop model produced by Vibrio cholerae O1 strains, compared with the cellular lysis or cytotoxic activity (CA) observed in cell culture. We studied nine V. cholerae O1 strains, obtained during the Mexican outbreak of cholera (1990-1993), which had CA in Vero and CHO cells. Hemolysin was monitored with the hemolysis test. Titers of CA were calculated by CD50, and the association between CA and cholera toxin (CT) production was discarded by means of neutralization tests using an anti-CT polyclonal antibody. The CT production was measured with ELISA test. The LAL assay was performed in order to study relationships between the CA and bacterial lipopolysaccharide. Strains with CA were evaluated in rabbit and rat ileal loop models; hemorrhagic fluid was also measured. Tissues from ileal loop were included in paraffin to detect intestinal epithelial damage. The hemolysin CA was not neutralized with the anti-CT polyclonal antibody. However, the associated factor of CA was heat labile. CA in cell cultures was not related to the bacterial lipopolysaccharide. The ileal loop test exhibited the presence of hemorrhagic tissue with inflammation. The V. cholerae O1 strains isolated were able to secrete hemolysin which, in turn, caused CA in cell cultures and produced the hemorrhagic and inflammatory effects observed in the ileal loop of rabbit and rat models.

Fetal midgut volvulus: report of eight cases.

PubMed

Sciarrone, A; Teruzzi, E; Pertusio, A; Bastonero, S; Errante, G; Todros, T; Viora, E

2016-01-01

To evaluate whether prenatal diagnosis of intestinal midgut volvulus (a rare condition due to the small bowel loops twisting) can improve the prognosis of the newborns. In our Prenatal Diagnosis Center, eight cases of intestinal volvulus observed between 2007 and 2014 were retrospectively considered. Ultrasonographic signs can be direct and specific (whirlpool sign, coffee bean sign) or indirect and non-specific (abdominal mass, dilated bowel loops, pseudocysts, ascites, polyhydramnios). Prenatal diagnosis was performed at 20-34 weeks of gestation. All newborns were exposed to an emergency surgery: the major complication was due to cystic fibrosis. An early suspicion of intestinal volvulus allows the clinician to refer the patient to a tertiary center so to confirm the diagnosis and perform an appropriate follow-up in order to identify the proper time of delivery. The prognosis of the babies with prenatal intestinal volvulus depends on the length of the segment involved, on the level of intestinal obstruction, on the presence of meconium peritonitis and on the gestational age at birth. Our experience, according with the literature, suggests that ascites and absence of abdominal peristalsis are ultrasonographic signs that, in the third trimester of pregnancy, correctly lead to an immediate delivery intervention.

Intimin, tir, and shiga toxin 1 do not influence enteropathogenic responses to shiga toxin-producing Escherichia coli in bovine ligated intestinal loops.

PubMed

Stevens, Mark P; Marchès, Olivier; Campbell, June; Huter, Veronika; Frankel, Gad; Phillips, Alan D; Oswald, Eric; Wallis, Timothy S

2002-02-01

Shiga toxin-producing Escherchia coli (STEC) comprises a group of attaching and effacing (A/E) enteric pathogens of animals and humans. Natural and experimental infection of calves with STEC may result in acute enteritis or subclinical infection, depending on serotype- and host-specific factors. To quantify intestinal secretory and inflammatory responses to STEC in the bovine intestine, serotypes that are associated with human disease (O103:H2 and O157:H7) were introduced into ligated mid-ileal loops in gnotobiotic and conventional calves, and fluid accumulation and recruitment of radiolabeled neutrophils were measured after 12 h. STEC serotype O103:H2, but not serotype O157:H7, elicited strong enteropathogenic responses. To determine if the inflammatory response to STEC O103:H2 in calves requires Shiga toxin 1 or intimate bacterial attachment to the intestinal epithelium, defined mutations were made in the stx1, eae, and tir genes. Our data indicate that some STEC induce intestinal inflammatory responses in calves by a mechanism that is independent of A/E-lesion formation, intimin, or Shiga toxin 1. This may have implications for strategies to reduce STEC carriage in cattle.

Comprehensive study of the intestinal stage of listeriosis in a rat ligated ileal loop system.

PubMed

Pron, B; Boumaila, C; Jaubert, F; Sarnacki, S; Monnet, J P; Berche, P; Gaillard, J L

1998-02-01

The intestinal stage of listeriosis was studied in a rat ligated ileal loop system. Listeria monocytogenes translocated to deep organs with similar efficiencies after inoculation of loops with or without Peyer's patches. Bacterial seeding of deep organs was demonstrated as early as 15 min after inoculation. It was dose dependent and nonspecific, as the delta inlAB, the delta hly, and the delta actA L. monocytogenes mutants and the nonpathogenic species, Listeria innocua, translocated similarly to wild-type L. monocytogenes strains. The levels of uptake of listeriae by Peyer's patches and villous intestine were similar and low, 50 to 250 CFU per cm2 of tissue. No listeria cells crossing the epithelial sheet of Peyer's patches and villous intestine were observed by transmission electron microscopy. The lack of significant interaction of listeriae and the follicle-associated epithelium of Peyer's patches was confirmed by scanning electron microscopy. The follicular tissue of Peyer's patches was a preferential site of Listeria replication. With all doses tested, the rate of bacterial growth was 10 to 20 times higher in Peyer's patches than in villous intestine. At early stages of Peyer's patch infection, listeriae were observed inside mononuclear cells of the dome area. Listeriae then disseminated throughout the follicular tissue except for the germinal center. The virulence determinants hly and, to a lesser extent, actA, but not inlAB, were required for the completion of this process. This study suggests that Peyer's patches are preferential sites for replication rather than for entry of L. monocytogenes, due to the presence of highly permissive mononuclear cells whose nature remains to be defined.

Comprehensive Study of the Intestinal Stage of Listeriosis in a Rat Ligated Ileal Loop System

PubMed Central

Pron, Benedicte; Boumaila, Claire; Jaubert, Francis; Sarnacki, Sabine; Monnet, Jean-Paul; Berche, Patrick; Gaillard, Jean-Louis

1998-01-01

The intestinal stage of listeriosis was studied in a rat ligated ileal loop system. Listeria monocytogenes translocated to deep organs with similar efficiencies after inoculation of loops with or without Peyer’s patches. Bacterial seeding of deep organs was demonstrated as early as 15 min after inoculation. It was dose dependent and nonspecific, as the ΔinlAB, the Δhly, and the ΔactA L. monocytogenes mutants and the nonpathogenic species, Listeria innocua, translocated similarly to wild-type L. monocytogenes strains. The levels of uptake of listeriae by Peyer’s patches and villous intestine were similar and low, 50 to 250 CFU per cm2 of tissue. No listeria cells crossing the epithelial sheet of Peyer’s patches and villous intestine were observed by transmission electron microscopy. The lack of significant interaction of listeriae and the follicle-associated epithelium of Peyer’s patches was confirmed by scanning electron microscopy. The follicular tissue of Peyer’s patches was a preferential site of Listeria replication. With all doses tested, the rate of bacterial growth was 10 to 20 times higher in Peyer’s patches than in villous intestine. At early stages of Peyer’s patch infection, listeriae were observed inside mononuclear cells of the dome area. Listeriae then disseminated throughout the follicular tissue except for the germinal center. The virulence determinants hly and, to a lesser extent, actA, but not inlAB, were required for the completion of this process. This study suggests that Peyer’s patches are preferential sites for replication rather than for entry of L. monocytogenes, due to the presence of highly permissive mononuclear cells whose nature remains to be defined. PMID:9453636

Steatorrhoea in rats with an intestinal cul-de-sac

PubMed Central

Hoet, P. P.; Eyssen, H.

1964-01-01

Steatorrhoea in rats with an intestinal cul-de-sac is mainly due to malabsorption of alimentary fats but faecal lipids of endogenous origin are also increased. Steatorrhoea depends on the site of the blind loop in the small intestine and is mainly caused by bacterial proliferation in the lumen of the gut. The aetiological role of Gram-positive anaerobic microbes, especially Clostridium welchii, is suggested. ImagesFIG. 3FIG. 4FIG. 5FIG. 6 PMID:14209913

Ion channel TRPV1-dependent activation of PTP1B suppresses EGFR-associated intestinal tumorigenesis

PubMed Central

de Jong, Petrus R.; Takahashi, Naoki; Harris, Alexandra R.; Lee, Jihyung; Bertin, Samuel; Jeffries, James; Jung, Michael; Duong, Jen; Triano, Amy I.; Lee, Jongdae; Niv, Yaron; Herdman, David S.; Taniguchi, Koji; Kim, Chang-Whan; Dong, Hui; Eckmann, Lars; Stanford, Stephanie M.; Bottini, Nunzio; Corr, Maripat; Raz, Eyal

2014-01-01

The intestinal epithelium has a high rate of turnover, and dysregulation of pathways that regulate regeneration can lead to tumor development; however, the negative regulators of oncogenic events in the intestinal epithelium are not fully understood. Here we identified a feedback loop between the epidermal growth factor receptor (EGFR), a known mediator of proliferation, and the transient receptor potential cation channel, subfamily V, member 1 (TRPV1), in intestinal epithelial cells (IECs). We found that TRPV1 was expressed by IECs and was intrinsically activated upon EGFR stimulation. Subsequently, TRPV1 activation inhibited EGFR-induced epithelial cell proliferation via activation of Ca2+/calpain and resulting activation of protein tyrosine phosphatase 1B (PTP1B). In a murine model of multiple intestinal neoplasia (ApcMin/+ mice), TRPV1 deficiency increased adenoma formation, and treatment of these animals with an EGFR kinase inhibitor reversed protumorigenic phenotypes, supporting a functional association between TRPV1 and EGFR signaling in IECs. Administration of a TRPV1 agonist suppressed intestinal tumorigenesis in ApcMin/+ mice, similar to — as well as in conjunction with — a cyclooxygenase-2 (COX-2) inhibitor, which suggests that targeting both TRPV1 and COX-2 has potential as a therapeutic approach for tumor prevention. Our findings implicate TRPV1 as a regulator of growth factor signaling in the intestinal epithelium through activation of PTP1B and subsequent suppression of intestinal tumorigenesis. PMID:25083990

Method for creating ideal tissue fusion in soft-tissue structures using radio frequency (RF) energy.

PubMed

Shields, Chelsea A; Schechter, David A; Tetzlaff, Phillip; Baily, Ali L; Dycus, Sean; Cosgriff, Ned

2004-01-01

Bipolar radiofrequency (RF) energy can successfully seal vascular structures up to 7 mm by fusing collagen and elastin in the lumen. Valleylab has created a system to expand this technology beyond vessel sealing with the development of a closed-loop, feedback-control RF generator that closely monitors tissue fusion. This generator, operating with a loop time of approximately 250 micros, continuously adjusts energy output, creating optimized soft-tissue fusion through structural protein amalgamation. In the first study, RF energy was applied to canine lung using the new-generation generator and lung-prototype device. A lobectomy was completed, sealing the lobar bronchus, parenchyma, and pulmonary vasculature. Chronic performance of the seals was evaluated at necropsy on postoperative days 7 and 14. In a second study, RF energy was applied to porcine small intestine using the same closed-loop generator and anastomosis prototype device. Acute tissue fusion was assessed qualitatively for hemostasis and seal quality. Terminal tissue evaluation was completed on postoperative day 7 and analyzed histopathologically. Histopathology confirmed acute and chronic tissue fusion in both the lung and intestine. Normal pathological healing was substantiated by angiogenesis, granulation, and proliferation of fibroblasts. Preliminary studies using canine lung and porcine small intestine demonstrate the potential of this closed-loop generator for soft-tissue amalgamation. Advanced monitoring capabilities make this fusion system applicable in many soft-tissue structures with adequate collagen and elastin. Further investigation of potential surgical applications needs to be completed.

Meckel's diverticulum incarcerated in a transmesocolic internal hernia

PubMed Central

Wu, Si-Yuan; Ho, Meng-Hsing; Hsu, Sheng-Der

2014-01-01

Intestinal obstruction is a common complication associated with Meckel’s diverticulum in adults. The diverticulum itself or its fibrous band can lead to an intestinal volvulus, intussusceptions, or closed-loop obstructions, which require surgery. The incarceration of Meckel’s diverticulum in either inguinal or femoral hernia sacs (Littre’s hernia) is another, less common, etiology underlying intestinal obstruction. This case report describes a 45-year-old man who had an obstruction associated with a Meckel’s diverticulum that passed through a congenital defect in the mesocolon into the right subphrenic space. The patient, who had not undergone abdominal surgery previously, came to the emergency room with acute onset of intermittent epigastric pain and abdominal distention. Computed tomography images showed the presence of a segment of the small bowel and a diverticulum in the right subphrenic space and paracolic gutter. The twisted mesentery and the dilated loops of the proximal small bowel were indicative of an intestinal volvulus and obstruction. Meckel’s diverticulum complicated by a transmesocolic internal hernia was diagnosed, and this condition was confirmed during emergency surgery. The patient’s postoperative recovery was uneventful. This case report highlights another presentation of Meckel’s diverticulum, that is, in combination with a transmesocolic internal hernia. This etiology may lead to an intestinal volvulus and necessitate early surgery. PMID:25309093

Intimin, Tir, and Shiga Toxin 1 Do Not Influence Enteropathogenic Responses to Shiga Toxin-Producing Escherichia coli in Bovine Ligated Intestinal Loops

PubMed Central

Stevens, Mark P.; Marchès, Olivier; Campbell, June; Huter, Veronika; Frankel, Gad; Phillips, Alan D.; Oswald, Eric; Wallis, Timothy S.

2002-01-01

Shiga toxin-producing Escherchia coli (STEC) comprises a group of attaching and effacing (A/E) enteric pathogens of animals and humans. Natural and experimental infection of calves with STEC may result in acute enteritis or subclinical infection, depending on serotype- and host-specific factors. To quantify intestinal secretory and inflammatory responses to STEC in the bovine intestine, serotypes that are associated with human disease (O103:H2 and O157:H7) were introduced into ligated mid-ileal loops in gnotobiotic and conventional calves, and fluid accumulation and recruitment of radiolabeled neutrophils were measured after 12 h. STEC serotype O103:H2, but not serotype O157:H7, elicited strong enteropathogenic responses. To determine if the inflammatory response to STEC O103:H2 in calves requires Shiga toxin 1 or intimate bacterial attachment to the intestinal epithelium, defined mutations were made in the stx1, eae, and tir genes. Our data indicate that some STEC induce intestinal inflammatory responses in calves by a mechanism that is independent of A/E-lesion formation, intimin, or Shiga toxin 1. This may have implications for strategies to reduce STEC carriage in cattle. PMID:11796630

Role of host xanthine oxidase in infection due to enteropathogenic and Shiga-toxigenic Escherichia coli.

PubMed

Crane, John K; Naeher, Tonniele M; Broome, Jacqueline E; Boedeker, Edgar C

2013-04-01

Xanthine oxidase (XO), also known as xanthine oxidoreductase, has long been considered an important host defense molecule in the intestine and in breastfed infants. Here, we present evidence that XO is released from and active in intestinal tissues and fluids in response to infection with enteropathogenic Escherichia coli (EPEC) and Shiga-toxigenic E. coli (STEC), also known as enterohemorrhagic E. coli (EHEC). XO is released into intestinal fluids in EPEC and STEC infection in a rabbit animal model. XO activity results in the generation of surprisingly high concentrations of uric acid in both cultured cell and animal models of infection. Hydrogen peroxide (H(2)O(2)) generated by XO activity triggered a chloride secretory response in intestinal cell monolayers within minutes but decreased transepithelial electrical resistance at 6 to 22 h. H(2)O(2) generated by XO activity was effective at killing laboratory strains of E. coli, commensal microbiotas, and anaerobes, but wild-type EPEC and STEC strains were 100 to 1,000 times more resistant to killing or growth inhibition by this pathway. Instead of killing pathogenic bacteria, physiologic concentrations of XO increased virulence by inducing the production of Shiga toxins from STEC strains. In vivo, exogenous XO plus the substrate hypoxanthine did not protect and instead worsened the outcome of STEC infection in the rabbit ligated intestinal loop model of infection. XO released during EPEC and STEC infection may serve as a virulence-inducing signal to the pathogen and not solely as a protective host defense.

Positive Regulatory Control Loop between Gut Leptin and Intestinal GLUT2/GLUT5 Transporters Links to Hepatic Metabolic Functions in Rodents

PubMed Central

Sakar, Yassine; Nazaret, Corinne; Lettéron, Philippe; Ait Omar, Amal; Avenati, Mathilde; Viollet, Benoît; Ducroc, Robert; Bado, André

2009-01-01

Background and Aims The small intestine is the major site of absorption of dietary sugars. The rate at which they enter and exit the intestine has a major effect on blood glucose homeostasis. In this study, we determine the effects of luminal leptin on activity/expression of GLUT2 and GLUT5 transporters in response to sugars intake and analyse their physiological consequences. Methodology Wistar rats, wild type and AMPKα2 −/− mice were used. In vitro and in vivo isolated jejunal loops were used to quantify transport of fructose and galactose in the absence and the presence of leptin. The effects of fructose and galactose on gastric leptin release were determined. The effects of leptin given orally without or with fructose were determined on the expression of GLUT2/5, on some gluconeogenesis and lipogenic enzymes in the intestine and the liver. Principal Findings First, in vitro luminal leptin activating its receptors coupled to PKCβII and AMPKα, increased insertion of GLUT2/5 into the brush-border membrane leading to enhanced galactose and fructose transport. Second in vivo, oral fructose but not galactose induced in mice a rapid and potent release of gastric leptin in gastric juice without significant changes in plasma leptin levels. Moreover, leptin given orally at a dose reproducing comparable levels to those induced by fructose, stimulated GLUT5-fructose transport, and potentiated fructose-induced: i) increase in blood glucose and mRNA levels of key gluconeogenesis enzymes; ii) increase in blood triglycerides and reduction of mRNA levels of intestinal and hepatic Fasting-induced adipocyte factor (Fiaf) and iii) increase in SREBP-1c, ACC-1, FAS mRNA levels and dephosphorylation/activation of ACC-1 in liver. Conclusion/Significance These data identify for the first time a positive regulatory control loop between gut leptin and fructose in which fructose triggers release of gastric leptin which, in turn, up-regulates GLUT5 and concurrently modulates metabolic functions in the liver. This loop appears to be a new mechanism (possibly pathogenic) by which fructose consumption rapidly becomes highly lipogenic and deleterious. PMID:19956534

A girl with spina bifida, an extra leg, and ectopic intestinal loops--a "foetus in foetu" or a whim of the neural crest?

PubMed

Lende, G; Wendemu, W; Mørk, S; Wester, K

2007-10-01

This article describes a girl with an extra leg attached to her lower back, combined with a spina bifida and a myelomeningocele. Despite lacking sensory or motor functions, the leg grew proportionately with the rest of the body. The bony structures were almost normal. A cross section showed fat tissue with some centrally situated blood vessels, nerve bundles, and muscular fragments. Proximally, an isolated colon loop was found. The extra leg and intestine respected the dorsal fascia, without connection with the peritoneal or retroperitoneal compartments. The finding is discussed with reference to existing hypotheses for limb formation.

Disposition of lipid-based formulation in the intestinal tract affects the absorption of poorly water-soluble drugs.

PubMed

Iwanaga, Kazunori; Kushibiki, Toshihiro; Miyazaki, Makoto; Kakemi, Masawo

2006-03-01

Solvent Green 3 (SG), a model poorly water-soluble compound, was orally administered to rats with soybean oil emulsion or the Self-microemulsifying drug delivery system (SMEDDS) composed of Gelucire44/14. The bioavailability of SG after oral administration with SMEDDS was 1.7-fold higher than that with soybean oil emulsion. The intestinal absorption of lipid-based formulations themselves was evaluated by the in situ closed loop method. The effect of lipase and bile salt on their absorption was also evaluated. SMEDDS itself was rapidly absorbed in the intestine even in the absence of lipase and bile salt, and the absorption was increased by the addition of lipase and bile salt. On the other hand, no soybean oil emulsion was absorbed in the absence of lipase and bile salt. However, mixed micelle prepared from emulsion by incubating soybean oil emulsion with lipase and bile salt was rapidly absorbed through the intestine. Without lipase and bile salt, SG was not absorbed after administration with soybean oil emulsion. Therefore, we concluded that the degradation of soybean oil emulsion was needed for SG to be absorbed through the intestine. Furthermore, we investigated the intestinal absorption of SG after oral administration to rats whose chylomicron synthesis were inhibited by pretreatment with colchicine. Colchicine completely inhibited the intestinal absorption of SG after administration with each lipid-based formulation, suggesting that SG was absorbed from the intestine via a lymphatic route. Absorption of the dosage formulation should be paid attention when poorly water-soluble drugs are orally administered with lipid-based formulation.

Intestinal alkaline phosphatase inhibits the proinflammatory nucleotide uridine diphosphate.

PubMed

Moss, Angela K; Hamarneh, Sulaiman R; Mohamed, Mussa M Rafat; Ramasamy, Sundaram; Yammine, Halim; Patel, Palak; Kaliannan, Kanakaraju; Alam, Sayeda N; Muhammad, Nur; Moaven, Omeed; Teshager, Abeba; Malo, Nondita S; Narisawa, Sonoko; Millán, José Luis; Warren, H Shaw; Hohmann, Elizabeth; Malo, Madhu S; Hodin, Richard A

2013-03-15

Uridine diphosphate (UDP) is a proinflammatory nucleotide implicated in inflammatory bowel disease. Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor capable of inhibiting intestinal inflammation. We used the malachite green assay to show that IAP dephosphorylates UDP. To study the anti-inflammatory effect of IAP, UDP or other proinflammatory ligands (LPS, flagellin, Pam3Cys, or TNF-α) in the presence or absence of IAP were applied to cell cultures, and IL-8 was measured. UDP caused dose-dependent increase in IL-8 release by immune cells and two gut epithelial cell lines, and IAP treatment abrogated IL-8 release. Costimulation with UDP and other inflammatory ligands resulted in a synergistic increase in IL-8 release, which was prevented by IAP treatment. In vivo, UDP in the presence or absence of IAP was instilled into a small intestinal loop model in wild-type and IAP-knockout mice. Luminal contents were applied to cell culture, and cytokine levels were measured in culture supernatant and intestinal tissue. UDP-treated luminal contents induced more inflammation on target cells, with a greater inflammatory response to contents from IAP-KO mice treated with UDP than from WT mice. Additionally, UDP treatment increased TNF-α levels in intestinal tissue of IAP-KO mice, and cotreatment with IAP reduced inflammation to control levels. Taken together, these studies show that IAP prevents inflammation caused by UDP alone and in combination with other ligands, and the anti-inflammatory effect of IAP against UDP persists in mouse small intestine. The benefits of IAP in intestinal disease may be partly due to inhibition of the proinflammatory activity of UDP.

Protective effect of aged garlic extract on the small intestinal damage of rats induced by methotrexate administration.

PubMed

Horie, T; Matsumoto, H; Kasagi, M; Sugiyama, A; Kikuchi, M; Karasawa, C; Awazu, S; Itakura, Y; Fuwa, T

1999-08-01

The methotrexate (MTX) administration to rats causes the damage of small intestine. The small intestinal damage was evaluated by measuring the intestinal permeability of the poorly absorbable compound, fluorescein isothiocyanate (FITC)-labeled dextran (average molecular weight, 4,400) (FD-4) using the in vitro everted intestine technique and by determining the FD-4 that appeared in plasma using the in situ closed loop intestine technique. The MTX administration to rats fed with the standard laboratory diet increased the small intestinal permeability of FD-4 due to the damage of the small intestine. Interestingly, the permeability of FD-4, when MTX was administered to rats fed with the aged garlic extract containing diet, was depressed almost to the level of control rats without the MTX treatment. The present study showed that the aged garlic extract protected the small intestine from the damage induced by the action of MTX on the crypt cells.

Alleviation by garlic of antitumor drug-induced damage to the intestine.

PubMed

Horie, T; Awazu, S; Itakura, Y; Fuwa, T

2001-03-01

Antitumour drugs such as methotrexate (MTX) and 5-fluorouracil (5-FU) induce intestinal damage. This is a serious side effect of cancer chemotherapy. The present studies examined whether or not aged garlic extract (AGE) protects against damage from these antitumor drugs. Both drugs were administered orally for 4 or 5 d to rats fed a standard laboratory diet with and without 2% AGE. The small intestinal absorption of the poorly absorbable compound, fluorescein isothiocyanate--labeled dextran (FD-4; average molecular weight, 4400) was used to evaluate the damage to the intestine using the in vitro everted intestine technique and the in situ intestinal loop technique. FD-4 absorption increased in the antitumour drug-treated rats fed the diet without garlic. Interestingly, FD-4 absorption was depressed in rats fed the diet containing AGE. These results suggest that AGE may protect the small intestine of rats from antitumour drug-induced damage.

Blind Loop Syndrome

MedlinePlus

... be caused by: Complications of abdominal surgery, including gastric bypass for obesity and gastrectomy to treat peptic ulcers and stomach cancer Structural problems in and around your small intestine, ...

Improvement of absorption enhancing effects of n-dodecyl-beta-D-maltopyranoside by its colon-specific delivery using chitosan capsules.

PubMed

Fetih, Gihan; Lindberg, Sara; Itoh, Katsuhito; Okada, Naoki; Fujita, Takuya; Habib, Fawsia; Artersson, Per; Attia, Mohammed; Yamamoto, Akira

2005-04-11

In general, absorption enhancing effects of various absorption enhancers were greater in the large intestine than those in the small intestinal regions. Therefore, the effectiveness of absorption enhancers is expected to be remarkably observed, if these enhancers can be delivered to the large intestine with some poorly absorbable drugs after oral administration. In this study, therefore, we examined whether chitosan capsules were effective for the colon-specific delivery of a certain absorption enhancer and can improve the absorption enhancing action of the absorption enhancer after oral administration. 5(6)-Carboxyfluorescein (CF) was used as a model drug to investigate the site-dependent effectiveness of various absorption enhancers by an in situ closed loop method. Sodium glycocholate (NaGC), n-dodecyl-beta-d-maltopyranoside (LM), sodium salicylate (NaSal) and sodium caprate (NaCap) were used as models of absorption enhancers in this study. Overall, the absorption enhancing effects of these enhancers for intestinal absorption of CF were greater in the colon than those in the jejunum and the ileum. Especially, among these enhancers tested in this study, LM showed much greater absorption enhancing effect in the colon than in the jejunum and the ileum. Therefore, LM was selected as a model absorption enhancer to examine the effect of chitosan capsules on the absorption enhancing effect of LM. When CF and LM were orally administered to rats using chitosan capsules, the plasma concentration of CF was much higher than those in other dosage forms including solution and gelatin capsules. Therefore, chitosan capsules may be useful carriers for colon-specific delivery of LM, thereby increasing its absorption enhancing effect from the intestinal membranes.

A Case of 2-Year-Old Child with Entero-Enteric Fistula Following Ingestion of 25 Magnets.

PubMed

Pogorelić, Zenon; Borić, Matija; Markić, Joško; Jukić, Miro; Grandić, Leo

Magnet ingestion usually does not cause serious complications, but in case of multiple magnet ingestion or ingestion of magnet with other metal it could cause intestinal obstruction, fistula formation or even perforation. We report case of intestinal obstruction and fistula formation following ingestion of 25 magnets in a 2-year-old girl. Intraoperatively omega shaped intestinal loop with fistula caused by two magnetic balls was found. Intestine trapped with magnetic balls was edematous and inflamed. Resection of intestinal segment was performed, followed by entero-enteric anastomosis. A total of 25 magnets were removed from resected intestine. Single magnet ingestion is treated as non-magnetic foreign body. Multiple magnet ingestion should be closely monitored and surgical approach could be the best option to prevent or to cure its complications.

Influence of fentanyl and morphine on intestinal circulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tverskoy, M.; Gelman, S.; Fowler, K.C.

The influence of fentanyl and morphine on the intestinal circulation was evaluated in an isolated loop preparation in 37 dogs anesthetized with pentobarbital intravenously. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mm Hg. A mixture of /sup 86/Rb and 9-micron spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A strong correlation was found between the clearances of rubidium and microspheres (r = 0.97, P less than 0.0001), suggesting that the shunting of 9-micron spheres through the intestinesmore » reflects the shunting of blood through nonnutritive vessels. Intravenous fentanyl decreased oxygen uptake (O/sub 2/up), and vascular resistance (VR), and increased blood flow (BF), rubidium and microsphere clearances (Cl-Rb, Cl-Sph, respectively), and permeability--surface area product (PS) in a dose-related fashion. Intravenous morphine in a dose of 1 mg X kg-1 increased Cl-Rb (nutritive BF) without changes in total (nutritive and nonnutritive) BF. This increase in nutritive BF is probably related to morphine-induced histamine release. Morphine in a dose of 5 mg X kg-1 was accompanied by vasoconstriction that was completely abolished by alpha-adrenoceptor blockade. The data suggest that morphine-induced intestinal vasoconstriction is mediated via a release of epinephrine, apparently from the adrenal medulla. It is concluded that changes in the intestinal circulation during anesthesia with narcotics might play a certain role in the cardiovascular homeostasis during anesthesia and surgery. An increase in oxygen content in portal venous blood, resulting from a decrease in intestinal oxygen uptake, should facilitate hepatic oxygenation.« less

[Intrauterine intestinal volvulus].

PubMed

Gawrych, Elzbieta; Chojnacka, Hanna; Wegrzynowski, Jerzy; Rajewska, Justyna

2009-07-01

Intrauterine intestinal volvulus is an extremely rare case of acute congenital intestinal obstruction. The diagnosis is usually possible in the third trimester of a pregnancy. Fetal midgut volvulus is most likely to be recognized by observing a typical clockwise whirlpool sign during color Doppler investigation. Multiple dilated intestinal loops with fluid levels are usually visible during the antenatal ultrasound as well. Physical and radiographic findings in the newborn indicate intestinal obstruction and an emergency surgery is required. The authors describe intrauterine volvulus in 3 female newborns in which surgical treatment was individualized. The decision about primary or delayed anastomosis after resection of the gangrenous part of the small bowel was made at the time of the surgery and depended on the general condition of the newborn, as well as presence or absence of meconium peritonitis. Double loop jejunostomy was performed in case of two newborns, followed by a delayed end-to-end anastomosis. In case of the third newborn, good blood supply of the small intestine after untwisting and 0.25% lignocaine injections into mesentery led to the assumption that the torsion was not complete and ischemia was reversible. In the two cases of incomplete rotation the cecum was sutured to the left abdominal wall to prevent further twisting. The postoperative course was uneventful and oral alimentation caused no problems. Physical development of all these children has been normal (current age: 1-2 years) and the parents have not observed any disorders or problems regarding passage of food through the alimentary canal. Prompt antenatal diagnosis of this surgical emergency and adequate choice of intervention may greatly reduce mortality due to intrauterine volvulus.

Imaging diagnosis--muscular hypertrophy of the small intestine and pseudodiverticula in a horse.

PubMed

Navas De Solís, Cristobal; Biscoe, Elisabeth W; Lund, Caleb M; Labbe, Karyn; Muñoz, Juan; Farnsworth, Kelly

2015-01-01

A 14-year-old Thoroughbred gelding was presented for chronic colic and weight loss. Transcutaneous and transrectal abdominal ultrasonography revealed distended, thickened small intestine with primary thickening of the muscularis and a focally more thickened loop with an echoic structure crossing the wall from the mucosa to the serosa. Visualization of diffuse thickening of the muscularis (muscular hypertrophy of the small intestine) and a focal lesion (pseudodiverticulum) helped clinicians make informed decisions. This case illustrates the importance of transabdominal and transrectal ultrasonography in horses with chronic colic and the relevance of considering the abnormalities in layering pattern of the intestinal wall. © 2014 American College of Veterinary Radiology.

Translocation of Candida albicans is related to the blood flow of individual intestinal villi.

PubMed

Gianotti, L; Alexander, J W; Fukushima, R; Childress, C P

1993-08-01

Splanchnic ischemia is associated with increased bacterial translocation, but previous observations showed that translocation of Candida albicans did not occur uniformly among individual intestinal villi. This study was performed to investigate the relationship between the degree of Candida translocation and the microcirculation of individual villi. Thiry-Vella intestinal loops were created in eight guinea pigs. One week later, the distal aorta and right carotid artery were cannulated, and systemic blood pressure was recorded throughout the entire experiment. C. albicans (1 x 10(10)) was introduced into the Thiry-Vella loop, and the animals underwent a 40% full-thickness burn. Systolic hypotension was observed in the first 75 minutes postburn; then the systemic blood pressure returned to a normal range. Four hours after burn, 8 x 10(7) microspheres (10 microns) were injected into the aorta. The animals were sacrificed, and the Thiry-Vella loops were harvested and processed for light microscopy. At the microscopic level, within each villus, both the number of beads trapped in the arterioles and the number of Candida translocated into the enterocytes were counted. An inverse linear correlation between number of beads and number of translocated yeast per individual villus was found (r = -0.78; P < 0.005). These data provide further evidence that blood flow is an important determinant of the magnitude of microbial translocation, even within individual villi.

Polyamidoamine dendrimers as novel potential absorption enhancers for improving the small intestinal absorption of poorly absorbable drugs in rats.

PubMed

Lin, Yulian; Fujimori, Takeo; Kawaguchi, Naoko; Tsujimoto, Yuiko; Nishimi, Mariko; Dong, Zhengqi; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

2011-01-05

Effects of polyamidoamine (PAMAM) dendrimers on the intestinal absorption of poorly absorbable drugs were examined by an in situ closed loop method in rats. 5(6)-Carboxyfluorescein (CF), fluorescein isothiocyanate-dextrans (FDs) with various molecular weights, calcitonin and insulin were used as model drugs of poorly absorbable drugs. The absorption of CF, FD4 and calcitonin from the rat small intestine was significantly enhanced in the presence of PAMAM dendrimers. The absorption-enhancing effects of PAMAM dendrimers for improving the small intestinal absorption of CF were concentration and generation dependent and a maximal absorption-enhancing effect was observed in the presence of 0.5% (w/v) G2 PAMAM dendrimer. However, G2 PAMAM dendrimer had almost no absorption-enhancing effect on the small intestinal absorption of macromolecular drugs including FD10 and insulin. Overall, the absorption-enhancing effects of G2 PAMAM dendrimer in the small intestine decreased as the molecular weights of drug increased. However, G2 PAMAM dendrimer did not enhance the intestinal absorption of these drugs with different molecular weights in the large intestine. Furthermore, we evaluated the intestinal membrane damage with or without G2 PAMAM dendrimer. G2 PAMAM dendrimer (0.5% (w/v)) significantly increased the activities of lactate dehydrogenase (LDH) and the amounts of protein released from the intestinal membranes, but the activities and amounts of these toxic markers were less than those in the presence of 3% Triton X-100 used as a positive control. Moreover, G2 PAMAM dendrimer at concentrations of 0.05% (w/v) and 0.1% (w/v) did not increase the activities and amounts of these toxic markers. These findings suggested that PAMAM dendrimers at lower concentrations might be potential and safe absorption enhancers for improving absorption of poorly absorbable drugs from the small intestine. Copyright © 2010 Elsevier B.V. All rights reserved.

A case of child death caused by intestinal volvulus following magnetic toy ingestion.

PubMed

Olczak, Mieszko; Skrzypek, Ewa

2015-05-01

An 8-year boy was admitted to the ER of one of Warsaw's pediatric hospitals with a history of having bloody vomiting the day before. During admission the boy collapsed and lost consciousness. CPR was unsuccessful. On medico-legal autopsy, two foreign objects (small magnetic spheres--0.5 cm in diameter) were found in two different places in the small and large intestines and were notably attracted magnetically one to another. A loop of approximately 1-m length with features of small intestinal hemorrhagic necrosis and small intestinal mechanical obstruction was found. The cause of death was intestinal volvulus and small intestinal mechanical obstruction caused by ingestion of foreign objects (two neodymium magnets). Most likely these small magnetic spheres were part of a popular toy, the safety of which, lately, has been widely discussed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of N(G)-nitro-L-arginine methyl ester on intestinal permeability following intestinal ischemia-reperfusion injury in a rat model.

PubMed

Luo, C C; Chen, H M; Chiu, C H; Lin, J N; Chen, J C

2001-07-01

Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis in premature infants. Previous studies suggested that continuous, endogenous formation of nitric oxide (NO) maintains the mucosal integrity of the intestine, thus protecting the gut from injuries from blood-borne toxins and tissue-destructive mediators. This study was undertaken to assess whether the inhibition of NO production causes an increase in intestinal permeability in rats following IRI. Sprague-Dawley rats weighing 200-300 g were divided into 4 groups: (1) untreated group (normal control); (2) ischemia-reperfusion group; (3) early N(G)-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO production, treatment group, and (4) late L-NAME treatment group. Transient IRI was induced by 30-min occlusion, followed by reperfusion of the isolated ileal loop. The L-NAME was administered 15 min before and after mesenteric ischemia as a 25-mg/kg bolus. Fluorescein isothiocyanate-dextran (FITC-D) was used to quantitatively assess the alteration in mucosal permeability of the intestine. There was no significant increase in the portal vein FITC-D level among normal controls, ischemia-reperfusion group and late L-NAME-treated group, but there was an approximately 6-fold increase in the early L-NAME treatment group. The pathological features of the intestine following IRI include denudation of the villus epithelium and reduction of villus height, associated with marked inflammatory cell infiltration over the lamina propria. These results suggest that endogenous NO may play a role in the protecting intestinal integrity after IRI. Copyright 2001 S. Karger AG, Basel

Intestinal alkaline phosphatase inhibits the proinflammatory nucleotide uridine diphosphate

PubMed Central

Hamarneh, Sulaiman R.; Mohamed, Mussa M. Rafat; Ramasamy, Sundaram; Yammine, Halim; Patel, Palak; Kaliannan, Kanakaraju; Alam, Sayeda N.; Muhammad, Nur; Moaven, Omeed; Teshager, Abeba; Malo, Nondita S.; Narisawa, Sonoko; Millán, José Luis; Warren, H. Shaw; Hohmann, Elizabeth; Malo, Madhu S.; Hodin, Richard A.

2013-01-01

Uridine diphosphate (UDP) is a proinflammatory nucleotide implicated in inflammatory bowel disease. Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor capable of inhibiting intestinal inflammation. We used the malachite green assay to show that IAP dephosphorylates UDP. To study the anti-inflammatory effect of IAP, UDP or other proinflammatory ligands (LPS, flagellin, Pam3Cys, or TNF-α) in the presence or absence of IAP were applied to cell cultures, and IL-8 was measured. UDP caused dose-dependent increase in IL-8 release by immune cells and two gut epithelial cell lines, and IAP treatment abrogated IL-8 release. Costimulation with UDP and other inflammatory ligands resulted in a synergistic increase in IL-8 release, which was prevented by IAP treatment. In vivo, UDP in the presence or absence of IAP was instilled into a small intestinal loop model in wild-type and IAP-knockout mice. Luminal contents were applied to cell culture, and cytokine levels were measured in culture supernatant and intestinal tissue. UDP-treated luminal contents induced more inflammation on target cells, with a greater inflammatory response to contents from IAP-KO mice treated with UDP than from WT mice. Additionally, UDP treatment increased TNF-α levels in intestinal tissue of IAP-KO mice, and cotreatment with IAP reduced inflammation to control levels. Taken together, these studies show that IAP prevents inflammation caused by UDP alone and in combination with other ligands, and the anti-inflammatory effect of IAP against UDP persists in mouse small intestine. The benefits of IAP in intestinal disease may be partly due to inhibition of the proinflammatory activity of UDP. PMID:23306083

Blind loop syndrome

MedlinePlus

Treatment most often starts with antibiotics for the excess bacteria growth, along with vitamin B12 supplements. If antibiotics are not effective, surgery may be needed to help food flow through the intestines.

[Treatment of postoperative abdominal hernias with polypropylene endoprosthesis].

PubMed

Chakhvadze, B Iu; Nakashidze, D Kh

2009-06-01

The results of the surgical treatment of 82 patients with postoperative abdominal hernias were analysed. All of the patients underwent surgery with polypropylene endoprosthesis. The choice of a hernioplasty method depended on relative volume of postoperative hernia. Middle-sized hernias were indications for reconstructive surgery (complete adaptation of muscular and aponeurotic layers was maintained). The large and gigantic hernias were indications for correcting surgery (specified diastasis of muscular and aponeurotic layers was maintained). In case of lacking of peritoneum (30 patients) greater omentum was used for isolation of the net from intestinal loops. It is concluded that greater omentum provides good extraperitonisation of transplant from intestinal loop and prevents complications due to contact of net with abdominal organs. Postoperative complications mainly were local and seen in 29% cases. There were no lethal outcomes.

Late effects of intraoperative radiation therapy on retroperitoneal tissues, intestine, and bile duct in a large animal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sindelar, W.F.; Tepper, J.E.; Kinslla, T.J.

1994-07-01

The late histopathological effects of intraoperative radiotherapy (IORT) on retroperitoneal tissues, intestine, and bile duct were investigated in dogs. Fourteen adult foxhounds were subjected to laparotomy and varying doses (0-45 Gy) of IORT (11 MeV electrons) delivered to retroperitoneal tissues including the great vessels and ureters, to a loop of defunctionalized small bowel, or to the extrahepatic bile duct. One control animal received an aortic transection and reanastomosis at the time of laparotomy; another control received laparotomy alone. This paper describes the late effects of single-fraction IORT occurring 3-5 years following treatment. Dogs receiving IORT to the retroperitoneum through amore » 4 X 15 cm portal showed few gross or histologic abnormalities at 20 Gy. At doses ranging from 30-45 Gy, radiation changes in normal tissues were consistently observed. Retroperitoneal fibrosis with encasement of the ureters and great vessels developed at doses {ge}30 Gy. Radiation changes were present in the aorta and vena cava at doses {ge}40 Gy. A 30 Gy dog developed an in-field malignant osteosarcoma at 3 years which invaded the vertebral column and compressed the spinal cord. A 40 Gy animal developed obstruction of the right ureter with fatal septic hydronephrosis at 4 years. Animals receiving IORT through a 5 cm IORT portal to an upper abdominal field which included a defunctionalized loop of small bowel, showed few gross or histologic abnormalities at a dose of 20 Gy. At 30 Gy, hyaline degeneration of the intestinal muscularis layer of the bowel occurred. At a dose of 45 Gy, internal intestinal fistulae developed. One 30 Gy animal developed right ureteral obstruction and hydronephrosis at 5 years. A dog receiving 30 Gy IORT through a 5 cm portal to the extrahepatic bile duct showed diffuse fibrosis through the gastroduodenal ligament. These canine studies contribute to the area of late tissue tolerance to IORT. 7 refs., 3 figs., 5 tabs.« less

Intestinal secretion of immunoglobulins and antibodies to Escherichia coli in the pig

PubMed Central

Porter, P.; Noakes, D. E.; Allen, W. D.

1970-01-01

Immunoglobulins and antibodies against Escherichia coli 0141 have been studied in porcine intestinal secretions obtained from Thiry Vella loops prepared in the mid jejunum of 4 animals. The molecular size of the secreted immunoglobulins were investigated by gel filtration and sucrose density gradient ultra-centrifugation. Intestinal IgM was found to have 7S characteristics and intestinal IgA mainly 11S characteristics similar to secretory IgA isolated from porcine milk. Immune inhibition studies with rabbit anti-IgA-globulin serum produced complete elimination of E. coli 0141 antibodies detected by direct haemagglutination. In one animal incomplete antibody assayed by antiglobulin haemagglutination was identified in fractions associated with IgM and IgG. Immunofluorescent studies were made to correlate immunoglobulins in the small intestinal tissue with weaning. ImagesFIG. 1FIG. 2FIG. 7 PMID:4193669

Suppression of intestinal tumorigenesis in Apc mutant mice upon Musashi-1 deletion.

PubMed

Wolfe, Andy R; Ernlund, Amanda; McGuinness, William; Lehmann, Carl; Carl, Kaitlyn; Balmaceda, Nicole; Neufeld, Kristi L

2017-02-15

Therapeutic strategies based on a specific oncogenic target are better justified when elimination of that particular oncogene reduces tumorigenesis in a model organism. One such oncogene, Musashi-1 ( Msi-1 ), regulates translation of target mRNAs and is implicated in promoting tumorigenesis in the colon and other tissues. Msi-1 targets include the tumor suppressor adenomatous polyposis coli ( Apc ), a Wnt pathway antagonist lost in ∼80% of all colorectal cancers. Cell culture experiments have established that Msi-1 is a Wnt target, thus positioning Msi-1 and Apc as mutual antagonists in a mutually repressive feedback loop. Here, we report that intestines from mice lacking Msi-1 display aberrant Apc and Msi-1 mutually repressive feedback, reduced Wnt and Notch signaling, decreased proliferation, and changes in stem cell populations, features predicted to suppress tumorigenesis. Indeed, mice with germline Apc mutations ( Apc Min ) or with the Apc 1322T truncation mutation have a dramatic reduction in intestinal polyp number when Msi-1 is deleted. Taken together, these results provide genetic evidence that Msi-1 contributes to intestinal tumorigenesis driven by Apc loss, and validate the pursuit of Msi-1 inhibitors as chemo-prevention agents to reduce tumor burden. © 2017. Published by The Company of Biologists Ltd.

Highly conserved type 1 pili promote enterotoxigenic E. coli pathogen-host interactions

PubMed Central

Rashu, Rasheduzzaman; Begum, Yasmin Ara; Ciorba, Matthew A.; Hultgren, Scott J.; Qadri, Firdausi

2017-01-01

Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host. Among genes significantly upregulated on cell contact are those encoding type 1 pili. We therefore investigated the role played by these pili in facilitating ETEC adhesion, and toxin delivery to model intestinal epithelia. We demonstrate that type 1 pili, encoded in the E. coli core genome, play an essential role in ETEC virulence, acting in concert with plasmid-encoded pathovar specific colonization factor (CF) fimbriae to promote optimal bacterial adhesion to cultured intestinal epithelium (CIE) and to epithelial monolayers differentiated from human small intestinal stem cells. Type 1 pili are tipped with the FimH adhesin which recognizes mannose with stereochemical specificity. Thus, enhanced production of highly mannosylated proteins on intestinal epithelia promoted FimH-mediated ETEC adhesion, while conversely, interruption of FimH lectin-epithelial interactions with soluble mannose, anti-FimH antibodies or mutagenesis of fimH effectively blocked ETEC adhesion. Moreover, fimH mutants were significantly impaired in delivery of both heat-stable and heat-labile toxins to the target epithelial cells in vitro, and these mutants were substantially less virulent in rabbit ileal loop assays, a classical model of ETEC pathogenesis. Collectively, our data suggest that these highly conserved pili play an essential role in virulence of these diverse pathogens. PMID:28531220

Graded effects of unregulated smooth muscle myosin on intestinal architecture, intestinal motility and vascular function in zebrafish.

PubMed

Abrams, Joshua; Einhorn, Zev; Seiler, Christoph; Zong, Alan B; Sweeney, H Lee; Pack, Michael

2016-05-01

Smooth muscle contraction is controlled by the regulated activity of the myosin heavy chain ATPase (Myh11). Myh11 mutations have diverse effects in the cardiovascular, digestive and genitourinary systems in humans and animal models. We previously reported a recessive missense mutation, meltdown (mlt), which converts a highly conserved tryptophan to arginine (W512R) in the rigid relay loop of zebrafish Myh11. The mlt mutation disrupts myosin regulation and non-autonomously induces invasive expansion of the intestinal epithelium. Here, we report two newly identified missense mutations in the switch-1 (S237Y) and coil-coiled (L1287M) domains of Myh11 that fail to complement mlt Cell invasion was not detected in either homozygous mutant but could be induced by oxidative stress and activation of oncogenic signaling pathways. The smooth muscle defect imparted by the mlt and S237Y mutations also delayed intestinal transit, and altered vascular function, as measured by blood flow in the dorsal aorta. The cell-invasion phenotype induced by the three myh11 mutants correlated with the degree of myosin deregulation. These findings suggest that the vertebrate intestinal epithelium is tuned to the physical state of the surrounding stroma, which, in turn, governs its response to physiologic and pathologic stimuli. Genetic variants that alter the regulation of smooth muscle myosin might be risk factors for diseases affecting the intestine, vasculature, and other tissues that contain smooth muscle or contractile cells that express smooth muscle proteins, particularly in the setting of redox stress. © 2016. Published by The Company of Biologists Ltd.

Detection of intestinal obstruction by radionuclide scan: case report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chaudhuri, T.K.

1976-11-01

The value of /sup 99m/Technetium-pertechnetate abdomen scan has recently been established in the diagnosis of Meckel's diverticulum, intussusception, and inflamed appendix. The purpose of this paper is to report a case with small intestinal obstruction secondary to fibrous adhesions which resulted from a previous surgery, in whom a /sup 99m/Technetium-pertechnetate abdomen scan showed increased radionuclide concentration in the area of dilated loop of bowel proximal to the site of obstruction.

Firewalls Prevent Systemic Dissemination of Vectors Derived from Human Adenovirus Type 5 and Suppress Production of Transgene-Encoded Antigen in a Murine Model of Oral Vaccination

PubMed Central

Revaud, Julien; Unterfinger, Yves; Rol, Nicolas; Suleman, Muhammad; Shaw, Julia; Galea, Sandra; Gavard, Françoise; Lacour, Sandrine A.; Coulpier, Muriel; Versillé, Nicolas; Havenga, Menzo; Klonjkowski, Bernard; Zanella, Gina; Biacchesi, Stéphane; Cordonnier, Nathalie; Corthésy, Blaise; Ben Arous, Juliette; Richardson, Jennifer P.

2018-01-01

To define the bottlenecks that restrict antigen expression after oral administration of viral-vectored vaccines, we tracked vectors derived from the human adenovirus type 5 at whole body, tissue, and cellular scales throughout the digestive tract in a murine model of oral delivery. After intragastric administration of vectors encoding firefly luciferase or a model antigen, detectable levels of transgene-encoded protein or mRNA were confined to the intestine, and restricted to delimited anatomical zones. Expression of luciferase in the form of multiple small bioluminescent foci in the distal ileum, cecum, and proximal colon suggested multiple crossing points. Many foci were unassociated with visible Peyer's patches, implying that transduced cells lay in proximity to villous rather than follicle-associated epithelium, as supported by detection of transgene-encoded antigen in villous epithelial cells. Transgene-encoded mRNA but not protein was readily detected in Peyer's patches, suggesting that post-transcriptional regulation of viral gene expression might limit expression of transgene-encoded antigen in this tissue. To characterize the pathways by which the vector crossed the intestinal epithelium and encountered sentinel cells, a fluorescent-labeled vector was administered to mice by the intragastric route or inoculated into ligated intestinal loops comprising a Peyer's patch. The vector adhered selectively to microfold cells in the follicle-associated epithelium, and, after translocation to the subepithelial dome region, was captured by phagocytes that expressed CD11c and lysozyme. In conclusion, although a large number of crossing events took place throughout the intestine within and without Peyer's patches, multiple firewalls prevented systemic dissemination of vector and suppressed production of transgene-encoded protein in Peyer's patches. PMID:29423380

A Positive Regulatory Loop between a Wnt-Regulated Non-coding RNA and ASCL2 Controls Intestinal Stem Cell Fate.

PubMed

Giakountis, Antonis; Moulos, Panagiotis; Zarkou, Vasiliki; Oikonomou, Christina; Harokopos, Vaggelis; Hatzigeorgiou, Artemis G; Reczko, Martin; Hatzis, Pantelis

2016-06-21

The canonical Wnt pathway plays a central role in stem cell maintenance, differentiation, and proliferation in the intestinal epithelium. Constitutive, aberrant activity of the TCF4/β-catenin transcriptional complex is the primary transforming factor in colorectal cancer. We identify a nuclear long non-coding RNA, termed WiNTRLINC1, as a direct target of TCF4/β-catenin in colorectal cancer cells. WiNTRLINC1 positively regulates the expression of its genomic neighbor ASCL2, a transcription factor that controls intestinal stem cell fate. WiNTRLINC1 interacts with TCF4/β-catenin to mediate the juxtaposition of its promoter with the regulatory regions of ASCL2. ASCL2, in turn, regulates WiNTRLINC1 transcriptionally, closing a feedforward regulatory loop that controls stem cell-related gene expression. This regulatory circuitry is highly amplified in colorectal cancer and correlates with increased metastatic potential and decreased patient survival. Our results uncover the interplay between non-coding RNA-mediated regulation and Wnt signaling and point to the diagnostic and therapeutic potential of WiNTRLINC1. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Meal-stimulated release of methionine-enkephalin into the canine jejunal lumen.

PubMed Central

Money, S R; Petroianu, A; Gintzler, A R; Jaffe, B M

1988-01-01

Application of enkephalins to the luminal surface of the bowel augments intestinal absorption. However, to date, endogenous enkephalins have not been demonstrated within intestinal luminal fluid. To determine whether enkephalins are present in the intestinal lumen, five adult dogs had 25-cm chronic jejunal Thiry-Vella loops constructed. Dogs were studied in the awake, fasted state. Jejunal loops were perfused with isoosmotic, neutral Krebs buffer containing protease inhibitors. After basal sampling, the dogs received a high fat meat meal. Collections were made during the meal and for 60 min postprandially. Luminal met-enkephalin levels were determined by radioimmunoassay and confirmed by HPLC. HPLC separation of luminal samples demonstrated two immunoreactive peaks which co-eluted with pure met-enkephalin and met-enkephalin-sulfoxide. Basal met-enkephalin outputs averaged 52 +/- 13 ng/min. The meal significantly increased mean luminal met-enkephalin output to 137 +/- 71 ng/min. During the initial 20-min postprandial period, output remained elevated (180 +/- 73 ng/min), after which it returned to basal levels. We conclude that met-enkephalin is present in the jejunal lumen, and that luminal release of this opioid is augmented by a meal. Images PMID:3343342

[Pathogenic activity modulation of Escherichia coli TL+ toxin with an isolated protein of Giardia intestinalis and a synthetic peptide].

PubMed

Jiménez-Cardoso, E; Eligio-García, L; Jiménez-Cardoso, J M; Angeles-Anguiano, E; Tobilla-Mercado, J M; Castañeda, G

2001-01-01

It is know that a protein from Giardia intestinalis works as a substrate for V. cholerae and Escherichia coli. The toxic activity of both activates protein G form intestinal mucosa with a pathogenic activity results. In the present study, the pathogenic activity of subunit A of Vibrio cholerae toxin (ADP-ribosyltranferase) using isolated fragments from: Giardia intestinalis and a synthetic peptide were used as modulators in vivo. Adult Neo Zealand males rabbits with ileal loop were prepared and different mixtures of heat labile enterotoxin obtained from Escherichia coli H10407 and ARF protein isolated by electrofocusing from Giardia intestinalis Portland I were inoculated in the loops. The toxin activity was evaluated by luminal liquid secretion and cyclic AMP concentration in tissues (each loop). ADP ribosyltranferase activity was modulated, due to a decreased of luminal secretion and cAMP in tissues. Such results were seen when synthetic peptide and subunit A from Vibrio cholerae were used. The ADP ribosyltranferase activity of heat labile Escherichia coli and Vibrio cholerae toxins were modified by in vitro and in vivo interaction with ARF protein, which modified pathogenic effect over rabbits intestinal epithelium.

Torsion and volvulus of the transverse and descending colon in a German shepherd dog.

PubMed

Halfacree, Z J; Beck, A L; Lee, K C L; Lipscomb, V J

2006-08-01

A German shepherd dog was presented two months after surgery for correction of acute gastric dilatation volvulus. The dog had been diagnosed with exocrine pancreatic insufficiency. Radiographs revealed marked gaseous distension of one loop of intestine with a generalised increase in intestinal gas content. A 360 degrees anticlockwise rotation of the descending and transverse colon, around the longitudinal axis of the mesocolon, was diagnosed at exploratory coeliotomy. The transverse and descending colon appeared uniformly necrotic and an end-to-end colo-colic resection and anastomosis was performed. The dog initially made satisfactory postoperative progress but was euthanased on the third postoperative day after it developed an intestinal intussusception.

Intestinal obstruction caused by omphalomesenteric duct remnant: usefulness of laparoscopy.

PubMed

Bueno Lledó, J; Serralta Serra, A; Planeéis Roig, M; Dobón Giménez, F; Ibáñez Palacín, F; Rodero Rodero, R

2003-10-01

The anomalies related to omphalomesenteric duct remnant constitute an uncommon cause of intestinal obstruction, of which Meckel"s diverticulum and its variants represent the most important clinical presentation. In most cases they are asymptomatic and usually affect young patients. When symptomatic, they usually present episodes of gastrointestinal bleeding or acute abdomen syndromes caused by strangulation of intestinal loops as a result of fibrous intraabdominal remnants or inflammation produced by the diverticulum. In most cases, the unexpected presence of these alterations makes intraoperative diagnosis necessary. Treatment is surgical and consists in exeresis of the diverticulum or the fibrous band causing the clinical picture. We report two cases of persistence of the vitelline duct resolved by laparoscopic approach.

Absorption-enhancing effects of gemini surfactant on the intestinal absorption of poorly absorbed hydrophilic drugs including peptide and protein drugs in rats.

PubMed

Alama, Tammam; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

2016-02-29

In general, the intestinal absorption of small hydrophilic molecules and macromolecules like peptides, after oral administration is very poor. Absorption enhancers are considered to be one of the most promising agents to enhance the intestinal absorption of drugs. In this research, we focused on a gemini surfactant, a new type of absorption enhancer. The intestinal absorption of drugs, with or without sodium dilauramidoglutamide lysine (SLG-30), a gemini surfactant, was examined by an in situ closed-loop method in rats. The intestinal absorption of 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) was significantly enhanced in the presence of SLG-30, such effect being reversible. Furthermore, the calcium levels in the plasma significantly decreased when calcitonin was co-administered with SLG-30, suggestive of the increased intestinal absorption of calcitonin. In addition, no significant increase in the of lactate dehydrogenase (LDH) activity or in protein release from the intestinal epithelium was observed in the presence of SLG-30, suggestive of the safety of this compound. These findings indicate that SLG-30 is an effective absorption-enhancer for improving the intestinal absorption of poorly absorbed drugs, without causing serious damage to the intestinal epithelium. Copyright © 2015 Elsevier B.V. All rights reserved.

Microvillus-Specific Protein Tyrosine Phosphatase SAP-1 Plays a Role in Regulating the Intestinal Paracellular Transport of Macromolecules.

PubMed

Mori, Shingo; Kamei, Noriyasu; Murata, Yoji; Takayama, Kozo; Matozaki, Takashi; Takeda-Morishita, Mariko

2017-09-01

The stomach cancer-associated protein tyrosine phosphatase 1 (SAP-1) is a receptor-type protein tyrosine phosphatase that is specifically expressed on the apical membrane of the intestinal epithelium. SAP-1 is known to maintain the balance of phosphorylation of proteins together with protein kinases; however, its biological function and impact on pharmacokinetics in the intestine remain unclear. The present study, therefore, aimed at clarifying the relationship between SAP-1 and the intestinal absorption behaviors of typical transporter substrates and macromolecules. The endogenous levels of glucose and total cholesterol in the blood were similar between wild-type and SAP-1-deficient mice (Sap1 -/- ), suggesting no contribution of SAP-1 to biogenic influx. Moreover, in vitro transport study with everted ileal sacs demonstrated that there was no difference in the absorption of breast cancer resistance protein, P-glycoprotein, and peptide transporter substrates between both mice. However, absorptive clearance of macromolecular model dextrans (FD-4 and FD-10) in Sap1 -/- mice was significantly higher than that in wild-type mice, and this was confirmed by the trend of increased FD-4 absorption from colonic loops of Sap1 -/- mice. Therefore, the results of this study suggest the partial contribution of SAP-1 to the regulated transport of hydrophilic macromolecules through paracellular tight junctions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Drug gastrointestinal absorption in rat: Strain and gender differences.

PubMed

Oltra-Noguera, Davinia; Mangas-Sanjuan, Victor; González-Álvarez, Isabel; Colon-Useche, Sarin; González-Álvarez, Marta; Bermejo, Marival

2015-10-12

Predictive animal models of intestinal drug absorption are essential tools in drug development to identify compounds with promising biopharmaceutical properties. In situ perfusion absorption studies are routinely used in the preclinical setting to screen drug candidates. The objective of this work is to explore the differences in magnitude and variability on intestinal absorption associated with rat strain and gender. Metoprolol and Verapamil absorption rate coefficients were determined using the in situ closed loop perfusion model in four strains of rats and in both genders. Strains used were Sprague-Dawley, Wistar-Han, Wistar-Unilever, Long-Evans and CD∗IGS. In the case of Metoprolol only CD∗IGS and Wistar Unilever showed differences between males and females. For Verapamil, Wistar Han and Sprague-Dawley strains do not show differences between male and female rats. That means that in these strains permeability data from male and female could be combined. In male rats, which are commonly used for permeability estimation, there were differences for Metoprolol permeability between Sprague-Dawley (with lower permeability values) and the other strains, while for Verapamil Sprague-Dawley and Wistar-Han showed the lower permeability values. In conclusion, the selection of rat's strain and gender for intestinal absorption experiments is a relevant element during study design and data from different strains may not be always comparable. Copyright © 2015 Elsevier B.V. All rights reserved.

Retained Capsule Endoscope.

PubMed

Aihole, Jayalaxmi S; Vishnumurthy, G S; Babu, M Narendra

2016-11-15

Capsule endoscopy was invented to visualize the entire small intestine in a non- invasive manner in adults. 1 y, 9 mo-old boy presented with generalized edema for last 3 months. His routine investigations, including the upper gastrointestinal endoscopy, colonoscopy, and contrast enhanced computed tomography scan (CECT) were normal. In view of clinical suspicion of protein losing enteropathy, we planned capsule endoscopy. The capsule was not passed even after 3 weeks. Laparoscopy revealed impacted capsule in a dilated intestinal loop proximal to an ileal stricuture. Capsule endoscopy should be used judiciously in children.

Effect of dietary fat on plasma glutathione peroxidase levels and intestinal absorption of /sup 75/Se-labeled sodium selenite in chicks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mutanen, M.L.; Mykkaenen, H.M.

1984-05-01

The effect of dietary fat on the availability of selenium was investigated in chicks fed either 4 or 20% butter, olive oil, rape oil, corn oil or sunflower oil in the diet for 3 weeks after hatching. Plasma glutathione peroxidase (GSH-Px) activity was used as an indicator of the body selenium status. In addition, the intestinal absorption of sodium selenite (/sup 75/Se-labeled) was determined by using both the in vivo ligated loop procedure and oral administration of the isotope. The plasma GSH-Px levels increased with increasing proportion of the polyunsaturated fatty acids in the diet. Increasing the amount of fatmore » from 4 to 20% significantly enhanced the GSH-Px activity in the groups receiving butter or olive oil, but had no effect in animals fed the unsaturated fats. The absorption of (/sup 75/Se)selenite from the ligated duodenal loops tended to be reduced in chicks fed corn oil or sunflower oil as compared to the animals receiving butter in their diet. On the other hand, the type of dietary fat did not appear to affect the absorption of the orally administered selenite. The present study demonstrates that the type of dietary fat can affect the plasma GSH-Px levels in chicks without altering the intestinal absorption of selenite. However, the results on the absorption of the intraduodenally injected sodium selenite suggest that dietary fat plays some role in the intestinal transport of selenium.« less

[Acute pancreatitis and afferent loop syndrome. Case report].

PubMed

Barajas-Fregoso, Elpidio Manuel; Romero-Hernández, Teodoro; Macías-Amezcua, Michel Dassaejv

2013-01-01

The afferent syndrome loop is a mechanic obstruction of the afferent limb before a Billroth II or Roux-Y reconstruction, secondary in most of case to distal or subtotal gastrectomy. Clinical case: Male 76 years old, with antecedent of cholecystectomy, gastric adenocarcinoma six years ago, with subtotal gastrectomy and Roux-Y reconstruction. Beginning a several abdominal pain, nausea and vomiting, abdominal distension, without peritoneal irritation sings. Amylase 1246 U/L, lipase 3381 U/L. Computed Tomography with thickness wall and dilatation of afferent loop, pancreas with diffuse enlargement diagnostic of acute pancreatitis secondary an afferent loop syndrome. The afferent loop syndrome is presented in 0.3%-1% in all cases with Billroth II reconstruction, with a mortality of up to 57%, the obstruction lead accumulation of bile, pancreatic and intestinal secretions, increasing the pressure and resulting in afferent limb, bile conduct and Wirsung conduct dilatation, triggering an inflammatory response that culminates in pancreatic inflammation. The severity of the presentation is related to the degree and duration of the blockage.

Selective binding and transcytosis of Ulex europaeus 1 lectin by mouse Peyer's patch M-cells in vivo.

PubMed

Clark, M A; Jepson, M A; Simmons, N L; Hirst, B H

1995-12-01

The in vivo interaction of the lectin Ulex europaeus agglutinin 1 with mouse Peyer's patch follicle-associated epithelial cells was studied in the mouse Peyer's patch gut loop model by immunofluorescence and electron microscopy. The lectin targets to mouse Peyer's patch M-cells and is rapidly endocytosed and transcytosed. These processes are accompanied by morphological changes in the M-cell microvilli and by redistribution of polymerised actin. The demonstration of selective binding and uptake of a lectin by intestinal M-cells in vivo suggests that M-cell-specific surface glycoconjugates might act as receptors for the selective adhesion/uptake of microorganisms.

Decreased activity and expression of intestinal oligopeptide transporter PEPT1 in rats with hyperthyroidism in vivo.

PubMed

Ashida, Kayoko; Katsura, Toshiya; Saito, Hideyuki; Inui, Ken-ichi

2004-06-01

To examine the effect of thyroid hormone status on PEPT1 in vivo, the activity and expression of PEPT1 in the small intestine were examined in euthyroid and hyperthyroid rats. Hyperthyroidism was induced by treating rats with L-thyroxine (12 mg/L) in the drinking water for 21 days. Transport activity was measured by everted small intestinal preparations and in situ intestinal loop technique. Expressions of PEPT1 mRNA and protein were evaluated by competitive polymerase chain reaction and Western blotting, respectively. The uptake of [14C]glycylsarcosine by everted small intestinal preparations was significantly decreased in hyperthyroid rats, whereas that of methyl-alpha-D-[14C(U)]-glucopyranoside was not altered. Kinetic analysis showed that the Vmax value for [14C]glycylsarcosine uptake was significantly decreased in hyperthyroid rats, whereas the Km value was not affected. The mean portal vein concentrations after intrajejunal administration of [14C]glycylsarcosine were also decreased in hyperthyroid rats. Moreover, hyperthyroidism caused a significant decrease in the expression of PEPT1 mRNA in the small intestine, whereas the expression of Na+/glucose cotransporter (SGLT1) mRNA was not changed. The level of PEPT1 protein was also decreased in the small intestine of hyperthyroid rats. These results indicate that in hyperthyroid rats, the activity and expression of PEPT1 were decreased in the small intestine.

Cosilencing Intestinal Transglutaminase-2 and Interleukin-15 Using Gelatin-Based Nanoparticles in an in Vitro Model of Celiac Disease.

PubMed

Attarwala, Husain; Clausen, Valerie; Chaturvedi, Prasoon; Amiji, Mansoor M

2017-09-05

In this study, we have developed a type B gelatin nanoparticle based siRNA delivery system for silencing of intestinal transglutaminase-2 (TG2) and interleukin-15 (IL-15) genes in cultured human intestinal epithelial cells (Caco-2) and murine alveolar macrophage cells (J774A.1). Small interfering RNA (siRNA) targeting the TG2 or IL-15 gene was encapsulated within gelatin nanoparticles using ethanol-water solvent displacement method. Size, charge, and morphology of gelatin nanoparticles were evaluated using a Zetasizer instrument and transmission electron microscopy. siRNA encapsulation efficiency was determined using an siRNA specific stem-loop quantitative polymerase chain reaction (qPCR) assay. Cellular uptake of siRNA-containing gelatin nanoparticles was determined using fluorescent microscopy and stem-loop qPCR assay. siRNA loading in the RISC (RNA-induced silencing complex) was determined by immunoprecipitation of argonaute 2 (AGO2) protein followed by stem-loop qPCR for siRNA quantification. Gene expression analysis of TG2, IL-15, and the proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), was performed using qPCR assays. Efficacy of silencing TG2 and IL-15 knockdown was evaluated in an in vitro model of celiac disease by utilizing immunogenic α-gliadin peptide p31-43 in cultured J774A.1 cells. siRNA-containing gelatin nanoparticles were spherical in shape with mean particle size and charge of 217 ± 8.39 nm and -6.2 ± 0.95 mV, respectively. siRNA loading efficiency within gelatin nanoparticles was found to be 89.3 ± 3.05%. Evaluations of cellular uptake using fluorescent microscopy showed rapid internalization of gelatin nanoparticles within 2 h of dosing, with cytosolic localization of delivered siRNA in Caco-2 cells. Gelatin nanoparticles showed greater intracellular siRNA exposure with a longer half-life, when compared to Lipofectamine-mediated siRNA delivery. Approximately 0.1% of total intracellular siRNA was associated in the RISC complex. A maximum knockdown of 60% was observed at 72 h post siRNA treatment for both TG2 and IL-15 genes, which corresponded to ∼200 copies of RISC associated siRNA. Further, efficacy of gelatin nanoparticle mediated knockdown of TG2 and IL-15 mRNA was tested in an in vitro model of celiac disease. Significant suppression in the levels of proinflammatory cytokines (TNF-α and IFN-γ) was observed in p31-43 stimulated J774A.1 cells upon either IL-15 or IL-15 + TG2 siRNA treatment. The results from this study indicate that gelatin nanoparticle mediated TG2 and IL-15 siRNA gene silencing is a very promising approach for the treatment of celiac disease.

EFFECT OF SIZE OF INTESTINAL DIVERSIONS IN OBESE PATIENTS WITH METABOLIC SYNDROME SUBMITTED TO GASTRIC BYPASS.

PubMed

Ramos, Rafael Jacques; Mottin, Cláudio Corá; Alves, Letícia Biscaino; Benzano, Daniela; Padoin, Alexandre Vontobel

There is no consensus on the ideal size of intestinal loops in gastric bypass of bariatric surgeries. To evaluate the metabolic outcome of patients submitted to gastric bypass with alimentary and biliopancreatic loops of different sizes. Was conducted a retrospective cohort study in diabetic obese patients (BMI≥35 kg/m2) with metabolic syndrome submitted to gastric bypass. The patients were divided into three groups according to the size of the intestinal loop: group 1, biliopancreatic limb 50 cm length and alimentary limb 100 cm length; group 2 , biliopancreatic limb 50 cm length and alimentary limb 150 cm length; and group 3, biliopancreatic limb 100 cm length and alimentary limb 150 cm length. The effect of gastric bypass with different sizes of intestinal loops in relation to the parameters that define metabolic syndrome was determined. Sixty-three patients were evaluated, and they had a mean age of 44.7±9.4 years. All were diabetics, with 62 (98.4%) being hypertensive and 51 (82.2%) dyslipidemic. The three groups were homogeneous in relation to the variables. In 24 months, there was a remission of systemic arterial hypertension in 65% of patients in group 1, 62.5% in group 2 and 68.4% in group 3. Remission of diabetes occurred in 85% of patients in group 1, 83% in group 2 and 84% in group 3. There was no statistical difference in %LEW between the groups, and waist measurements decreased in a homogeneous way in all groups. The size of loops also had no influence on the improvement in dyslipidemia. Variation in size of intestinal loops does not appear to influence improvement in metabolic syndrome in this group of patients. Não há consenso sobre o tamanho ideal das alças intestinais no bypass gástrico em Y-de-Roux em cirurgias bariátricas. Avaliar os desfechos metabólicos de pacientes submetidos ao bypass gástrico com alça intestinal alimentar e biliopancreática de tamanhos diferentes. Realizou-se coorte retrospectiva em pacientes obesos (IMC≥35 kg/m2) diabéticos com síndrome metabólica submetidos ao bypass gástrico em Y-de-Roux. Foram divididos em três grupos conforme a dimensão das alças intestinais: grupo 1, alça biliopancreática de 50 cm e alça alimentar de 100 cm; grupo 2, alça biliopancreática de 50 cm e alça alimentar de 150 cm e grupo 3, alça biliopancreática de 100 cm e alça alimentar de 150 cm. Foram avaliados os parâmetros que compõem a síndrome metabólica. Incluíram-se 63 pacientes, com média de idade de 44.7±9.4 anos. Todos eram diabéticos, 62 (98.4%) hipertensos e 51 (82.2%) dislipidêmicos. Os três grupos eram homogêneos em relação às variáveis estudadas. Em 24 meses houve remissão da hipertensão arterial sistêmica em 65% do grupo 1, 62.5% no grupo 2 e 68.4% no grupo 3. A remissão do diabete melito tipo 2 ocorreu em 85% dos pacientes do grupo 1, 83% no grupo 2, e 84% no grupo 3. Não houve diferença estatística na porcentagem de perda do excesso de peso entre os grupos e as medidas da cintura abdominal reduziram de forma homogênea em todos os grupos. A dimensão das alças também não influenciou na melhora da dislipidemia. A variação da dimensão das alças intestinais não influenciou na melhora da síndrome metabólica neste grupo de pacientes.

Aryl hydrocarbon receptor and intestinal immunity.

PubMed

Lamas, Bruno; Natividad, Jane M; Sokol, Harry

2018-04-07

Aryl hydrocarbon receptor (AhR) is a member of the basic helix-loop-helix-(bHLH) superfamily of transcription factors, which are associated with cellular responses to environmental stimuli, such as xenobiotics and oxygen levels. Unlike other members of bHLH, AhR is the only bHLH transcription factor that is known to be ligand activated. Early AhR studies focused on understanding the role of AhR in mediating the toxicity and carcinogenesis properties of the prototypic ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In recent years, however, it has become apparent that, in addition to its toxicological involvement, AhR is highly receptive to a wide array of endogenous and exogenous ligands, and that its activation leads to a myriad of key host physiological functions. In this study, we review the current understanding of the functions of AhR in the mucosal immune system with a focus on its role in intestinal barrier function and intestinal immune cells, as well as in intestinal homeostasis.

Increased intestinal absorption in the rat caused by sodium lauryl sulphate, and its possible relation to the cAMP system.

PubMed

Briseid, G; Briseid, K; Kirkevold, K

1976-01-01

The increases in the absorption of ouabain, phenolsulphonphthalein and pralidoxime caused by 17 mM sodium lauryl sulphate (SLS) from jejunal loops of anaesthetized rats were significantly reduced if sodium and chloride (Briseid et al., 1974) or chloride and bicarbonate were replaced by other ions in the loop fluid. Separate substitutions of sodium, chloride of bicarbonate did not significantly alter the SLS-caused absorption, except that the substitution of choline for sodium reduced the absorption of pralidoxime, both in the presence and in the absence of SLS. The increases in the absorption of phenolsulphonphthalein and pralidoxime caused by SLS were potentiated by theophylline (25 mM) and reduced by imidazole (25 mM). The addition of dibutyryl cyclic AMP (2.5 mM) to the loop fluid increased this absorption of the test substances. This effect was reduced by imidazole, but under the experimental conditions it was not potentiated by theophylline. Determinations of cyclic AMP in the rat intestinal mucosa showed that the level of this substance was significantly higher in the presence than in the absence of SLS. The experimental conditions were as described for the absorption experiments. It is concluded that the data obtained support the idea of an increased level of cyclic AMP as the main basis for the effect of SLS on the absorption.

Inhibition of Heat-Stable Toxin-Induced Intestinal Salt and Water Secretion by a Novel Class of Guanylyl Cyclase C Inhibitors.

PubMed

Bijvelds, Marcel J C; Loos, Michaela; Bronsveld, Inez; Hellemans, Ann; Bongartz, Jean-Pierre; Ver Donck, Luc; Cox, Eric; de Jonge, Hugo R; Schuurkes, Jan A J; De Maeyer, Joris H

2015-12-01

Many enterotoxigenic Escherichia coli strains produce the heat-stable toxin, STa, which, by activation of the intestinal receptor-enzyme guanylyl cyclase (GC) C, triggers an acute, watery diarrhea. We set out to identify GCC inhibitors that may be of benefit for the treatment of infectious diarrheal disease. Compounds that inhibit STa-induced cyclic guanosine 3',5'-monophosphate (cGMP) production were selected by performing cyclase assays on cells and membranes containing GCC, or the related GCA. The effect of leads on STa/GCC-dependent activation of the cystic fibrosis transmembrane conductance regulator anion channel was investigated in T84 cells, and in porcine and human intestinal tissue. Their effect on STa-provoked fluid transport was assessed in ligated intestinal loops in piglets. Four N-2-(propylamino)-6-phenylpyrimidin-4-one-substituted piperidines were shown to inhibit GCC-mediated cellular cGMP production. The half maximal inhibitory concentrations were ≤ 5 × 10(-7) mol/L, whereas they were >10 times higher for GCA. In T84 monolayers, these leads blocked STa/GCC-dependent, but not forskolin/adenylyl cyclase-dependent, cystic fibrosis transmembrane conductance regulator activity. GCC inhibition reduced STa-provoked anion secretion in pig jejunal tissue, and fluid retention and cGMP levels in STa-exposed loops. These GCC inhibitors blocked STa-provoked anion secretion in rectal biopsy specimens. We have identified a novel class of GCC inhibitors that may form the basis for development of future therapeutics for (infectious) diarrheal disease. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A complication to be aware of: hyperkalaemia following propranolol therapy for an infant with intestinal haemangiomatozis.

PubMed

Belen, Burcu; Oguz, Aynur; Okur, Arzu; Dalgic, Buket

2014-05-19

Infantile haemangiomas, benign vascular tumours seen in 4-10% of infants are characterised by their spontaneous remission following a 3-9 month period of dynamic growth. Propranolol has been reported to be used as a successful treatment of severe symptomatic infantile haemangiomas. Hyperkalaemia has not been recognised as a serious effect of propranolol since recently. Here, we would like to portray a 2-year-old male patient with intestinal haemangiomatosis who presented with severe hyperkalaemia and was successfully managed with hydration, loop diuretics, potassium binding granules, inhaler β-2 agonists and insulin. To date, this is the first case of intestinal haemangiomatosis complicated with severe hyperkalaemia. Our case suggested the idea of close monitorisation of potassium levels as well as haemodynamic status at the initialisation of the propranolol treatment. 2014 BMJ Publishing Group Ltd.

A complication to be aware of: hyperkalaemia following propranolol therapy for an infant with intestinal haemangiomatozis

PubMed Central

Belen, Burcu; Oguz, Aynur; Okur, Arzu; Dalgic, Buket

2014-01-01

Infantile haemangiomas, benign vascular tumours seen in 4–10% of infants are characterised by their spontaneous remission following a 3–9 month period of dynamic growth. Propranolol has been reported to be used as a successful treatment of severe symptomatic infantile haemangiomas. Hyperkalaemia has not been recognised as a serious effect of propranolol since recently. Here, we would like to portray a 2-year-old male patient with intestinal haemangiomatosis who presented with severe hyperkalaemia and was successfully managed with hydration, loop diuretics, potassium binding granules, inhaler β-2 agonists and insulin. To date, this is the first case of intestinal haemangiomatosis complicated with severe hyperkalaemia. Our case suggested the idea of close monitorisation of potassium levels as well as haemodynamic status at the initialisation of the propranolol treatment. PMID:24842358

Clostridium perfringens epsilon toxin increases the small intestinal permeability in mice and rats.

PubMed

Goldstein, Jorge; Morris, Winston E; Loidl, César Fabián; Tironi-Farinati, Carla; Tironi-Farinatti, Carla; McClane, Bruce A; Uzal, Francisco A; Fernandez Miyakawa, Mariano E

2009-09-18

Epsilon toxin is a potent neurotoxin produced by Clostridium perfringens types B and D, an anaerobic bacterium that causes enterotoxaemia in ruminants. In the affected animal, it causes oedema of the lungs and brain by damaging the endothelial cells, inducing physiological and morphological changes. Although it is believed to compromise the intestinal barrier, thus entering the gut vasculature, little is known about the mechanism underlying this process. This study characterizes the effects of epsilon toxin on fluid transport and bioelectrical parameters in the small intestine of mice and rats. The enteropooling and the intestinal loop tests, together with the single-pass perfusion assay and in vitro and ex vivo analysis in Ussing's chamber, were all used in combination with histological and ultrastructural analysis of mice and rat small intestine, challenged with or without C. perfringens epsilon toxin. Luminal epsilon toxin induced a time and concentration dependent intestinal fluid accumulation and fall of the transepithelial resistance. Although no evident histological changes were observed, opening of the mucosa tight junction in combination with apoptotic changes in the lamina propria were seen with transmission electron microscopy. These results indicate that C. perfringens epsilon toxin alters the intestinal permeability, predominantly by opening the mucosa tight junction, increasing its permeability to macromolecules, and inducing further degenerative changes in the lamina propria of the bowel.

The protective activity of tea catechins against experimental infection by Vibrio cholerae O1.

PubMed

Toda, M; Okubo, S; Ikigai, H; Suzuki, T; Suzuki, Y; Hara, Y; Shimamura, T

1992-01-01

Tea catechins inhibited the fluid accumulation induced by cholera toxin in sealed adult mice. The catechins also reduced fluid accumulation by Vibrio cholerae O1 in ligated intestinal loops of rabbits. These findings suggest that tea catechins may possess protective activity against V. cholerae O1.

Small intestinal bacterial overgrowth syndrome

PubMed Central

Bures, Jan; Cyrany, Jiri; Kohoutova, Darina; Förstl, Miroslav; Rejchrt, Stanislav; Kvetina, Jaroslav; Vorisek, Viktor; Kopacova, Marcela

2010-01-01

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 gastrointestinal tract. There are several endogenous defence mechanisms for preventing bacterial overgrowth: gastric acid secretion, intestinal motility, intact ileo-caecal valve, immunoglobulins within intestinal secretion and bacteriostatic properties of pancreatic and biliary secretion. Aetiology of SIBO is usually complex, associated with disorders of protective antibacterial mechanisms (e.g. achlorhydria, pancreatic exocrine insufficiency, immunodeficiency syndromes), anatomical abnormalities (e.g. small intestinal obstruction, diverticula, fistulae, surgical blind loop, previous ileo-caecal resections) and/or motility disorders (e.g. scleroderma, autonomic neuropathy in diabetes mellitus, post-radiation enteropathy, small intestinal pseudo-obstruction). In some patients more than one factor may be involved. Symptoms related to SIBO are bloating, diarrhoea, malabsorption, weight loss and malnutrition. The gold standard for diagnosing SIBO is still microbial investigation of jejunal aspirates. Non-invasive hydrogen and methane breath tests are most commonly used for the diagnosis of SIBO using glucose or lactulose. Therapy for SIBO must be complex, addressing all causes, symptoms and complications, and fully individualised. It should include treatment of the underlying disease, nutritional support and cyclical gastro-intestinal selective antibiotics. Prognosis is usually serious, determined mostly by the underlying disease that led to SIBO. PMID:20572300

Chronic Intestinal Pseudo-obstruction: Clinical and Manometric Characteristics in the Chilean Population

PubMed Central

de Arce, Edith Pérez; Landskron, Glauben; Hirsch, Sandra; Defilippi, Carlos; Madrid, Ana María

2017-01-01

Background/Aims Chronic intestinal pseudo-obstruction (CIPO) is a rare syndrome characterized by a failure of the propulsion of intraluminal contents and recurrent symptoms of partial bowel obstruction in the absence of mechanical obstruction. Regional variations of the intestinal compromise have been described. Intestinal manometry can indicate the pathophysiology and prognosis. Our objective is to establish the demographic and clinical characteristics of group Chilean patients and analyze the motility of the small intestine and its prognostic value. Methods Patients with symptoms of intestinal pseudo-obstruction with dilated bowel loops were included, in all of whom a manometry of the small intestine was performed using perfused catheters. Results Of the 64 patients included, 51 women (average age 41.5 ± 17.6 years), 54 primary and 10 secondary CIPO were included. Dilatation of the small intestine was the only finding in 38 patients; in the remaining, the compromise was associated with other segments, primarily the colon. Forty-nine patients underwent 65 surgeries, mainly exploratory laparotomies and colectomies. Intestinal manometry was performed on all patients; 4 “patterns” were observed: neuropathic (n = 26), myopathic (n = 3), mixed (n = 24), and a group without motor activity (n = 11). The most relevant findings were the complex migrating motor disorders and decreased frequency and propagation of contractions. The 9 patients who died had a severe myopathic compromise. Conclusions In our series, isolated small bowel compromise was the most common disorder. Neuropathic motor compromise was observed in most of the patients. Mortality was associated with severe myopathic compromise. PMID:27669829

Antisecretory activity from the flowers of Chiranthodendron pentadactylon and its flavonoids on intestinal fluid accumulation induced by Vibrio cholerae toxin in rats.

PubMed

Velázquez, Claudia; Calzada, Fernando; Esquivel, Baldomero; Barbosa, Elizabeth; Calzada, Samuel

2009-12-10

The flowers of Chiranthodendron pentadactylon Larreat. (Sterculiaceae) has been traditionally used as folk medicine in Mexico for the treatment of gastrointestinal disorders such as diarrhea and dysentery. This study aimed to assess the antisecretory activity which supports the therapeutic use of Chiranthodendron pentadactylon and its flavonoids to treat diarrhea. The methanol extract of Chiranthodendron pentadactylon, subsequent fractions, and flavonoids were evaluated on cholera toxin-induced intestinal secretion in rat jejunal loops model. Three antisecretory flavonoids were isolated by bioassay-guided purification, namely, isoquercitrin 3, (+)-catechin 4 and (-)-epicatechin 5. Among them, epicatechin exhibited the most potent antisecretory activity with ID(50) of 8.3 microM/kg. Its potency was close that of to loperamide (ID(50) 6.1 microM/kg), drug used as control. Isoquercitrin (ID(50) 19.2 microM/kg) and catechin (ID(50) 51.7 microM/kg) showed moderate and weak activity, respectively. The results of the present study lend some support to the anecdotal report for the traditional use of the flowers of Chiranthodendron pentadactylon in the control of dysentery.

Why is cytoskeletal contraction required for cardiac fusion before but not after looping begins?

NASA Astrophysics Data System (ADS)

Shi, Yunfei; Varner, Victor D.; Taber, Larry A.

2015-02-01

Cytoskeletal contraction is crucial to numerous morphogenetic processes, but its role in early heart development is poorly understood. Studies in chick embryos have shown that inhibiting myosin-II-based contraction prior to Hamburger-Hamilton (HH) stage 10 (33 h incubation) impedes fusion of the mesodermal heart fields that create the primitive heart tube (HT), as well as the ensuing process of cardiac looping. If contraction is inhibited at or after looping begins at HH10, however, fusion and looping proceed relatively normally. To explore the mechanisms behind this seemingly fundamental change in behavior, we measured spatiotemporal distributions of tissue stiffness, stress, and strain around the anterior intestinal portal (AIP), the opening to the foregut where contraction and cardiac fusion occur. The results indicate that stiffness and tangential tension decreased bilaterally along the AIP with distance from the embryonic midline. The gradients in stiffness and tension, as well as strain rate, increased to peaks at HH9 (30 h) and decreased afterward. Exposure to the myosin II inhibitor blebbistatin reduced these effects, suggesting that they are mainly generated by active cytoskeletal contraction, and finite-element modeling indicates that the measured mechanical gradients are consistent with a relatively uniform contraction of the endodermal layer in conjunction with constraints imposed by the attached mesoderm. Taken together, our results suggest that, before HH10, endodermal contraction pulls the bilateral heart fields toward the midline where they fuse to create the HT. By HH10, however, the fusion process is far enough along to enable apposing cardiac progenitor cells to keep ‘zipping’ together during looping without the need for continued high contractile forces. These findings should shed new light on a perplexing question in early heart development.

Effect of surface chemistry on nanoparticle interaction with gastrointestinal mucus and distribution in the gastrointestinal tract following oral and rectal administration in the mouse.

PubMed

Maisel, Katharina; Ensign, Laura; Reddy, Mihika; Cone, Richard; Hanes, Justin

2015-01-10

It is believed that mucoadhesive surface properties on particles delivered to the gastrointestinal (GI) tract improve oral absorption or local targeting of various difficult-to-deliver drug classes. To test the effect of nanoparticle mucoadhesion on distribution of nanoparticles in the GI tract, we orally and rectally administered nano- and microparticles that we confirmed possessed surfaces that were either strongly mucoadhesive or non-mucoadhesive. We found that mucoadhesive particles (MAP) aggregated in mucus in the center of the GI lumen, far away from the absorptive epithelium, both in healthy mice and in a mouse model of ulcerative colitis (UC). In striking contrast, water absorption by the GI tract rapidly and uniformly transported non-mucoadhesive mucus-penetrating particles (MPP) to epithelial surfaces, including reaching the surfaces between villi in the small intestine. When using high gavage fluid volumes or injection into ligated intestinal loops, common methods for assessing oral drug and nanoparticle absorption, we found that both MAP and MPP became well-distributed throughout the intestine, indicating that the barrier properties of GI mucus were compromised. In the mouse colorectum, MPP penetrated into mucus in the deeply in-folded surfaces to evenly coat the entire epithelial surface. Moreover, in a mouse model of UC, MPP were transported preferentially into the disrupted, ulcerated tissue. Our results suggest that delivering drugs in non-mucoadhesive MPP is likely to provide enhanced particle distribution, and thus drug delivery, in the GI tract, including to ulcerated tissues. Copyright © 2014 Elsevier B.V. All rights reserved.

Ontogenetic development of intestinal length and relationships to diet in an Australasian fish family (Terapontidae)

PubMed Central

2013-01-01

Background One of the most widely accepted ecomorphological relationships in vertebrates is the negative correlation between intestinal length and proportion of animal prey in diet. While many fish groups exhibit this general pattern, other clades demonstrate minimal, and in some cases contrasting, associations between diet and intestinal length. Moreover, this relationship and its evolutionary derivation have received little attention from a phylogenetic perspective. This study documents the phylogenetic development of intestinal length variability, and resultant correlation with dietary habits, within a molecular phylogeny of 28 species of terapontid fishes. The Terapontidae (grunters), an ancestrally euryhaline-marine group, is the most trophically diverse of Australia’s freshwater fish families, with widespread shifts away from animal-prey-dominated diets occurring since their invasion of fresh waters. Results Description of ontogenetic development of intestinal complexity of terapontid fishes, in combination with ancestral character state reconstruction, demonstrated that complex intestinal looping (convolution) has evolved independently on multiple occasions within the family. This modification of ontogenetic development drives much of the associated interspecific variability in intestinal length evident in terapontids. Phylogenetically informed comparative analyses (phylogenetic independent contrasts) showed that the interspecific differences in intestinal length resulting from these ontogenetic developmental mechanisms explained ~65% of the variability in the proportion of animal material in terapontid diets. Conclusions The ontogenetic development of intestinal complexity appears to represent an important functional innovation underlying the extensive trophic differentiation seen in Australia’s freshwater terapontids, specifically facilitating the pronounced shifts away from carnivorous (including invertebrates and vertebrates) diets evident across the family. The capacity to modify intestinal morphology and physiology may also be an important facilitator of trophic diversification during other phyletic radiations. PMID:23441994

Use of monoclonal antibodies developed against chicken coccidia (Eimeria) to study invasion and development of Eimeria reichenowi in Florida sandhill cranes (Grus canadensis).

PubMed

Augustine, P; Olsen, G; Danforth, H; Gee, G; Novilla, M

2001-03-01

Eimeria gruis and Eimeria reichenowi are common coccidial parasites of a number of species of cranes. Until recently, little was known about either the site for invasion or the dynamics of early development of the crane coccidia because of the difficulty of identifying sporozoites and early developmental stages of these parasites by conventional staining methods. In the present study, monoclonal antibodies (MAbs) elicited against Eimeria spp. of chickens and turkeys were found to cross-react with sporozoites and developmental stages of E. reichenowi in the tissues of Florida sandhill cranes (Grus canadensis). With these Mabs, E. reichenowi sporozoites were found in specimens taken at 6 hr postinoculation (PI) from just proximal to Meckel's diverticulum in the jejunum to the ileocecal juncture. Fewer were found in the ceca and rectum and none in the duodenal loop. At 24 hr PI, there were markedly fewer sporozoites and their location had shifted to the duodenum. No stages were seen in intestinal cells at 5 days PI (DPI), but trophozoites had developed in the liver and spleen. At 10 DPI, sexual stages were detected in the intestine from the duodenal loop through Meckel's diverticulum but not in other organs. By 14 DPI, numerous developmental stages were detected in the intestine (ceca and jejunum), liver, and lungs but not in the heart, kidney, or brain. The number, location, and maturity of the stages in the ceca differed markedly from those in the jejunum.

Use of monoclonal antibodies developed against chicken coccidia (Eimeria) to study invasion and development of Eimeria reichenowi in Florida sandhill cranes (Grus canadensis)

USGS Publications Warehouse

Augustine, P.C.; Olsen, Glenn H.; Danforth, H.D.; Gee, G.F.; Novilla, M.

2001-01-01

Eimeria gruis and Eimeria reichenowi are common coccidial parasites of a number of species of cranes. Until recently, little was known about either the site for invasion or the dynamics of early development of the crane coccidia because of the difficulty of identifying sporozoites and early developmental stages of these parasites by conventional staining methods. In the present study, monoclonal antibodies (MAbs) elicited against Eimeria spp. of chickens and turkeys were found to cross-react with sporozoites and developmental stages of E. reichenowi in the tissues of Florida sandhill cranes (Grus canadensis). With these Mabs, E. reichenowi sporozoites were found in specimens taken at 6 hr postinoculation (PI) from just proximal to Meckel's diverticulum in the jejunum to the ileocecal juncture. Fewer were found in the ceca and rectum and none in the duodenal loop. At 24 hr PI, there were markedly fewer sporozoites and their location had shifted to the duodenum. No stages were seen in intestinal cells at 5 days PI (DPI), but trophozoites had developed in the liver and spleen. At 10 DPI, sexual stages were detected in the intestine from the duodenal loop through Meckel's diverticulum but not in other organs. By 14 DPI, numerous developmental stages were detected in the intestine (ceca and jejunum), liver, and lungs but not in the heart, kidney, or brain. The number, location, and maturity of the stages in the ceca differed markedly from those in the jejunum.

Systems Biology Analysis of Gene Expression during In Vivo Mycobacterium avium paratuberculosis Enteric Colonization Reveals Role for Immune Tolerance

PubMed Central

Khare, Sangeeta; Lawhon, Sara D.; Drake, Kenneth L.; Nunes, Jairo E. S.; Figueiredo, Josely F.; Rossetti, Carlos A.; Gull, Tamara; Everts, Robin E.; Lewin, Harris A.; Galindo, Cristi L.; Garner, Harold R.; Adams, Leslie Garry

2012-01-01

Survival and persistence of Mycobacterium avium subsp. paratuberculosis (MAP) in the intestinal mucosa is associated with host immune tolerance. However, the initial events during MAP interaction with its host that lead to pathogen survival, granulomatous inflammation, and clinical disease progression are poorly defined. We hypothesize that immune tolerance is initiated upon initial contact of MAP with the intestinal Peyer's patch. To test our hypothesis, ligated ileal loops in neonatal calves were infected with MAP. Intestinal tissue RNAs were collected (0.5, 1, 2, 4, 8 and 12 hrs post-infection), processed, and hybridized to bovine gene expression microarrays. By comparing the gene transcription responses of calves infected with the MAP, informative complex patterns of expression were clearly visible. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis, and genes were grouped into the specific pathways and gene ontology categories to create a holistic model. This model revealed three different phases of responses: i) early (30 min and 1 hr post-infection), ii) intermediate (2, 4 and 8 hrs post-infection), and iii) late (12 hrs post-infection). We describe here the data that include expression profiles for perturbed pathways, as well as, mechanistic genes (genes predicted to have regulatory influence) that are associated with immune tolerance. In the Early Phase of MAP infection, multiple pathways were initiated in response to MAP invasion via receptor mediated endocytosis and changes in intestinal permeability. During the Intermediate Phase, perturbed pathways involved the inflammatory responses, cytokine-cytokine receptor interaction, and cell-cell signaling. During the Late Phase of infection, gene responses associated with immune tolerance were initiated at the level of T-cell signaling. Our study provides evidence that MAP infection resulted in differentially regulated genes, perturbed pathways and specifically modified mechanistic genes contributing to the colonization of Peyer's patch. PMID:22912686

Poly(vinyl methyl ether/maleic anhydride)-Doped PEG-PLA Nanoparticles for Oral Paclitaxel Delivery To Improve Bioadhesive Efficiency.

PubMed

Wang, Qian; Li, Chan; Ren, Tianyang; Chen, Shizhu; Ye, Xiaoxia; Guo, Hongbo; He, Haibing; Zhang, Yu; Yin, Tian; Liang, Xing-Jie; Tang, Xing

2017-10-02

Bioadhesive nanoparticles based on poly(vinyl methyl ether/maleic anhydride) (PVMMA) and poly(ethylene glycol) methyl ether-b-poly(d,l-lactic acid) (mPEG-b-PLA) were produced by the emulsification solvent evaporation method. Paclitaxel was utilized as the model drug, with an encapsulation efficiency of up to 90.2 ± 4.0%. The nanoparticles were uniform and spherical in shape and exhibited a sustained drug release compared with Taxol. m-NPs also exhibited favorable bioadhesive efficiency at the same time. Coumarin 6 or DiR-loaded nanoparticles with/without PVMMA (C6-m-NPs/DiR-m-NPs or C6-p-NPs/DiR-p-NPs) were used for cellular uptake and intestinal adhesion experiments, respectively. C6-m-NPs were shown to enhance cellular uptake, and caveolae/lipid raft mediated endocytosis was the primary route for the uptake of the nanoparticles. Favorable bioadhesive efficiency led to prolonged retention in the intestine reflected by the fluorescence in isolated intestines ex vivo. In a ligated intestinal loops model, C6-m-NPs showed a clear advantage for transporting NPs across the mucus layer over C6-p-NPs and free C6. The apparent permeability coefficient (Papp) of PTX-m-NPs through Caco-2/HT29 monolayers was 1.3- and 1.6-fold higher than PTX-p-NPs and Taxol, respectively, which was consistent with the AUC 0-t of different PTX formulations after oral administration in rats. PTX-m-NPs also exhibited a more effective anticancer efficacy, with an IC 50 of 0.2 ± 1.4 μg/mL for A549 cell lines, further demonstrating the advantage of bioadhesive nanoparticles. The bioadhesive nanoparticles m-NPs demonstrated both mucus permeation and epithelial absorption, and thus, this bioadhesive drug delivery system has the potential to improve the bioavailability of drugs that are insoluble in the gastrointestinal environment.

Transient, heat-induced thermal resistance in the small intestine of mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hume, S.P.; Marigold, J.C.L.

Heat-induced thermal resistance has been investigated in mouse jejunum by assaying crypt survival 24 h after treatment. Hyperthermia was achieved by immersing an exteriorized loop of intestine in a bath of Krebs-Ringer solution. Two approaches have been used. In the first, thermal survival curves were obtained following single hyperthermal treatments at temperatures in the range 42 to 44/sup 0/C. Transient thermal resistance, inducted by a plateau in the crypt survival curve, developed during heating at temperatures around 42.5/sup 0/C after 60 to 80 min. In the second series of experiments, a priming heat treatment (40.0, 41.0, 41.5, or 42.0/sup 0/Cmore » for 60 min) was followed at varying intervals by a test treatment at 43.0/sup 0/C. A transient resistance to the second treatment was induced, the extent and time of development being dependent upon the priming treatment. Crypt survival curves for thermally resistant intestine showed an increase in thermal D/sub 0/ and a decrease in n compared with curves from previously unheated intestine.« less

Primary small intestine tumour as the cause of gastrointestinal tract occlusion.

PubMed

Fabiszewski, Arkadiusz; Brycht, Łukasz; Jackowski, Marek

2011-03-01

The following paper presents the case of a 40-year-old patient staying in our Clinic between 2 March 2010 and 12 March 2010 due to the symptoms of permeable occlusion of gastrointestinal tract. This is a patient with a several weeks' history of non-specific abdominal pain, vomiting and significant weight loss (ca 20 kg). Until recently he has not suffered from any serious illnesses. In the performed abdominal ultrasound, gastroscopy and colonoscopy no pathology was affirmed. CT scan with intravenous and oral contrast showed significantly widened intestinal loops with residual liquid matter in the stomach, duodenum and a part of the jejunum without any distinguishing pathological mass, and also single mesenteric lymph nodes and para-aortic nodes enlarged to the size of 12 mm. The patient was qualified for laparatomy. During the surgery, a 4-cm tumour of the jejunum, concentrically narrowing intestinal lumen was found. Segmental resection of the small intestine was performed with side to side anastomosis with the use of a linear stapler. Currently the general condition of the patient is good, without any ailments, and the patient is undergoing systemic treatment.

Inhibitory effect and mechanism of acarbose combined with gymnemic acid on maltose absorption in rat intestine

PubMed Central

Luo, Hong; Wang, Le Feng; Imoto, Toshiaki; Hiji, Yasutake

2001-01-01

AIM: To compare the combinative and individual effect of acarbose and gymnemic acid (GA) on maltose absorption and hydrolysis in small intestine to determine whether nutrient control in diabetic care can be improved by combination of them. METHODS: The absorption and hydrolysis of maltose were studied by cyclic perfusion of intestinal loops in situ and motility of the intestine was recorded with the intestinal ring in vitro using Wistar rats. RESULTS: The total inhibitory rate of maltose absorption was improved by the combination of GA (0.1 g/L-1.0 g/L) and acarbose (0.1 mmol/L-2.0 mmol/L) throughout their effective duration (P < 0.05, U test of Mann-Whitney), although the improvement only could be seen at a low dosage during the first hour. With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3 h and the inhibitory effect onset of GA was fastened to 15 min. GA suppressed the intestinal mobility with a good correlation (r = 0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2 mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1 g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers. CONCLUSION: There are augmented effects of acarbose and GA, which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination. PMID:11819725

Efficacy, safety and mechanism of HP-β-CD-PEI polymers as absorption enhancers on the intestinal absorption of poorly absorbable drugs in rats.

PubMed

Zhang, Hailong; Huang, Xiaoyan; Zhang, Yongjing; Gao, Yang

2017-03-01

Oral bioavailability of some hydrophilic therapeutic macromolecules was very poor, thus leading to their limited application in clinic. To investigate the efficacy, safety and mechanism of HP-β-CD-PEI polymers on the intestinal absorption of some poorly absorbable drugs in rats. Effects of HP-β-CD-PEI polymers on the intestinal absorptions of drugs were investigated by an in situ closed loop method in rats. The safety of HP-β-CD-PEI polymer was evaluated by measurement of lactate dehydrogenase (LDH) activity and amount of protein released from rat intestinal perfusate. The absorption enhancing mechanisms were explored by the measurement of zeta potential, transepithelial electrical resistance (TEER) and in vitro transport of FD4 (a paracellular marker) across rat intestinal membranes, respectively. HP-β-CD-PEI polymers, especially HP-β-CD-PEI 1800 , demonstrated excellent absorption enhancing effects on drug absorption in a concentration-dependent manner and the enhancing effect was more efficient in the small intestine than that in the large intestine. Five percent (w/v) HP-β-CD-PEI 1800 obviously decreased the TEER, accompanied with increase in the intestinal transport of FD4, indicating that absorption enhancing actions of HP-β-CD-PEI polymers were possibly performed by loosening tight junctions of intestinal epithelium cells, thereby increasing drug permeation via a paracellular pathway. A good liner relationship between absorption enhancing effects of HP-β-CD-PEI polymers and their zeta potentials suggested the contribution of positive charge on the surface of these polymers to their absorption enhancing effects. HP-β-CD-PEI polymers might be potential and safe absorption enhancers for improving oral delivery of poorly absorbable macromolecules including peptides and proteins.

Dendrorchis pampae sp. n. (Digenea: Gorgoderidae) from Cynopoecilus melanotaenia (Cyprinodontiformes: Cynolebiidae) a killifish from southern Brazil, with an emended diagnosis of Dendrorchis.

PubMed

Monteiro, C M; Wendt, E W; Zebral, Y D

2018-04-15

A new species of Dendrorchis is described and compared with others in the genus. The parasites were found in the swim bladder of the annual killifish Cynopoecilus melanotaenia. Hosts were collected from a seasonal wetland in southern Brazil. The main characteristics of D. pampae are: genital pore in the intestinal bifurcation region elongate and lobed vitellaria uterine loops limited to the acetabular region and to the rear end of the body; and wide intestinal caeca. An emended diagnosis of the genus Dendrorchis includes the characteristics of the new species. This is the first record of an adult digenean in an annual killifish from South America.

Down-regulation of intestinal epithelial innate response by probiotic yeasts isolated from kefir.

PubMed

Romanin, David; Serradell, María; González Maciel, Dolores; Lausada, Natalia; Garrote, Graciela L; Rumbo, Martín

2010-06-15

Kefir is obtained by milk fermentation with a complex microbial population included in a matrix of polysaccharide and proteins. Several health-promoting activities has been attributed to kefir consumption. The aim of this study was to select microorganisms from kefir able to down-regulate intestinal epithelial innate response and further characterize this activity. Caco-2 cells stably transfected with a human CCL20 promoter luciferase reporter were used to screen a collection of 24 yeast and 23 bacterial strains isolated from kefir. The Toll-like receptor 5 agonist, flagellin was used to activate the reporter cells, while pre-incubation with the selected strains was tested to identify strains with the capacity to inhibit cell activation. In this system, 21 yeast strains from the genera Saccharomyces, Kluyveromyces and Issatchenkia inhibited almost 100% of the flagellin-dependent activation, whereas only some lactobacilli strains showed a partial effect. K. marxianus CIDCA 8154 was selected for further characterization. Inhibitory activity was confirmed at transcriptional level on Caco-2/TC-7 and HT-29 cells upon flagellin stimulation. A similar effect was observed using other pro-inflammatory stimulation such as IL-1beta and TNF-alpha. Pre-incubation with yeasts induced a down-regulation of NF-kappaB signalling in epithelial cells in vitro, as well as expression of other pro-inflammatory chemokines such as CXCL8 and CXCL2. Furthermore, modulation of CCL20 mRNA expression upon flagellin stimulation was evidenced in vivo, in a mouse ligated intestinal loop model. Results indicate kefir contains microorganisms able to abolish the intestinal epithelial inflammatory response that could explain some of the properties attributed to this fermented milk. Copyright 2010 Elsevier B.V. All rights reserved.

pH-sensitive thiolated nanoparticles facilitate the oral delivery of insulin in vitro and in vivo

NASA Astrophysics Data System (ADS)

Zhang, Yan; Lin, Xia; Du, Xuli; Geng, Sicong; Li, Hongren; Sun, Hong; Tang, Xing; Xiao, Wei

2015-02-01

In this work, we designed and developed a delivery system composed of enteric Eudragit L100-cysteine/reduced glutathione nanoparticles (Eul-cys/GSH NPs) for oral delivery of insulin. First, interactions between Eul-cys and mucin glycoproteins, which are believed to be the result of disulfide bonds, were confirmed using rheology experiments. Subsequently, the insulin-loaded Eul-cys/GSH NPs were prepared by the diffusion method using the rich gel network multipore structure at the surface of the Eul-cys when the pH was higher than the p Ka of Eul-cys polymer. The Eul-cys/GSH NPs obtained were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy. The results obtained showed that the average particle size ranged from 240 to 280 nm, and the particles were almost spherical in shape. The in vitro drug release results showed that the Eul-cys/GSH NPs retained a large amount of insulin in simulated gastric fluid, while a significant insulin release was found in simulated intestinal fluid. The in situ release study suggested that NPs released a greater amount of FITC-insulin (49.2 %) into the intestinal mucus layer compared with that of FITC-insulin solution (16.4 %), which facilitating insulin delivery through the intestinal mucosa. Eul-cys/GSH NPs exhibited promising mucoadhesive properties demonstrated using an in vitro cell model. Consequently, NPs were introduced into the ileum loop of healthy rats, thus enhancing the intestinal absorption of insulin and providing a prolonged reduction in blood glucose levels. These results suggest that Eul-cys/GSH NPs may be a promising delivery system for the treatment of diabetes.

Caecal volvulus: a consequence of acute cholecystitis

PubMed Central

Anjum, Ghulam Ali; Jaberansari, Sarah; Habeeb, Kayode

2013-01-01

Caecal volvulus is an uncommon cause of closed loop intestinal obstruction which can lead to caecal gangrene and high mortality. Delay in diagnosis is one of the causes of this high mortality. Caecal volvulus is reported to be associated with previous abdominal surgery in most cases. We present the first reported case of caecal volvulus following/associated with acute cholecystitis. PMID:23749828

Endogenous molecular network reveals two mechanisms of heterogeneity within gastric cancer.

PubMed

Li, Site; Zhu, Xiaomei; Liu, Bingya; Wang, Gaowei; Ao, Ping

2015-05-30

Intratumor heterogeneity is a common phenomenon and impedes cancer therapy and research. Gastric cancer (GC) cells have generally been classified into two heterogeneous cellular phenotypes, the gastric and intestinal types, yet the mechanisms of maintaining two phenotypes and controlling phenotypic transition are largely unknown. A qualitative systematic framework, the endogenous molecular network hypothesis, has recently been proposed to understand cancer genesis and progression. Here, a minimal network corresponding to such framework was found for GC and was quantified via a stochastic nonlinear dynamical system. We then further extended the framework to address the important question of intratumor heterogeneity quantitatively. The working network characterized main known features of normal gastric epithelial and GC cell phenotypes. Our results demonstrated that four positive feedback loops in the network are critical for GC cell phenotypes. Moreover, two mechanisms that contribute to GC cell heterogeneity were identified: particular positive feedback loops are responsible for the maintenance of intestinal and gastric phenotypes; GC cell progression routes that were revealed by the dynamical behaviors of individual key components are heterogeneous. In this work, we constructed an endogenous molecular network of GC that can be expanded in the future and would broaden the known mechanisms of intratumor heterogeneity.

Endogenous molecular network reveals two mechanisms of heterogeneity within gastric cancer

PubMed Central

Li, Site; Zhu, Xiaomei; Liu, Bingya; Wang, Gaowei; Ao, Ping

2015-01-01

Intratumor heterogeneity is a common phenomenon and impedes cancer therapy and research. Gastric cancer (GC) cells have generally been classified into two heterogeneous cellular phenotypes, the gastric and intestinal types, yet the mechanisms of maintaining two phenotypes and controlling phenotypic transition are largely unknown. A qualitative systematic framework, the endogenous molecular network hypothesis, has recently been proposed to understand cancer genesis and progression. Here, a minimal network corresponding to such framework was found for GC and was quantified via a stochastic nonlinear dynamical system. We then further extended the framework to address the important question of intratumor heterogeneity quantitatively. The working network characterized main known features of normal gastric epithelial and GC cell phenotypes. Our results demonstrated that four positive feedback loops in the network are critical for GC cell phenotypes. Moreover, two mechanisms that contribute to GC cell heterogeneity were identified: particular positive feedback loops are responsible for the maintenance of intestinal and gastric phenotypes; GC cell progression routes that were revealed by the dynamical behaviors of individual key components are heterogeneous. In this work, we constructed an endogenous molecular network of GC that can be expanded in the future and would broaden the known mechanisms of intratumor heterogeneity. PMID:25962957

Dipeptide transport and hydrolysis in isolated loops of rat small intestine: effects of stereospecificity.

PubMed Central

Lister, N; Sykes, A P; Bailey, P D; Boyd, C A; Bronk, J R

1995-01-01

1. Isolated jejunal loops of rat small intestine were perfused by a single pass of bicarbonate Krebs-Ringer solution containing either D- or L-phenylalanine or one of eight dipeptides formed from D- or L-alanine plus D- or L-phenylalanine. 2. At 0.5 mM L-phenylalanyl-L-alanine increased serosal phenylalanine appearance to forty times the control rate giving a value similar to that found with 0.5 mM free L-phenylalanine. No serosal dipeptide could be detected. 3. Perfusions with the two mixed dipeptides with N-terminal D-amino acids (D-alanyl-L-phenylalanine and D-phenylalanyl-L-alanine) gave rise to the appearance of intact dipeptides in the serosal secretions although there were substantial differences in their rates of absorption and subsequent hydrolysis. 4. L-Alanyl-D-phenylalanine was absorbed from the lumen three to five times as fast as L-phenylalanyl-D-alanine. At 1 mM L-alanyl-D-phenylalanine transferred D-phenylalanine across the epithelial layer at more than seven times the rate found with the same concentration of the free D-amino acid. 5. Perfusions with D-alanyl-D-phenylalanine or D-phenylalanyl-D-alanine showed that these two dipeptides are poor substrates for both transport and hydrolysis by the rat small intestine. 6. Analysis of mucosal tissue extracts after perfusion with the two mixed dipeptides with N-terminal D-amino acids revealed that both dipeptides were accumulated within the mucosa and suggested that exit across the basolateral membrane was rate limiting for transepithelial dipeptide transport. Images Figure 5 PMID:7602518

YghJ, the secreted metalloprotease of pathogenic E. coli induces hemorrhagic fluid accumulation in mouse ileal loop.

PubMed

Tapader, Rima; Bose, Dipro; Pal, Amit

2017-04-01

YghJ, also known as SslE (Secreted and surface associated lipoprotein) is a cell surface associated and secreted lipoprotein harbouring M60 metalloprotease domain. Though the gene is known to be conserved among both pathogenic and commensal Escherichia coli isolates, the expression and secretion of YghJ was found to be higher among diverse E. coli pathotypes. YghJ, secreted from intestinal pathogens such as enterotoxigenic E. coli (ETEC) and enteropathogenic E. coli (EPEC) has been demonstrated to possess mucinase activity and hence facilitates colonization of these enteric pathogens to intestinal epithelial cells. Importantly, YghJ is also reported to be secreted from extraintestinal pathogenic E. coli isolates. In our previous study we have shown that YghJ, purified from a neonatal septicemic E. coli isolate could trigger induction of various proinflammatory cytokines in vitro. This led us to investigate the role of YghJ in causing in vivo tissue hemorrhage. In the present study, we validate the earlier in vitro finding and have showed that YghJ can cause extensive tissue damage in mouse ileum and is also able to induce significant fluid accumulation in a dose dependent manner in a mouse ileal loop (MIL) assay. Hence, our present study not only confirms the pathogenic potential of YghJ in sepsis pathophysiology but also indicates the enterotoxic ability of YghJ which makes it an important virulence determinant of intestinal pathogenic E. coli. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Study of the antireflux action of the Roux-en-Y jejunal loop in reconstruction after gastrectomy and nutritional status in the follow-up].

PubMed

Rea, Teresa; Bartolacci, Mauro; Leombruni, Edoardo; Brizzi, Felice; Picardi, Nicola

2005-01-01

The Roux-en-Y recostruction after total or subtotal gastrectomy for gastric cancer is frequently performed to prevent esophageal alkaline reflux. Also after total gastrectomy and end-to-side gastrojejunal anastomosis, as usual in former experience, the alkaline reflux can be efficaciously treated by conversion in an esophago-jejunal Roux-en-Y procedure. The main factor preventing reflux is the length of jejunal loop, at least of 35-40 cm. The recostruction with a Roux-en-Y jejunal loop offers the advantage to meet together two primary requirements: the restoration of digestive travel from esophagus to intestine, and the prevention of on alcaline reflux esophagitis, both with relevant simplicity and without a time-consuming surgical technique. Also as a consequence the postoperative morbidity is decreased. The obvious suitable requirement is a sufficient lenght of the jejunal loop for a reservoir of the ingested food and to oppose the antiperistaltic jejunal movements thanks to the effects of the new activated jejunal pace-maker.

Activation of AMPK Inhibits Cholera Toxin Stimulated Chloride Secretion in Human and Murine Intestine

PubMed Central

Hoekstra, Nadia; Collins, Danielle; Collaco, Anne; Baird, Alan W.; Winter, Desmond C.; Ameen, Nadia; Geibel, John P.; Kopic, Sascha

2013-01-01

Increased intestinal chloride secretion through chloride channels, such as the cystic fibrosis transmembrane conductance regulator (CFTR), is one of the major molecular mechanisms underlying enterotoxigenic diarrhea. It has been demonstrated in the past that the intracellular energy sensing kinase, the AMP-activated protein kinase (AMPK), can inhibit CFTR opening. We hypothesized that pharmacological activation of AMPK can abrogate the increased chloride flux through CFTR occurring during cholera toxin (CTX) mediated diarrhea. Chloride efflux was measured in isolated rat colonic crypts using real-time fluorescence imaging. AICAR and metformin were used to activate AMPK in the presence of the secretagogues CTX or forskolin (FSK). In order to substantiate our findings on the whole tissue level, short-circuit current (SCC) was monitored in human and murine colonic mucosa using Ussing chambers. Furthermore, fluid accumulation was measured in excised intestinal loops. CTX and forskolin (FSK) significantly increased chloride efflux in isolated colonic crypts. The increase in chloride efflux could be offset by using the AMPK activators AICAR and metformin. In human and mouse mucosal sheets, CTX and FSK increased SCC. AICAR and metformin inhibited the secretagogue induced rise in SCC, thereby confirming the findings made in isolated crypts. Moreover, AICAR decreased CTX stimulated fluid accumulation in excised intestinal segments. The present study suggests that pharmacological activation of AMPK effectively reduces CTX mediated increases in intestinal chloride secretion, which is a key factor for intestinal water accumulation. AMPK activators may therefore represent a supplemental treatment strategy for acute diarrheal illness. PMID:23935921

Changes in intestinal absorption of nutrients and brush border glycoproteins after total parenteral nutrition in rats.

PubMed Central

Miura, S; Tanaka, S; Yoshioka, M; Serizawa, H; Tashiro, H; Shiozaki, H; Imaeda, H; Tsuchiya, M

1992-01-01

The effect of total parenteral nutrition on nutrients absorption and glycoprotein changes of brush border membrane was examined in rat small intestine. In total parenteral nutrition rats, a marked decrease in activity of brush border enzymes was observed mainly in the proximal and middle segments of the intestine. Galactose perfusion of jejunal segment showed that hexose absorption was significantly inhibited, while intestinal absorption of glycine or dipeptide, glycylglycine was not significantly affected by total parenteral nutrition treatment. When brush border membrane glycoprotein profile was examined by [3H]-glucosamine or [3H]-fucose incorporation into jejunal loops, significant changes were observed in the glycoprotein pattern of brush border membrane especially in the high molecular weight range over 120 kDa after total parenteral nutrition treatment, suggesting strong dependency of glycoprotein synthesis on luminal substances. Molecular weight of sucrase isomaltase in brush border membrane detected by specific antibody showed no significant difference, however, in total parenteral nutrition and control rats. Also, molecular weight of specific sodium glucose cotransporter of intestinal brush border membrane detected by selective photoaffinity labelling was not altered in total parenteral nutrition rats. It may be that prolonged absence of oral food intake may produce significant biochemical changes in brush border membrane glycoprotein and absorptive capacity of small intestine, but these changes were not observed in all brush border membrane glycoproteins. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1582592

Successful treatment of recurrent cholangitis by constructing a hepaticojejunostomy with long Roux-en-Y limb in a long-term surviving patient after a Whipple procedure for pancreatic adenocarcinoma.

PubMed

Tsalis, Konstantinos; Antoniou, Nikolaos; Koukouritaki, Zambia; Patridas, Dimitrios; Sakkas, Leonidas; Kyziridis, Dimitrios; Lazaridis, Charalampos

2014-08-20

Female, 74. Recurrent cholangitis. -. -. -. Gastroenterology and Hepatology. Unusual clinical course. Cholangitis may result from biliary obstruction (e.g., biliary or anastomotic stenosis, or foreign bodies) or occur in the presence of normal biliary drainage. Although reflux of intestinal contents into the biliary tree after hepaticojejunostomy appears to be a rare complication, it is important to emphasize that there are few available surgical therapeutic techniques. A 74-year-old woman presented to our hospital after 17 years of episodes of cholangitis. The patient had undergone a pancreatoduodenectomy (Whipple procedure) 18 years earlier due to pancreatic adenocarcinoma. The reconstruction was achieved through the sequential placement of pancreatic, biliary, and retrocolic gastric anastomosis into the same jejunal loop. The postoperative course was uneventful and the patient received adjuvant chemotherapy. Approximately 6 months after the initial operation, the patient started having episodes of cholangitis. Over the next 17 years she experienced several febrile episodes presumed to be secondary to cholangitis. A computing tomography (CT) scan of the abdomen revealed intrahepatic bile ducts partially filled with orally administered contrast material (Gastrografin). Magnetic resonance cholangiopancreatography (MRCP) showed dilatation of the left intrahepatic bile ducts. A percutaneous transhepatic cholangiography showed that the bilioenteric anastomosis was normal, without stenosis. Based on these findings, a diagnosis of a short loop between the hepaticojejunostomy and the gastrojejunostomy permitting the reflux of intestinal juice into the biliary tree was made. During the re-operation, a new hepaticojejunal anastomosis in a 100-cm long Roux-en-Y loop was performed to prevent the reflux of the intestinal fluid into the biliary tree. The patient was discharged on postoperative day 10. One year after the second procedure, the patient enjoys good health and has been free of fever and abdominal pain and has not received any antibiotic therapy. Lengthening the efferent Roux-en-Y limb should be considered as a therapeutic option when treating a patient with recurrent episodes of cholangitis after hepaticojejunostomy.

In vitro smooth muscle contractility before and after relief of experimental obstruction in the rat: application to the surgical management of ileal dilatation.

PubMed

Haraux, Elodie; Canarelli, Jean-Pierre; Khorsi, Hafida; Delanaud, Stéphane; Bach, Véronique; Gay-Quéheillard, Jérome

2014-03-01

Bowel dilatation occurs proximal to an obstruction and predisposes to intestinal dysmotility. The present study sought to determine whether or not changes in smooth muscle contractility and the thickness of the proximal, dilated bowel wall can be reversed following relief of the obstruction. Three groups of seven male Wistar rats were studied. In 8-week-old animals in a control group and a sham-operated group, a small segment of bowel (designated as R1 for controls and R2 for shams) was resected 5.0 cm from the cecum. In the third (operated) group, a narrow, isoperistaltic intestinal loop was created proximal to an end-to-end anastomosis of the ileum in 4-week-old animals. When these animals were 6 weeks old, the loop was re-anastomosed to the distal small bowel (after resection of the loop's distal portion, referred to as R3). Two weeks later, a small segment of bowel was resected proximal to the anastomosis (R4). We evaluated the thickness of the smooth muscle layers and the in vitro contractile responses of circular smooth muscle ileal strips (R1-R4) to electrical stimulation and pharmacological stimulation (with KCl, acetylcholine (ACh), substance P, N(G)-nitro-l-arginine methyl ester (L-NAME) and histamine). The amplitudes of contraction in response to electrical and Ach-mediated stimulation were higher for R3 than for R4 (P<0.001), R1 and R2 (both P<0.05). Compared with R1 and R2, the smooth muscle layer was three times as thick in R3 (P<0.001) and 2.5 times as thick in R4 (P<0.01). Our study provides evidence of the possible recovery of intestinal motility (in response to neurotransmitters involved in gut function) after the relief of an obstruction. If ileal motility can conceivably return to normal values, conservative surgical procedures in pediatric patients should be preferred (in order to leave a sufficient length of bowel and avoid short bowel syndrome). © 2013 Elsevier Inc. All rights reserved.

[[Estimation of bilio-oigestive and interintestinal anastomoses, formed in accordance to method of a high-frequency electric welding of tissues, in experiment].

PubMed

Hutsuliak, A I

2016-08-01

In the experiment on 50 rabbits cholecysto-entero and entero-entero anastomoses were formed on intestinal Roux loop. In 35 animals (the main group) a single layer evert- ing anastomoses by using high frequence (HF) electric welding method were formed, in 15 (the comparison group) single row suture anastomoses has been done. The anas- tomosis sufficiency were performed by using hydropressure, pneumopressure meth- ods and breakload test. It was established that all anastomoses formed by HF-electric welding method were passable and hermetic, also had strong sufficiency. Strength of weld joint in the postoperative period increased in a linear progression and after 3 weeks almost reached strength intact intestine (240-250 mm Hg).

Scallop DMT functions as a Ca2+ transporter.

PubMed

Toyohara, Haruhiko; Yamamoto, Sayuri; Hosoi, Masatomi; Takagi, Masaya; Hayashi, Isao; Nakao, Kenji; Kaneko, Shuji

2005-05-09

We identified a DMT (divalent metal transporter) homologous protein that functions as a Ca(2+) transporter. Scallop DMT cDNA encodes a 539-amino-acid protein with 12 putative membrane-spanning domains and has a consensus transport motif in the fourth extracellular loop. Since its mRNA is significantly expressed in the gill and intestine, it is assumed that scallop DMT transports Ca(2+) from seawater by the gill and from food by the intestine. Scallop DMT lacks the iron-responsive element commonly found in iron-regulatory proteins, suggesting that it is free of the post-transcriptional regulation from intracellular Fe(2+) concentration. Scallop DMT distinctly functions as a Ca(2+) transporter unlike other DMTs, however, it also transports Fe(2+) and Cd(2+) similar to them.

[Prevention of side effects and complications after operation for partial ileal bypass].

PubMed

Mirchuk, K K; Sedletskiĭ, Iu I

2014-01-01

Side effects and complications of the application of partial ileal bypass used for dislipidemia were analyzed in 162 patients with atherosclerosis. It was shown, that the partial ileal bypass operation could lead to the development of series of undesirable side effects such as diarrhea, hypovitaminosis B12, off-state intestine enteritis. The application of modification of partial ileal bypass such as formation of ileo-ileoanastomosis 5-6 cm long near ileocecal valve with the maintenance of its functions disposed the diarrhea and minimized the risk of the development of hypovitaminosis B12 after operation. It is possible to prevent the development of enteritis of off-state loop of the small intestine by using microanastomosis between off-state and functioning iliac intestine. The partial ileal bypass operation didn't influence on body weight, wouldn't increase the risk of stone formation in the gallbladder and kidneys. The risk of the development of hypovitaminosis B12 is minimal after operation.

Clinics in diagnostic imaging (171). Caecal volvulus with underlying intestinal malrotation.

PubMed

Ooi, Su Kai Gideon; Tan, Tien Jin; Ngu, James Chi Yong

2016-11-01

A 46-year-old Chinese woman with a history of cholecystectomy and appendicectomy presented to the emergency department with symptoms of intestinal obstruction. Physical examination revealed central abdominal tenderness but no clinical features of peritonism. Plain radiography of the abdomen revealed a grossly distended large bowel loop with the long axis extending from the right lower abdomen toward the epigastrium, and an intraluminal air-fluid level. These findings were suspicious for an acute caecal volvulus, which was confirmed on subsequent contrast-enhanced computed tomography (CT) of the abdomen and pelvis. CT demonstrated an abnormal positional relationship between the superior mesenteric vein and artery, indicative of an underlying intestinal malrotation. This case highlights the utility of preoperative imaging in establishing the diagnosis of an uncommon cause of bowel obstruction. It also shows the importance of recognising the characteristic imaging features early, so as to ensure appropriate and expedient management, thus reducing patient morbidity arising from complications. Copyright: © Singapore Medical Association.

Clinical, ultrasonographic, and pathologic findings in 70 camels (Camelus dromedarius) with Johne’s disease

PubMed Central

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Hashad, Mahmoud; Buczinski, Sébastien

2012-01-01

This study evaluated the use of ultrasonography for the diagnosis of Johne’s disease in camels (Camelus dromedarius). Seventy camels with confirmed Johne’s disease were examined by ultrasonography and subsequent necropsy; 15 healthy camels were included as controls. The most outstanding findings were visible enlargement of the mesenteric lymph nodes in 52 (74%) camels. Lesions had either echogenic (26%; n = 18) or anechoic (69%; n = 48) capsule and the contents were either anechoic (21%; n = 15), echogenic (27%; n = 19), or heterogeneous (46%; n = 32). Clumps of echogenic tissue interspersed with fluid pockets were imaged between the intestinal loops in 9 (13%) camels. There was mild, moderate, or severe thickening and corrugation of the intestinal wall, excessive anechoic fluid in the abdominal cavity in 18 (26%) camels, increased hepatic brightness in 30 (43%) camels, and pericardial and pleural effusions in 22 (31%) camels. Sensitivity values for detecting intestinal lesions and enlarged mesenteric lymph nodes were 95% and 84%, respectively. PMID:23115369

Clinical, ultrasonographic, and pathologic findings in 70 camels (Camelus dromedarius) with Johne's disease.

PubMed

Tharwat, Mohamed; Al-Sobayil, Fahd; Ali, Ahmed; Hashad, Mahmoud; Buczinski, Sébastien

2012-05-01

This study evaluated the use of ultrasonography for the diagnosis of Johne's disease in camels (Camelus dromedarius). Seventy camels with confirmed Johne's disease were examined by ultrasonography and subsequent necropsy; 15 healthy camels were included as controls. The most outstanding findings were visible enlargement of the mesenteric lymph nodes in 52 (74%) camels. Lesions had either echogenic (26%; n = 18) or anechoic (69%; n = 48) capsule and the contents were either anechoic (21%; n = 15), echogenic (27%; n = 19), or heterogeneous (46%; n = 32). Clumps of echogenic tissue interspersed with fluid pockets were imaged between the intestinal loops in 9 (13%) camels. There was mild, moderate, or severe thickening and corrugation of the intestinal wall, excessive anechoic fluid in the abdominal cavity in 18 (26%) camels, increased hepatic brightness in 30 (43%) camels, and pericardial and pleural effusions in 22 (31%) camels. Sensitivity values for detecting intestinal lesions and enlarged mesenteric lymph nodes were 95% and 84%, respectively.

Organo-axial volvulus of the small intestine: radiological case report and consideration for its mechanism.

PubMed

Ishiguro, Toshitaka; Hiyama, Takashi; Nasu, Katsuhiro; Akashi, Yoshimasa; Minami, Manabu

2017-07-01

Gastrointestinal volvulus is mainly classified into two subtypes, mesentero-axial volvulus and organo-axial volvulus. The detailed imaging findings of organo-axial volvulus of the small intestine have never been reported as far as we know. In this article, we report a case of organo-axial volvulus of the small intestine, focusing on the computed tomography (CT) findings. An 80-year-old man was radiologically diagnosed as having organo-axial volvulus of the terminal ileum and it was confirmed by open surgery without adhesion or any other anatomical abnormalities. CT showed two specific findings, split-bowel sign and rotating-C sign, which we think reflect pathophysiologic features of organo-axial volvulus. We think the pathogenic mechanism of organo-axial volvulus can be explained by the convergence of the reversed-rotational twist following the formation of a twisted but non-obstructive circular loop, even if there is no adhesion. Radiologists should be aware that organo-axial volvulus can occur even in the small intestine, and in the case of small bowel obstruction with single transition point, the two pathophysiologic signs mentioned above must be looked for to diagnose the possibility of organo-axial volvulus.

Effects of a single dose of menadione on the intestinal calcium absorption and associated variables.

PubMed

Marchionatti, Ana M; Díaz de Barboza, Gabriela E; Centeno, Viviana A; Alisio, Arturo E; Tolosa de Talamoni, Nori G

2003-08-01

The effect of a single large dose of menadione on intestinal calcium absorption and associated variables was investigated in chicks fed a normal diet. The data show that 2.5 micro mol of menadione/kg of b.w. causes inhibition of calcium transfer from lumen-to-blood within 30 min. This effect seems to be related to oxidative stress provoked by menadione as judged by glutathione depletion and an increment in the total carbonyl group content produced at the same time. Two enzymes presumably involved in calcium transcellular movement, such as alkaline phosphatase, located in the brush border membrane, and Ca(2+)- pump ATPase, which sits in the basolateral membrane, were also inhibited. The enzyme inhibition could be due to alterations caused by the appearance of free hydroxyl groups, which are triggered by glutathione depletion. Addition of glutathione monoester to the duodenal loop caused reversion of the menadione effect on both intestinal calcium absorption and alkaline phosphatase activity. In conclusion, menadione shifts the balance of oxidative and reductive processes in the enterocyte towards oxidation causing deleterious effects on intestinal Ca(2+) absorption and associated variables, which could be prevented by administration of oral glutathione monoester.

Oral insulin delivery using P(MAA-g-EG) hydrogels: effects of network morphology on insulin delivery characteristics.

PubMed

Nakamura, Koji; Murray, Robert J; Joseph, Jeffrey I; Peppas, Nicholas A; Morishita, Mariko; Lowman, Anthony M

2004-03-24

Hydrogels of poly(methacrylic acid-g-ethylene glycol) were prepared using different reaction water contents in order to vary the network mesh size, swelling behavior and insulin loading/release kinetics. Gels prepared with greater reaction solvent contents swelled to a greater degree and had a larger network mesh size. All of the hydrogels were able to incorporate insulin and protected it from release in acidic media. At higher pH (7.4), the release rates increased with reaction solvent content. Using a closed loop animal model, all of the insulin loaded formulations produced significant insulin absorption in the upper small intestine combined with hypoglycemic effects. In these studies, bioavailabilities ranged from 4.6% to 7.2% and were dependent on reaction solvent content.

Antisecretory activity of plants used to treat gastrointestinal disorders in Mexico.

PubMed

Velázquez, Claudia; Calzada, Fernando; Torres, Javier; González, Felipe; Ceballos, Guillermo

2006-01-03

Aqueous and methanolic extracts from 26 medicinal plants used in Mexico to treat gastrointestinal disorders were screened to evaluate their antisecretory activity on cholera toxin-induced intestinal secretion in rat jejunal loops model. Extracts were tested at a dose of 300 mg/kg. From 56 samples tested, both extracts from Chiranthodendron pentadactylon, Hippocratea excelsa and Ocimum basilicum were the most potent with inhibition values ranging from 68.0 to 87.6%. On the other hand, the methanolic extract of Geranium mexicanum (aerial parts) and the aqueous extract of Bocconia frutescens showed the highest activity with inhibition values of 93.4 and 86.0%, respectively. The results obtained in this study give some scientific support to the use of the Mexican medicinal plants employed for the treatment of gastrointestinal disorders such as diarrhea.

Molecular imaging analysis of intestinal insulin absorption boosted by cell-penetrating peptides by using positron emission tomography.

PubMed

Kamei, Noriyasu; Morishita, Mariko; Kanayama, Yousuke; Hasegawa, Koki; Nishimura, Mie; Hayashinaka, Emi; Wada, Yasuhiro; Watanabe, Yasuyoshi; Takayama, Kozo

2010-08-17

Molecular imaging technique by use of positron emission tomography (PET) is a noninvasive tool that allows one to quantitatively analyze the function of endogenous molecules and the pharmacokinetics of therapeutic agents in vivo. This technique is expected to be useful for evaluating the effectiveness of diverse drug delivery systems. We demonstrated previously that intestinal insulin absorption is increased significantly by coadministration of cell-penetrating peptides (CPPs), which are taken up effectively by several cells. However, the distribution behavior of insulin whose absorption is increased by CPPs is not clear. We used PET imaging and quantitatively analyzed the intestinal absorption and subsequent distribution of insulin and the effect of CPPs on its absorption and distribution. An unlabeled insulin solution containing tracer insulin, (68)Ga-DOTA-insulin, was administered with or without CPPs into a rat ileal closed loop. PET imaging showed that the CPPs, particularly D-R8 and L-penetratin, significantly increased the (68)Ga-DOTA-insulin level in the liver, kidney, and circulation. After absorption from the intestine, the (68)Ga-DOTA-insulin passed rapidly through the liver and accumulated in the kidney. The increase in the hepatic and renal distribution of (68)Ga-DOTA-insulin by each CPP coadministration was similar manner as that in intestinal absorption, suggesting that the increased accumulation of insulin in the liver and kidney induced by coadministration of CPPs was associated with the increased intestinal absorption of insulin. This is the first study to show that PET imaging enables one to quantitatively analyze the distribution behavior of intestinally absorbed insulin in several organs. This imaging methodology is likely to be useful for developing effective drug delivery systems targeted to specific organs. Copyright 2010 Elsevier B.V. All rights reserved.

Small bowel enteroclysis in surgically treated obesity.

PubMed

Coppola, V; Verrengia, D; Gatta, G; Alfinito, M; Alfano, L; D'Agostino, F

1998-11-01

To define the indications, technical limitations and diagnostic yeld of small bowel transbuccal enema in the follow-up of surgical jejunoileal shunting in patients with complicated severe essential obesity. Three patients were submitted to surgical diversion: two of them underwent an intestinal bypass after Payne-De Wind (isoperistaltic end-to-side jejunoileostomy) and the other after Scott (end-to-end jejunoileostomy). The latter refers to intestinal recanalization and antiperistaltic lower end-to-side gastroenteric restoration. Radiologic studies are the only means to depict the surgical small bowel. Radiographic follow-up needs barium sulfate administration and therefore cannot be performed any sooner than 30 days postoperatively. In the last three years the classic transbuccal enema has been performed with a Rollandi tube (with a terminal opening and a balloon). Both the anastomosis and the blind loop are difficult to demonstrate. Jejunoileal bypass can be used to treat severe obsity uncontrollable otherwise, to reduce food absorption. Different severe complications may result and small bowel studies may permit to show late local complications. Small bowel enema is also indispensable in bypass reversal. There are no alternatives to this radiologic examination which is however very difficult to perform, because of the changes made by previous operation(s), and to interpret because the anastomosis, the sutured loop and wall changes are often poorly demonstrated.

Intestinal Glucose Absorption Was Reduced by Vertical Sleeve Gastrectomy via Decreased Gastric Leptin Secretion.

PubMed

Du, Jinpeng; Hu, Chaojie; Bai, Jie; Peng, Miaomiao; Wang, Qingbo; Zhao, Ning; Wang, Yu; Wang, Guobin; Tao, Kaixiong; Wang, Geng; Xia, Zefeng

2018-06-18

The unique effects of gastric resection after vertical sleeve gastrectomy (VSG) on type 2 diabetes mellitus remain unclear. This work aimed to investigate the effects of VSG on gastric leptin expression and intestinal glucose absorption in high-fat diet-induced obesity. Male C57BL/6J mice were fed a high-fat diet (HFD) to induce obesity. HFD mice were randomized into VSG and sham-operation groups, and the relevant parameters were measured at 8 weeks postoperation. Higher gastric leptin expression and increased intestinal glucose transport were observed in the HFD mice. Furthermore, VSG reduced gastric leptin expression and the intestinal absorption of alimentary glucose. Both exogenous leptin replenishment during the oral glucose tolerance test (OGTT) and the addition of leptin into the everted isolated jejunum loops in vitro restored the glucose transport capacity in VSG-operated mice, and this effect was abolished when the glucose transporter GLUT2 was blocked with phloretin. Moreover, phloretin almost completely suppressed glucose transport in the HFD mice. Intestinal immunohistochemistry in the obese mice showed increased GLUT2 and diminished sodium glucose co-transporter 1 (SGLT-1) in the apical membrane of enterocytes. Decreased GLUT2 and enhanced SGLT1 were observed following VSG. VSG also reduced the phosphorylation status of protein kinase C isoenzyme β II (PKCβ II) in the jejunum, which was stimulated by the combination of leptin and glucose. Our data demonstrated that the decreased secretion of gastric leptin in VSG results in a decrease in intestinal glucose absorption via modulation of GLUT2 translocation.

Laparoscopic intestinal derotation: original technique.

PubMed

Valle, Mario; Federici, Orietta; Tarantino, Enrico; Corona, Francesco; Garofalo, Alfredo

2009-06-01

The intestinal derotation technique, introduced by Cattel and Valdoni 40 years ago, is carried out using a laparoscopic procedure, which is described here for the first time. The method is effective in the treatment of malign lesions of the III and IV duodenum and during laparoscopic subtotal colectomy with anastomosis between the ascending colon and the rectum. Ultimately, the procedure allows for the verticalization of the duodenal C and the anterior positioning of the mesenteric vessels, facilitating biopsy and resection of the III and IV duodenal portions and allowing anastomosis of the ascending rectum, avoiding both subtotal colectomy and the risk of torsion of the right colic loop. Although the procedure calls for extensive experience with advanced video-laparoscopic surgery, it is both feasible and repeatable. In our experience we have observed no mortality or morbidity.

The Role of Secretory Immunoglobulin A in the Natural Sensing of Commensal Bacteria by Mouse Peyer's Patch Dendritic Cells*

PubMed Central

Rol, Nicolas; Favre, Laurent; Benyacoub, Jalil; Corthésy, Blaise

2012-01-01

The mammalian gastrointestinal (GI) tract harbors a diverse population of commensal species collectively known as the microbiota, which interact continuously with the host. From very early in life, secretory IgA (SIgA) is found in association with intestinal bacteria. It is considered that this helps to ensure self-limiting growth of the microbiota and hence participates in symbiosis. However, the importance of this association in contributing to the mechanisms ensuring natural host-microorganism communication is in need of further investigation. In the present work, we examined the possible role of SIgA in the transport of commensal bacteria across the GI epithelium. Using an intestinal loop mouse model and fluorescently labeled bacteria, we found that entry of commensal bacteria in Peyer's patches (PP) via the M cell pathway was mediated by their association with SIgA. Preassociation of bacteria with nonspecific SIgA increased their dynamics of entry and restored the reduced transport observed in germ-free mice known to have a marked reduction in intestinal SIgA production. Selective SIgA-mediated targeting of bacteria is restricted to the tolerogenic CD11c+CD11b+CD8− dendritic cell subset located in the subepithelial dome region of PPs, confirming that the host is not ignorant of its resident commensals. In conclusion, our work supports the concept that SIgA-mediated monitoring of commensal bacteria targeting dendritic cells in the subepithelial dome region of PPs represents a mechanism whereby the host mucosal immune system controls the continuous dialogue between the host and commensal bacteria. PMID:23027876

Fidaxomicin Inhibits Clostridium difficile Toxin A-Mediated Enteritis in the Mouse Ileum

PubMed Central

Koon, Hon Wai; Ho, Samantha; Hing, Tressia C.; Cheng, Michelle; Chen, Xinhua; Ichikawa, Yoshi; Kelly, Ciarán P.

2014-01-01

Clostridium difficile infection (CDI) is a common, debilitating infection with high morbidity and mortality. C. difficile causes diarrhea and intestinal inflammation by releasing two toxins, toxin A and toxin B. The macrolide antibiotic fidaxomicin was recently shown to be effective in treating CDI, and its beneficial effect was associated with fewer recurrent infections in CDI patients. Since other macrolides possess anti-inflammatory properties, we examined the possibility that fidaxomicin alters C. difficile toxin A-induced ileal inflammation in mice. The ileal loops of anesthetized mice were injected with fidaxomicin (5, 10, or 20 μM), and after 30 min, the loops were injected with purified C. difficile toxin A or phosphate-buffered saline alone. Four hours after toxin A administration, ileal tissues were processed for histological evaluation (epithelial cell damage, neutrophil infiltration, congestion, and edema) and cytokine measurements. C. difficile toxin A caused histologic damage, evidenced by increased mean histologic score and ileal interleukin-1β (IL-1β) protein and mRNA expression. Treatment with fidaxomicin (20 μM) or its primary metabolite, OP-1118 (120 μM), significantly inhibited toxin A-mediated histologic damage and reduced the mean histology score and ileal IL-1β protein and mRNA expression. Both fidaxomicin and OP-1118 reduced toxin A-induced cell rounding in human colonic CCD-18Co fibroblasts. Treatment of ileal loops with vancomycin (20 μM) and metronidazole (20 μM) did not alter toxin A-induced histologic damage and IL-1β protein expression. In addition to its well known antibacterial effects against C. difficile, fidaxomicin may possess anti-inflammatory activity directed against the intestinal effects of C. difficile toxins. PMID:24890583

Adult zebrafish intestine resection: a novel model of short bowel syndrome, adaptation, and intestinal stem cell regeneration.

PubMed

Schall, K A; Holoyda, K A; Grant, C N; Levin, D E; Torres, E R; Maxwell, A; Pollack, H A; Moats, R A; Frey, M R; Darehzereshki, A; Al Alam, D; Lien, C; Grikscheit, T C

2015-08-01

Loss of significant intestinal length from congenital anomaly or disease may lead to short bowel syndrome (SBS); intestinal failure may be partially offset by a gain in epithelial surface area, termed adaptation. Current in vivo models of SBS are costly and technically challenging. Operative times and survival rates have slowed extension to transgenic models. We created a new reproducible in vivo model of SBS in zebrafish, a tractable vertebrate model, to facilitate investigation of the mechanisms of intestinal adaptation. Proximal intestinal diversion at segment 1 (S1, equivalent to jejunum) was performed in adult male zebrafish. SBS fish emptied distal intestinal contents via stoma as in the human disease. After 2 wk, S1 was dilated compared with controls and villus ridges had increased complexity, contributing to greater villus epithelial perimeter. The number of intervillus pockets, the intestinal stem cell zone of the zebrafish increased and contained a higher number of bromodeoxyuridine (BrdU)-labeled cells after 2 wk of SBS. Egf receptor and a subset of its ligands, also drivers of adaptation, were upregulated in SBS fish. Igf has been reported as a driver of intestinal adaptation in other animal models, and SBS fish exposed to a pharmacological inhibitor of the Igf receptor failed to demonstrate signs of intestinal adaptation, such as increased inner epithelial perimeter and BrdU incorporation. We describe a technically feasible model of human SBS in the zebrafish, a faster and less expensive tool to investigate intestinal stem cell plasticity as well as the mechanisms that drive intestinal adaptation. Copyright © 2015 the American Physiological Society.

Adult zebrafish intestine resection: a novel model of short bowel syndrome, adaptation, and intestinal stem cell regeneration

PubMed Central

Schall, K. A.; Holoyda, K. A.; Grant, C. N.; Levin, D. E.; Torres, E. R.; Maxwell, A.; Pollack, H. A.; Moats, R. A.; Frey, M. R.; Darehzereshki, A.; Al Alam, D.; Lien, C.

2015-01-01

Loss of significant intestinal length from congenital anomaly or disease may lead to short bowel syndrome (SBS); intestinal failure may be partially offset by a gain in epithelial surface area, termed adaptation. Current in vivo models of SBS are costly and technically challenging. Operative times and survival rates have slowed extension to transgenic models. We created a new reproducible in vivo model of SBS in zebrafish, a tractable vertebrate model, to facilitate investigation of the mechanisms of intestinal adaptation. Proximal intestinal diversion at segment 1 (S1, equivalent to jejunum) was performed in adult male zebrafish. SBS fish emptied distal intestinal contents via stoma as in the human disease. After 2 wk, S1 was dilated compared with controls and villus ridges had increased complexity, contributing to greater villus epithelial perimeter. The number of intervillus pockets, the intestinal stem cell zone of the zebrafish increased and contained a higher number of bromodeoxyuridine (BrdU)-labeled cells after 2 wk of SBS. Egf receptor and a subset of its ligands, also drivers of adaptation, were upregulated in SBS fish. Igf has been reported as a driver of intestinal adaptation in other animal models, and SBS fish exposed to a pharmacological inhibitor of the Igf receptor failed to demonstrate signs of intestinal adaptation, such as increased inner epithelial perimeter and BrdU incorporation. We describe a technically feasible model of human SBS in the zebrafish, a faster and less expensive tool to investigate intestinal stem cell plasticity as well as the mechanisms that drive intestinal adaptation. PMID:26089336

A mathematical model of intestinal oedema formation.

PubMed

Young, Jennifer; Rivière, Béatrice; Cox, Charles S; Uray, Karen

2014-03-01

Intestinal oedema is a medical condition referring to the build-up of excess fluid in the interstitial spaces of the intestinal wall tissue. Intestinal oedema is known to produce a decrease in intestinal transit caused by a decrease in smooth muscle contractility, which can lead to numerous medical problems for the patient. Interstitial volume regulation has thus far been modelled with ordinary differential equations, or with a partial differential equation system where volume changes depend only on the current pressure and not on updated tissue stress. In this work, we present a computational, partial differential equation model of intestinal oedema formation that overcomes the limitations of past work to present a comprehensive model of the phenomenon. This model includes mass and momentum balance equations which give a time evolution of the interstitial pressure, intestinal volume changes and stress. The model also accounts for the spatially varying mechanical properties of the intestinal tissue and the inhomogeneous distribution of fluid-leaking capillaries that create oedema. The intestinal wall is modelled as a multi-layered, deforming, poroelastic medium, and the system of equations is solved using a discontinuous Galerkin method. To validate the model, simulation results are compared with results from four experimental scenarios. A sensitivity analysis is also provided. The model is able to capture the final submucosal interstitial pressure and total fluid volume change for all four experimental cases, and provide further insight into the distribution of these quantities across the intestinal wall.

Active intestinal absorption of fluoroquinolone antibacterial agent ciprofloxacin by organic anion transporting polypeptide, Oatp1a5.

PubMed

Arakawa, Hiroshi; Shirasaka, Yoshiyuki; Haga, Makoto; Nakanishi, Takeo; Tamai, Ikumi

2012-09-01

Fluoroquinolone antimicrobial drugs are absorbed efficiently after oral administration despite of their hydrophilic nature, implying an involvement of carrier-mediated transport in their membrane transport process. It has been that several fluoroquinolones are substrates of organic anion transporter polypeptides OATP1A2 expressed in human intestine derived Caco-2 cells. In the present study, to clarify the involvement of OATP in intestinal absorption of ciprofloxacin, the contribution of Oatp1a5, which is expressed at the apical membranes of rat enterocytes, to intestinal absorption of ciprofloxacin was investigated in rats. The intestinal membrane permeability of ciprofloxacin was measured by in situ and the vascular perfused closed loop methods. The disappeared and absorbed amount of ciprofloxacin from the intestinal lumen were increased markedly in the presence of 7,8-benzoflavone, a breast cancer resistance protein inhibitor, and ivermectin, a P-glycoprotein inhibitor, while it was decreased significantly in the presence of these inhibitors in combination with naringin, an Oatp1a5 inhibitor. Furthermore, the Oatp1a5-mediated uptake of ciprofloxacin was saturable with a K(m) value of 140 µm, and naringin inhibited the uptake with an IC(50) value of 18 µm by Xenopus oocytes expressing Oatp1a5. Naringin reduced the permeation of ciprofloxacin from the mucosal-to-serosal side, with an IC(50) value of 7.5 µm by the Ussing-type chamber method. The estimated IC(50) values were comparable to that of Oatp1a5. These data suggest that Oatp1a5 is partially responsible for the intestinal absorption of ciprofloxacin. In conclusion, the intestinal absorption of ciprofloxacin could be affected by influx transporters such as Oatp1a5 as well as the efflux transporters such as P-gp and Bcrp. Copyright © 2012 John Wiley & Sons, Ltd.

Molecular weight dependence of permselectivity to rat small intestinal blood-lymph barrier for exogenous macromolecules absorbed from lumen.

PubMed

Yoshikawa, H; Takada, K; Muranishi, S

1984-01-01

The permselectivity to the small intestinal blood-lymph barrier for the exogenous macromolecules absorbed from the lumen was investigated using in situ rat closed loop experiment. We chose the fluorescein isothiocyanate-labelled dextran (FD) as macromolecule and lipid-surfactant mixed micelles as an absorption promoter. The mean molecular weights of FDs used were 10500, 17500, 39000 and 64200 (abbreviated: FD10 , 20, 40 and 70). The lymph/plasma ratios of FDs concentrations during 5 h post administration were 0.2-1.2 ( FD10 ), 0.4-1.3 ( FD20 ), 1.3-7.2 ( FD40 ) and 2.6-11.9 ( FD70 ), respectively. The FD40 and FD70 levels in the lymph were significantly higher than those in the plasma. The cumulative amounts (% of the absorbed quantity) of FDs in the lymph from the lumen of the small intestine for 5 h after administration were 0.46% ( FD10 ), 0.51% ( FD20 ), 1.17% ( FD40 ) and 1.89% ( FD70 ), respectively. These findings suggest that the threshold molecular weight of FD for the transfer into the lymphatics with higher level compared to the blood concentration from the lumen across the small intestinal blood-lymph barrier exists between 17500 and 39000.

DUSP5 is methylated in CIMP-high colorectal cancer but is not a major regulator of intestinal cell proliferation and tumorigenesis.

PubMed

Tögel, Lars; Nightingale, Rebecca; Wu, Rui; Chüeh, Anderly C; Al-Obaidi, Sheren; Luk, Ian; Dávalos-Salas, Mercedes; Chionh, Fiona; Murone, Carmel; Buchanan, Daniel D; Chatterton, Zac; Sieber, Oliver M; Arango, Diego; Tebbutt, Niall C; Williams, David; Dhillon, Amardeep S; Mariadason, John M

2018-01-29

The ERK signalling pathway regulates key cell fate decisions in the intestinal epithelium and is frequently dysregulated in colorectal cancers (CRCs). Variations in the dynamics of ERK activation can induce different biological outcomes and are regulated by multiple mechanisms, including activation of negative feedback loops involving transcriptional induction of dual-specificity phosphatases (DUSPs). We have found that the nuclear ERK-selective phosphatase DUSP5 is downregulated in colorectal tumours and cell lines, as previously observed in gastric and prostate cancer. The DUSP5 promoter is methylated in a subset of CRC cell lines and primary tumours, particularly those with a CpG island methylator phenotype (CIMP). However, this epigenetic change alone could not account for reduced DUSP5 expression in CRC cells. Functionally, DUSP5 depletion failed to alter ERK signalling or proliferation in CRC cell lines, and its transgenic overexpression in the mouse intestine had minimal impact on normal intestinal homeostasis or tumour development. Our results suggest that DUSP5 plays a limited role in regulating ERK signalling associated with the growth of colorectal tumours, but that methylation the DUSP5 gene promoter can serve as an additional means of identifying CIMP-high colorectal cancers.

Adrenergic mediation of the intestinal antisecretory action of opiates administered into the central nervous system.

PubMed

Brown, D R; Miller, R J

1984-10-01

The antisecretory effects of the stable enkephalin analogs, [D-Ala2-Met5] enkephalinamide (DAMA) and [D-Ala2-D-Leu5] enkephalin, and the opiate drug morphine were evaluated on fluid secretion induced by cholera toxin in isolated loops of the jejunum and proximal and distal ileum in anesthetized rats. Intracerebroventricular administration of DAMA (0.03-3 micrograms) or [D-Ala2-D-Leu5] enkephalin (1.0-10 micrograms) dose-dependently reduced secretion in the jejunum without affecting fluid movement in the other small intestinal segments. Morphine in doses up to 30 micrograms i.c.v. had no significant antisecretory effects. Intravenous administration of DAMA, at doses up to 3000 micrograms/kg, had little effect on intestinal fluid accumulation. The antisecretory action of DAMA (3 micrograms i.c.v.) was completely blocked by pretreatment with the alpha adrenergic antagonist phentolamine and after peripheral sympathectomy induced by guanethidine. In contrast, DAMA activity was preserved in adrenal demedullated rats. DAMA had no significant effects upon mean arterial blood pressure or on blood acid-base balance. These results suggest that the antisecretory effects of opiates are, at least partly, mediated at sites within the central nervous system. These actions are probably a consequence of increased activity in sympathetic nerve fibers innervating the upper small intestine.

Quantitative mRNA analysis of muscarinic acetylcholine receptors in the intestine of dairy cows with spontaneous caecal dilatation-dislocation.

PubMed

Ontsouka, E C; Steiner, A; Bruckmaier, R M; Blum, J W; Meylan, M

2009-05-01

Muscarinic receptors mediate acetylcholine-induced muscular contractions. In this study, mRNA levels of muscarinic receptor subtypes 2 and 3 (M(2) and M(3)) in the ileum, caecum, proximal loop of the ascending colon (PLAC) and external loop of the spiral colon (ELSC) were determined by quantitative polymerase chain reaction in seven cows with caecal dilatation-dislocation (CDD) and seven healthy control cows. Levels of M(2) were significantly lower in the caecum, PLAC and ELSC and levels of M(3) were significantly lower in the ileum, caecum, PLAC and ELSC of cows with CDD compared to healthy cows (P<0.05). Down-regulation of M(3) may play a role in the pathogenesis of CDD.

Conformational Sampling in Template-Free Protein Loop Structure Modeling: An Overview

PubMed Central

Li, Yaohang

2013-01-01

Accurately modeling protein loops is an important step to predict three-dimensional structures as well as to understand functions of many proteins. Because of their high flexibility, modeling the three-dimensional structures of loops is difficult and is usually treated as a “mini protein folding problem” under geometric constraints. In the past decade, there has been remarkable progress in template-free loop structure modeling due to advances of computational methods as well as stably increasing number of known structures available in PDB. This mini review provides an overview on the recent computational approaches for loop structure modeling. In particular, we focus on the approaches of sampling loop conformation space, which is a critical step to obtain high resolution models in template-free methods. We review the potential energy functions for loop modeling, loop buildup mechanisms to satisfy geometric constraints, and loop conformation sampling algorithms. The recent loop modeling results are also summarized. PMID:24688696

Conformational sampling in template-free protein loop structure modeling: an overview.

PubMed

Li, Yaohang

2013-01-01

Accurately modeling protein loops is an important step to predict three-dimensional structures as well as to understand functions of many proteins. Because of their high flexibility, modeling the three-dimensional structures of loops is difficult and is usually treated as a "mini protein folding problem" under geometric constraints. In the past decade, there has been remarkable progress in template-free loop structure modeling due to advances of computational methods as well as stably increasing number of known structures available in PDB. This mini review provides an overview on the recent computational approaches for loop structure modeling. In particular, we focus on the approaches of sampling loop conformation space, which is a critical step to obtain high resolution models in template-free methods. We review the potential energy functions for loop modeling, loop buildup mechanisms to satisfy geometric constraints, and loop conformation sampling algorithms. The recent loop modeling results are also summarized.

Carrier-mediated transport of riboflavin in the rat colon.

PubMed

Yuasa, H; Hirobe, M; Tomei, S; Watanabe, J

2000-03-01

Carriers involved in riboflavin transport have generally been presumed to be localized in the upper small intestine. However, using a closed loop technique, we found that in the rat colon the absorption of riboflavin could be significantly reduced by raising the concentration from 0.1 to 200 microM and by adding lumiflavin, an analogue of riboflavin. These results suggest that saturable transport by the carrier that is specific for riboflavin and analogues may also be involved in riboflavin absorption in the colon. At the lower concentration of 0.1 microM, carrier-mediated transport was suggested to prevail, compared with passive transport, both in the colon and the small intestine. Furthermore, carrier-mediated transport in the colon was comparable with that in the small intestine. This study is the first to suggest carrier-mediated riboflavin transport in the colon. Although the riboflavin transport system in the colon needs to be subjected to more detailed investigation of its transport functions and role in riboflavin absorption after oral administration, it would be of interest to explore potential use of this carrier as a system for drug delivery.

Comparative transcriptome analysis by RNAseq of necrotic enteritis Clostridium perfringens during in vivo colonization and in vitro conditions.

PubMed

Parreira, Valeria R; Russell, Kay; Athanasiadou, Spiridoula; Prescott, John F

2016-08-12

Necrotic enteritis (NE) caused by netB-positive type A Clostridium perfringens is an important bacterial disease of poultry. Through its complex regulatory system, C. perfringens orchestrates the expression of a collection of toxins and extracellular enzymes that are crucial for the development of the disease; environmental conditions play an important role in their regulation. In this study, and for the first time, global transcriptomic analysis was performed on ligated intestinal loops in chickens colonized with a netB-positive C. perfringens strain, as well as the same strain propagated in vitro under various nutritional and environmental conditions. Analysis of the respective pathogen transcriptomes revealed up to 673 genes that were significantly expressed in vivo. Gene expression profiles in vivo were most similar to those of C. perfringens grown in nutritionally-deprived conditions. Taken together, our results suggest a bacterial transcriptome responses to the early stages of adaptation, and colonization of, the chicken intestine. Our work also reveals how netB-positive C. perfringens reacts to different environmental conditions including those in the chicken intestine.

RasGRP1 opposes proliferative EGFR–SOS1–Ras signals and restricts intestinal epithelial cell growth

PubMed Central

Depeille, Philippe; Henricks, Linda M.; van de Ven, Robert A. H.; Lemmens, Ed; Wang, Chih-Yang; Matli, Mary; Werb, Zena; Haigis, Kevin M.; Donner, David; Warren, Robert; Roose, Jeroen P.

2015-01-01

The character of EGFR signals can influence cell fate but mechanistic insights into intestinal EGFR-Ras signalling are limited. Here we show that two distinct Ras nucleotide exchange factors, RasGRP1 and SOS1, lie downstream of EGFR but act in functional opposition. RasGRP1 is expressed in intestinal crypts where it restricts epithelial growth. High RasGRP1 expression in colorectal cancer (CRC) patient samples correlates with a better clinical outcome. Biochemically, we find that RasGRP1 creates a negative feedback loop that limits proliferative EGFR–SOS1–Ras signals in CRC cells. Genetic Rasgrp1 depletion from mice with either an activating mutation in KRas or with aberrant Wnt signalling due to a mutation in Apc resulted in both cases in exacerbated Ras–ERK signalling and cell proliferation. The unexpected opposing cell biological effects of EGFR–RasGRP1 and EGFR–SOS1 signals in the same cell shed light on the intricacy of EGFR-Ras signalling in normal epithelium and carcinoma. PMID:26005835

Elucidating pathways of Toxoplasma gondii invasion in the gastrointestinal tract: involvement of the tight junction protein occludin.

PubMed

Weight, Caroline M; Jones, Emily J; Horn, Nikki; Wellner, Nikolaus; Carding, Simon R

2015-10-01

Toxoplasma gondii is an obligate intracellular parasite infecting one third of the world's population. The small intestine is the parasite's primary route of infection, although the pathway of epithelium transmigration remains unclear. Using an in vitro invasion assay and live imaging we showed that T. gondii (RH) tachyzoites infect and transmigrate between adjacent intestinal epithelial cells in polarized monolayers without altering barrier integrity, despite eliciting the production of specific inflammatory mediators and chemokines. During invasion, T. gondii co-localized with occludin. Reducing the levels of endogenous cellular occludin with specific small interfering RNAs significantly reduced the ability of T. gondii to penetrate between and infect epithelial cells. Furthermore, an in vitro invasion and binding assays using recombinant occludin fragments established the capacity of the parasite to bind occludin and in particular to the extracellular loops of the protein. These findings provide evidence for occludin playing a role in the invasion of T. gondii in small intestinal epithelial cells. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Protons act as a transmitter for muscle contraction in C. elegans.

PubMed

Beg, Asim A; Ernstrom, Glen G; Nix, Paola; Davis, M Wayne; Jorgensen, Erik M

2008-01-11

Muscle contraction is normally mediated by the release of neurotransmitters from motor neurons. Here we demonstrate that protons can act as a direct transmitter from intestinal cells to stimulate muscle contraction. During the C. elegans defecation motor program the posterior body muscles contract even in the absence of neuronal inputs or vesicular neurotransmission. In this study, we demonstrate that the space between the intestine and the muscle is acidified just prior to muscle contraction and that the release of caged protons is sufficient to induce muscle contraction. PBO-4 is a putative Na+/H+ ion exchanger expressed on the basolateral membrane of the intestine, juxtaposed to the posterior body muscles. In pbo-4 mutants the extracellular space is not acidified and the muscles fail to contract. The pbo-5 and pbo-6 genes encode subunits of a "cys-loop" proton-gated cation channel required for muscles to respond to acidification. In heterologous expression assays the PBO receptor is half-maximally activated at a pH of 6.8. The identification of the mechanisms for release and reception of proton signals establishes a highly unusual mechanism for intercellular communication.

Effect of Npt2b deletion on intestinal and renal inorganic phosphate (Pi) handling.

PubMed

Ikuta, Kayo; Segawa, Hiroko; Sasaki, Shohei; Hanazaki, Ai; Fujii, Toru; Kushi, Aoi; Kawabata, Yuka; Kirino, Ruri; Sasaki, Sumire; Noguchi, Miwa; Kaneko, Ichiro; Tatsumi, Sawako; Ueda, Otoya; Wada, Naoko A; Tateishi, Hiromi; Kakefuda, Mami; Kawase, Yosuke; Ohtomo, Shuichi; Ichida, Yasuhiro; Maeda, Akira; Jishage, Kou-Ichi; Horiba, Naoshi; Miyamoto, Ken-Ichi

2018-06-01

Hyperphosphatemia is common in chronic kidney disease and is associated with morbidity and mortality. The intestinal Na + -dependent phosphate transporter Npt2b is thought to be an important molecular target for the prevention of hyperphosphatemia. The role of Npt2b in the net absorption of inorganic phosphate (Pi), however, is controversial. In the present study, we made tamoxifen-inducible Npt2b conditional knockout (CKO) mice to analyze systemic Pi metabolism, including intestinal Pi absorption. Although the Na + -dependent Pi transport in brush-border membrane vesicle uptake levels was significantly decreased in the distal intestine of Npt2b CKO mice compared with control mice, plasma Pi and fecal Pi excretion levels were not significantly different. Data obtained using the intestinal loop technique showed that Pi uptake in Npt2b CKO mice was not affected at a Pi concentration of 4 mM, which is considered the typical luminal Pi concentration after meals in mice. Claudin, which may be involved in paracellular pathways, as well as claudin-2, 12, and 15 protein levels were significantly decreased in the Npt2b CKO mice. Thus, Npt2b deficiency did not affect Pi absorption within the range of Pi concentrations that normally occurs after meals. These findings indicate that abnormal Pi metabolism may also be involved in tight junction molecules such as Cldns that are affected by Npt2b deficiency.

Down-regulation of NF-κB signaling by Gordonia bronchialis prevents the activation of gut epithelial cells.

PubMed

Smaldini, Paola L; Stanford, John; Romanin, David E; Fossati, Carlos A; Docena, Guillermo H

2014-08-01

The immunomodulatory power of heat-killed Gordonia bronchialis was studied on gut epithelial cells activated with pro-inflammatory stimuli (flagellin, TNF-α or IL-1β). Light emission of luciferase-transfected epithelial cells and mRNA expression of IL-1β, TNF-α, IL-6, CCL20, IL-8 and MCP-1 were measured. NF-κB activation was assessed by immunofluorescence and immunoblotting, and induction of reactive oxygen species (ROS) was evaluated. In vivo inhibitory properties of G. bronchialis were studied with ligated intestinal loop assay and in a mouse model of food allergy. G. bronchialis promoted the down-regulation of the expression of CCL20 and IL-1β on activated epithelial cells in a dose-dependent manner. A concomitant blocking of nuclear p65 translocation with increased production of ROS was found. In vivo experiments confirmed the inhibition of CCL20 expression and the suppression of IgE sensitization and hypersensitivity symptoms in the food allergy mouse model. In conclusion, heat-killed G. bronchialis inhibited the activation of NF-κB pathway in human epithelial cells, and suppressed the expression of CCL20. These results indicate that G. bronchialis may be used to modulate the initial steps of innate immune activation, which further suppress the allergic sensitization. This approach may be exploited as a therapy for intestinal inflammation. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Modulating effect of polyethylene glycol on the intestinal transport and absorption of prednisolone, methylprednisolone and quinidine in rats by in-vitro and in-situ absorption studies.

PubMed

Shen, Qi; Li, Wenji; Lin, Yulian; Katsumi, Hidemasa; Okada, Naoki; Sakane, Toshiyasu; Fujita, Takuya; Yamamoto, Akira

2008-12-01

The effects of polyethylene glycol 20000 (PEG 20000) on the intestinal absorption of prednisolone, methylprednisolone and quinidine, three P-glycoprotein (P-gp) substrates, across the isolated rat intestinal membranes were examined by an in-vitro diffusion chamber system. The serosal-to-mucosal (secretory) transport of these P-gp substrates was greater than their mucosal-to-serosal (absorptive) transport, indicating that their net movement across the intestinal membranes was preferentially in the secretory direction. The polarized secretory transport of these drugs was remarkably diminished and their efflux ratios decreased in the presence of PEG 20000. In addition, PEG 20000 did not affect the transport of Lucifer yellow, a non-P-gp substrate. The intestinal membrane toxicity of PEG 20000 was evaluated by measuring the release of alkaline phosphatase (ALP) and protein from the intestinal membranes. The release of ALP and protein was enhanced in the presence of 20 mM sodium deoxycholate (NaDC), a positive control, while these biological parameters did not change in the presence of 0.1-5% (w/v) PEG 20000. These findings indicated that the intestinal membrane damage caused by PEG 20000 was not a main reason for the enhanced absorptive transport of these P-gp substrates in the presence of PEG 20000. Furthermore, the transepithelial electrical resistance (TEER) of rat jejunal membranes in the presence or absence of PEG 20000 was measured by a diffusion chamber method. PEG 20000 (0.1-5.0 % w/v) did not change the TEER values of the rat jejunal membranes, indicating that the increase in the absorptive transport of these P-gp substrates might not be due to the increased transport of these P-gp substrates via a paracellular pathway caused by PEG 20000. Finally, the effect of PEG 20000 on the intestinal absorption of quinidine was examined by an in-situ closed-loop method. The intestinal absorption of quinidine was significantly enhanced in the presence of 0.1-1.0% (w/v) PEG 20000. These findings suggest that PEG 20000 might be a useful excipient to improve the intestinal absorption of quinidine, which is mainly secreted by a P-gp-mediated efflux system in the intestine.

On the nature of fast sausage waves in coronal loops

NASA Astrophysics Data System (ADS)

Bahari, Karam

2018-05-01

The effect of the parameters of coronal loops on the nature of fast sausage waves are investigated. To do this three models of the coronal loop considered, a simple loop model, a current-carrying loop model and a model with radially structured density called "Inner μ" profile. For all the models the Magnetohydrodynamic (MHD) equations solved analytically in the linear approximation and the restoring forces of oscillations obtained. The ratio of the magnetic tension force to the pressure gradient force obtained as a function of the distance from the axis of the loop. In the simple loop model for all values of the loop parameters the fast sausages wave have a mixed nature of Alfvénic and fast MHD waves, in the current-carrying loop model with thick annulus and low density contrast the fast sausage waves can be considered as purely Alfvénic wave in the core region of the loop, and in the "Inner μ" profile for each set of the parameters of the loop the wave can be considered as a purely Alfvénic wave in some regions of the loop.

The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model.

PubMed

Kwak, Dong Shin; Lee, Oh Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon

2016-05-23

DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.

Guanylyl Cyclase C Hormone Axis at the Intersection of Obesity and Colorectal Cancer.

PubMed

Blomain, Erik S; Merlino, Dante J; Pattison, Amanda M; Snook, Adam E; Waldman, Scott A

2016-09-01

Obesity has emerged as a principal cause of mortality worldwide, reflecting comorbidities including cancer risk, particularly in colorectum. Although this relationship is established epidemiologically, molecular mechanisms linking colorectal cancer and obesity continue to be refined. Guanylyl cyclase C (GUCY2C), a membrane-bound guanylyl cyclase expressed in intestinal epithelial cells, binds the paracrine hormones guanylin and uroguanylin, inducing cGMP signaling in colorectum and small intestine, respectively. Guanylin is the most commonly lost gene product in sporadic colorectal cancer, and its universal loss early in transformation silences GUCY2C, a tumor suppressor, disrupting epithelial homeostasis underlying tumorigenesis. In small intestine, eating induces endocrine secretion of uroguanylin, the afferent limb of a novel gut-brain axis that activates hypothalamic GUCY2C-cGMP signaling mediating satiety opposing obesity. Recent studies revealed that diet-induced obesity suppressed guanylin and uroguanylin expression in mice and humans. Hormone loss reflects reversible calorie-induced endoplasmic reticulum stress and the associated unfolded protein response, rather than the endocrine, adipokine, or inflammatory milieu of obesity. Loss of intestinal uroguanylin secretion silences the hypothalamic GUCY2C endocrine axis, creating a feed-forward loop contributing to hyperphagia in obesity. Importantly, calorie-induced guanylin loss silences the GUCY2C-cGMP paracrine axis underlying obesity-induced epithelial dysfunction and colorectal tumorigenesis. Indeed, genetically enforced guanylin replacement eliminated diet-induced intestinal tumorigenesis in mice. Taken together, these observations suggest that GUCY2C hormone axes are at the intersection of obesity and colorectal cancer. Moreover, they suggest that hormone replacement that restores GUCY2C signaling may be a novel therapeutic paradigm to prevent both hyperphagia and intestinal tumorigenesis in obesity. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Guanylyl Cyclase C Hormone Axis at the Intersection of Obesity and Colorectal Cancer

PubMed Central

Blomain, Erik S.; Merlino, Dante J.; Pattison, Amanda M.; Snook, Adam E.

2016-01-01

Obesity has emerged as a principal cause of mortality worldwide, reflecting comorbidities including cancer risk, particularly in colorectum. Although this relationship is established epidemiologically, molecular mechanisms linking colorectal cancer and obesity continue to be refined. Guanylyl cyclase C (GUCY2C), a membrane-bound guanylyl cyclase expressed in intestinal epithelial cells, binds the paracrine hormones guanylin and uroguanylin, inducing cGMP signaling in colorectum and small intestine, respectively. Guanylin is the most commonly lost gene product in sporadic colorectal cancer, and its universal loss early in transformation silences GUCY2C, a tumor suppressor, disrupting epithelial homeostasis underlying tumorigenesis. In small intestine, eating induces endocrine secretion of uroguanylin, the afferent limb of a novel gut-brain axis that activates hypothalamic GUCY2C-cGMP signaling mediating satiety opposing obesity. Recent studies revealed that diet-induced obesity suppressed guanylin and uroguanylin expression in mice and humans. Hormone loss reflects reversible calorie-induced endoplasmic reticulum stress and the associated unfolded protein response, rather than the endocrine, adipokine, or inflammatory milieu of obesity. Loss of intestinal uroguanylin secretion silences the hypothalamic GUCY2C endocrine axis, creating a feed-forward loop contributing to hyperphagia in obesity. Importantly, calorie-induced guanylin loss silences the GUCY2C-cGMP paracrine axis underlying obesity-induced epithelial dysfunction and colorectal tumorigenesis. Indeed, genetically enforced guanylin replacement eliminated diet-induced intestinal tumorigenesis in mice. Taken together, these observations suggest that GUCY2C hormone axes are at the intersection of obesity and colorectal cancer. Moreover, they suggest that hormone replacement that restores GUCY2C signaling may be a novel therapeutic paradigm to prevent both hyperphagia and intestinal tumorigenesis in obesity. PMID:27251363

Intestinal Permeability of β-Lapachone and Its Cyclodextrin Complexes and Physical Mixtures.

PubMed

Mangas-Sanjuan, Victor; Gutiérrez-Nieto, Jorge; Echezarreta-López, Magdalena; González-Álvarez, Isabel; González-Álvarez, Marta; Casabó, Vicente-Germán; Bermejo, Marival; Landin, Mariana

2016-12-01

β-Lapachone (βLAP) is a promising, poorly soluble, antitumoral drug. βLAP combination with cyclodextrins (CDs) improves its solubility and dissolution but there is not enough information about the impact of cyclodextrins on βLAP intestinal permeability. The objectives of this work were to characterize βLAP intestinal permeability and to elucidate cyclodextrins effect on the dissolution properties and on the intestinal permeability. The final goal was to evaluate CDs influence on the oral absorption of βLAP. Binary systems (physical mixtures and inclusion complexes) including βLAP and CDs (β-cyclodextrin: βCD, random-methyl-β-cyclodextrin: RMβCD and sulfobutylether-β-cyclodextrin: SBEβCD) have been prepared and analysed by differential scanning calorimetry. βLAP (and its combinations with CDs) absorption rate coefficients and effective permeability values have been determined in vitro in MDCK or MDCK-Mdr1 monolayers and in situ in rat by a closed loop perfusion technique. DSC results confirmed the formation of the inclusion complexes. βLAP-CDs inclusion complexes improve drug solubility and dissolution rate in comparison with physical mixtures. βLAP presented a high permeability value which can provide complete oral absorption. Its oral absorption is limited by its low solubility and dissolution rate. Cyclodextrin (both as physical mixtures and inclusion complexes) showed a positive effect on the intestinal permeability of βLAP. Complexation with CDs does not reduce βLAP intestinal permeability in spite of the potential negative effect of the reduction in free fraction of the drug. The use of RMβCD or SBEβCD inclusion complexes could benefit βLAP oral absorption by enhancing its solubility, dissolution rate and permeability.

Waardenburg syndrome presenting with constipation since birth.

PubMed

Gupta, R; Sharma, S B; Mathur, P; Agrawal, L D

2014-12-01

Shah-Waardenburg syndrome is Waardenburg syndrome associated with Hirschsprung's disease. A 10-day-old full-term male neonate of Waardenburg syndrome presented with constipation since birth along with features of small bowel obstruction. Exploratory laparotomy revealed distended proximal jejunal and ileal loops along with microcolon; an ileostomy was performed. Postoperatively patient developed sepsis and died. Histopathology confirmed total colonic aganglionosis. Suspect familial Shah-Waardenburg syndrome in a neonate of Waardenburg syndrome presenting with constipation since birth or intestinal obstruction.

Epithelial cell kinase-B61: an autocrine loop modulating intestinal epithelial migration and barrier function.

PubMed

Rosenberg, I M; Göke, M; Kanai, M; Reinecker, H C; Podolsky, D K

1997-10-01

Epithelial cell kinase (Eck) is a member of a large family of receptor tyrosine kinases whose functions remain largely unknown. Expression and regulation of Eck and its cognate ligand B61 were analyzed in the human colonic adenocarcinoma cell line Caco-2. Immunocytochemical staining demonstrated coexpression of Eck and B61 in the same cells, suggestive of an autocrine loop. Eck levels were maximal in preconfluent cells. In contrast, B61 levels were barely detectable in preconfluent cells and increased progressively after the cells reached confluence. Caco-2 cells cultured in the presence of added B61 showed a significant reduction in the levels of dipeptidyl peptidase and sucrase-isomaltase mRNA, markers of Caco-2 cell differentiation. Cytokines interleukin-1beta (IL-1beta), basic fibroblast growth factor, IL-2, epidermal growth factor, and transforming growth factor-beta modulated steady-state levels of Eck and B61 mRNA and regulated Eck activation as assessed by tyrosine phosphorylation. Functionally, stimulation of Eck by B61 resulted in increased proliferation, enhanced barrier function, and enhanced restitution of injured epithelial monolayers. These results suggest that the Eck-B61 interaction, a target of regulatory peptides, plays a role in intestinal epithelial cell development, migration, and barrier function, contributing to homeostasis and preservation of continuity of the epithelial barrier.

Assessment of inflammatory activity in Crohn's disease by means of dynamic contrast-enhanced MRI.

PubMed

Pupillo, V A; Di Cesare, E; Frieri, G; Limbucci, N; Tanga, M; Masciocchi, C

2007-09-01

Our aim was to perform a dynamic study of contrast enhancement of the intestinal wall in patients with Crohn's disease to quantitatively assess local inflammatory activity. We studied a population of 50 patients with histologically proven Crohn's disease. Magnetic resonance imaging (MRI) was performed using a 1.5-T magnet with a phased-array coil and acquisition of T2-weighted single-shot fast spin echo (SSFSE) half Fourier sequences before intravenous administration of gadolinium, and T1-weighted fast spoiled gradient (FSPGR) fat-saturated sequences before and after contrast administration. Before the examination, patents received oral polyethylene glycol (PEG) (1,000 ml for adults; 10 ml/Kg of body weight for children). Regions of interest (ROI) were placed on the normal and diseased intestinal wall to assess signal intensity and rate of increase in contrast enhancement over time. Data were compared with the Crohn's Disease Activity Index (CDAI). The diseased bowel wall showed early and intense uptake of contrast that increases over time until a plateau is reached. In patients in the remission phase after treatment, signal intensity was only slightly higher in diseased bowel loops than in healthy loops. There was a significant correlation between the peak of contrast uptake and CDAI. Dynamic MRI is a good technique for quantifying local inflammatory activity of bowel wall in patients with Crohn's disease.

Analytical model development for the prediction of the frictional resistance of a capsule endoscope inside an intestine.

PubMed

Kim, J S; Sung, I H; Kim, Y T; Kim, D E; Jang, Y H

2007-11-01

For the purpose of optimizing the design of the locomotion mechanism as well as the body shape of a self-propelled capsule endoscope, an analytical model for the prediction of frictional resistance of the capsule moving inside the small intestine was first developed. The model was developed by considering the contact geometry and viscoelasticity of the intestine, based on the experimental investigations on the material properties of the intestine and the friction of the capsule inside the small intestine. In order to verify the model and to investigate the distributions of various stress components applied to the capsule, finite element (FE) analyses were carried out. The comparison of the frictional resistance between the predicted and the experimental values suggested that the proposed model could predict the frictional force of the capsule with reasonable accuracy. Also, the FE analysis results of various stress components revealed the stress relaxation of the intestine and explained that such stress relaxation characteristics of the intestine resulted in lower frictional force as the speed of the capsule decreased. These results suggested that the frontal shape of the capsule was critical to the design of the capsule with desired frictional performance. It was shown that the proposed model can provide quantitative estimation of the frictional resistance of the capsule under various moving conditions inside the intestine. The model is expected to be useful in the design optimization of the capsule locomotion inside the intestine.

Intestinal absorption of hawthorn flavonoids--in vitro, in situ and in vivo correlations.

PubMed

Zuo, Zhong; Zhang, Li; Zhou, Limin; Chang, Qi; Chow, Moses

2006-11-25

Our previous studies identified hyperoside (HP), isoquercitrin (IQ) and epicatechin (EC) to be the major active flavonoid components of the hawthorn phenolic extract from hawthorn fruits demonstrating inhibitory effect on in vitro Cu(+2)-mediated low density lipoproteins oxidation. Among these three hawthorn flavonoids, EC was the only one detectable in plasma after the oral administration of hawthorn phenolic extract to rats. The present study aims to investigate the intestinal absorption mechanisms of these three hawthorn flavonoids by in vitro Caco-2 monolayer model, rat in situ intestinal perfusion model and in vivo pharmacokinetics studies in rats. In addition, in order to investigate the effect of the co-occurring components in hawthorn phenolic extract on the intestinal absorption of these three major hawthorn flavonoids, intestinal absorption transport profiles of HP, IQ and EC in forms of individual pure compound, mixture of pure compounds and hawthorn phenolic extract were studied and compared. The observations from in vitro Caco-2 monolayer model and in situ intestinal perfusion model indicated that all three studied hawthorn flavonoids have quite limited permeabilities. EC and IQ demonstrated more extensive metabolism in the rat in situ intestinal perfusion model and in vivo study than in Caco-2 monolayer model. Moreover, results from the Caco-2 monolayer model, rat in situ intestinal perfusion model as well as the in vivo pharmacokinetics studies in rats consistently showed that the co-occurring components in hawthorn phenolic extract might not have significant effect on the intestinal absorption of the three major hawthorn flavonoids studied.

Effects of Digested Onion Extracts on Intestinal Gene Expression: An Interspecies Comparison Using Different Intestine Models

PubMed Central

Govers, Coen; van der Meulen, Jan; van Hoef, Angeline; Stoopen, Geert; Hamers, Astrid; Hoekman, Arjan; de Vos, Ric; Bovee, Toine F. H.; Smits, Mari; Mes, Jurriaan J.

2016-01-01

Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, we explored the applicability of in vitro (human Caco-2 cells) and ex vivo intestine models (rat precision cut intestine slices and the pig in-situ small intestinal segment perfusion (SISP) technique) to study the effect of food compounds. In vitro digested yellow (YOd) and white onion extracts (WOd) were used as model food compounds and transcriptomics was applied to obtain more insight into which extent mode of actions depend on the model. The three intestine models shared 9,140 genes which were used to compare the responses to digested onions between the models. Unsupervised clustering analysis showed that genes up- or down-regulated by WOd in human Caco-2 cells and rat intestine slices were similarly regulated by YOd, indicating comparable modes of action for the two onion species. Highly variable responses to onion were found in the pig SISP model. By focussing only on genes with significant differential expression, in combination with a fold change > 1.5, 15 genes showed similar onion-induced expression in human Caco-2 cells and rat intestine slices and 2 overlapping genes were found between the human Caco-2 and pig SISP model. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions in all three models. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Taken together, our data indicate that each of the in vitro and ex vivo intestine models used in this study, taking into account their limitations, can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies. PMID:27631494

Effects of Digested Onion Extracts on Intestinal Gene Expression: An Interspecies Comparison Using Different Intestine Models.

PubMed

de Wit, Nicole J W; Hulst, Marcel; Govers, Coen; van der Meulen, Jan; van Hoef, Angeline; Stoopen, Geert; Hamers, Astrid; Hoekman, Arjan; de Vos, Ric; Bovee, Toine F H; Smits, Mari; Mes, Jurriaan J; Hendriksen, Peter J M

2016-01-01

Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, we explored the applicability of in vitro (human Caco-2 cells) and ex vivo intestine models (rat precision cut intestine slices and the pig in-situ small intestinal segment perfusion (SISP) technique) to study the effect of food compounds. In vitro digested yellow (YOd) and white onion extracts (WOd) were used as model food compounds and transcriptomics was applied to obtain more insight into which extent mode of actions depend on the model. The three intestine models shared 9,140 genes which were used to compare the responses to digested onions between the models. Unsupervised clustering analysis showed that genes up- or down-regulated by WOd in human Caco-2 cells and rat intestine slices were similarly regulated by YOd, indicating comparable modes of action for the two onion species. Highly variable responses to onion were found in the pig SISP model. By focussing only on genes with significant differential expression, in combination with a fold change > 1.5, 15 genes showed similar onion-induced expression in human Caco-2 cells and rat intestine slices and 2 overlapping genes were found between the human Caco-2 and pig SISP model. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions in all three models. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Taken together, our data indicate that each of the in vitro and ex vivo intestine models used in this study, taking into account their limitations, can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies.

Coronal Loops: Observations and Modeling of Confined Plasma.

PubMed

Reale, Fabio

Coronal loops are the building blocks of the X-ray bright solar corona. They owe their brightness to the dense confined plasma, and this review focuses on loops mostly as structures confining plasma. After a brief historical overview, the review is divided into two separate but not independent parts: the first illustrates the observational framework, the second reviews the theoretical knowledge. Quiescent loops and their confined plasma are considered and, therefore, topics such as loop oscillations and flaring loops (except for non-solar ones, which provide information on stellar loops) are not specifically addressed here. The observational section discusses the classification, populations, and the morphology of coronal loops, its relationship with the magnetic field, and the loop stranded structure. The section continues with the thermal properties and diagnostics of the loop plasma, according to the classification into hot, warm, and cool loops. Then, temporal analyses of loops and the observations of plasma dynamics, hot and cool flows, and waves are illustrated. In the modeling section, some basics of loop physics are provided, supplying fundamental scaling laws and timescales, a useful tool for consultation. The concept of loop modeling is introduced and models are divided into those treating loops as monolithic and static, and those resolving loops into thin and dynamic strands. More specific discussions address modeling the loop fine structure and the plasma flowing along the loops. Special attention is devoted to the question of loop heating, with separate discussion of wave (AC) and impulsive (DC) heating. Large-scale models including atmosphere boxes and the magnetic field are also discussed. Finally, a brief discussion about stellar coronal loops is followed by highlights and open questions.

Targeting immunoproteasome and glutamine supplementation prevent intestinal hyperpermeability.

PubMed

Ghouzali, Ibtissem; Lemaitre, Caroline; Bahlouli, Wafa; Azhar, Saïda; Bôle-Feysot, Christine; Meleine, Mathieu; Ducrotté, Philippe; Déchelotte, Pierre; Coëffier, Moïse

2017-01-01

Intestinal hyperpermeability has been reported in several intestinal and non-intestinal disorders. We aimed to investigate the role of the ubiquitin proteasome system in gut barrier regulation in two mice models: the water avoidance stress model (WAS) and a post-inflammatory model (post-TNBS). Both models were applied in C57BL/6 male mice (n=7-8/group); Proteasome was targeted by injection of a selective proteasome inhibitor or by using knock-out mice for β2i proteasome subunit. Finally, glutamine supplementation was evaluated. In both models (WAS at day 10, post-TNBS at day 28), we observed an increase in proteasome trypsin-like activity and in inducible β2/constitutive β2 subunit protein expression ratio, associated with an increase in intestinal permeability. Moreover, intestinal hyperpermeability was blunted by intraperitoneal injection of selective proteasome inhibitor in WAS and post-TNBS mice. Of note, knock-out mice for the β2i subunit exhibited a significant decrease in intestinal permeability and fecal pellet output during WAS. Glutamine supplementation also improved colonic permeability in both models. In conclusion, the proteasome system is altered in the colonic mucosa of WAS and post-TNBS mice with increased trypsin-like activity. Associated intestinal hyperpermeability was blunted by immunoproteasome inhibition. Copyright © 2016 Elsevier B.V. All rights reserved.

Evidence for Nonuniform Heating of Coronal Loops Inferred from Multithread Modeling of TRACE Data

NASA Astrophysics Data System (ADS)

Aschwanden, Markus J.; Nightingale, Richard W.; Alexander, David

2000-10-01

The temperature Te(s) and density structure ne(s) of active region loops in EUV observed with TRACE is modeled with a multithread model, synthesized from the summed emission of many loop threads that have a distribution of maximum temperatures and that satisfy the steady state Rosner-Tucker-Vaiana (RTV) scaling law, modified by Serio et al. for gravitational stratification (called RTVSp in the following). In a recent Letter, Reale & Peres demonstrated that this method can explain the almost isothermal appearance of TRACE loops (observed by Lenz et al.) as derived from the filter-ratio method. From model-fitting of the 171 and 195 Å fluxes of 41 loops, which have loop half-lengths in the range of L=4-320 Mm, we find that (1) the EUV loops consist of near-isothermal loop threads with substantially smaller temperature gradients than are predicted by the RTVSp model; (2) the loop base pressure, p0~0.3+/-0.1 dynes cm-2, is independent of the loop length L, and it agrees with the RTVSp model for the shortest loops but exceeds the RTVSp model up to a factor of 35 for the largest loops; and (3) the pressure scale height is consistent with hydrostatic equilibrium for the shortest loops but exceeds the temperature scale height up to a factor of ~3 for the largest loops. The data indicate that cool EUV loops in the temperature range of Te~0.8-1.6 MK cannot be explained with the static steady state RTVSp model in terms of uniform heating but are fully consistent with Serio's model in the case of nonuniform heating (RTVSph), with heating scale heights in the range of sH=17+/-6 Mm. This heating function provides almost uniform heating for small loops (L<~20 Mm), but restricts heating to the footpoints of large loops (L~50-300 Mm).

The protective activity of tea against infection by Vibrio cholerae O1.

PubMed

Toda, M; Okubo, S; Ikigai, H; Suzuki, T; Suzuki, Y; Shimamura, T

1991-02-01

Extracts of black tea exhibited bactericidal activity against Vibrio cholerae O1. The tea extract inhibited the haemolysin activity of V. cholerae O1, El Tor and the morphological changes of Chinese hamster ovary cells induced by cholera toxin. Tea extract also reduced fluid accumulation induced by cholera toxin in sealed adult mice and by V. cholerae O1 in ligated intestinal loops of rabbits. These findings suggest that tea has protective activity against V. cholerae O1.

Report of a Case and Review of Literature of Internal Hernia through Peritoneal Defect in Pouch of Douglas: A Rare Occurrence.

PubMed

Muthukumar, Vamseedharan; Venugopal, Sarveswaran; Subramaniam, Surees Kumar

2017-01-01

Intestinal obstruction attributable to internal hernia as a cause is a rare phenomenon with a reported incidence of 0.6%-5.8%. Internal hernias ensuing as a result of defect in the pouch of Douglas is extremely rare with only six such cases reported so far in the literature. We present a case of 74-year-old posthysterectomy status female who presented with features of intestinal obstruction. Intraoperatively, the site of obstruction was found to be a rent in the peritoneum of the pouch of Douglas through which a loop of ileum was found herniating. The viability of the bowel was confirmed, and the defect was closed. The postoperative course was uneventful. This report presents an extremely rare type of internal hernia caused by defect in the pouch of Douglas and review of the literature so far available.

Repeat laparotomy for the treatment of septic peritonitis in a Bornean orangutan (Pongo pygmaeus pygmaeus).

PubMed

Pollock, Patrick J; Doyle, Ronan; Tobin, Emma; Davison, Kate; Bainbridge, John

2008-09-01

A 9-yr-old female Bornean orangutan (Pongo pygmaeus pygmaeus) presented with a 48-hr history of depression, lethargy, anorexia, and mucoid discharge from the rectum. Clinical, radiographic, and ultrasonographic examination demonstrated the presence of multiple distended loops of intestine, intestinal adhesions, and free gas within the abdomen. During exploratory laparotomy, fibrinopurulent diffuse peritonitis as a result of a ruptured intrapelvic abscess with associated large bowel adhesions was evident. The abdomen was thoroughly lavaged, necrotic debris and abscess wall removed, and fibrinous adhesions disrupted. The orangutan was kept sedated for 48 hr to allow for intensive care. Six months later, when the orangutan presented with similar clinical signs, ultrasonographic examination demonstrated the presence of a pelvic abscess. The previous procedure was repeated with the addition of a hysterectomy. This report is the first documentation of long-term management following surgical intervention for internal abdominal abscessation and septic peritonitis in a great ape.

Strangulating intestinal obstructions in four captive elephants (Elephas maximus and Loxodonta africana).

PubMed

Wiedner, Ellen B; Peddie, James; Peddie, Linda Reeve; Abou-Madi, Noha; Kollias, George V; Doyle, Charles; Lindsay, William A; Isaza, Ramiro; Terrell, Scott; Lynch, Tim M; Johnson, Kari; Johnson, Gary; Sammut, Charlie; Daft, Barbara; Uzal, Francisco

2012-03-01

Three captive-born (5-day-old, 8-day-old, and 4-yr-old) Asian elephants (Elephas maximus) and one captive-born 22-yr-old African elephant (Loxodonta africana) from three private elephant facilities and one zoo in the United States presented with depression, anorexia, and tachycardia as well as gastrointestinal signs of disease including abdominal distention, decreased borborygmi, tenesmus, hematochezia, or diarrhea. All elephants showed some evidence of discomfort including agitation, vocalization, or postural changes. One animal had abnormal rectal findings. Nonmotile bowel loops were seen on transabdominal ultrasound in another case. Duration of signs ranged from 6 to 36 hr. All elephants received analgesics and were given oral or rectal fluids. Other treatments included warm-water enemas or walking. One elephant underwent exploratory celiotomy. Three animals died, and the elephant taken to surgery was euthanized prior to anesthetic recovery. At necropsy, all animals had severe, strangulating intestinal lesions.

HIV-1 evades virus-specific IgG2 and IgA class switching by targeting systemic and intestinal B cells via long-range intercellular conduits

PubMed Central

Xu, Weifeng; Santini, Paul A.; Sullivan, John S.; He, Bing; Shan, Meimei; Ball, Susan C.; Dyer, Wayne B.; Ketas, Thomas J.; Chadburn, Amy; Cohen-Gould, Leona; Knowles, Daniel M.; Chiu, April; Sanders, Rogier W.; Chen, Kang; Cerutti, Andrea

2009-01-01

Contact-dependent communication between immune cells generates protection, but also facilitates viral spread. We found that macrophages formed long-range actin-propelled conduits in response to negative factor (Nef), a human immunodeficiency virus type-1 (HIV-1) protein with immunosuppressive functions. Conduits attenuated immunoglobulin G2 (IgG2) and IgA class switching in systemic and intestinal lymphoid follicles by shuttling Nef from infected macrophages to B cells through a guanine exchange factor-dependent pathway involving the amino-terminal anchor, central core and carboxy-terminal flexible loop of Nef. By showing stronger virus-specific IgG2 and IgA responses in patients harboring Nef-deficient virions, our data suggest that HIV-1 exploits intercellular highways as a “Trojan horse” to deliver Nef to B cells and evade humoral immunity systemically and at mucosal sites of entry. PMID:19648924

Geometric estimation of intestinal contraction for motion tracking of video capsule endoscope

NASA Astrophysics Data System (ADS)

Mi, Liang; Bao, Guanqun; Pahlavan, Kaveh

2014-03-01

Wireless video capsule endoscope (VCE) provides a noninvasive method to examine the entire gastrointestinal (GI) tract, especially small intestine, where other endoscopic instruments can barely reach. VCE is able to continuously provide clear pictures in short fixed intervals, and as such researchers have attempted to use image processing methods to track the video capsule in order to locate the abnormalities inside the GI tract. To correctly estimate the speed of the motion of the endoscope capsule, the radius of the intestinal track must be known a priori. Physiological factors such as intestinal contraction, however, dynamically change the radius of the small intestine, which could bring large errors in speed estimation. In this paper, we are aiming to estimate the radius of the contracted intestinal track. First a geometric model is presented for estimating the radius of small intestine based on the black hole on endoscopic images. To validate our proposed model, a 3-dimentional virtual testbed that emulates the intestinal contraction is then introduced in details. After measuring the size of the black holes on the test images, we used our model to esimate the radius of the contracted intestinal track. Comparision between analytical results and the emulation model parameters has verified that our proposed method could preciously estimate the radius of the contracted small intestine based on endoscopic images.

An update on the potential role of intestinal first-pass metabolism for the prediction of drug-drug interactions: the role of PBPK modeling.

PubMed

Alqahtani, Saeed; Bukhari, Ishfaq; Albassam, Ahmed; Alenazi, Maha

2018-05-28

The intestinal absorption process is a combination of several events that are governed by various factors. Several transport mechanisms are involved in drug absorption through enterocytes via active and/or passive processes. The transported molecules then undergo intestinal metabolism, which together with intestinal transport may affect the systemic availability of drugs. Many studies have provided clear evidence on the significant role of intestinal first-pass metabolism on drug bioavailability and degree of drug-drug interactions (DDIs). Areas covered: This review provides an update on the role of intestinal first-pass metabolism in the oral bioavailability of drugs and prediction of drug-drug interactions. It also provides a comprehensive overview and summary of the latest update in the role of PBPK modeling in prediction of intestinal metabolism and DDIs in humans. Expert opinion: The contribution of intestinal first-pass metabolism in the oral bioavailability of drugs and prediction of DDIs has become more evident over the last few years. Several in vitro, in situ, and in vivo models have been developed to evaluate the role of first-pass metabolism and to predict DDIs. Currently, physiologically based pharmacokinetic modeling is considered the most valuable tool for the prediction of intestinal first-pass metabolism and DDIs.

Alkaline Phosphatase for the Prevention of Intestinal and Renal Injury in a Rat Model of Cardiopulmonary Bypass with Deep Hypothermic Circulatory Arrest

DTIC Science & Technology

2017-09-01

primary outcome), physiologic, and biomarker evidence of intestinal and kidney injury in this model with administration of escalating doses of bovine...these techniques is necessary for surgical repair, the associated ischemia-reperfusion injury to the intestines and kidneys can lead to substantial...prevention of intestinal and kidney injury after pediatric cardiopulmonary bypass with deep hypothermic circulatory arrest. In this model, we place 5-10kg

Biowaiver or Bioequivalence: Ambiguity in Sildenafil Citrate BCS Classification.

PubMed

Miranda, Claudia; Pérez-Rodríguez, Zenia; Hernández-Armengol, Rosario; Quiñones-García, Yaidel; Betancourt-Purón, Tania; Cabrera-Pérez, Miguel Ángel

2018-05-01

The aim of the present study is to contribute to the scientific characterization of sildenafil citrate according to the Biopharmaceutics Classification System, following the World Health Organization (WHO) guidelines for biowaivers. The solubility and intestinal permeability data of sildenafil citrate were collected from literature; however, the experimental solubility studies are inconclusive and its "high permeability" suggests an API in the borderline of BCS Class I and Class II. The pH-solubility profile was determined using the saturation shake-flask method over the pH range of 1.2-6.8 at a temperature of 37 °C in aqueous media. The intestinal permeability was determined in rat by a closed-loop in situ perfusion method (the Doluisio technique). The solubility of sildenafil citrate is pH-dependent and at pH 6.8 the dose/solubility ratio obtained does not meet the WHO criteria for "high solubility." The high permeability values obtained by in situ intestinal perfusion in rat reinforce the published permeability data for sildenafil citrate. The experimental results obtained and the data available in the literature suggest that sildenafil citrate is clearly a Class II of BCS, according to the current biopharmaceutics classification system and WHO guidance.

Protein loop modeling using a new hybrid energy function and its application to modeling in inaccurate structural environments.

PubMed

Park, Hahnbeom; Lee, Gyu Rie; Heo, Lim; Seok, Chaok

2014-01-01

Protein loop modeling is a tool for predicting protein local structures of particular interest, providing opportunities for applications involving protein structure prediction and de novo protein design. Until recently, the majority of loop modeling methods have been developed and tested by reconstructing loops in frameworks of experimentally resolved structures. In many practical applications, however, the protein loops to be modeled are located in inaccurate structural environments. These include loops in model structures, low-resolution experimental structures, or experimental structures of different functional forms. Accordingly, discrepancies in the accuracy of the structural environment assumed in development of the method and that in practical applications present additional challenges to modern loop modeling methods. This study demonstrates a new strategy for employing a hybrid energy function combining physics-based and knowledge-based components to help tackle this challenge. The hybrid energy function is designed to combine the strengths of each energy component, simultaneously maintaining accurate loop structure prediction in a high-resolution framework structure and tolerating minor environmental errors in low-resolution structures. A loop modeling method based on global optimization of this new energy function is tested on loop targets situated in different levels of environmental errors, ranging from experimental structures to structures perturbed in backbone as well as side chains and template-based model structures. The new method performs comparably to force field-based approaches in loop reconstruction in crystal structures and better in loop prediction in inaccurate framework structures. This result suggests that higher-accuracy predictions would be possible for a broader range of applications. The web server for this method is available at http://galaxy.seoklab.org/loop with the PS2 option for the scoring function.

Sequence-structure relationships in RNA loops: establishing the basis for loop homology modeling.

PubMed

Schudoma, Christian; May, Patrick; Nikiforova, Viktoria; Walther, Dirk

2010-01-01

The specific function of RNA molecules frequently resides in their seemingly unstructured loop regions. We performed a systematic analysis of RNA loops extracted from experimentally determined three-dimensional structures of RNA molecules. A comprehensive loop-structure data set was created and organized into distinct clusters based on structural and sequence similarity. We detected clear evidence of the hallmark of homology present in the sequence-structure relationships in loops. Loops differing by <25% in sequence identity fold into very similar structures. Thus, our results support the application of homology modeling for RNA loop model building. We established a threshold that may guide the sequence divergence-based selection of template structures for RNA loop homology modeling. Of all possible sequences that are, under the assumption of isosteric relationships, theoretically compatible with actual sequences observed in RNA structures, only a small fraction is contained in the Rfam database of RNA sequences and classes implying that the actual RNA loop space may consist of a limited number of unique loop structures and conserved sequences. The loop-structure data sets are made available via an online database, RLooM. RLooM also offers functionalities for the modeling of RNA loop structures in support of RNA engineering and design efforts.

Establishing Caenorhabditis elegans as a model for Mycobacterium avium subspecies hominissuis infection and intestinal colonization

PubMed Central

Everman, Jamie L.; Ziaie, Navid R.; Bechler, Jessica; Bermudez, Luiz E.

2015-01-01

ABSTRACT The nematode Caenorhabditis elegans has become a model system for studying the disease interaction between pathogens and the host. To determine whether the transparent nematode could serve as a useful model for Mycobacterium avium subspecies hominissuis (MAH) infection of the intestinal tract, worms were fed MAH and assayed for the effects of the bacterial infection on the worm. It was observed during feeding that viable MAH increases in the intestinal lumen in a time dependent manner. Ingestion of MAH was deemed non-toxic to worms as MAH-fed populations have similar survival curves to those fed E. coli strain OP50. Pulse-chase analysis using E. coli strain OP50 revealed that MAH colonize the intestinal tract, as viable MAH remain within the intestine after the assay. Visualization of intestinal MAH using histology and transmission electron microscopy demonstrates that MAH localizes to the intestinal lumen, as well as establishes direct contact with intestinal epithelium. Bacterial colonization appears to have a detrimental effect on the microvilli of the intestinal epithelial cells. The MAH ΔGPL/4B2 strain with a mutation in glycopeptidolipid production is deficient in binding to human epithelial cells (HEp-2), as well as deficient in its ability to bind to and colonize the intestinal tract of C. elegans as efficiently as wild-type MAH. These data indicate the C. elegans may serve as a useful model system for MAH pathogenesis and in determining the mechanisms used by MAH during infection and colonization of the intestinal epithelium. PMID:26405050

Oral rice-based vaccine induces passive and active immunity against enterotoxigenic E. coli-mediated diarrhea in pigs.

PubMed

Takeyama, Natsumi; Yuki, Yoshikazu; Tokuhara, Daisuke; Oroku, Kazuki; Mejima, Mio; Kurokawa, Shiho; Kuroda, Masaharu; Kodama, Toshiaki; Nagai, Shinya; Ueda, Susumu; Kiyono, Hiroshi

2015-09-22

Enterotoxigenic Escherichia coli (ETEC) causes severe diarrhea in both neonatal and weaned pigs. Because the cholera toxin B subunit (CTB) has a high level of amino acid identity to the ETEC heat-labile toxin (LT) B-subunit (LTB), we selected MucoRice-CTB as a vaccine candidate against ETEC-induced pig diarrhea. When pregnant sows were orally immunized with MucoRice-CTB, increased amounts of antigen-specific IgG and IgA were produced in their sera. CTB-specific IgG was secreted in the colostrum and transferred passively to the sera of suckling piglets. IgA antibodies in the colostrum and milk remained high with a booster dose after farrowing. Additionally, when weaned minipigs were orally immunized with MucoRice-CTB, production of CTB-specific intestinal SIgA, as well as systemic IgG and IgA, was induced. To evaluate the cross-protective effect of MucoRice-CTB against ETEC diarrhea, intestinal loop assay with ETEC was conducted. The fluid volume accumulated in the loops of minipigs immunized with MucoRice-CTB was significantly lower than that in control minipigs, indicating that MucoRice-CTB-induced cross-reactive immunity could protect weaned pigs from diarrhea caused by ETEC. MucoRice-CTB could be a candidate oral vaccine for inducing both passive and active immunity to protect both suckling and weaned piglets from ETEC diarrhea. Copyright © 2015 Elsevier Ltd. All rights reserved.

Three-Dimensional Organotypic Co-Culture Model of Intestinal Epithelial Cells and Macrophages to Study "Salmonella Enterica" Colonization Patterns

NASA Technical Reports Server (NTRS)

Ott, Mark; Yang, J; Barilla, J.; Crabbe, A.; Sarker, S. F.; Liu, Y.

2017-01-01

Three-dimensional/3-D organotypic models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by 2-D monolayers and respond to Salmonella in ways that reflect in vivo infections. To further enhance the physiological relevance of 3-D models to more closely approximate in vivo intestinal microenvironments during infection, we developed and validated a novel 3-D intestinal co-culture model containing multiple epithelial cell types and phagocytic macrophages, and applied to study enteric infection by different Salmonella pathovars.

Models of antimicrobial pressure on intestinal bacteria of the treated host populations.

PubMed

Volkova, V V; Cazer, C L; Gröhn, Y T

2017-07-01

Antimicrobial drugs are used to treat pathogenic bacterial infections in animals and humans. The by-stander enteric bacteria of the treated host's intestine can become exposed to the drug or its metabolites reaching the intestine in antimicrobially active form. We consider which processes and variables need to be accounted for to project the antimicrobial concentrations in the host's intestine. Those include: the drug's fraction (inclusive of any active metabolites) excreted in bile; the drug's fractions and intestinal segments of excretion via other mechanisms; the rates and intestinal segments of the drug's absorption and re-absorption; the rates and intestinal segments of the drug's abiotic and biotic degradation in the intestine; the digesta passage time through the intestinal segments; the rates, mechanisms, and reversibility of the drug's sorption to the digesta and enteric microbiome; and the volume of luminal contents in the intestinal segments. For certain antimicrobials, the antimicrobial activity can further depend on the aeration and chemical conditions in the intestine. Model forms that incorporate the inter-individual variation in those relevant variables can support projections of the intestinal antimicrobial concentrations in populations of treated host, such as food animals. To illustrate the proposed modeling framework, we develop two examples of treatments of bovine respiratory disease in beef steers by oral chlortetracycline and injectable third-generation cephalosporin ceftiofur. The host's diet influences the digesta passage time, volume, and digesta and microbiome composition, and may influence the antimicrobial loss due to degradation and sorption in the intestine. We consider two diet compositions in the illustrative simulations. The examples highlight the extent of current ignorance and need for empirical data on the variables influencing the selective pressures imposed by antimicrobial treatments on the host's intestinal bacteria.

Enterohemorrhagic Escherichia coli infection has donor-dependent effect on human gut microbiota and may be antagonized by probiotic yeast during interaction with Peyer's patches.

PubMed

Thévenot, J; Cordonnier, C; Rougeron, A; Le Goff, O; Nguyen, H T T; Denis, S; Alric, M; Livrelli, V; Blanquet-Diot, S

2015-11-01

Enterohemorrhagic Escherichia coli (EHEC) are major food-borne pathogens responsible for serious infections ranging from mild diarrhea to hemorrhagic colitis and life-threatening complications. Shiga toxins (Stxs) are the main virulence factor of EHEC. The antagonistic effect of a prophylactic treatment with the probiotic strain Saccharomyces cerevisiae against EHEC O157:H7 was investigated using complementary in vitro human colonic model and in vivo murine ileal loop assays. In vitro, the probiotic treatment had no effect on O157:H7 survival but favorably influenced gut microbiota activity through modulation of short-chain fatty acid production, increasing acetate production and decreasing that of butyrate. Both pathogen and probiotic strains had individual-dependent effects on human gut microbiota. For the first time, stx expression was followed in human colonic environment: at 9 and 12 h post EHEC infection, probiotic treatment significantly decreased stx mRNA levels. Besides, in murine ileal loops, the probiotic yeast specifically exerted a trophic effect on intestinal mucosa and inhibited O157:H7 interactions with Peyer's patches and subsequent hemorrhagic lesions. Taken together, the results suggest that S. cerevisiae may be useful in the fight against EHEC infection and that host associated factors such as microbiota could influence clinical evolution of EHEC infection and the effectiveness of probiotics.

A Key Claudin Extracellular Loop Domain is Critical for Epithelial Barrier Integrity

PubMed Central

Mrsny, Randall J.; Brown, G. Thomas; Gerner-Smidt, Kirsten; Buret, Andre G.; Meddings, Jon B.; Quan, Clifford; Koval, Michael; Nusrat, Asma

2008-01-01

Intercellular tight junctions (TJs) regulate epithelial barrier properties. Claudins are major structural constituents of TJs and belong to a large family of tetra-spanning membrane proteins that have two predicted extracellular loops (ELs). Given that claudin-1 is widely expressed in epithelia, we further defined the role of its EL domains in determining TJ function. The effects of several claudin-1 EL mimetic peptides on epithelial barrier structure and function were examined. Incubation of model human intestinal epithelial cells with a 27-amino acid peptide corresponding to a portion of the first EL domain (Cldn-153–80) reversibly interfered with epithelial barrier function by inducing the rearrangement of key TJ proteins: occludin, claudin-1, junctional adhesion molecule-A, and zonula occludens-1. Cldn-153–80 associated with both claudin-1 and occludin, suggesting both the direct interference with the ability of these proteins to assemble into functional TJs and their close interaction under physiological conditions. These effects were specific for Cldn-153–80, because peptides corresponding to other claudin-1 EL domains failed to influence TJ function. Furthermore, the oral administration of Cldn-153–80 to rats increased paracellular gastric permeability. Thus, the identification of a critical claudin-1 EL motif, Cldn-153–80, capable of regulating TJ structure and function, offers a useful adjunct to treatments that require drug delivery across an epithelial barrier. PMID:18349130

Role of the ultrasonographic 'whirlpool sign' in intestinal volvulus: a systematic review and meta-analysis.

PubMed

Enyuma, Callistus O A; Adam, Ahmed; Aigbodion, Sunday J; McDowall, Jared; Gerber, Louis; Buchanan, Sean; Laher, Abdullah E

2018-05-08

Intestinal volvulus is a potentially life-threatening condition that occurs when loops of bowel twist around its supporting mesentery and associated vasculature. Clinicians often rely on various radiological investigations for prompt diagnosis to avoid complications such as bowel infarction. This review assesses the clinical reliability of the ultrasonographic whirlpool sign (WS) in the diagnosis of intestinal volvulus. In adherence with the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) statement, a systematic search of BMJ Best Practice, Cochrane Database of Systematic Reviews, EMBASE, Google Scholar, PubMed, Scopus and Web of Science databases was performed (August 2017), using relevant search terms. Selected studies were ranked for quality and relevance using the CASP (Critical Appraisal Skills Program) tool. Sixteen articles (1640 participants) were assessed. The mean and median sample size was 102.5 (SD ± 192.23) and 28 (range 7-770), respectively. The WS was positive in 212 of 255 (83.1%) patients with intestinal volvulus. Meta-analysis of the studies that provided sufficient data resulted in a pooled sensitivity and specificity of 87.42% (95% confidence interval (CI): 81.05-92.25) and 98.63% (95% CI: 97.88-99.18), respectively, with an estimated summary effect of 5.28 (95% CI: 4.47-6.08, P < 0.001). There was negligible inter-study heterogeneity, which was suggested by an I 2 statistic of 0% (95% CI: 0.00-76.34) and a τ 2 parameter of 0 (95% CI: 0.00-5.35). Though the pooled sensitivity was less than ideal (87.42%), this review and meta-analysis nevertheless supports the reliability of the ultrasonographic WS as an acceptable indicator of intestinal volvulus. © 2018 Royal Australasian College of Surgeons.

Stimulation of synthesis and release of brain-derived neurotropic factor from intestinal smooth muscle cells by substance P and pituitary adenylate cyclase-activating peptide.

PubMed

Al-Qudah, M; Alkahtani, R; Akbarali, H I; Murthy, K S; Grider, J R

2015-08-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin present in the intestine where it participates in survival and growth of enteric neurons, augmentation of enteric circuits, and stimulation of intestinal peristalsis and propulsion. Previous studies largely focused on the role of neural and mucosal BDNF. The expression and release of BDNF from intestinal smooth muscle and the interaction with enteric neuropeptides has not been studied in gut. The expression and secretion of BDNF from smooth muscle cultured from the rabbit intestinal longitudinal muscle layer in response to substance P (SP) and pituitary adenylate cyclase-activating peptide (PACAP) was measured by western blot and enzyme-linked immunosorbent assay. BDNF mRNA was measured by reverse-transcription polymerase chain reaction. The expression of BNDF protein and mRNA was greater in smooth muscle cells (SMCs) from the longitudinal muscle than from circular muscle layer. PACAP and SP increased the expression of BDNF protein and mRNA in cultured longitudinal SMCs. PACAP and SP also stimulated the secretion of BDNF from cultured longitudinal SMCs. Chelation of intracellular calcium with BAPTA (1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) prevented SP-induced increase in BDNF mRNA and protein expression and SP-induced secretion of BDNF. Neuropeptides known to be present in enteric neurons innervating the longitudinal layer increase the expression of BDNF mRNA and protein in SMCs and stimulate the release of BDNF. Considering the ability of BDNF to enhance smooth muscle contraction, this autocrine loop may partially explain the characteristic hypercontractility of longitudinal muscle in inflammatory bowel disease. © 2015 John Wiley & Sons Ltd.

Stimulation of Synthesis and Release of Brain-Derived Neurotropic Factor (BDNF) from Intestinal Smooth Muscle Cells by Substance P and Pituitary Adenylate Cyclase-Activating Peptide (PACAP)

PubMed Central

Al-Qudah, M.; Alkahtani, R.; Akbarali, H.I.; Murthy, K.S.; Grider, J.R.

2015-01-01

Background Brain-derived neurotrophic factor (BDNF) is a neurotrophin present in the intestine where it participates in survival and growth of enteric neurons, augmentation of enteric circuits, and stimulation of intestinal peristalsis and propulsion. Previous studies largely focused on the role of neural and mucosal BDNF. The expression and release of BDNF from intestinal smooth muscle and the interaction with enteric neuropeptides has not been studied in gut. Methods The expression and secretion of BDNF from smooth muscle cultured from rabbit longitudinal intestinal muscle in response to substance P and pituitary adenylate cyclase activating peptide (PACAP) was measured by western blot and ELISA. BDNF mRNA was measured by rt-PCR. Key Results The expression of BNDF protein and mRNA was greater in smooth muscle cells from the longitudinal muscle than from circular muscle layer. PACAP and substance P increased the expression of BDNF protein and mRNA in cultured longitudinal smooth muscle cells. PACAP and substance P also stimulated the secretion of BDNF from cultured longitudinal smooth muscle cells. Chelation of intracellular calcium with BAPTA prevented substance P-induced increase in BDNF mRNA and protein expression as well as substance P-induced secretion of BDNF. Conclusions & Inferences Neuropeptides known to be present in enteric neurons innervating the longitudinal layer increase the expression of BDNF mRNA and protein in smooth muscle cells and stimulate the release of BDNF. Considering the ability of BDNF to enhance smooth muscle contraction, this autocrine loop may partially explain the characteristic hypercontractility of longitudinal muscle in inflammatory bowel disease. PMID:26088546

The Use of Low Molecular Weight Protamine Chemical Chimera to Enhance Monomeric Insulin Intestinal Absorption

PubMed Central

He, Huining; Sheng, Jianyong; David, Allan E.; Kwon, Young Min; Zhang, Jian; Huang, Yongzhuo; Wang, Jianxin; Yang, Victor C.

2013-01-01

Although oral delivery of insulin offers a number of unmatched advantages, it nevertheless is beset by the poor permeability of insulin molecules through the epithelial cell membranes of the intestinal mucosal layer. We previously reported the development of low molecular weight protamine (LMWP) as a nontoxic yet potent cell penetrating peptide, of which via covalent linkage was capable of translocating protein cargos through the membranes of almost all cell types. It is therefore hypothesized that LMWP could be practically employed as a safe and effective tool to deliver insulin across the intestinal mucosal membrane, thereby augmenting its absorption through the GI tract. However, formulating 1:1 monomeric insulin/LMWP conjugate presents a tall order of challenge, as the acidic insulin and basic LMWP would automatically form tight aggregates through electrostatic interactions. In this paper, we developed an innovative conjugation strategy to solve this problem, by using succinimidyl-[(N-maleimidopropionamido)-polyethyleneglycol] ester (NHS-PEG-MAL) as an intermediate cross-linker during the coupling process. Both SDS-PAGE and MALDI-TOF mass spectroscopy confirmed the formation of a homogeneous, monomeric (1:1 ratio) insulin/LMWP conjugate without encountering the conventional problem of substrate aggregation. Cell culture studies demonstrated that transport of the Insulin-PEG-LMWP conjugate across the intestinal mucosal monolayer was augmented by almost five folds compared to native insulin. Furthermore, results from the in situ loop absorption tests in rats showed that systemic pharmacological bioavailability of insulin was significantly enhanced after its conjugation with LMWP. Overall, the presented chemical conjugation with LMWP could offer a reliable and safe means to improve the intestinal permeability of therapeutic peptides/proteins, shedding light of the possibility for their effective oral delivery. PMID:23863452

Small intestinal model for electrically propelled capsule endoscopy

PubMed Central

2011-01-01

The aim of this research is to propose a small intestine model for electrically propelled capsule endoscopy. The electrical stimulus can cause contraction of the small intestine and propel the capsule along the lumen. The proposed model considered the drag and friction from the small intestine using a thin walled model and Stokes' drag equation. Further, contraction force from the small intestine was modeled by using regression analysis. From the proposed model, the acceleration and velocity of various exterior shapes of capsule were calculated, and two exterior shapes of capsules were proposed based on the internal volume of the capsules. The proposed capsules were fabricated and animal experiments were conducted. One of the proposed capsules showed an average (SD) velocity in forward direction of 2.91 ± 0.99 mm/s and 2.23 ± 0.78 mm/s in the backward direction, which was 5.2 times faster than that obtained in previous research. The proposed model can predict locomotion of the capsule based on various exterior shapes of the capsule. PMID:22177218

Higgs boson mass in the standard model at two-loop order and beyond

DOE PAGES

Martin, Stephen P.; Robertson, David G.

2014-10-01

We calculate the mass of the Higgs boson in the standard model in terms of the underlying Lagrangian parameters at complete 2-loop order with leading 3-loop corrections. A computer program implementing the results is provided. The program also computes and minimizes the standard model effective potential in Landau gauge at 2-loop order with leading 3-loop corrections.

Exogenous glucagon-like peptide-2 improves outcomes of intestinal adaptation in a distal-intestinal resection neonatal piglet model of short bowel syndrome.

PubMed

Suri, Megha; Turner, Justine M; Sigalet, David L; Wizzard, Pamela R; Nation, Patrick N; Ball, Ron O; Pencharz, Paul B; Brubaker, Patricia L; Wales, Paul W

2014-10-01

Endogenous glucagon-like peptide-2 (GLP-2) levels and intestinal adaptation are reduced in distal-intestinal resection animal models of short bowel syndrome (SBS) that lack remnant ileum. We hypothesized that exogenous GLP-2 would improve intestinal adaptation in a distal-intestinal resection neonatal piglet model of SBS. In all, 35 piglets were randomized to 2 treatment and 3 surgical groups: control (sham), 75% mid-intestinal resection (JI), and 75% distal-intestinal resection (JC). Parenteral nutrition (PN) commenced on day 1 and was weaned as enteral nutrition (EN) advanced. IV GLP-2 (11 nmol/kg/d) or saline was initiated on day 2. Piglets were maintained for 14 d. Clinical, functional, morphological, and histological outcomes were obtained. JC-GLP-2 piglets had fewer days on PN (10.0 ± 0.6 vs. 13.8 ± 0.2), more days on EN (4.0 ± 0.6 vs. 0.2 ± 0.2), a higher percentage of EN at termination (92 ± 5 vs. 52 ± 10%), fewer days of diarrhea (8.0 ± 0.7 vs. 12.3 ± 0.4), increased intestinal length (19 ± 4 vs. -5 ± 3%), and deeper jejunal crypts (248 ± 21 vs. 172 ± 12 μm), compared with saline piglets. GLP-2 therapy improves clinical, morphological, and histological outcomes of intestinal adaptation in a distal-intestinal resection model of SBS. Since this anatomical subtype represents the majority of clinical cases of neonatal SBS, these results support a potential role for GLP-2 therapy in pediatric SBS.

Discovery of Specific Inhibitors for Intestinal E. coli   β-Glucuronidase through In Silico Virtual Screening

PubMed Central

Cheng, Ta-Chun; Cheng, Kai-Wen; Leu, Yu-Lin; Chuang, Chih-Hung; Huang, Chien-Chaio; Hsieh, Yuan-Chin; Chang, Long-Sen; Cheng, Tian-Lu

2015-01-01

Glucuronidation is a major metabolism process of detoxification for carcinogens, 4-(methylnitrosamino)-1-(3-pyridy)-1-butanone (NNK) and 1,2-dimethylhydrazine (DMH), of reactive oxygen species (ROS). However, intestinal E. coli    β-glucuronidase (eβG) has been considered pivotal to colorectal carcinogenesis. Specific inhibition of eβG may prevent reactivating the glucuronide-carcinogen and protect the intestine from ROS-mediated carcinogenesis. In order to develop specific eβG inhibitors, we found that 59 candidate compounds obtained from the initial virtual screening had high inhibition specificity against eβG but not human βG. In particular, we found that compounds 7145 and 4041 with naphthalenylidene-benzenesulfonamide (NYBS) are highly effective and selective to inhibit eβG activity. Compound 4041  (IC50 = 2.8 μM) shows a higher inhibiting ability than compound 7145  (IC50 = 31.6 μM) against eβG. Furthermore, the molecular docking analysis indicates that compound 4041 has two hydrophobic contacts to residues L361 and I363 in the bacterial loop, but 7145 has one contact to L361. Only compound 4041 can bind to key residue (E413) at active site of eβG via hydrogen-bonding interactions. These novel NYBS-based eβG specific inhibitors may provide as novel candidate compounds, which specifically inhibit eβG to reduce eβG-based carcinogenesis and intestinal injury. PMID:25839056

Discovery of specific inhibitors for intestinal E. coli  β-glucuronidase through in silico virtual screening.

PubMed

Cheng, Ta-Chun; Chuang, Kuo-Hsiang; Roffler, Steve R; Cheng, Kai-Wen; Leu, Yu-Lin; Chuang, Chih-Hung; Huang, Chien-Chaio; Kao, Chien-Han; Hsieh, Yuan-Chin; Chang, Long-Sen; Cheng, Tian-Lu; Chen, Chien-Shu

2015-01-01

Glucuronidation is a major metabolism process of detoxification for carcinogens, 4-(methylnitrosamino)-1-(3-pyridy)-1-butanone (NNK) and 1,2-dimethylhydrazine (DMH), of reactive oxygen species (ROS). However, intestinal E. coli   β-glucuronidase (eβG) has been considered pivotal to colorectal carcinogenesis. Specific inhibition of eβG may prevent reactivating the glucuronide-carcinogen and protect the intestine from ROS-mediated carcinogenesis. In order to develop specific eβG inhibitors, we found that 59 candidate compounds obtained from the initial virtual screening had high inhibition specificity against eβG but not human βG. In particular, we found that compounds 7145 and 4041 with naphthalenylidene-benzenesulfonamide (NYBS) are highly effective and selective to inhibit eβG activity. Compound 4041  (IC50 = 2.8 μM) shows a higher inhibiting ability than compound 7145  (IC50 = 31.6 μM) against eβG. Furthermore, the molecular docking analysis indicates that compound 4041 has two hydrophobic contacts to residues L361 and I363 in the bacterial loop, but 7145 has one contact to L361. Only compound 4041 can bind to key residue (E413) at active site of eβG via hydrogen-bonding interactions. These novel NYBS-based eβG specific inhibitors may provide as novel candidate compounds, which specifically inhibit eβG to reduce eβG-based carcinogenesis and intestinal injury.

[Interintestinal anastomoses formation using permanent magnet in surgical treatment of children with intestinal stomas].

PubMed

Gatkin, E Ja; Razumovskij, A Ju; Korsunskij, A A; Konovalov, A K; Sergeev, A V; Vinogradov, A Ja; Sein, V A

2015-01-01

It was analyzed the results of treatment of 48 children aged from 1 month to 14 years. In these observations by the 6th - 7th days after doubleintestinalstoma formation magnetic dies with inductance from 300 to 360 mTl and energy force at least 255 kJ/m3 were introduced into lumen of afferent and efferent intestinal loops. Attractive or compression force between dies was 600 g, i.e. force per 1 cm2 was 200 g according to dies' surface 1.12.83.0 cm. Magnets are not only surgical instruments but also physiotherapeutic devices improving microcirculation and stimulating regeneration in the area of anastomosis. Interintestinal anastomosis has been completely formed for 5-7 days. Thereafter magnetic dies have been removed. Stool was normalized in 45 of 48 observations after surgery (1-3 times daily). Intestinal discharge from ileostomy reduced to minimal amount. In 2 patients irregular bowel movements was observed due to adhesive stenosis of interintestinal anastomosis. Magnetic dies can't be established in 1 case due to adhesive process. Hospital stay was from 10 to 25 days in 41 children. 7 patients were discharged for outpatient treatment later. All children were under observation for the period 2-4 months after discharge. Signs of hypotrophy including body weight deficit within 10% of age norm were diagnosed only in 3 children with prematurity degree I-II. Hereafter children were repeatedly hospitalized; intestinal stomas were surgically removed using conventional technique. Thus complete convalescence was obtained.

Small bowel obstruction caused by Anisakis and Meckel's diverticulum: a rare case.

PubMed

Carbotta, G; Laforgia, R; Milella, Michele; Sederino, M G; Minafra, M; Fortarezza, F; Piscitelli, D; Palasciano, N

2016-01-01

Anisakiasis is a parasitic infection caused by the ingestion of raw fish contaminated by larval nematodes of Anisakis species. Intestinal or extraintestinal manifestations are rated to > 4% and >1% respectively. A 61-year old patient was admitted to our General Surgical and Emergency Unit because of sudden abdominal pain, vomit and constipation. He had eaten raw fish 3 days before admission. Laboratory data showed high levels of WBC and PCR. CT scanning showed "dilation of jejunum and ileum loops, thickening of the terminal ileum and cecum and signs of inflammation of the intestinal wall and mesentery". The following emergency surgical procedure was performed: laparotomy with evidence of obstruction of the small bowels, a giant Meckel's diverticulum, resection of terminal ileum and cecum and ileocolonic anastomosis. At the microscopic examination, the intestinal wall appeared occupied by a transmural inflammatory infiltrate, mainly eosinophilic, edema and nematode larvae, referable to Anisakis, surrounded by necrotic-inflammatory material. Moreover, there was evidence of giant a Meckel's diverticulum. Normally, enteric anisakiasis exhibits leukocytosis with eosinophilia and high CRP levels. There are cases of successful medical treatment and other cases of endoscopic treatment avoiding surgical procedure. In our case, enteric Anisakias had not been taken into consideration at the moment of the operation and only histopathology could reveal Anisakis larvae inside the intestinal wall. Our surgical approach is considered in literature as the best one for this clinical presentation. Those patients need to be better studied and more attention should be paid to their history.

Obturator hernia: A diagnostic challenge.

PubMed

Kulkarni, Sanjeev R; Punamiya, Aditya R; Naniwadekar, Ramchandra G; Janugade, Hemant B; Chotai, Tejas D; Vimal Singh, T; Natchair, Arafath

2013-01-01

Obturator hernia is an extremely rare type of hernia with relatively high mortality and morbidity. Its early diagnosis is challenging since the signs and symptoms are non specific. Here in we present a case of 70 years old women who presented with complaints of intermittent colicky abdominal pain and vomiting. Plain radiograph of abdomen showed acute dilatation of stomach. Ultrasonography showed small bowel obstruction at the mid ileal level with evidence of coiled loops of ileum in pelvis. On exploration, Right Obstructed Obturator hernia was found. The obstructed Intestine was reduced and resected and the obturator foramen was closed with simple sutures. Postoperative period was uneventful. Obturator hernia is a rare pelvic hernia and poses a diagnostic challenge. Obturator hernia occurs when there is protrusion of intra-abdominal contents through the obturator foramen in the pelvis. The signs and symptoms are non specific and generally the diagnosis is made during exploration for the intestinal obstruction, one of the four cardinal features. Others are pain on the medial aspect of thigh called as Howship Rombergs sign, repeated attacks of Intestinal Obstruction and palpable mass on the medial aspect of thigh. Obturator hernia is a rare but significant cause of intestinal obstruction especially in emaciated elderly woman and a diagnostic challenge for the Doctors. CT scan is valuable to establish preoperative diagnosis. Surgery either open or laproscopic, is the only treatment. The need for the awareness is stressed and CT scan can be helpful. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Effects of fasting and refeeding on gene expression of slc15a1a, a gene encoding an oligopeptide transporter (PepT1), in the intestine of Mozambique tilapia.

PubMed

Orozco, Zenith Gaye A; Soma, Satoshi; Kaneko, Toyoji; Watanabe, Soichi

2017-01-01

The tissue distribution of slc15a1a, a gene that encodes an oligopeptide transporter, PepT1, and its response to fasting and refeeding were investigated in the intestinal epithelium of Mozambique tilapia for a better understanding of its role on nutrient absorption. The slc15a1a was predominantly expressed in the absorptive epithelia of the anterior part of the intestine, suggesting that digested oligopeptides are primarily absorbed in the anterior intestine. The response of slc15a1a to fasting was evaluated at 1, 2, 4, 7 and 14days after the last feeding. Fasting revealed a biphasic effect, where short-term fasting significantly upregulated slc15a1a expression and long-term fasting resulted in downregulation. The expression level continued to decrease and fell below the pre-fasted level from day 4 to 14. Proximal (the hepatic loop, HL) and distal parts (the proximal major coil, PMC) of the anterior intestine showed different magnitudes of responses to fasting; slc15a1a expression in the PMC showed greater upregulation and downregulation than that in the HL. Refeeding significantly stimulated slc15a1a expression at day 3, although the expression did not exceed the pre-fasted level. Observed responses of slc15a1a to fasting and refeeding suggest that the expression level of this gene can serve as a sensitive indicator of the changes that may occur in altering nutritional conditions. These findings contribute to a better understanding of the role of PepT1 in nutrition and of the complex mechanisms underlying the absorption of oligopeptides and amino acids in the intestine, and may lead to development of possible means to manipulate the absorption processes for the improvement of growth and other metabolic and physiological conditions in fish. Copyright © 2016. Published by Elsevier Inc.

Starved Guts: Morphologic and Functional Intestinal Changes in Malnutrition.

PubMed

Attia, Suzanna; Feenstra, Marjon; Swain, Nathan; Cuesta, Melina; Bandsma, Robert H J

2017-11-01

Malnutrition contributes significantly to death and illness worldwide and especially to the deaths of children younger than 5 years. The relation between intestinal changes in malnutrition and morbidity and mortality has not been well characterized; however, recent research indicates that the functional and morphologic changes of the intestine secondary to malnutrition itself contribute significantly to these negative clinical outcomes and may be potent targets of intervention. The aim of this review was to summarize current knowledge of experimental and clinically observed changes in the intestine from malnutrition preclinical models and human studies. Limited clinical studies have shown villous blunting, intestinal inflammation, and changes in the intestinal microbiome of malnourished children. In addition to these findings, experimental data using various animal models of malnutrition have found evidence of increased intestinal permeability, upregulated intestinal inflammation, and loss of goblet cells. More mechanistic studies are urgently needed to improve our understanding of malnutrition-related intestinal dysfunction and to identify potential novel targets for intervention.

Human Primary Intestinal Epithelial Cells as an Improved In Vitro Model for Cryptosporidium parvum Infection

PubMed Central

Cabada, Miguel M.; Nichols, Joan; Gomez, Guillermo; White, A. Clinton

2013-01-01

The study of human intestinal pathogens has been limited by the lack of methods for the long-term culture of primary human intestinal epithelial cells (PECs). The development of infection models with PECs would allow a better understanding of host-parasite interactions. The objective of this study was to develop a novel method for prolonged in vitro cultivation of PECs that can be used to study Cryptosporidium infection. We isolated intact crypts from human intestines removed during weight loss surgery. The fragments of intestinal layers were cultivated with culture medium supplemented with growth factors and antiapoptotic molecules. After 7 days, the PECs formed self-regenerating cell clusters, forming villi that resemble intestinal epithelium. The PECs proliferated and remained viable for at least 60 days. The cells expressed markers for intestinal stem cells, epithelial cells, and mature enterocytes. The PECs were infected with Cryptosporidium. In contrast to older models in which parasite numbers decay, the burden of parasites increased for >120 h. In summary, we describe here a novel method for the cultivation of self-regenerating human epithelial cells from small intestinal crypts, which contain both intestinal stem cells and mature villus cells. We present data that suggest these cells support Cryptosporidium better than existing cell lines. PECs should provide an improved tool for studying host-parasite interactions involving Cryptosporidium and other intestinal pathogens. PMID:23509153

A dual-loop model of the human controller

NASA Technical Reports Server (NTRS)

Hess, R. A.

1977-01-01

A representative model of the human controller in single-axis compensatory tracking tasks that exhibits an internal feedback loop which is not evident in single-loop models now in common use is presented. This hypothetical inner-loop involves a neuromuscular command signal derived from the time rate of change of controlled element output which is due to control activity. It is not contended that the single-loop human controller models now in use are incorrect, but that they contain an implicit but important internal loop closure, which, if explicitly considered, can account for a good deal of the adaptive nature of the human controller in a systematic manner.

Intestinal organoids: A model of intestinal fibrosis for evaluating anti-fibrotic drugs

PubMed Central

Rodansky, Eva S.; Johnson, Laura A.; Huang, Sha; Spence, Jason R.; Higgins, Peter D. R.

2016-01-01

Background & Aims Intestinal fibrosis is a critical complication of Crohn’s disease (CD). Current in vitro models of intestinal fibrosis cannot model the complex intestinal architecture, while in vivo rodent models do not fully recapitulate human disease and have limited utility for large-scale screening. Here, we exploit recent advances in stem cell derived human intestinal organoids (HIOs) as a new human model of fibrosis in CD. Methods Human pluripotent stem cells were differentiated into HIOs. We identified myofibroblasts, the key effector cells of fibrosis, by immunofluorescence staining for alpha-smooth muscle actin (αSMA), vimentin, and desmin. We examined the fibrogenic response of HIOs by treatment with transforming growth factor beta (TGFβ) in the presence or absence of the anti-fibrotic drug spironolactone. Fibrotic response was assayed by expression of fibrogenic genes (COL1A1 (collagen, type I, alpha 1), ACTA2 (alpha smooth muscle actin), FN1 (fibronectin 1), MYLK (myosin light chain kinase), and MKL1 (megakaryoblastic leukemia (translocation) 1)) and proteins (αSMA). Results Immunofluorescent staining of organoids identified a population of myofibroblasts within the HIO mesenchyme. TGFβ stimulation of HIOs produced a dose-dependent pro-fibrotic response. Spironolactone treatment blocked the fibrogenic response of HIOs to TGFβ. Conclusions HIOs contain myofibroblasts and respond to a pro-fibrotic stimulus in a manner that is consistent with isolated human myofibroblasts. HIOs are a promising model system that might bridge the gap between current in vitro and in vivo models of intestinal fibrosis in IBD. PMID:25828392

Research on the Dynamic Hysteresis Loop Model of the Residence Times Difference (RTD)-Fluxgate

PubMed Central

Wang, Yanzhang; Wu, Shujun; Zhou, Zhijian; Cheng, Defu; Pang, Na; Wan, Yunxia

2013-01-01

Based on the core hysteresis features, the RTD-fluxgate core, while working, is repeatedly saturated with excitation field. When the fluxgate simulates, the accurate characteristic model of the core may provide a precise simulation result. As the shape of the ideal hysteresis loop model is fixed, it cannot accurately reflect the actual dynamic changing rules of the hysteresis loop. In order to improve the fluxgate simulation accuracy, a dynamic hysteresis loop model containing the parameters which have actual physical meanings is proposed based on the changing rule of the permeability parameter when the fluxgate is working. Compared with the ideal hysteresis loop model, this model has considered the dynamic features of the hysteresis loop, which makes the simulation results closer to the actual output. In addition, other hysteresis loops of different magnetic materials can be explained utilizing the described model for an example of amorphous magnetic material in this manuscript. The model has been validated by the output response comparison between experiment results and fitting results using the model. PMID:24002230

A Revised Model for Dosimetry in the Human Small Intestine

DOE Office of Scientific and Technical Information (OSTI.GOV)

John Poston; Nasir U. Bhuiyan; R. Alex Redd

2005-02-28

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.

On higher order discrete phase-locked loops.

NASA Technical Reports Server (NTRS)

Gill, G. S.; Gupta, S. C.

1972-01-01

An exact mathematical model is developed for a discrete loop of a general order particularly suitable for digital computation. The deterministic response of the loop to the phase step and the frequency step is investigated. The design of the digital filter for the second-order loop is considered. Use is made of the incremental phase plane to study the phase error behavior of the loop. The model of the noisy loop is derived and the optimization of the loop filter for minimum mean-square error is considered.

Current systems of coronal loops in 3D MHD simulations

NASA Astrophysics Data System (ADS)

Warnecke, J.; Chen, F.; Bingert, S.; Peter, H.

2017-11-01

Aims: We study the magnetic field and current structure associated with a coronal loop. Through this we investigate to what extent the assumptions of a force-free magnetic field break down and where they might be justified. Methods: We analyze a three-dimensional (3D) magnetohydrodynamic (MHD) model of the solar corona in an emerging active region with the focus on the structure of the forming coronal loops. The lower boundary of this simulation is taken from a model of an emerging active region. As a consequence of the emerging magnetic flux and the horizontal motions at the surface a coronal loop forms self-consistently. We investigate the current density along magnetic field lines inside (and outside) this loop and study the magnetic and plasma properties in and around this loop. The loop is defined as the bundle of field lines that coincides with enhanced emission in extreme UV. Results: We find that the total current along the emerging loop changes its sign from being antiparallel to parallel to the magnetic field. This is caused by the inclination of the loop together with the footpoint motion. Around the loop, the currents form a complex non-force-free helical structure. This is directly related to a bipolar current structure at the loop footpoints at the base of the corona and a local reduction of the background magnetic field (I.e., outside the loop) caused by the plasma flow into and along the loop. Furthermore, the locally reduced magnetic pressure in the loop allows the loop to sustain a higher density, which is crucial for the emission in extreme UV. The action of the flow on the magnetic field hosting the loop turns out to also be responsible for the observed squashing of the loop. Conclusions: The complex magnetic field and current system surrounding it can only be modeled in 3D MHD models where the magnetic field has to balance the plasma pressure. A one-dimensional coronal loop model or a force-free extrapolation cannot capture the current system and the complex interaction of the plasma and the magnetic field in the coronal loop, despite the fact that the loop is under low-β conditions.

A chronic oral reference dose for hexavalent chromium-induced intestinal cancer†

PubMed Central

Thompson, Chad M; Kirman, Christopher R; Proctor, Deborah M; Haws, Laurie C; Suh, Mina; Hays, Sean M; Hixon, J Gregory; Harris, Mark A

2014-01-01

High concentrations of hexavalent chromium [Cr(VI)] in drinking water induce villous cytotoxicity and compensatory crypt hyperplasia in the small intestines of mice (but not rats). Lifetime exposure to such cytotoxic concentrations increases intestinal neoplasms in mice, suggesting that the mode of action for Cr(VI)-induced intestinal tumors involves chronic wounding and compensatory cell proliferation of the intestine. Therefore, we developed a chronic oral reference dose (RfD) designed to be protective of intestinal damage and thus intestinal cancer. A physiologically based pharmacokinetic model for chromium in mice was used to estimate the amount of Cr(VI) entering each intestinal tissue section (duodenum, jejunum and ileum) from the lumen per day (normalized to intestinal tissue weight). These internal dose metrics, together with corresponding incidences for diffuse hyperplasia, were used to derive points of departure using benchmark dose modeling and constrained nonlinear regression. Both modeling techniques resulted in similar points of departure, which were subsequently converted to human equivalent doses using a human physiologically based pharmacokinetic model. Applying appropriate uncertainty factors, an RfD of 0.006 mg kg–1 day–1 was derived for diffuse hyperplasia—an effect that precedes tumor formation. This RfD is protective of both noncancer and cancer effects in the small intestine and corresponds to a safe drinking water equivalent level of 210 µg l–1. This concentration is higher than the current federal maximum contaminant level for total Cr (100 µg l–1) and well above levels of Cr(VI) in US drinking water supplies (typically ≤ 5 µg l–1). © 2013 The Authors. Journal of Applied Toxicology published by John Wiley & Sons, Ltd. PMID:23943231

Animal models of intestinal fibrosis: new tools for the understanding of pathogenesis and therapy of human disease

PubMed Central

Rieder, Florian; Kessler, Sean; Sans, Miquel

2012-01-01

Fibrosis is a serious condition complicating chronic inflammatory processes affecting the intestinal tract. Advances in this field that rely on human studies have been slow and seriously restricted by practical and logistic reasons. As a consequence, well-characterized animal models of intestinal fibrosis have emerged as logical and essential systems to better define and understand the pathophysiology of fibrosis. In point of fact, animal models allow the execution of mechanistic studies as well as the implementation of clinical trials with novel, pathophysiology-based therapeutic approaches. This review provides an overview of the currently available animal models of intestinal fibrosis, taking into consideration the methods of induction, key characteristics of each model, and underlying mechanisms. Currently available models will be classified into seven categories: spontaneous, gene-targeted, chemical-, immune-, bacteria-, and radiation-induced as well as postoperative fibrosis. Each model will be discussed in regard to its potential to create research opportunities to gain insights into the mechanisms of intestinal fibrosis and stricture formation and assist in the development of effective and specific antifibrotic therapies. PMID:22878121

Digestion modeling in the small intestine: impact of dietary fiber.

PubMed

Taghipoor, M; Barles, G; Georgelin, C; Licois, J R; Lescoat, P

2014-12-01

In this work, the modeling of the digestion in the small intestine is developed by investigating specifically the effects of dietary fiber. As our previous model, this new version takes into account the three main phenomena of digestion: transit of the bolus, degradation of feedstuffs and absorption through the intestinal wall. However the two main physiochemical characteristics of dietary fiber, namely viscosity and water holding capacity, lead us to substantially modify our initial model by emphasizing the role of water and its intricated dynamics with dry matter in the bolus. Various numerical simulations given by this new model are qualitatively in agreement with the positive effect of insoluble dietary fiber on the velocity of bolus and on its degradation all along the small intestine. These simulations reproduce the negative effect of soluble dietary fiber on digestion as it has been experimentally observed. Although, this model is generic and contains a large number of parameters but, to the best of our knowledge, it is among the first qualitative dynamical models of fiber influence on intestinal digestion. Copyright © 2014 Elsevier Inc. All rights reserved.

Intestinal absorption differences of major bioactive compounds of Gegenqinlian Decoction between normal and bacterial diarrheal mini-pigs in vitro and in situ.

PubMed

Ling, Xiao; Xiang, Yuqiang; Chen, Feilong; Tang, Qingfa; Zhang, Wei; Tan, Xiaomei

2018-04-15

Intestinal condition plays an important role in drug absorption and metabolism, thus the effects of varied gastrointestinal diseases such as infectious diarrhea on the intestinal function are crucial for drug absorption. However, due to the lack of suitable models, the differences of absorption and metabolism of drugs between the diarrheal and normal intestines are rarely reported. Thus, in this study, Escherichia coli diarrhea model was induced in mini-pigs and single-pass intestinal perfusion and intestinal mucosal enzyme metabolism experiments were conducted. A simple and rapid ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine the concentrations of 9 major components in Gegen Qinlian decoction (GQD). Samples were pretreated by protein precipitation with methanol and naringin and prednisolone were used as internal standards. The validated method demonstrated adequate sensitivity, selectivity, and process efficiency for the bioanalysis of 9 compounds. Results of intestinal perfusion showed that puerarin, daidzein, daidzin and baicalin and berberine were absorbed faster in diarrheal jejunum than in normal intestines (p < 0.05). However, puerarin, daidzin and liquiritin were metabolized more slowly in diarrheal intestine after incubation compared with the normal group (p < 0.05). The concentrations of daidzein in both perfusion and metabolism and wogonin in metabolism were significantly increased (p < 0.05). In conclusion, absorption and metabolism of GQD were significantly different between the diarrheal and normal intestines, which suggest that bacterial diarrheal mini-pigs model can be used in the intestinal absorption study and is worthy to be applied in the other intestinal absorption study of anti- diarrheal drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

Intestinal Carriage of Carbapenemase-Producing Organisms: Current Status of Surveillance Methods

PubMed Central

Jacobs, Michael R.; Wilson, Brigid; Kaye, Keith; Donskey, Curtis J.; Perez, Federico

2015-01-01

SUMMARY Carbapenemases have become a significant mechanism for broad-spectrum β-lactam resistance in Enterobacteriaceae and other Gram-negative bacteria such as Pseudomonas and Acinetobacter spp. Intestinal carriage of carbapenemase-producing organisms (CPOs) is an important source of transmission. Isolation of carriers is one strategy that can be used to limit the spread of these bacteria. In this review, we critically examine the clinical performance, advantages, and disadvantages of methods available for the detection of intestinal carriage of CPOs. Culture-based methods (Centers for Disease Control and Prevention [CDC] protocols, chromogenic media, specialized agars, and double-disk synergy tests) for detecting carriage of CPOs are convenient due to their ready availability and low cost, but their limited sensitivity and long turnaround time may not always be optimal for infection control practices. Contemporary nucleic acid amplification techniques (NAATs) such as real-time PCR, hybridization assays, loop-mediated isothermal amplification (LAMP), or a combined culture and NAAT approach may provide fast results and/or added sensitivity and specificity compared with culture-based methods. Infection control practitioners and clinical microbiologists should be aware of the strengths and limitations of available methods to determine the most suitable approach for their medical facility to fit their infection control needs. PMID:26511484

Congenital Vitelline Band Causing Intestinal Obstruction in an Adult with a Double Inferior Vena Cava

PubMed Central

Pussepitiya, Kumari; Samarasinghe, Bandula; Wickramasinghe, Nuwan

2016-01-01

Introduction. Vitelline artery remnants are rare causes of intra-abdominal bands leading to bowel obstruction. These bands may be associated with Meckel's diverticulum. Double inferior vena cava (IVC) is a rare presentation and is usually identified incidentally. Case Presentation. A sixty-year-old male presented with progressive vomiting for five days and he was clinically diagnosed with intestinal obstruction. Plain X-ray abdomen showed evidence of small bowel obstruction. CT scan of the abdomen revealed dilated small bowel loops with a small outpouching in the distal ileum with a band like structure attached to it. In the CT, left sided patent IVC draining into the left renal vein was identified. Left external iliac vein was in continuity with the left IVC. Left internal iliac vein was draining into the right IVC. Exploratory laparotomy revealed a Meckel's diverticulum with a band identified as the vitelline remnant attached to its apex and inserting at the anterior abdominal wall near the umbilicus. Discussion. Meckel's diverticulum with vitelline bands, although rare, should be borne in mind in adult patients with intestinal obstruction. Identification of this anomaly can be difficult in imaging studies. Presence of double IVC should be mentioned in the imaging findings to prevent possible catastrophic complications during surgery. PMID:27843667

The Salmonella dublin virulence plasmid mediates systemic but not enteric phases of salmonellosis in cattle.

PubMed Central

Wallis, T S; Paulin, S M; Plested, J S; Watson, P R; Jones, P W

1995-01-01

Plasmid-bearing and plasmid-free isolates and a plasmid-cured strain of Salmonella dublin were compared for virulence in calves. The plasmid-bearing strains were highly virulent, causing severe enteric and systemic disease with high mortality. In contrast, the plasmid-free strains caused diarrhea but only low mortality. The infection kinetics of a wild-type and a derivative plasmid-cured strain were compared. Both strains were isolated in high numbers from intestinal sites at 3 and 6 days after oral challenge and were isolated at comparable frequencies from systemic sites at 3 days, but not at 6 days, when the wild-type strain was predominant. The strains were equally invasive in intestinal epithelia with and without Peyer's patch and elicited comparable secretory and inflammatory responses and intestinal pathology in ligated ileal loops. The effect of the virulence plasmid on growth kinetics and on the outer membrane protein profile was assessed in an in vivo growth chamber. The virulence plasmid did not influence either extracellular growth or the expression of major outer membrane proteins. These observations demonstrate that the virulence plasmid is not involved in either the enteric phase of infection or the systemic dissemination of S. dublin but probably mediates the persistence of S. dublin at systemic sites. PMID:7790094

Two-loop renormalization of gaugino masses in general supersymmetric gauge models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamada, Y.

1994-01-03

We calculate the two-loop renormalization group equations for the running gaugino masses in general supersymmetry (SUSY) gauge models, improving our previous result. We also study its consequences on the unification of the gaugino masses in the SUSY SU(5) model. The two-loop correction to the one-loop relation [ital m][sub [ital i

Changes of intestinal mucosal and plasma PYY in a diarrhea model rat and influence of loperamide as the treatment agent for diarrhea.

PubMed

Hirotani, Yoshihiko; Mikajiri, Kyoko; Ikeda, Kenji; Myotoku, Michiaki; Kurokawa, Nobuo

2008-09-01

Peptide YY (PYY) is produced by endocrine cells in the lower gastrointestinal tract. The main functions of PYY are antisecretory effects in the colon and inhibition of gastrointestinal motility. We chose PYY as an index of the intrinsic factor in diarrhea and examined the influence of changes induced in a diarrhea rat model by administration of 4 types of laxative and loperamide hydrochloride (loperamide) as an agent for the treatment of diarrhea. A specific radioimmunoassay was performed to determine plasma and intestinal mucosal PYY concentrations. PYY in the rat intestinal tissue extract was distributed at a high density in the lower intestinal mucosa. In the diarrhea rat model, multiple changes in PYY concentrations in the intestinal mucosa and plasma were observed. In rats administered castor oil and sodium picosulfate, the intestinal mucosal PYY levels significantly decreased in a dose-dependent manner. Plasma PYY levels significantly decreased only in rats administered magnesium citrate. Next, we examined the influence of loperamide administration on the intestinal mucosa and plasma PYY concentrations in these rats. Loperamide administration resulted in multiple changes in plasma and intestinal mucosa PYY concentrations, along with an improvement in the diarrhea. Our research showed that the endocrine hormone PYY is involved in the onset of diarrhea, the course of the condition, and the manifestation of medicinal effects in the lower intestine.

Functional and structural characterization of a β-glucosidase involved in saponin metabolism from intestinal bacteria.

PubMed

Yan, Shan; Wei, Peng-Cheng; Chen, Qiao; Chen, Xin; Wang, Shi-Cheng; Li, Jia-Ru; Gao, Chuan

2018-02-19

Saponins are natural glycosides widely used in medicine and the food industry. Although saponin metabolism in human is dependent on intestinal microbes, few involving bacteria enzymes have been identified. We cloned BlBG3, a GH3 β-glucosidase from Bifidobacterium longum, from human stool. We found that BlBG3 catalyzes the hydrolysis of glycoside furostanol and ginsenoside Rb1 at higher efficiency than other microbial β-glucosidases. Structural analysis of BlBG3 in complex with d-glucose revealed its three unique loops, which form a deep pocket and participate in substrate binding. To understand how substrate is bound to the pocket, molecular docking was performed and the binding interactions of protobioside with BlBG3 were revealed. Mutational study suggested that R484 and H642 are critical for enzymatic activity. Our study presents the first structural and functional analysis of a saponin-processing enzyme from human microbiota. Copyright © 2018 Elsevier Inc. All rights reserved.

Non perianal fistulas in Crohn's disease and short bowel syndrome: what we can do?

PubMed

Zildzic, Muharem; Alibegovic, Ervin

2009-01-01

Crohn's disease (CD) is a lifelong disease arising from an interaction between genetic and environmental factors, but seen predominantly in the developed countries of the world. The precise etiology is unknown and therefore a causal treatment is not yet available. Fistulating Crohn's disease includes fistulas arising in the perianal area, together with those communicating between the intestine and other organs or the abdominal wall. Non perianal fistulas include fistulas communicating with other viscera (urinary bladder, vagina), loops of intestine (enteroenteral fistulas) or the abdominal wall (enterocutaneus fistulas). The diagnostic approach is a crucial aspect in the management of fistulating CD as the findings influence the therapeutic strategy. Short bowel syndrome caused by extensive bowel resection should be initially treated with nutritional support and can caused serious treatment and reevaluating problems. We review this uncommon manifestation in a high risk patient after multiple operations and severely shortened bowel and also with non perianal fistulating CD.

Enteric colonization by staphylococcus delphini in four ferret kits with diarrhoea.

PubMed

Gary, J M; Langohr, I M; Lim, A; Bolin, S; Bolin, C; Moore, I; Kiupel, M

2014-11-01

Four, 1-to 4-week-old ferret kits were submitted to the Diagnostic Center for Population and Animal Health at Michigan State University for post-mortem examination. Grossly, multiple bowel loops in all ferret kits were distended by mucoid faecal material. Microscopically, there was no evidence of inflammation or notable alteration to the normal mucosal morphology. Gram-positive coccoid bacteria colonized variable segments of the small intestine. These bacteria were identified as Staphylococcus delphini by phenotypic and molecular analyses. Enzyme-linked immunosorbent assay for detection of Staphylococcus enterotoxins was positive and polymerase chain reaction detected the gene for Staphylococcus enterotoxin E in the isolates. The hypersecretory diarrhoea in these ferret kits may have been associated with colonization of the small intestine by S. delphini, cultures of which were shown in vitro to be potentially capable of producing enterotoxin E. The condition described in these ferrets is similar to 'sticky' kit syndrome in mink. Copyright © 2014 Elsevier Ltd. All rights reserved.

[A rare case of intussusception in a seventeen year old boy: diagnosis, management and review of the literature.

PubMed

Rossi, Enrica; Basile, Massimo; Narese, Donatella; Ognibene, Noemi; Poggesi, Sara; Cangelosi, Marta; Defilippi, Claudio

2017-04-01

Intussusception is the most common cause of intestinal obstruction and acute abdomen in the first year of life. Approximately in the 80% of cases intussusception occurs when the last ileal loop is pulled into the cecum, passing through the ileocecal valve, and finally resulting in the displacement of cecum in the upper abdominal. It could be related with mesenteric adenitis because enlarged lymph nodes, together with peristalsis, can serve as "lead point". Other forms of intussusception are ileo-ileal and colo-colic. The aetiology in infants and adults can be very variable and most often linked with secondary causes, such as benign or malignant lesions (polyps, tumors, lymphomas, intestinal duplication cyst, Meckel's diverticulum). In this paper we describe a rare case of idiopathic ileo-ileal intussusception in a 17 year old boy. We also discuss, with a careful analysis of the literature, the diagnostic and therapeutic protocol in case of intussusception ileo-colic approved at the Meyer Children's Hospital.

Some properties of purified Escherichia coli heat-stable enterotoxin II.

PubMed Central

Hitotsubashi, S; Fujii, Y; Yamanaka, H; Okamoto, K

1992-01-01

We examined the biological properties of purified Escherichia coli heat-stable enterotoxin II (STII) using mouse intestinal loop assays and compared these properties with those of heat-stable enterotoxin I (STI) and cholera toxin (CT). The action of STII over time differed from those of STI and CT. STII did not alter cyclic GMP or cyclic AMP levels in intestinal mucosal cells. Our results supported the idea that the mechanism of action of STII in inducing fluid secretion is different from the mechanisms of action of STI and CT. This hypothesis was further supported by the fact that an anti-STII neutralizing serum did not neutralize the activities of STI and CT. Subsequently, we examined the involvement of prostaglandins in the action of STII. The level of prostaglandin E2 in the fluid accumulated as a result of the action of STII increased, and the prostaglandin synthesis inhibitors aspirin and indomethacin significantly reduced the response to STII. These results implicate prostaglandin E2 in the mechanism of action of STII. Images PMID:1398961

Distinct intestinal adaptation for vitamin B12 and bile acid absorption revealed in a new mouse model of massive ileocecal resection.

PubMed

Matsumoto, Yuka; Mochizuki, Wakana; Akiyama, Shintaro; Matsumoto, Taichi; Nozaki, Kengo; Watanabe, Mamoru; Nakamura, Tetsuya

2017-09-15

Ileocecal resection (ICR), one of several types of intestinal resection that results in short bowel syndrome (SBS), causes severe clinical disease in humans. We here describe a mouse model of massive ICR in which 75% of the distal small intestine is removed. We demonstrate that mice underwent 75% ICR show severe clinical signs and high mortality, which may recapitulate severe forms of human SBS, despite an adaptive response throughout the remnant intestine. By using this model, we also investigated whether the epithelium of the remnant intestine shows enhanced expression of factors involved in region-specific functions of the ileum. Cubn mRNA and its protein product, which play an essential role in vitamin B12 absorption in the ileum, are not compensatory up-regulated in any part of the remnant intestine, demonstrating a clear contrast with post-operative up-regulation of genes involved in bile acid absorption. Our study suggests that functional adaptation by phenotypical changes in the intestinal epithelium is not a general feature for nutrient absorption systems that are confined to the ileum. We also propose that the mouse model developed in this study will become a unique system to facilitate studies on SBS with ICR in humans. © 2017. Published by The Company of Biologists Ltd.

3D MHD Models of Active Region Loops

NASA Technical Reports Server (NTRS)

Ofman, Leon

2004-01-01

Present imaging and spectroscopic observations of active region loops allow to determine many physical parameters of the coronal loops, such as the density, temperature, velocity of flows in loops, and the magnetic field. However, due to projection effects many of these parameters remain ambiguous. Three dimensional imaging in EUV by the STEREO spacecraft will help to resolve the projection ambiguities, and the observations could be used to setup 3D MHD models of active region loops to study the dynamics and stability of active regions. Here the results of 3D MHD models of active region loops are presented, and the progress towards more realistic 3D MHD models of active regions. In particular the effects of impulsive events on the excitation of active region loop oscillations, and the generation, propagations and reflection of EIT waves are shown. It is shown how 3D MHD models together with 3D EUV observations can be used as a diagnostic tool for active region loop physical parameters, and to advance the science of the sources of solar coronal activity.

Rebamipide ameliorates radiation-induced intestinal injury in a mouse model.

PubMed

Shim, Sehwan; Jang, Hyo-Sun; Myung, Hyun-Wook; Myung, Jae Kyung; Kang, Jin-Kyu; Kim, Min-Jung; Lee, Seung Bum; Jang, Won-Suk; Lee, Sun-Joo; Jin, Young-Woo; Lee, Seung-Sook; Park, Sunhoo

2017-08-15

Radiation-induced enteritis is a major side effect in cancer patients undergoing abdominopelvic radiotherapy. Radiation exposure produces an uncontrolled inflammatory cascade and epithelial cell loss leading to impaired epithelial barrier function. The goal of this study was to determine the effect of rebamipide on regeneration of the intestinal epithelia after radiation injury. The abdomens of C57BL/6 mice were exposed to 13Gy of irradiation (IR) and then the mice were treated with rebamipide. Upon IR, intestinal epithelia were destroyed structurally at the microscopic level and bacterial translocation was increased. The intestinal damage reached a maximum level on day 6 post-IR and intestinal regeneration occurred thereafter. We found that rebamipide significantly ameliorated radiation-induced intestinal injury. In mice treated with rebamipide after IR, intestinal barrier function recovered and expression of the tight junction components of the intestinal barrier were upregulated. Rebamipide administration reduced radiation-induced intestinal mucosal injury. The levels of proinflammatory cytokines and matrix metallopeptidase 9 (MMP9) were significantly reduced upon rebamipide administration. Intestinal cell proliferation and β-catenin expression also increased upon rebamipide administration. These data demonstrate that rebamipide reverses impairment of the intestinal barrier by increasing intestinal cell proliferation and attenuating the inflammatory response by inhibiting MMP9 and proinflammatory cytokine expression in a murine model of radiation-induced enteritis. Copyright © 2017 Elsevier Inc. All rights reserved.

A New Method for Setting Calculation Sequence of Directional Relay Protection in Multi-Loop Networks

NASA Astrophysics Data System (ADS)

Haijun, Xiong; Qi, Zhang

2016-08-01

Workload of relay protection setting calculation in multi-loop networks may be reduced effectively by optimization setting calculation sequences. A new method of setting calculation sequences of directional distance relay protection in multi-loop networks based on minimum broken nodes cost vector (MBNCV) was proposed to solve the problem experienced in current methods. Existing methods based on minimum breakpoint set (MBPS) lead to more break edges when untying the loops in dependent relationships of relays leading to possibly more iterative calculation workloads in setting calculations. A model driven approach based on behavior trees (BT) was presented to improve adaptability of similar problems. After extending the BT model by adding real-time system characters, timed BT was derived and the dependency relationship in multi-loop networks was then modeled. The model was translated into communication sequence process (CSP) models and an optimization setting calculation sequence in multi-loop networks was finally calculated by tools. A 5-nodes multi-loop network was applied as an example to demonstrate effectiveness of the modeling and calculation method. Several examples were then calculated with results indicating the method effectively reduces the number of forced broken edges for protection setting calculation in multi-loop networks.

Three-Dimensional Coculture Of Human Small-Intestine Cells

NASA Technical Reports Server (NTRS)

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

1994-01-01

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).

What causes the spatial heterogeneity of bacterial flora in the intestine of zebrafish larvae?

PubMed

Yang, Jinyou; Shimogonya, Yuji; Ishikawa, Takuji

2018-06-07

Microbial flora in the intestine has been thoroughly investigated, as it plays an important role in the health of the host. Jemielita et al. (2014) showed experimentally that Aeromonas bacteria in the intestine of zebrafish larvae have a heterogeneous spatial distribution. Although bacterial aggregation is important biologically and clinically, there is no mathematical model describing the phenomenon and its mechanism remains largely unknown. In this study, we developed a computational model to describe the heterogeneous distribution of bacteria in the intestine of zebrafish larvae. The results showed that biological taxis could cause the bacterial aggregation. Intestinal peristalsis had the effect of reducing bacterial aggregation through mixing function. Using a scaling argument, we showed that the taxis velocity of bacteria must be larger than the sum of the diffusive velocity and background bulk flow velocity to induce bacterial aggregation. Our model and findings will be useful to further the scientific understanding of intestinal microbial flora. Copyright © 2018 Elsevier Ltd. All rights reserved.

Enthalpy-Based Thermal Evolution of Loops: III. Comparison of Zero-Dimensional Models

NASA Technical Reports Server (NTRS)

Cargill, P. J.; Bradshaw, Stephen J.; Klimchuk, James A.

2012-01-01

Zero dimensional (0D) hydrodynamic models, provide a simple and quick way to study the thermal evolution of coronal loops subjected to time-dependent heating. This paper presents a comparison of a number of 0D models that have been published in the past and is intended to provide a guide for those interested in either using the old models or developing new ones. The principal difference between the models is the way the exchange of mass and energy between corona, transition region and chromosphere is treated, as plasma cycles into and out of a loop during a heating-cooling cycle. It is shown that models based on the principles of mass and energy conservation can give satisfactory results at some, or, in the case of the Enthalpy Based Thermal Evolution of Loops (EBTEL) model, all stages of the loop evolution. Empirical models can lead to low coronal densities, spurious delays between the peak density and temperature, and, for short heating pulses, overly short loop lifetimes.

Heating and dynamics of two flare loop systems observed by AIA and EIS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Y.; Ding, M. D.; Qiu, J., E-mail: yingli@nju.edu.cn

2014-02-01

We investigate heating and evolution of flare loops in a C4.7 two-ribbon flare on 2011 February 13. From Solar Dynamics Observatory/Atmospheric Imaging Assembly (AIA) imaging observations, we can identify two sets of loops. Hinode/EUV Imaging Spectrometer (EIS) spectroscopic observations reveal blueshifts at the feet of both sets of loops. The evolution and dynamics of the two sets are quite different. The first set of loops exhibits blueshifts for about 25 minutes followed by redshifts, while the second set shows stronger blueshifts, which are maintained for about one hour. The UV 1600 observation by AIA also shows that the feet ofmore » the second set of loops brighten twice. These suggest that continuous heating may be present in the second set of loops. We use spatially resolved UV light curves to infer heating rates in the few tens of individual loops comprising the two loop systems. With these heating rates, we then compute plasma evolution in these loops with the 'enthalpy-based thermal evolution of loops' model. The results show that, for the first set of loops, the synthetic EUV light curves from the model compare favorably with the observed light curves in six AIA channels and eight EIS spectral lines, and the computed mean enthalpy flow velocities also agree with the Doppler shift measurements by EIS. For the second set of loops modeled with twice-heating, there are some discrepancies between modeled and observed EUV light curves in low-temperature bands, and the model does not fully produce the prolonged blueshift signatures as observed. We discuss possible causes for the discrepancies.« less

Mechanical Intestinal Obstruction in a Porcine Model: Effects of Intra-Abdominal Hypertension. A Preliminary Study

PubMed Central

Sánchez-Margallo, F. M.; Latorre, R.; López-Albors, O.; Wise, R.; Malbrain, M. L. N. G.; Castellanos, G.

2016-01-01

Introduction Mechanical intestinal obstruction is a disorder associated with intra-abdominal hypertension and abdominal compartment syndrome. As the large intestine intraluminal and intra-abdominal pressures are increased, so the patient’s risk for intestinal ischaemia. Previous studies have focused on hypoperfusion and bacterial translocation without considering the concomitant effect of intra-abdominal hypertension. The objective of this study was to design and evaluate a mechanical intestinal obstruction model in pigs similar to the human pathophysiology. Materials and Methods Fifteen pigs were divided into three groups: a control group (n = 5) and two groups of 5 pigs with intra-abdominal hypertension induced by mechanical intestinal obstruction. The intra-abdominal pressures of 20 mmHg were maintained for 2 and 5 hours respectively. Hemodynamic, respiratory and gastric intramucosal pH values, as well as blood tests were recorded every 30 min. Results Significant differences between the control and mechanical intestinal obstruction groups were noted. The mean arterial pressure, cardiac index, dynamic pulmonary compliance and abdominal perfusion pressure decreased. The systemic vascular resistance index, central venous pressure, pulse pressure variation, airway resistance and lactate increased within 2 hours from starting intra-abdominal hypertension (p<0.05). In addition, we observed increased values for the peak and plateau airway pressures, and low values of gastric intramucosal pH in the mechanical intestinal obstruction groups that were significant after 3 hours. Conclusion The mechanical intestinal obstruction model appears to adequately simulate the pathophysiology of intestinal obstruction that occurs in humans. Monitoring abdominal perfusion pressure, dynamic pulmonary compliance, gastric intramucosal pH and lactate values may provide insight in predicting the effects on endorgan function in patients with mechanical intestinal obstruction. PMID:26849559

Influence of betaine and salinomycin on intestinal absorption of methionine and glucose and on the ultrastructure of intestinal cells and parasite developmental stages in chicks infected with Eimeria acervulina.

PubMed

Augustine, P C; Danforth, H D

1999-01-01

The effect of betaine and salinomycin on absorption of methionine and glucose in tissue from the duodenal loops of Eimeria acervulina-infected chicks was determined. Differences in the ultrastructure of the intestinal cells and parasite developmental stages were also examined. With a drug-resistant isolate of E. acervulina, methionine absorption was significantly higher in chicks fed a basal diet supplemented with 0.15% betaine as compared with absorption in chicks fed the unsupplemented basal diet. Addition of 66 ppm salinomycin to the diet containing betaine did not further enhance absorption. Conversely, with a drug-sensitive isolate, methionine absorption was significantly higher in chicks fed a diet supplemented with both betaine and salinomycin than in chicks fed the unsupplemented basal diet. Tissue from chicks fed any of the supplemented diets was usually significantly heavier than that from chicks fed the unsupplemented diet, even when weight gains of the birds were similar. Glucose absorption was similar in all diet groups. Epithelial cells in coccidia-infected and uninfected chicks fed diets supplemented with betaine or betaine plus salinomycin were less electron dense than cells from chicks fed diets that were not supplemented with betaine. Merozoites of E. acervulina in chicks fed diets supplemented with salinomycin had extensive membrane disruption and vacuolization, but the damage was prevented when betaine was added to the diet. Numerous merozoites and intact schizonts were seen in the intestinal lumen of chicks fed the diet containing betaine plus salinomycin.

Peritonitis secondary to spontaneous perforation of a primary gastrointestinal stromal tumour of the small intestine: A case report and a literature review.

PubMed

Alessiani, Mario; Gianola, Marco; Rossi, Sabina; Perfetti, Vittorio; Serra, Piero; Zelaschi, Daniela; Magnani, Enzo; Cobianchi, Lorenzo

2015-01-01

A few cases of acute abdomen caused by perforation of small-intestinal gastrointestinal stromal tumours (GISTs) have been reported in the literature. Together with a review of the published cases, here we report a case of an elderly patient with peritonitis due to spontaneous perforation of a GIST of the jejunum. An 82-year-old man was admitted to the emergency unit of our hospital with fever and severe abdominal pain. An abdominal enhanced computed tomography scan detected a 6cm solid mass in the left upper quadrant adherent to a jejunal loop and surrounded by free fluid and free air. Due to the radiological features of the mass, the diagnosis of a perforation of a GIST arising from the jejunum wall was suspected. The patient underwent emergency laparotomy. Intraoperative findings confirmed diffuse peritonitis secondary to jejunal tumour perforation. A segmental resection of the jejunum containing the mass was performed followed by a mechanical end-to-side anastomosis. The histopathologic examination of the mass confirmed the diagnosis of a perforated GIST of the small intestine (high-risk category). The post-operative course was uneventful and the patient was treated with adjuvant imatinib therapy. Twenty-one other cases of spontaneous perforation of small intestine GISTs are reported in the literature and are summarized in the present review. The described case is the tip of the iceberg and spontaneous rupture or perforation of GISTs are a far more frequent first presentation of this rare tumour. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

A LabVIEW model incorporating an open-loop arterial impedance and a closed-loop circulatory system.

PubMed

Cole, R T; Lucas, C L; Cascio, W E; Johnson, T A

2005-11-01

While numerous computer models exist for the circulatory system, many are limited in scope, contain unwanted features or incorporate complex components specific to unique experimental situations. Our purpose was to develop a basic, yet multifaceted, computer model of the left heart and systemic circulation in LabVIEW having universal appeal without sacrificing crucial physiologic features. The program we developed employs Windkessel-type impedance models in several open-loop configurations and a closed-loop model coupling a lumped impedance and ventricular pressure source. The open-loop impedance models demonstrate afterload effects on arbitrary aortic pressure/flow inputs. The closed-loop model catalogs the major circulatory waveforms with changes in afterload, preload, and left heart properties. Our model provides an avenue for expanding the use of the ventricular equations through closed-loop coupling that includes a basic coronary circuit. Tested values used for the afterload components and the effects of afterload parameter changes on various waveforms are consistent with published data. We conclude that this model offers the ability to alter several circulatory factors and digitally catalog the most salient features of the pressure/flow waveforms employing a user-friendly platform. These features make the model a useful instructional tool for students as well as a simple experimental tool for cardiovascular research.

Intestinal inflammation induces genotoxicity to extraintestinal tissues and cell types in mice

PubMed Central

Westbrook, Aya M.; Wei, Bo; Braun, Jonathan; Schiestl, Robert H.

2011-01-01

Chronic intestinal inflammation leads to increased risk of colorectal and small intestinal cancers, and is also associated with extraintestinal manifestations such as lymphomas, other solid cancers, and autoimmune disorders. We have previously found that acute and chronic intestinal inflammation causes DNA damage to circulating peripheral leukocytes, manifesting a systemic effect in genetic and chemically-induced models of intestinal inflammation. This study addresses the scope of tissue targets and genotoxic damage induced by inflammation-associated genotoxicity. Using several experimental models of intestinal inflammation, we analyzed various types of DNA damage in leukocyte subpopulations of the blood, spleen, mesenteric and peripheral lymph nodes; and, in intestinal epithelial cells, hepatocytes, and the brain. Genotoxicity in the form of DNA single and double stranded breaks accompanied by oxidative base damage was found in leukocyte subpopulations of the blood, diverse lymphoid organs, intestinal epithelial cells, and hepatocytes. The brain did not demonstrate significant levels of DNA double strand breaks as measured by γ-H2AX immunostaining. CD4+ and CD8+ T-cells were most sensitive to DNA damage versus other cell types in the peripheral blood. In vivo measurements and in vitro modeling suggested that genotoxicity was induced by increased levels of systemically circulating proinflammatory cytokines. Moreover, genotoxicity involved increased damage rather than reduced repair, since it not associated with decreased expression of the DNA double-strand break recognition and repair protein, ataxia telangiectasia mutated (ATM). These findings suggest that levels of intestinal inflammation contribute to the remote tissue burden of genotoxicity, with potential effects on non-intestinal diseases and cancer. PMID:21520038

Adenosine A2B receptor modulates intestinal barrier function under hypoxic and ischemia/reperfusion conditions.

PubMed

Yang, Yang; Qiu, Yuan; Wang, Wensheng; Xiao, Weidong; Liang, Hongyin; Zhang, Chaojun; Yang, Hanwenbo; Teitelbaum, Daniel H; Sun, Li-Hua; Yang, Hua

2014-01-01

Intestinal barrier function failure from ischemia/reperfusion (I/R) and acute hypoxia has been implicated as a critical determinant in the predisposition to intestinal inflammation and a number of inflammatory disorders. Here, we identified the role of Adenosine A2B receptor (A2BAR) in the regulation of intestinal barrier function under I/R and acute hypoxic conditions. C57BL/6J mice were used, and were randomized into three groups: Sham, I/R, IR+PSB1115 (a specific A2BAR antagonist) groups. After surgery, the small bowel was harvested for immunohistochemical staining, RNA and protein content, and intestinal permeability analyses. Using an epithelial cell culture model, we investigated the influence of hypoxia on the epithelial function, and the role of A2BAR in the expressions of tight junction and epithelial permeability. The expressions of Claudin-1, occludin and ZO-1 were detected by RT-PCR and Western-Blot. Epithelial barrier function was assessed with transepithelial resistance (TER). The A2BAR antagonist, PSB1115, significantly increased tight junction protein expression after intestinal I/R or acute hypoxia conditions. PSB1115 also attenuated the disrupted distribution of TJ proteins. Furthermore, inhibition of A2BAR attenuated the decrease in TER induced by I/R or acute hypoxic conditions, and maintained intestinal barrier function. Antagonism of A2BAR activity improves intestinal epithelial structure and barrier function in a mouse model of intestinal I/R and a cell model of acute hypoxia. These findings support a potentially destructive role for A2BAR under intestinal I/R and acute hypoxic conditions.

Effect of Zinc in Enteropathogenic Escherichia coli Infection▿ †

PubMed Central

Crane, John K.; Naeher, Tonniele M.; Shulgina, Irina; Zhu, Chengru; Boedeker, Edgar C.

2007-01-01

Enteropathogenic Escherichia coli (EPEC) infection triggers the release of ATP from host intestinal cells, and the ATP is broken down to ADP, AMP, and adenosine in the lumen of the intestine. Ecto-5′-nucleotidase (CD73) is the main enzyme responsible for the conversion of 5′-AMP to adenosine, which triggers fluid secretion from host intestinal cells and also has growth-promoting effects on EPEC bacteria. In a recent study, we examined the role of the host enzyme CD73 in EPEC infection by testing the effect of ecto-5′-nucleotidase inhibitors. Zinc was a less potent inhibitor of ecto-5′-nucleotidase in vitro than the nucleotide analog α,β-methylene-ADP, but in vivo, zinc was much more efficacious in preventing EPEC-induced fluid secretion in rabbit ileal loops than α,β-methylene-ADP. This discrepancy between the in vitro and in vivo potencies of the two inhibitors prompted us to search for potential targets of zinc other than ecto-5′-nucleotidase. Zinc, at concentrations that produced little or no inhibition of EPEC growth, caused a decrease in the expression of EPEC protein virulence factors, such as bundle-forming pilus (BFP), EPEC secreted protein A, and other EPEC secreted proteins, and reduced EPEC adherence to cells in tissue culture. The effects of zinc were not mimicked by other transition metals, such as manganese, iron, copper, or nickel, and the effects were not reversed by an excess of iron. Quantitative real-time PCR showed that zinc reduced the abundance of the RNAs encoded by the bfp gene, by the plasmid-encoded regulator (per) gene, by the locus for the enterocyte effacement (LEE)-encoded regulator (ler) gene, and by several of the esp genes. In vivo, zinc reduced EPEC-induced fluid secretion into ligated rabbit ileal loops, decreased the adherence of EPEC to rabbit ileum, and reduced histopathological damage such as villus blunting. Some of the beneficial effects of zinc on EPEC infection appear to be due to the action of the metal on EPEC bacteria as well as on the host. PMID:17875638

RCD+: Fast loop modeling server.

PubMed

López-Blanco, José Ramón; Canosa-Valls, Alejandro Jesús; Li, Yaohang; Chacón, Pablo

2016-07-08

Modeling loops is a critical and challenging step in protein modeling and prediction. We have developed a quick online service (http://rcd.chaconlab.org) for ab initio loop modeling combining a coarse-grained conformational search with a full-atom refinement. Our original Random Coordinate Descent (RCD) loop closure algorithm has been greatly improved to enrich the sampling distribution towards near-native conformations. These improvements include a new workflow optimization, MPI-parallelization and fast backbone angle sampling based on neighbor-dependent Ramachandran probability distributions. The server starts by efficiently searching the vast conformational space from only the loop sequence information and the environment atomic coordinates. The generated closed loop models are subsequently ranked using a fast distance-orientation dependent energy filter. Top ranked loops are refined with the Rosetta energy function to obtain accurate all-atom predictions that can be interactively inspected in an user-friendly web interface. Using standard benchmarks, the average root mean squared deviation (RMSD) is 0.8 and 1.4 Å for 8 and 12 residues loops, respectively, in the challenging modeling scenario in where the side chains of the loop environment are fully remodeled. These results are not only very competitive compared to those obtained with public state of the art methods, but also they are obtained ∼10-fold faster. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Precision-cut intestinal slices: alternative model for drug transport, metabolism, and toxicology research.

PubMed

Li, Ming; de Graaf, Inge A M; Groothuis, Geny M M

2016-01-01

The absorption, distribution, metabolism, excretion and toxicity (ADME-tox) processes of drugs are of importance and require preclinical investigation intestine in addition to the liver. Various models have been developed for prediction of ADME-tox in the intestine. In this review, precision-cut intestinal slices (PCIS) are discussed and highlighted as model for ADME-tox studies. This review provides an overview of the applications and an update of the most recent research on PCIS as an ex vivo model to study the transport, metabolism and toxicology of drugs and other xenobiotics. The unique features of PCIS and the differences with other models as well as the translational aspects are also discussed. PCIS are a simple, fast, and reliable ex vivo model for drug ADME-tox research. Therefore, PCIS are expected to become an indispensable link in the in vitro-ex vivo-in vivo extrapolation, and a bridge in translation of animal data to the human situation. In the future, this model may be helpful to study the effects of interorgan interactions, intestinal bacteria, excipients and drug formulations on the ADME-tox properties of drugs. The optimization of culture medium and the development of a (cryo)preservation technique require more research.

Extrusion without a motor: a new take on the loop extrusion model of genome organization

PubMed Central

Johnson, J.; Michieletto, D.; Morozov, A. N.; Nicodemi, M.; Cook, P. R.; Marenduzzo, D.

2018-01-01

ABSTRACT Chromatin loop extrusion is a popular model for the formation of CTCF loops and topological domains. Recent HiC data have revealed a strong bias in favour of a particular arrangement of the CTCF binding motifs that stabilize loops, and extrusion is the only model to date which can explain this. However, the model requires a motor to generate the loops, and although cohesin is a strong candidate for the extruding factor, a suitable motor protein (or a motor activity in cohesin itself) has yet to be found. Here we explore a new hypothesis: that there is no motor, and thermal motion within the nucleus drives extrusion. Using theoretical modelling and computer simulations we ask whether such diffusive extrusion could feasibly generate loops. Our simulations uncover an interesting ratchet effect (where an osmotic pressure promotes loop growth), and suggest, by comparison to recent in vitro and in vivo measurements, that diffusive extrusion can in principle generate loops of the size observed in the data. Extra View on : C. A. Brackley, J. Johnson, D. Michieletto, A. N. Morozov, M. Nicodemi, P. R. Cook, and D. Marenduzzo “Non-equilibrium chromosome looping via molecular slip-links”, Physical Review Letters 119 138101 (2017) PMID:29300120

A theoretical analysis of anatomical and functional intestinal slow wave re-entry.

PubMed

Du, Peng; O'Grady, Gregory; Cheng, Leo K

2017-07-21

Intestinal bioelectrical slow waves are a key regulator of intestinal motility. Peripheral pacemakers, ectopic initiations and sustained periods of re-entrant activities have all been experimentally observed to be important factors in setting the frequency of intestinal slow waves, but the tissue-level mechanisms underpinning these activities are unclear. This theoretical analysis aimed to define the initiation, maintenance, and termination criteria of two classes of intestinal re-entrant activities: anatomical re-entry and functional re-entry. Anatomical re-entry was modeled in a three-dimensional (3D) cylindrical model, and functional rotor was modeled in a 2D rectangle model. A single-pulse stimulus was used to invoke an anatomical re-entry and a prolonged refractory block was used to invoke the rotor. In both cases, the simulated re-entrant activities operated at frequencies above the baseline entrainment frequency. The anatomical re-entry simulation results demonstrated that a temporary functional refractory block would be required to initiate the re-entrant activity in a single direction around the cylindrical model. The rotor could be terminated by a single-pulse stimulus delivered around the core of the rotor. In conclusion, the simulation results provide the following new insights into the mechanisms of intestinal re-entry: (i) anatomical re-entry is only maintained within a specific range of velocities, outside of which the re-entrant activities become either an ectopic activity or simultaneous activations of the intestinal wall; (ii) a maintained rotor entrained slow waves faster in the antegrade direction than in the retrograde direction. Simulations are shown to be a valuable tool for achieving novel insights into the mechanisms of intestinal slow wave dysrhythmia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of humic acids on intestinal viscosity, leaky gut and ammonia excretion in a 24 hr feed restriction model to induce intestinal permeability in broiler chickens.

PubMed

Maguey-Gonzalez, Jesús A; Michel, Matias A; Baxter, Mikayla F A; Tellez, Guillermo; Moore, Philip A; Solis-Cruz, Bruno; Hernández-Patlan, Daniel; Merino-Guzman, Rubén; Hernandez-Velasco, Xochitl; Latorre, Juan D; Hargis, Billy M; Gomez-Rosales, Sergio; Tellez-Isaias, Guillermo

2018-04-30

The purpose of this study was to evaluate the effect of humic acids (HA) on intestinal viscosity, leaky gut and ammonia excretion in a 24 hr feed restriction (FR) model to induce intestinal permeability in chickens. One-day-old male Cobb-Vantress broilers were randomly allocated to one of two groups (n = 25 chickens), with or without 0.2% of isolated HA from worm-compost, and placed in brooder batteries. Chicks had ad libitum access to water and feed for 14 days. Intestinal permeability was induced by 24 hr FR starting at 14 days. At 15 days of age, chickens in both groups were given an appropriate dose of fluorescein isothiocyanate dextran (FITC-d) by oral gavage. Intestine and liver samples were also collected to evaluate viscosity and bacterial translocation (BT), respectively. An increase (p < .05) in intestinal viscosity was observed in the experimental group consuming 0.2% of HA and was confirmed in a published in vitro digestion model that simulates the chemical and physical conditions of the crop, proventriculus and intestine of chickens. Furthermore, the treated group also showed a significant reduction in FITC-d, liver BT and ammonia in the manure. These results suggest that HA have a positive impact in intestinal integrity in chickens. © 2018 Japanese Society of Animal Science.

Chemical form of selenium affects its uptake, transport and glutathione peroxidase activity in the human intestinal Caco-2 cell model

USDA-ARS?s Scientific Manuscript database

Determining the effect of selenium (Se) chemical form on uptake and transport in human intestinal cells is critical to assess Se bioavailability. In the present study, we measured the uptake and transport of various Se compounds in the human intestinal Caco-2 cell model. We found that two sources...

Late complication of open inguinal hernia repair: small bowel obstruction caused by intraperitoneal mesh migration.

PubMed

Ferrone, Roberto; Scarone, Pier Carlo; Natalini, Gianni

2003-09-01

We describe a case of small bowel obstruction due to prosthetic mesh migration. A 67-year-old male, who had undergone prosthetic repair of inguinal hernia 3 years before, was admitted for a mechanical small bowel obstruction. Laparotomy revealed the penultimate ileal loop choked by an adhesion drawing it towards a polypropylene mesh, firmly attached to the parietal peritoneum of the inguinal region. The intestinal loop was released; the mesh was embedded deep with continuous whip suture after folding the parietal peritoneum. The patient was dismissed on the 11th postoperative day surgically healed. The "tension-free" technique is undoubtedly the gold standard for hernia repair. However, it is not free of complications, mostly due to technical errors, of which the surgeon must be aware, both when he is responsible for correcting defects in the wall, as well as when he has to face an occlusion in a patient who has undergone plastic surgery for inguinal hernia.

Evaluation of the reverse transcription loop-mediated isothermal amplification (RT-LAMP) as a screening method for the detection of influenza viruses in the fecal materials of water birds.

PubMed

Yoshida, Hiromi; Sakoda, Yoshihiro; Endo, Mayumi; Motoshima, Masayuki; Yoshino, Fumi; Yamamoto, Naoki; Okamatsu, Masatoshi; Soejima, Takahiro; Senba, Syouhei; Kanda, Hidetoshi; Kida, Hiroshi

2011-06-01

Migratory water birds are a natural reservoir for influenza A viruses. Viruses replicate in the intestines of ducks and are shed with the fecal materials. Virus isolation from collected fecal materials, therefore, is an integral part of the surveillance of avian influenza in water birds. In the present study, reverse transcription loop-mediated isothermal amplification (RT-LAMP) was assessed for its usefulness in detecting the RNA of influenza A viruses in fecal materials. It was found that, RT-LAMP specifically and sensitively detects the matrix gene of influenza A viruses. Influenza A viruses were isolated from the fecal materials in which viral RNA were detected by RT-LAMP in 35 min. The present findings indicate that RT-LAMP is useful as a high throughput screening method for field samples prior to virus isolation, allowing the processing of hundreds of samples per day.

Animal models of ischemia-reperfusion-induced intestinal injury: progress and promise for translational research

PubMed Central

Gonzalez, Liara M.; Moeser, Adam J.

2014-01-01

Research in the field of ischemia-reperfusion injury continues to be plagued by the inability to translate research findings to clinically useful therapies. This may in part relate to the complexity of disease processes that result in intestinal ischemia but may also result from inappropriate research model selection. Research animal models have been integral to the study of ischemia-reperfusion-induced intestinal injury. However, the clinical conditions that compromise intestinal blood flow in clinical patients ranges widely from primary intestinal disease to processes secondary to distant organ failure and generalized systemic disease. Thus models that closely resemble human pathology in clinical conditions as disparate as volvulus, shock, and necrotizing enterocolitis are likely to give the greatest opportunity to understand mechanisms of ischemia that may ultimately translate to patient care. Furthermore, conditions that result in varying levels of ischemia may be further complicated by the reperfusion of blood to tissues that, in some cases, further exacerbates injury. This review assesses animal models of ischemia-reperfusion injury as well as the knowledge that has been derived from each to aid selection of appropriate research models. In addition, a discussion of the future of intestinal ischemia-reperfusion research is provided to place some context on the areas likely to provide the greatest benefit from continued research of ischemia-reperfusion injury. PMID:25414098

Ex Vivo and In Situ Evaluation of 'Dispelling-Wind' Chinese Medicine Herb-Drugs on Intestinal Absorption of Chlorogenic Acid.

PubMed

Zhai, Lixiang; Shi, Jun; Xu, Weitong; Heinrich, Michael; Wang, Jianying; Deng, Wenji

2015-12-01

This study aims to investigate the additive or synergistic effects and mechanism of intestinal absorption of extracts from two commonly used 'dispelling-wind' TCM botanical drugs [roots of Angelica dahurica (Hoffm.) Benth. & Hook. f. ex Franch. & Sav. (RAD) and Saposhnikovia divaricata (Turcz.) Schischk. (RSD)] using chlorogenic acid as a marker substance. Ex vivo everted intestinal sac and in situ single pass perfusion methods using rats were employed to investigate the effects of two TCM botanical drugs extracts on the intestinal absorption of chlorogenic acid. Both the extracts of RAD and RSD showed synergistic properties on the intestinal absorption of chlorogenic acid. The verapamil (a P-gp inhibitor) and intestinal dysbacteriosis model induced by norfloxacin increased the P(app) and K(a) of intestinal absorption of chlorogenic acid. These synergistic effects on intestinal absorption in a rat model can be correlated with the inhibition of P-gp and regulation of gut microbiota. This experimental approach has helped to better understand changes in the absorption of chlorogenic acid under different conditions. Copyright © 2015 John Wiley & Sons, Ltd.

Inverted Temperature Loops in The Quiet Corona: Properties and Physical Origin

NASA Astrophysics Data System (ADS)

Huang, Z.; van der Holst, B.; Frazin, R. A.; Nuevo, F.; Vásquez, A. M.; Manchester, W.; Sokolov, I.; Gombosi, T. I.

2013-12-01

Huang et al. 2012 revealed the existence of inverted temperature ("down") loops, in which temperature decreases with height, as well as the usual ("up") loops, in which the temperature increases with height, in the quiet solar Corona. It was shown that the "down" loops are mostly located at low latitudes and "up" loops most often appear in high latitudes. A recent study by Nuevo et al. 2013 confirmed this discovery and further showed that the "down" loop population is greatest at solar minimum; and strongly decreases with solar activity. Moreover, the "down" loops were found to be associated with values of the plasma beta greater than about unity, while the "up" loops were associated with much smaller values of beta. Here, we review the properties of "up" and "down" loops, and employ a state-of-the-art global MHD model to understand the physics of these loops as well as to investigate their thermodynamic stability. The 3D MHD model uses a phenomenological wave dissipation model based on wave reflection (proportional to the Alfvén speed gradients) and turbulent dissipation.

Dynamic simulation of perturbation responses in a closed-loop virtual arm model.

PubMed

Du, Yu-Fan; He, Xin; Lan, Ning

2010-01-01

A closed-loop virtual arm (VA) model has been developed in SIMULINK environment by adding spinal reflex circuits and propriospinal neural networks to the open-loop VA model developed in early study [1]. An improved virtual muscle model (VM4.0) is used to speed up simulation and to generate more precise recruitment of muscle force at low levels of muscle activation. Time delays in the reflex loops are determined by their synaptic connections and afferent transmission back to the spinal cord. Reflex gains are properly selected so that closed-loop responses are stable. With the closed-loop VA model, we are developing an approach to evaluate system behaviors by dynamic simulation of perturbation responses. Joint stiffness is calculated based on simulated perturbation responses by a least-squares algorithm in MATLAB. This method of dynamic simulation will be essential for further evaluation of feedforward and reflex control of arm movement and position.

Technologies for Future Precision Strike Missile Systems (les Technologies des futurs systemes de missiles pour frappe de precision)

DTIC Science & Technology

2001-07-01

hardware - in - loop (HWL) simulation is also developed...Firings / Engine Tests Structure Test Hardware In - Loop Simulation Subsystem Test Lab Tests Seeker Actuators Sensors Electronics Propulsion Model Aero Model...Structure Test Hardware In - Loop Simulation Subsystem Test Lab Tests Seeker Actuators Sensors Electronics Propulsion Model Aero Model Model

An individual based computational model of intestinal crypt fission and its application to predicting unrestrictive growth of the intestinal epithelium.

PubMed

Pin, Carmen; Parker, Aimee; Gunning, A Patrick; Ohta, Yuki; Johnson, Ian T; Carding, Simon R; Sato, Toshiro

2015-02-01

Intestinal crypt fission is a homeostatic phenomenon, observable in healthy adult mucosa, but which also plays a pathological role as the main mode of growth of some intestinal polyps. Building on our previous individual based model for the small intestinal crypt and on in vitro cultured intestinal organoids, we here model crypt fission as a budding process based on fluid mechanics at the individual cell level and extrapolated predictions for growth of the intestinal epithelium. Budding was always observed in regions of organoids with abundant Paneth cells. Our data support a model in which buds are biomechanically initiated by single stem cells surrounded by Paneth cells which exhibit greater resistance to viscoelastic deformation, a hypothesis supported by atomic force measurements of single cells. Time intervals between consecutive budding events, as simulated by the model and observed in vitro, were 2.84 and 2.62 days, respectively. Predicted cell dynamics was unaffected within the original crypt which retained its full capability of providing cells to the epithelium throughout fission. Mitotic pressure in simulated primary crypts forced upward migration of buds, which simultaneously grew into new protruding crypts at a rate equal to 1.03 days(-1) in simulations and 0.99 days(-1) in cultured organoids. Simulated crypts reached their final size in 4.6 days, and required 6.2 days to migrate to the top of the primary crypt. The growth of the secondary crypt is independent of its migration along the original crypt. Assuming unrestricted crypt fission and multiple budding events, a maximal growth rate of the intestinal epithelium of 0.10 days(-1) is predicted and thus approximately 22 days are required for a 10-fold increase of polyp size. These predictions are in agreement with the time reported to develop macroscopic adenomas in mice after loss of Apc in intestinal stem cells.

A mechanistic model of small intestinal starch digestion and glucose uptake in the cow.

PubMed

Mills, J A N; France, J; Ellis, J L; Crompton, L A; Bannink, A; Hanigan, M D; Dijkstra, J

2017-06-01

The high contribution of postruminal starch digestion (up to 50%) to total-tract starch digestion on energy-dense, starch-rich diets demands that limitations to small intestinal starch digestion be identified. A mechanistic model of the small intestine was described and evaluated with regard to its ability to simulate observations from abomasal carbohydrate infusions in the dairy cow. The 7 state variables represent starch, oligosaccharide, glucose, and pancreatic amylase in the intestinal lumen, oligosaccharide and glucose in the unstirred water layer at the intestinal wall, and intracellular glucose of the enterocyte. Enzymatic hydrolysis of starch was modeled as a 2-stage process involving the activity of pancreatic amylase in the lumen and of oligosaccharidase at the brush border of the enterocyte confined within the unstirred water layer. The Na + -dependent glucose transport into the enterocyte was represented along with a facilitative glucose transporter 2 transport system on the basolateral membrane. The small intestine is subdivided into 3 main sections, representing the duodenum, jejunum, and ileum for parameterization. Further subsections are defined between which continual digesta flow is represented. The model predicted nonstructural carbohydrate disappearance in the small intestine for cattle unadapted to duodenal infusion with a coefficient of determination of 0.92 and a root mean square prediction error of 25.4%. Simulation of glucose disappearance for mature Holstein heifers adapted to various levels of duodenal glucose infusion yielded a coefficient of determination of 0.81 and a root mean square prediction error of 38.6%. Analysis of model behavior identified limitations to the efficiency of small intestinal starch digestion with high levels of duodenal starch flow. Limitations to individual processes, particularly starch digestion in the proximal section of the intestine, can create asynchrony between starch hydrolysis and glucose uptake capacity. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Feasibility and scalability of spring parameters in distraction enterogenesis in a murine model.

PubMed

Huynh, Nhan; Dubrovsky, Genia; Rouch, Joshua D; Scott, Andrew; Stelzner, Matthias; Shekherdimian, Shant; Dunn, James C Y

2017-07-01

Distraction enterogenesis has been investigated as a novel treatment for short bowel syndrome (SBS). With variable intestinal sizes, it is critical to determine safe, translatable spring characteristics in differently sized animal models before clinical use. Nitinol springs have been shown to lengthen intestines in rats and pigs. Here, we show spring-mediated intestinal lengthening is scalable and feasible in a murine model. A 10-mm nitinol spring was compressed to 3 mm and placed in a 5-mm intestinal segment isolated from continuity in mice. A noncompressed spring placed in a similar fashion served as a control. Spring parameters were proportionally extrapolated from previous spring parameters to accommodate the smaller size of murine intestines. After 2-3 wk, the intestinal segments were examined for size and histology. Experimental group with spring constants, k = 0.2-1.4 N/m, showed intestinal lengthening from 5.0 ± 0.6 mm to 9.5 ± 0.8 mm (P < 0.0001), whereas control segments lengthened from 5.3 ± 0.5 mm to 6.4 ± 1.0 mm (P < 0.02). Diameter increased similarly in both groups. Isolated segment perforation was noted when k ≥ 0.8 N/m. Histologically, lengthened segments had increased muscularis thickness and crypt depth in comparison to normal intestine. Nitinol springs with k ≤ 0.4 N/m can safely yield nearly 2-fold distraction enterogenesis in length and diameter in a scalable mouse model. Not only does this study derive the safe ranges and translatable spring characteristics in a scalable murine model for patients with short bowel syndrome, it also demonstrates the feasibility of spring-mediated intestinal lengthening in a mouse, which can be used to study underlying mechanisms in the future. Copyright © 2017 Elsevier Inc. All rights reserved.

Bayesian Action-Perception loop modeling: Application to trajectory generation and recognition using internal motor simulation

NASA Astrophysics Data System (ADS)

Gilet, Estelle; Diard, Julien; Palluel-Germain, Richard; Bessière, Pierre

2011-03-01

This paper is about modeling perception-action loops and, more precisely, the study of the influence of motor knowledge during perception tasks. We use the Bayesian Action-Perception (BAP) model, which deals with the sensorimotor loop involved in reading and writing cursive isolated letters and includes an internal simulation of movement loop. By using this probabilistic model we simulate letter recognition, both with and without internal motor simulation. Comparison of their performance yields an experimental prediction, which we set forth.

Protein Loop Structure Prediction Using Conformational Space Annealing.

PubMed

Heo, Seungryong; Lee, Juyong; Joo, Keehyoung; Shin, Hang-Cheol; Lee, Jooyoung

2017-05-22

We have developed a protein loop structure prediction method by combining a new energy function, which we call E PLM (energy for protein loop modeling), with the conformational space annealing (CSA) global optimization algorithm. The energy function includes stereochemistry, dynamic fragment assembly, distance-scaled finite ideal gas reference (DFIRE), and generalized orientation- and distance-dependent terms. For the conformational search of loop structures, we used the CSA algorithm, which has been quite successful in dealing with various hard global optimization problems. We assessed the performance of E PLM with two widely used loop-decoy sets, Jacobson and RAPPER, and compared the results against the DFIRE potential. The accuracy of model selection from a pool of loop decoys as well as de novo loop modeling starting from randomly generated structures was examined separately. For the selection of a nativelike structure from a decoy set, E PLM was more accurate than DFIRE in the case of the Jacobson set and had similar accuracy in the case of the RAPPER set. In terms of sampling more nativelike loop structures, E PLM outperformed E DFIRE for both decoy sets. This new approach equipped with E PLM and CSA can serve as the state-of-the-art de novo loop modeling method.

Mathematical Modeling of Loop Heat Pipes

NASA Technical Reports Server (NTRS)

Kaya, Tarik; Ku, Jentung; Hoang, Triem T.; Cheung, Mark L.

1998-01-01

The primary focus of this study is to model steady-state performance of a Loop Heat Pipe (LHP). The mathematical model is based on the steady-state energy balance equations at each component of the LHP. The heat exchange between each LHP component and the surrounding is taken into account. Both convection and radiation environments are modeled. The loop operating temperature is calculated as a function of the applied power at a given loop condition. Experimental validation of the model is attempted by using two different LHP designs. The mathematical model is tested at different sink temperatures and at different elevations of the loop. Tbc comparison of the calculations and experimental results showed very good agreement (within 3%). This method proved to be a useful tool in studying steady-state LHP performance characteristics.

Renewable Energy Generation and Storage Models | Grid Modernization | NREL

Science.gov Websites

-the-loop testing Projects Generator, Plant, and Storage Modeling, Simulation, and Validation NREL power plants. Power Hardware-in-the-Loop Testing NREL researchers are developing software-and-hardware -combined simulation testing methods known as power hardware-in-the-loop testing. Power hardware in the loop

N-Loop Learning: Part II--An Empirical Investigation

ERIC Educational Resources Information Center

Simonin, Bernard L.

2017-01-01

Purpose: Through a survey of firm's experiences with strategic alliances and a structural equation modeling approach, the aim of this study is to stimulate further interest in modeling and empirical research in the area of N-loop learning. Although the concepts of single-loop and double-loop learning, in particular, are well established in the…

Comparative assessment of the efficacy of closed helical loop and T-loop for space closure in lingual orthodontics-a finite element study.

PubMed

Chacko, Ajay; Tikku, Tripti; Khanna, Rohit; Maurya, Rana Pratap; Srivastava, Kamna

2018-05-28

Retraction in lingual orthodontics has biomechanical differences when compared to labial orthodontics, which is not yet established. Thus, we have intended to compare the biomechanical characteristics of closed helical loop and T-loop on 1 mm activation with 30° of compensatory curvatures during retraction in lingual orthodontics. STb lingual brackets were indirectly bonded to maxillary typhodont model that was scanned to obtain FEM model. Closed helical loop (2 × 7 mm) and T-loop (6 × 2 × 7 mm) of 0.016″ × 0.016″ TMA wire were modeled without preactivation bends. Preactivation bends at 30° were given in the software. Boundary conditions were set. The force (F) and moment (M) of both the loops were determined on 1 mm activation, using ANSYS software. M/F ratio was also calculated for both the loops. T-loop exerted less force, thus increased M/F ratio as compared to closed helical loop on 1 mm activation. When torque has to be preserved in the anterior segment during retraction in lingual orthodontics, T-loop can be preferred over closed helical loop.

The absorption and first-pass metabolism of [14C]-1,3-dinitrobenzene in the isolated vascularly perfused rat small intestine.

PubMed

Adams, P C; Rickert, D E

1996-11-01

We tested the hypothesis that the small intestine is capable of the first-pass, reductive metabolism of xenobiotics. A simplified version of the isolated vascularly perfused rat small intestine was developed to test this hypothesis with 1,3-dinitrobenzene (1,3-DNB) as a model xenobiotic. Both 3-nitroaniline (3-NA) and 3-nitroacetanilide (3-NAA) were formed and absorbed following intralumenal doses of 1,3-DNB (1.8 or 4.2 mumol) to isolated vascularly perfused rat small intestine. Dose, fasting, or antibiotic pretreatment had no effect on the absorption and metabolism of 1,3-DNB in this model system. The failure of antibiotic pretreatment to alter the metabolism of 1,3-DNA indicated that 1,3-DNB metabolism was mammalian rather than microfloral in origin. All data from experiments initiated with lumenal 1,3-DNB were fit to a pharmacokinetic model (model A). ANOVA analysis revealed that dose, fasting, or antibiotic pretreatment had no statistically significant effect on the model-dependent parameters. 3-NA (1.5 mumol) was administered to the lumen of isolated vascularly perfused rat small intestine to evaluate model A predictions for the absorption and metabolism of this metabolite. All data from experiments initiated with 3-NA were fit to a pharmacokinetic model (model B). Comparison of corresponding model-dependent pharmacokinetic parameters (i.e. those parameters which describe the same processes in models A and B) revealed quantitative differences. Evidence for significant quantitative differences in the pharmacokinetics or metabolism of formed versus preformed 3-NA in rat small intestine may require better definition of the rate constants used to describe tissue and lumenal processes or identification and incorporation of the remaining unidentified metabolites into the models.

Static and Impulsive Models of Solar Active Regions

NASA Technical Reports Server (NTRS)

Patsourakos, S.; Klimchuk, James A.

2008-01-01

The physical modeling of active regions (ARs) and of the global coronal is receiving increasing interest lately. Recent attempts to model ARs using static equilibrium models were quite successful in reproducing AR images of hot soft X-ray (SXR) loops. They however failed to predict the bright EUV warm loops permeating ARs: the synthetic images were dominated by intense footpoint emission. We demonstrate that this failure is due to the very weak dependence of loop temperature on loop length which cannot simultaneously account for both hot and warm loops in the same AR. We then consider time-dependent AR models based on nanoflare heating. We demonstrate that such models can simultaneously reproduce EUV and SXR loops in ARs. Moreover, they predict radial intensity variations consistent with the localized core and extended emissions in SXR and EUV AR observations respectively. We finally show how the AR morphology can be used as a gauge of the properties (duration, energy, spatial dependence, repetition time) of the impulsive heating.

THE CORONAL LOOP INVENTORY PROJECT: EXPANDED ANALYSIS AND RESULTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schmelz, J. T.; Christian, G. M.; Chastain, R. A., E-mail: jschmelz@usra.edu

We have expanded upon earlier work that investigates the relative importance of coronal loops with isothermal versus multithermal cross-field temperature distributions. These results are important for determining if loops have substructure in the form of unresolved magnetic strands. We have increased the number of loops targeted for temperature analysis from 19 to 207 with the addition of 188 new loops from multiple regions. We selected all loop segments visible in the 171 Å images of the Atmospheric Imaging Assembly (AIA) that had a clean background. Eighty-six of the new loops were rejected because they could not be reliably separated frommore » the background in other AIA filters. Sixty-one loops required multithermal models to reproduce the observations. Twenty-eight loops were effectively isothermal, that is, the plasma emission to which AIA is sensitive could not be distinguished from isothermal emission, within uncertainties. Ten loops were isothermal. Also, part of our inventory was one small flaring loop, one very cool loop whose temperature distribution could not be constrained by the AIA data, and one loop with inconclusive results. Our survey can confirm an unexpected result from the pilot study: we found no isothermal loop segments where we could properly use the 171-to-193 ratio method, which would be similar to the analysis done for many loops observed with TRACE and EIT. We recommend caution to observers who assume the loop plasma is isothermal, and hope that these results will influence the direction of coronal heating models and the effort modelers spend on various heating scenarios.« less

Equilibrium models of coronal loops that involve curvature and buoyancy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hindman, Bradley W.; Jain, Rekha, E-mail: hindman@solarz.colorado.edu

2013-12-01

We construct magnetostatic models of coronal loops in which the thermodynamics of the loop is fully consistent with the shape and geometry of the loop. This is achieved by treating the loop as a thin, compact, magnetic fibril that is a small departure from a force-free state. The density along the loop is related to the loop's curvature by requiring that the Lorentz force arising from this deviation is balanced by buoyancy. This equilibrium, coupled with hydrostatic balance and the ideal gas law, then connects the temperature of the loop with the curvature of the loop without resorting to amore » detailed treatment of heating and cooling. We present two example solutions: one with a spatially invariant magnetic Bond number (the dimensionless ratio of buoyancy to Lorentz forces) and the other with a constant radius of the curvature of the loop's axis. We find that the density and temperature profiles are quite sensitive to curvature variations along the loop, even for loops with similar aspect ratios.« less

Iterative LQG Controller Design Through Closed-Loop Identification

NASA Technical Reports Server (NTRS)

Hsiao, Min-Hung; Huang, Jen-Kuang; Cox, David E.

1996-01-01

This paper presents an iterative Linear Quadratic Gaussian (LQG) controller design approach for a linear stochastic system with an uncertain open-loop model and unknown noise statistics. This approach consists of closed-loop identification and controller redesign cycles. In each cycle, the closed-loop identification method is used to identify an open-loop model and a steady-state Kalman filter gain from closed-loop input/output test data obtained by using a feedback LQG controller designed from the previous cycle. Then the identified open-loop model is used to redesign the state feedback. The state feedback and the identified Kalman filter gain are used to form an updated LQC controller for the next cycle. This iterative process continues until the updated controller converges. The proposed controller design is demonstrated by numerical simulations and experiments on a highly unstable large-gap magnetic suspension system.

The piglet as a model for studying dietary components in infant diets: effects of galacto-oligosaccharides on intestinal functions.

PubMed

Alizadeh, A; Akbari, P; Difilippo, E; Schols, H A; Ulfman, L H; Schoterman, M H C; Garssen, J; Fink-Gremmels, J; Braber, S

2016-02-28

Prebiotic oligosaccharides, including galacto-oligosaccharides (GOS), are used in infant formula to mimic human milk oligosaccharides, which are known to have an important role in the development of the intestinal microbiota and the immune system in neonates. The maturation of the intestines in piglets closely resembles that of human neonates and infants. Hence, a neonatal piglet model was used to study the multi-faceted effect of dietary GOS in early life. Naturally farrowed piglets were separated from the mother sow 24-48 h postpartum and received a milk replacer with or without the addition of GOS for 3 or 26 d, whereafter several indicators of intestinal colonisation and maturation were measured. Dietary GOS was readily fermented in the colon, leading to a decreased pH, an increase in butyric acid in caecum digesta and an increase in lactobacilli and bifidobacteria numbers at day 26. Histomorphological changes were observed in the intestines of piglets fed a GOS diet for 3 or 26 d. In turn, differences in the intestinal disaccharidase activity were observed between control and GOS-fed piglets. The mRNA expression of various tight junction proteins was up-regulated in the intestines of piglet fed a GOS diet and was not accompanied by an increase in protein expression. GOS also increased defensin porcine β-defensin-2 in the colon and secretory IgA levels in saliva. In conclusion, by applying a neonatal piglet model, it could be demonstrated that a GOS-supplemented milk replacer promotes the balance of the developing intestinal microbiota, improves the intestinal architecture and seems to stimulate the intestinal defence mechanism.

A class of all digital phase locked loops - Modeling and analysis

NASA Technical Reports Server (NTRS)

Reddy, C. P.; Gupta, S. C.

1973-01-01

An all digital phase locked loop which tracks the phase of the incoming signal once per carrier cycle is proposed. The different elements and their functions, and the phase lock operation are explained in detail. The general digital loop operation is governed by a nonlinear difference equation from which a suitable model is developed. The lock range for the general model is derived. The performance of the digital loop for phase step and frequency step inputs for different levels of quantization without loop filter are studied. The analytical results are checked by simulating the actual system on the digital computer.

Modeling of the relationship between dipeptide structure and dipeptide stability, permeability, and ACE inhibitory activity.

PubMed

Foltz, Martin; van Buren, Leo; Klaffke, Werner; Duchateau, Guus S M J E

2009-09-01

Selected di- and tripeptides exhibit angiotensin-I converting enzyme (ACE) inhibitory activity in vitro. However, the efficacy in vivo is most likely limited for most peptides due to low bioavailability. The purpose of this study was to identify descriptors of intestinal stability, permeability, and ACE inhibitory activity of dipeptides. A total of 228 dipeptides were synthesized; intestinal stability was obtained by in vitro digestion, intestinal permeability using Caco-2 cells and ACE inhibitory activity by an in vitro assay. Databases were constructed to study the relationship between structure and activity, permeability, and stability. Quantitative structure-activity relationship (QSAR) modeling was performed based on computed models using partial least squares regression based on 400 molecular descriptors. QSAR modeling of dipeptide stability revealed high correlation coefficients (R > 0.65) for models based on Z and X scales. However, amino acid (AA) clustering showed the best results in describing stability of dipeptides. The N-terminal AA residues Asp, Gly, and Pro as well as the C-terminal residues Pro, Ser, Thr, and Asp stabilize dipeptides toward luminal enzymatic peptide hydrolysis. QSAR modeling did not reveal significant correlation models for intestinal permeability. 2D-fingerprint models were identified describing ACE inhibitory activity of dipeptides. The intestinal stability of 12 peptides was predicted. Peptides were synthesized and stability was confirmed in simulated digestion experiments. Based on the results, specific dipeptides can be designed to meet both stability and activity criteria. However, postabsorptive ACE inhibitory activities of dipeptides in vivo are most likely limited due to the very low intestinal permeability of dipeptides.

Porcine models of digestive disease: the future of large animal translational research

PubMed Central

Gonzalez, Liara M.; Moeser, Adam J.; Blikslager, Anthony T.

2015-01-01

There is increasing interest in non-rodent translational models for the study of human disease. The pig, in particular, serves as a useful animal model for the study of pathophysiological conditions relevant to the human intestine. This review assesses currently used porcine models of gastrointestinal physiology and disease and provides a rationale for the use of these models for future translational studies. The pig has proven its utility for the study of fundamental disease conditions such as ischemia/ reperfusion injury, stress-induced intestinal dysfunction, and short bowel syndrome. Pigs have also shown great promise for the study of intestinal barrier function, surgical tissue manipulation and intervention, as well as biomaterial implantation and tissue transplantation. Advantages of pig models highlighted by these studies include the physiological similarity to human intestine as well as to mechanisms of human disease. Emerging future directions for porcine models of human disease include the fields of transgenics and stem cell biology, with exciting implications for regenerative medicine. PMID:25655839

Simulating nanostorm heating in coronal loops using hydrodynamics and non-thermal particle evolution

NASA Astrophysics Data System (ADS)

Migliore, Christina; Winter, Henry; Murphy, Nicholas

2018-01-01

The solar corona is filled with loop-like structures that appear bright against the background when observed in the extreme ultraviolet (EUV). These loops have several remarkable properties that are not yet well understood. Warm loops (∼ 1 MK) appear to be ∼ 2 ‑ 9 times as dense at their apex as the predictions of hydrostatic atmosphere models. These loops also appear to be of constant cross-section despite the fact that the field strength in a potential magnetic field should decrease in the corona, causing the loops to expand. It is not clear why many active region loops appear to be of constant cross-section. Theories range from an internal twist of the magnetic field to observational effects. In this work we simulate active region loops heated by nanoflare storms using a dipolar magnetic field. We calculate the hydrodynamic properties for each loop using advanced hydrodynamics codes to simulate the corona and chromospheric response and basic dipole models to represent the magnetic fields of the loops. We show that even modest variations of the magnetic field strength along the loop can lead to drastic changes in the density profiles of active region loops, and they can also explain the overpressure at the apex of these loops. Synthetic AIA images of each loop are made to show the observable consequences of varying magnetic field strengths along the loop’s axis of symmetry. We also show how this work can lead to improved modeling of larger solar and stellar flares.

Suppression of heating of coronal loops rooted in opposite polarity sunspot umbrae

NASA Astrophysics Data System (ADS)

Tiwari, Sanjiv K.; Thalmann, Julia K.; Moore, Ronald L.; Panesar, Navdeep; Winebarger, Amy R.

2016-05-01

EUV observations of active region (AR) coronae reveal the presence of loops at different temperatures. To understand the mechanisms that result in hotter or cooler loops, we study a typical bipolar AR, near solar disk center, which has moderate overall magnetic twist and at least one fully developed sunspot of each polarity. From AIA 193 and 94 A images we identify many clearly discernible coronal loops that connect plage or a sunspot of one polarity to an opposite-polarity plage region. The AIA 94 A images show dim regions in the umbrae of the spots. To see which coronal loops are rooted in a dim umbral area, we performed a non-linear force-free field (NLFFF) modeling using photospheric vector magnetic field measurements obtained with the HMI onboard SDO. After validation of the NLFFF model by comparison of calculated model field lines and observed loops in AIA 193 and 94, we specify the photospheric roots of the model field lines. The model field then shows the coronal magnetic loops that arch from the dim umbral areas of the opposite polarity sunspots. Because these coronal loops are not visible in any of the coronal EUV and X-ray images of the AR, we conclude they are the coolest loops in the AR. This result suggests that the loops connecting opposite polarity umbrae are the least heated because the field in umbrae is so strong that the convective braiding of the field is strongly suppressed.We hypothesize that the convective freedom at the feet of a coronal loop, together with the strength of the field in the body of the loop, determines the strength of the heating. In particular, we expect the hottest coronal loops to have one foot in an umbra and the other foot in opposite-polarity penumbra or plage (coronal moss), the areas of strong field in which convection is not as strongly suppressed as in umbra. Many transient, outstandingly bright, loops in the AIA 94 movie of the AR do have this expected rooting pattern. We will also present another example of AR in which we find a similar rooting pattern of coronal loops.

Decrease in oral bioavailability of ciclosporin by intravenous pulse of methylprednisolone succinate in rats.

PubMed

Konishi, Hiroki; Sumi, Masaki; Shibata, Nobuhito; Takada, Kanji; Minouchi, Tokuzo; Yamaji, Akira

2004-10-01

We examined the effects of high-dose methylprednisolone on the bioavailability of orally administered ciclosporin in rats. To emulate the clinical protocol of methylprednisolone pulse therapy, methylprednisolone sodium succinate (MPS), a prodrug of methylprednisolone, was intravenously administered as repeated doses (66.3 mg kg(-1)) for 3 days. The area under the blood ciclosporin concentration versus time curve after oral administration was significantly reduced by 60% by pulse treatment with MPS. Based on our previous finding that the total body clearance of ciclosporin was reduced by about 20% by the same methylprednisolone pulse protocol, the extent of reduction in the oral bioavailability of ciclosporin was estimated to be approximately 50%, indicating a drug interaction between high-dose methylprednisolone and orally administered ciclosporin, which affected the absorption process. In rats treated with MPS, an in-situ efflux experiment using rhodamine-123 demonstrated that the reverse transport function of P-glycoprotein (P-gp) in the small intestine was significantly enhanced, although there was no significant increase in the intestinal microsomal activity of triazolam alpha- and 4-hydroxylation, metabolic probes for CYP3A. In addition, a significant decrease was observed in the amount of secreted bile acids serving as an enhancer of gastrointestinal absorption of ciclosporin in MPS treatment. To directly estimate the absorptive capacity, an in-situ absorption test was conducted using a closed-loop of small intestine in control and MPS-treated rats. Intestinal absorption of ciclosporin was significantly decreased, not only in the absence of bile flow but also by treatment with MPS, which well reflected the change in the in-vivo pharmacokinetic behaviour of ciclosporin after methylprednisolone pulsing. These results demonstrate that bioavailability of ciclosporin is markedly reduced by MPS pulse treatment, and the mechanism of this interaction was confirmed to involve enhancement of small-intestinal P-gp function and decrease in bile secretion.

A minimal mathematical model combining several regulatory cycles from the budding yeast cell cycle.

PubMed

Sriram, K; Bernot, G; Képès, F

2007-11-01

A novel topology of regulatory networks abstracted from the budding yeast cell cycle is studied by constructing a simple nonlinear model. A ternary positive feedback loop with only positive regulations is constructed with elements that activates the subsequent element in a clockwise fashion. A ternary negative feedback loop with only negative regulations is constructed with the elements that inhibit the subsequent element in an anticlockwise fashion. Positive feedback loop exhibits bistability, whereas the negative feedback loop exhibits limit cycle oscillations. The novelty of the topology is that the corresponding elements in these two homogeneous feedback loops are linked by the binary positive feedback loops with only positive regulations. This results in the emergence of mixed feedback loops in the network that displays complex behaviour like the coexistence of multiple steady states, relaxation oscillations and chaos. Importantly, the arrangement of the feedback loops brings in the notion of checkpoint in the model. The model also exhibits domino-like behaviour, where the limit cycle oscillations take place in a stepwise fashion. As the aforementioned topology is abstracted from the budding yeast cell cycle, the events that govern the cell cycle are considered for the present study. In budding yeast, the sequential activation of the transcription factors, cyclins and their inhibitors form mixed feedback loops. The transcription factors that involve in the positive regulation in a clockwise orientation generates ternary positive feedback loop, while the cyclins and their inhibitors that involve in the negative regulation in an anticlockwise orientation generates ternary negative feedback loop. The mutual regulation between the corresponding elements in the transcription factors and the cyclins and their inhibitors generates binary positive feedback loops. The bifurcation diagram constructed for the whole system can be related to the different events of the cell cycle in terms of dynamical system theory. The checkpoint mechanism that plays an important role in different phases of the cell cycle are accounted for by silencing appropriate feedback loops in the model.

MULTI-STRAND CORONAL LOOP MODEL AND FILTER-RATIO ANALYSIS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bourouaine, Sofiane; Marsch, Eckart, E-mail: bourouaine@mps.mpg.d

2010-01-10

We model a coronal loop as a bundle of seven separate strands or filaments. Each of the loop strands used in this model can independently be heated (near their left footpoints) by Alfven/ion-cyclotron waves via wave-particle interactions. The Alfven waves are assumed to penetrate the strands from their footpoints, at which we consider different wave energy inputs. As a result, the loop strands can have different heating profiles, and the differential heating can lead to a varying cross-field temperature in the total coronal loop. The simulation of Transition Region and Coronal Explorer (TRACE) observations by means of this loop modelmore » implies two uniform temperatures along the loop length, one inferred from the 171:195 filter ratio and the other from the 171:284 ratio. The reproduced flat temperature profiles are consistent with those inferred from the observed extreme-ultraviolet coronal loops. According to our model, the flat temperature profile is a consequence of the coronal loop consisting of filaments, which have different temperatures but almost similar emission measures in the cross-field direction. Furthermore, when we assume certain errors in the simulated loop emissions (e.g., due to photometric uncertainties in the TRACE filters) and use the triple-filter analysis, our simulated loop conditions become consistent with those of an isothermal plasma. This implies that the use of TRACE or EUV Imaging Telescope triple filters for observation of a warm coronal loop may not help in determining whether the cross-field isothermal assumption is satisfied or not.« less

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice

PubMed Central

Gul, Sarah S.; Hamilton, A. Rebecca L.; Munoz, Alexander R.; Phupitakphol, Tanit; Liu, Wei; Hyoju, Sanjiv K.; Economopoulos, Konstantinos P.; Morrison, Sara; Hu, Dong; Zhang, Weifeng; Gharedaghi, Mohammad Hadi; Huo, Haizhong; Hamarneh, Sulaiman R.; Hodin, Richard A.

2017-01-01

Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE’s inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP’s protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks. PMID:27997218

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice.

PubMed

Gul, Sarah S; Hamilton, A Rebecca L; Munoz, Alexander R; Phupitakphol, Tanit; Liu, Wei; Hyoju, Sanjiv K; Economopoulos, Konstantinos P; Morrison, Sara; Hu, Dong; Zhang, Weifeng; Gharedaghi, Mohammad Hadi; Huo, Haizhong; Hamarneh, Sulaiman R; Hodin, Richard A

2017-01-01

Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE's inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP's protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks.

Preinduced intestinal HSP70 improves visceral hypersensitivity and abnormal intestinal motility in PI-IBS mouse model.

PubMed

Lan, Cheng; Sun, Xiao-Ning; Zhou, Xu-Chun; Yang, Bo; Huang, Bai-Li; Deng, Tao-Zhi; He, Zhou-Tao; Han, Xiang-Yang

2016-03-01

To investigate the impact of the preinduced intestinal heat shock protein 70 (HSP70) on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome (PI-IBS) mouse model. Eighty-four female C57BL/6 mice were randomly assigned to four groups: control group (n = 21) and induction + PI-IBS group (n = 21), PI-IBS group (n = 21) and induction group (n = 21). The mice in PI-IBS group were infected in vivo with Trichinella spiralis by oral administration. The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test. The intestinal HSP70 protein and mRNA level was measured by Western blot and real-time PCR. Meanwhile, the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA. Compared with their counterparts in PI-IBS group, the animals in the Induction + PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical figures, including abdominal withdrawal reflex score, intestine transportation time and Bristol scores (P < 0.05). Meanwhile, the intestinal post-inflammatory cytokines remarkably changed, including increased IL-10 level and decreased TNF-α level (P < 0.05). Intestinal HSP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Intestine-specific Disruption of Hypoxia-inducible Factor (HIF)-2α Improves Anemia in Sickle Cell Disease.

PubMed

Das, Nupur; Xie, Liwei; Ramakrishnan, Sadeesh K; Campbell, Andrew; Rivella, Stefano; Shah, Yatrik M

2015-09-25

Sickle cell disease (SCD) is caused by genetic defects in the β-globin chain. SCD is a frequently inherited blood disorder, and sickle cell anemia is a common type of hemoglobinopathy. During anemia, the hypoxic response via the transcription factor hypoxia-inducible factor (HIF)-2α is highly activated in the intestine and is essential in iron absorption. Intestinal disruption of HIF-2α protects against tissue iron accumulation in iron overload anemias. However, the role of intestinal HIF-2α in regulating anemia in SCD is currently not known. Here we show that in mouse models of SCD, disruption of intestinal HIF-2α significantly decreased tissue iron accumulation. This was attributed to a decrease in intestinal iron absorptive genes, which were highly induced in a mouse model of SCD. Interestingly, disruption of intestinal HIF-2α led to a robust improvement in anemia with an increase in RBC, hemoglobin, and hematocrit. This was attributed to improvement in RBC survival, hemolysis, and insufficient erythropoiesis, which is evident from a significant decrease in serum bilirubin, reticulocyte counts, and serum erythropoietin following intestinal HIF-2α disruption. These data suggest that targeting intestinal HIF-2α has a significant therapeutic potential in SCD pathophysiology. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Complex, multi-scale small intestinal topography replicated in cellular growth substrates fabricated via chemical vapor deposition of Parylene C.

PubMed

Koppes, Abigail N; Kamath, Megha; Pfluger, Courtney A; Burkey, Daniel D; Dokmeci, Mehmet; Wang, Lin; Carrier, Rebecca L

2016-08-22

Native small intestine possesses distinct multi-scale structures (e.g., crypts, villi) not included in traditional 2D intestinal culture models for drug delivery and regenerative medicine. The known impact of structure on cell function motivates exploration of the influence of intestinal topography on the phenotype of cultured epithelial cells, but the irregular, macro- to submicron-scale features of native intestine are challenging to precisely replicate in cellular growth substrates. Herein, we utilized chemical vapor deposition of Parylene C on decellularized porcine small intestine to create polymeric intestinal replicas containing biomimetic irregular, multi-scale structures. These replicas were used as molds for polydimethylsiloxane (PDMS) growth substrates with macro to submicron intestinal topographical features. Resultant PDMS replicas exhibit multiscale resolution including macro- to micro-scale folds, crypt and villus structures, and submicron-scale features of the underlying basement membrane. After 10 d of human epithelial colorectal cell culture on PDMS substrates, the inclusion of biomimetic topographical features enhanced alkaline phosphatase expression 2.3-fold compared to flat controls, suggesting biomimetic topography is important in induced epithelial differentiation. This work presents a facile, inexpensive method for precisely replicating complex hierarchal features of native tissue, towards a new model for regenerative medicine and drug delivery for intestinal disorders and diseases.

Low Speed and High Speed Correlation of SMART Active Flap Rotor Loads

NASA Technical Reports Server (NTRS)

Kottapalli, Sesi B. R.

2010-01-01

Measured, open loop and closed loop data from the SMART rotor test in the NASA Ames 40- by 80- Foot Wind Tunnel are compared with CAMRAD II calculations. One open loop high-speed case and four closed loop cases are considered. The closed loop cases include three high-speed cases and one low-speed case. Two of these high-speed cases include a 2 deg flap deflection at 5P case and a test maximum-airspeed case. This study follows a recent, open loop correlation effort that used a simple correction factor for the airfoil pitching moment Mach number. Compared to the earlier effort, the current open loop study considers more fundamental corrections based on advancing blade aerodynamic conditions. The airfoil tables themselves have been studied. Selected modifications to the HH-06 section flap airfoil pitching moment table are implemented. For the closed loop condition, the effect of the flap actuator is modeled by increased flap hinge stiffness. Overall, the open loop correlation is reasonable, thus confirming the basic correctness of the current semi-empirical modifications; the closed loop correlation is also reasonable considering that the current flap model is a first generation model. Detailed correlation results are given in the paper.

Changes in intestinal fluid and mucosal immune responses to cholera toxin in Giardia muris infection and binding of cholera toxin to Giardia muris trophozoites.

PubMed

Ljungström, I; Holmgren, J; Svennerholm, A M; Ferrante, A

1985-10-01

The effect of Giardia muris infection on the diarrheal response and gut mucosal antibody response to cholera toxin was examined in mice. The results obtained showed that the fluid accumulation in intestinal loops exposed to cholera toxin was increased in mice infected with a low number (5 X 10(4) ) of G. muris cysts compared with the response in noninfected mice. This effect was associated with a marked reduction in absorption of oral rehydration fluid from the intestine. In contrast, mice infected with a high dose (2 X 10(5) ) of cysts showed a marked decrease in fluid accumulation in response to the toxin. This decrease might be related to the finding that both G. muris and Giardia lamblia trophozoites can bind significant amounts of cholera toxin. Evidence is presented which suggests that the gut mucosal antibody response, mainly immunoglobulin A but also immunoglobulin G, to an immunization course with perorally administered cholera toxin was depressed in mice infected with G. muris. The reduction in antibody levels was particularly evident when the primary immunization was made very early after infection. The serum antitoxin antibodies to the oral immunization with cholera toxin were, however, not affected. Likewise, the delayed-type hypersensitivity response against sheep erythrocytes in animals primed subcutaneously with sheep erythrocytes was not modified during the course of G. muris infection.

The Trade-Off Mechanism in Mammalian Circadian Clock Model with Two Time Delays

NASA Astrophysics Data System (ADS)

Yan, Jie; Kang, Xiaxia; Yang, Ling

Circadian clock is an autonomous oscillator which orchestrates the daily rhythms of physiology and behaviors. This study is devoted to explore how a positive feedback loop affects the dynamics of mammalian circadian clock. We simplify an experimentally validated mathematical model in our previous work, to a nonlinear differential equation with two time delays. This simplified mathematical model incorporates the pacemaker of mammalian circadian clock, a negative primary feedback loop, and a critical positive auxiliary feedback loop, Rev-erbα/Cry1 loop. We perform analytical studies of the system. Delay-dependent conditions for the asymptotic stability of the nontrivial positive steady state of the model are investigated. We also prove the existence of Hopf bifurcation, which leads to self-sustained oscillation of mammalian circadian clock. Our theoretical analyses show that the oscillatory regime is reduced upon the participation of the delayed positive auxiliary loop. However, further simulations reveal that the auxiliary loop can enable the circadian clock gain widely adjustable amplitudes and robust period. Thus, the positive auxiliary feedback loop may provide a trade-off mechanism, to use the small loss in the robustness of oscillation in exchange for adaptable flexibility in mammalian circadian clock. The results obtained from the model may gain new insights into the dynamics of biological oscillators with interlocked feedback loops.

Deciphering microbial interactions in synthetic human gut microbiome communities.

PubMed

Venturelli, Ophelia S; Carr, Alex C; Fisher, Garth; Hsu, Ryan H; Lau, Rebecca; Bowen, Benjamin P; Hromada, Susan; Northen, Trent; Arkin, Adam P

2018-06-21

The ecological forces that govern the assembly and stability of the human gut microbiota remain unresolved. We developed a generalizable model-guided framework to predict higher-dimensional consortia from time-resolved measurements of lower-order assemblages. This method was employed to decipher microbial interactions in a diverse human gut microbiome synthetic community. We show that pairwise interactions are major drivers of multi-species community dynamics, as opposed to higher-order interactions. The inferred ecological network exhibits a high proportion of negative and frequent positive interactions. Ecological drivers and responsive recipient species were discovered in the network. Our model demonstrated that a prevalent positive and negative interaction topology enables robust coexistence by implementing a negative feedback loop that balances disparities in monospecies fitness levels. We show that negative interactions could generate history-dependent responses of initial species proportions that frequently do not originate from bistability. Measurements of extracellular metabolites illuminated the metabolic capabilities of monospecies and potential molecular basis of microbial interactions. In sum, these methods defined the ecological roles of major human-associated intestinal species and illuminated design principles of microbial communities. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Validation of UHPLC-MS/MS methods for the determination of kaempferol and its metabolite 4-hydroxyphenyl acetic acid, and application to in vitro blood-brain barrier and intestinal drug permeability studies.

PubMed

Moradi-Afrapoli, Fahimeh; Oufir, Mouhssin; Walter, Fruzsina R; Deli, Maria A; Smiesko, Martin; Zabela, Volha; Butterweck, Veronika; Hamburger, Matthias

2016-09-05

Sedative and anxiolytic-like properties of flavonoids such as kaempferol and quercetin, and of some of their intestinal metabolites, have been demonstrated in pharmacological studies. However, routes of administration were shown to be critical for observing in vivo activity. Therefore, the ability to cross intestinal and blood-brain barriers was assessed in cell-based models for kaempferol (KMF), and for the major intestinal metabolite of KMF, 4-hydroxyphenylacetic acid (4-HPAA). Intestinal transport studies were performed with Caco-2 cells, and blood-brain barrier transport studies with an immortalized monoculture human model and a primary triple-co-culture rat model. UHPLC-MS/MS methods for KMF and 4-HPAA in Ringer-HEPES buffer and in Hank's balanced salt solution were validated according to industry guidelines. For all methods, calibration curves were fitted by least-squares quadratic regression with 1/X(2) as weighing factor, and mean coefficients of determination (R(2)) were >0.99. Data obtained with all barrier models showed high intestinal and blood-brain barrier permeation of KMF, and no permeability of 4-HPAA, when compared to barrier integrity markers. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of fucoidan on intestinal flora and intestinal barrier function in rats with breast cancer.

PubMed

Xue, Meilan; Ji, Xinqiang; Liang, Hui; Liu, Ying; Wang, Bing; Sun, Lingling; Li, Weiwei

2018-02-21

Recent research studies have shown that the intestinal flora are related to the occurrence and progress of breast cancer. This study investigates the effect of fucoidan on intestinal flora and intestinal barrier function in rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancers. Sixty female Sprague-Dawley rats were randomly assigned to the control group, the model group, and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg per kg bw (body weight), respectively. Intestinal histopathological analysis was performed and 16S rDNA high-throughput sequencing was used to provide an overview of the intestinal flora composition. The contents of d-lactic acid (d-LA), diamine oxidase (DAO) and endotoxin in plasma were detected by ELISA. Expression levels of the tight junction (TJ) proteins, phosphorylated p38 MAPK and ERK1/2 were measured using western blotting. Our results suggested that the intestinal wall of the model group was damaged. However, after fucoidan intervention, the villi were gradually restored. ELISA showed that the levels of plasma endotoxin, d-LA and DAO decreased in the F1 and F2 groups compared to those in the model group. Fucoidan treatment also increased the expressions of ZO-1, occludin, claudin-1 and claudin-8. Furthermore, the expression levels of phosphorylated p38 MAPK and ERK1/2 were upregulated in fucoidan treatment groups. The results of 16S rDNA high-throughput sequencing indicated that fucoidan increased the diversity of the intestinal microbiota and induced changes in microbial composition, with the increased Bacteroidetes/Firmicutes phylum ratio. In conclusion, the supplement of fucoidan could improve the fecal microbiota composition and repair the intestinal barrier function. The study suggested the use of fucoidan as an intestinal flora modulator for potential prevention of breast cancer.

Prolonged exposure to 1,25(OH)2D3 and high ionized calcium induces FGF-23 production in intestinal epithelium-like Caco-2 monolayer: A local negative feedback for preventing excessive calcium transport.

PubMed

Rodrat, Mayuree; Wongdee, Kannikar; Panupinthu, Nattapon; Thongbunchoo, Jirawan; Teerapornpuntakit, Jarinthorn; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

2018-02-15

Overdose of oral calcium supplement and excessive intestinal calcium absorption can contribute pathophysiological conditions, e.g., nephrolithiasis, vascular calcification, dementia, and cardiovascular accident. Since our previous investigation has indicated that fibroblast growth factor (FGF)-23 could abolish the 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ]-enhanced calcium absorption, we further hypothesized that FGF-23 produced locally in the enterocytes might be part of a local negative feedback loop to regulate calcium absorption. Herein, 1,25(OH) 2 D 3 was found to enhance the transcellular calcium transport across the epithelium-like Caco-2 monolayer, and this stimulatory effect was diminished by preceding prolonged exposure to high-dose 1,25(OH) 2 D 3 or high concentration of apical ionized calcium. Pretreatment with a neutralizing antibody for FGF-23 prevented this negative feedback regulation of calcium hyperabsorption induced by 1,25(OH) 2 D 3 . FGF-23 exposure completely abolished the 1,25(OH) 2 D 3 -enhanced calcium transport. Western blot analysis revealed that FGF-23 expression was upregulated in a dose-dependent manner by 1,25(OH) 2 D 3 or apical calcium exposure. Finally, calcium-sensing receptor (CaSR) inhibitors were found to prevent the apical calcium-induced suppression of calcium transport. In conclusion, prolonged exposure to high apical calcium and calcium hyperabsorption were sensed by CaSR, which, in turn, increased FGF-23 expression to suppress calcium transport. This local negative feedback loop can help prevent unnecessary calcium uptake and its detrimental consequences. Copyright © 2018 Elsevier Inc. All rights reserved.

Intestinal alkaline phosphatase regulates protective surface microclimate pH in rat duodenum.

PubMed

Mizumori, Misa; Ham, Maggie; Guth, Paul H; Engel, Eli; Kaunitz, Jonathan D; Akiba, Yasutada

2009-07-15

Regulation of localized extracellular pH (pH(o)) maintains normal organ function. An alkaline microclimate overlying the duodenal enterocyte brush border protects the mucosa from luminal acid. We hypothesized that intestinal alkaline phosphatase (IAP) regulates pH(o) due to pH-sensitive ATP hydrolysis as part of an ecto-purinergic pH regulatory system, comprised of cell-surface P2Y receptors and ATP-stimulated duodenal bicarbonate secretion (DBS). To test this hypothesis, we measured DBS in a perfused rat duodenal loop, examining the effect of the competitive alkaline phosphatase inhibitor glycerol phosphate (GP), the ecto-nucleoside triphosphate diphosphohydrolase inhibitor ARL67156, and exogenous nucleotides or P2 receptor agonists on DBS. Furthermore, we measured perfusate ATP concentration with a luciferin-luciferase bioassay. IAP inhibition increased DBS and luminal ATP output. Increased luminal ATP output was partially CFTR dependent, but was not due to cellular injury. Immunofluorescence localized the P2Y(1) receptor to the brush border membrane of duodenal villi. The P2Y(1) agonist 2-methylthio-ADP increased DBS, whereas the P2Y(1) antagonist MRS2179 reduced ATP- or GP-induced DBS. Acid perfusion augmented DBS and ATP release, further enhanced by the IAP inhibitor l-cysteine, and reduced by the exogenous ATPase apyrase. Furthermore, MRS2179 or the highly selective P2Y(1) antagonist MRS2500 co-perfused with acid induced epithelial injury, suggesting that IAP/ATP/P2Y signalling protects the mucosa from acid injury. Increased DBS augments IAP activity presumably by raising pH(o), increasing the rate of ATP degradation, decreasing ATP-mediated DBS, forming a negative feedback loop. The duodenal epithelial brush border IAP-P2Y-HCO(3-) surface microclimate pH regulatory system effectively protects the mucosa from acid injury.

Furosemide suppresses ileal and colonic contractility via interactions with GABA-A receptor in mice.

PubMed

Kaewsaro, Kannaree; Nualplub, Suparp; Bumrungsri, Sara; Khuituan, Pissared

2017-11-01

The loop diuretic furosemide has an action to inhibit Na + -K + -2Cl - co-transporter at the thick ascending limb of Henle's loop resulting in diuresis. Furosemide also has the non-diuretic effects by binding to GABA-A receptor which may involve the gastrointestinal tract. The aim of this study was to investigate the effects of furosemide on smooth muscle contractions in mice ileum and proximal colon. Each intestinal segment suspended in an organ bath was connected to a force transducer. Signal output of mechanical activity was amplified and recorded for analysis using PowerLab System. After equilibration, the intestine was directly exposed to furosemide, GABA, GABA-A receptor agonist (muscimol), or muscarinic receptor antagonist (atropine). Furosemide (50, 100 and 500 μmol L -1 ) acutely reduced the amplitude of ileal and colonic contraction. In the ileum, 1 mmol L -1 GABA and 10-60 μmol L -1 muscimol significantly increased the amplitude, whereas in the colon, 50-100 mmol L -1 GABA and 60 μmol L -1 muscimol decreased the contractions. The contractions were also significantly suppressed by atropine. To investigate the mechanisms underlying the inhibiting effect of furosemide, furosemide was added to the organ bath prior to the addition of muscimol or atropine. A comparison of furosemide combined with muscimol or atropine group and furosemide group showed no significant difference of the ileal contraction, but the amplitude of colonic contraction significantly decreased when compared to adding furosemide alone. These results suggest that furosemide can reduce the ileal and proximal colonic contraction mediated by blocking and supporting of GABA-A receptor, respectively, resulting in decreased acetylcholine release. © 2017 John Wiley & Sons Australia, Ltd.

A class of all digital phase locked loops - Modelling and analysis.

NASA Technical Reports Server (NTRS)

Reddy, C. P.; Gupta, S. C.

1972-01-01

An all digital phase locked loop which tracks the phase of the incoming signal once per carrier cycle is proposed. The different elements and their functions, and the phase lock operation are explained in detail. The general digital loop operation is governed by a non-linear difference equation from which a suitable model is developed. The lock range for the general model is derived. The performance of the digital loop for phase step, and frequency step inputs for different levels of quantization without loop filter, are studied. The analytical results are checked by simulating the actual system on the digital computer.

Polyakov loop modeling for hot QCD

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fukushima, Kenji; Skokov, Vladimir

Here, we review theoretical aspects of quantum chromodynamics (QCD) at finite temperature. The most important physical variable to characterize hot QCD is the Polyakov loop, which is an approximate order parameter for quark deconfinement in a hot gluonic medium. Additionally to its role as an order parameter, the Polyakov loop has rich physical contents in both perturbative and non-perturbative sectors. This review covers a wide range of subjects associated with the Polyakov loop from topological defects in hot QCD to model building with coupling to the Polyakov loop.

Polyakov loop modeling for hot QCD

DOE PAGES

Fukushima, Kenji; Skokov, Vladimir

2017-06-19

Here, we review theoretical aspects of quantum chromodynamics (QCD) at finite temperature. The most important physical variable to characterize hot QCD is the Polyakov loop, which is an approximate order parameter for quark deconfinement in a hot gluonic medium. Additionally to its role as an order parameter, the Polyakov loop has rich physical contents in both perturbative and non-perturbative sectors. This review covers a wide range of subjects associated with the Polyakov loop from topological defects in hot QCD to model building with coupling to the Polyakov loop.

USE OF A PHYSIOLOGICALLY BASED TOXICOKINETIC MODEL TO SIMULATE CHRONIC DIETARY EXPOSURE IN FISH

EPA Science Inventory

A physiologically based toxicokinetic (PBTK) model was developed to describe dietary uptake of hydrophobic organic chemicals by fish. The GI tract was modeled as four compartments corresponding to the stomach, pyloric ceca, upper intestine, and lower intestine. Partitioning coeff...

Evidence of suppressed heating of coronal loops rooted in opposite polarity sunspot umbrae

NASA Astrophysics Data System (ADS)

Tiwari, Sanjiv K.; Thalmann, Julia K.; Winebarger, Amy R.; Panesar, Navdeep K.; Moore, Ronald

2015-04-01

Observations of active region (AR) coronae in different EUV wavelengths reveal the presence of various loops at different temperatures. To understand the mechanisms that result in hotter or cooler loops, we study a typical bipolar AR, near solar disk center, which has moderate overall magnetic twist and at least one fully developed sunspot of each polarity. From AIA 193 and 94 A images we identify many clearly discernible coronal loops that connect opposite-polarity plage or a sunspot to a opposite-polarity plage region. The AIA 94 A images show dim regions in the umbrae of the spots. To see which coronal loops are rooted in a dim umbral area, we performed a non-linear force-free field (NLFFF) modeling using photospheric vector magnetic field measurements obtained with the Heliosesmic Magnetic Imager (HMI) onboard SDO. After validation of the NLFFF model by comparison of calculated model field lines and observed loops in AIA 193 and 94 A, we specify the photospheric roots of the model field lines. The model field then shows the coronal magnetic loops that arch from the dim umbral area of the positive-polarity sunspot to the dim umbral area of a negative-polarity sunspot. Because these coronal loops are not visible in any of the coronal EUV and X-ray images of the AR, we conclude they are the coolest loops in the AR. This result suggests that the loops connecting opposite polarity umbrae are the least heated because the field in umbrae is so strong that the convective braiding of the field is strongly suppressed.From this result, we further hypothesize that the convective freedom at the feet of a coronal loop, together with the strength of the field in the body of the loop, determines the strength of the heating. In particular, we expect the hottest coronal loops to have one foot in an umbra and the other foot in opposite-polarity penumbra or plage (coronal moss), the areas of strong field in which convection is not as strongly suppressed as in umbrae. Many transient, outstandingly bright, loops in the AIA 94 A movie of the AR do have this expected rooting pattern.

Constant replenishment from circulating monocytes maintains the macrophage pool in adult intestine

PubMed Central

Scott, Charlotte L.; Perdiguero, Elisa Gomez; Geissmann, Frederic; Henri, Sandrine; Malissen, Bernard; Osborne, Lisa C.; Artis, David; Mowat, Allan McI.

2014-01-01

The paradigm that resident macrophages in steady-state tissues are derived from embryonic precursors has never been investigated in the intestine, which contains the largest pool of macrophages. Using fate mapping models and monocytopenic mice, together with bone marrow chimeric and parabiotic models, we show that embryonic precursors seeded the intestinal mucosa and demonstrated extensive in situ proliferation in the neonatal period. However these cells did not persist in adult intestine. Instead, they were replaced around the time of weaning by the CCR2-dependent influx of Ly6Chi monocytes that differentiated locally into mature, anti-inflammatory macrophages. This process was driven largely by the microbiota and had to be continued throughout adult life to maintain a normal intestinal macrophage pool. PMID:25151491

Adherence of Escherichia coli O157:H7 to epithelial cells in vitro and in pig gut loops is affected by bacterial culture conditions

PubMed Central

Yin, Xianhua; Feng, Yanni; Wheatcroft, Roger; Chambers, James; Gong, Joshua; Gyles, Carlton L.

2011-01-01

The objectives of this study were to determine the effect of bacterial culture conditions on adherence of enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain 86-24 in vivo to pig enterocytes and to compare the results with adherence in vitro to cultured HEp-2 and IPEC-J2 cells. Growth of O157:H7 in MacConkey broth (MB) resulted in almost no adherence to both HEp-2 and IPEC-J2 cells; prior exposure of the bacteria to pH 2.5 reduced adherence. There was greater adherence by bacteria from static cultures than by those from shaken cultures and by bacteria cultured in brain–heart infusion (BHI) plus NaHCO3 (BHIN) than by bacteria cultured in BHI. In contrast, in pig ileal loops, bacteria cultured in MB adhered well to enterocytes, and prior exposure to pH 2.5 had no effect on adherence. Among several media tested for their effect on bacterial adherence in the pig intestine, MB and BHIN proved to be the best. Bacterial adherence was dose-dependent and was more extensive in the ileum than in the colon. This study demonstrated that there are remarkable differences between culture conditions that promote adherence of an EHEC O157:H7 strain in vitro and in vivo, that culture conditions profoundly affect adherence to epithelial cells in vitro and in vivo, and that pig ileal loops are better suited to adherence studies than are colon loops. PMID:21731177

THE LITTLEST HIGGS MODEL AND ONE-LOOP ELECTROWEAK PRECISION CONSTRAINTS.

DOE Office of Scientific and Technical Information (OSTI.GOV)

CHEN, M.C.; DAWSON,S.

2004-06-16

We present in this talk the one-loop electroweak precision constraints in the Littlest Higgs model, including the logarithmically enhanced contributions from both fermion and scalar loops. We find the one-loop contributions are comparable to the tree level corrections in some regions of parameter space. A low cutoff scale is allowed for a non-zero triplet VEV. Constraints on various other parameters in the model are also discussed. The role of triplet scalars in constructing a consistent renormalization scheme is emphasized.

Finite Feedback Cycling in Structural Equation Models

ERIC Educational Resources Information Center

Hayduk, Leslie A.

2009-01-01

In models containing reciprocal effects, or longer causal loops, the usual effect estimates assume that any effect touching a loop initiates an infinite cycling of effects around that loop. The real world, in contrast, might permit only finite feedback cycles. I use a simple hypothetical model to demonstrate that if the world permits only a few…

Aerospace applications of SINDA/FLUINT at the Johnson Space Center

NASA Technical Reports Server (NTRS)

Ewert, Michael K.; Bellmore, Phillip E.; Andish, Kambiz K.; Keller, John R.

1992-01-01

SINDA/FLUINT has been found to be a versatile code for modeling aerospace systems involving single or two-phase fluid flow and all modes of heat transfer. Several applications of SINDA/FLUINT are described in this paper. SINDA/FLUINT is being used extensively to model the single phase water loops and the two-phase ammonia loops of the Space Station Freedom active thermal control system (ATCS). These models range from large integrated system models with multiple submodels to very detailed subsystem models. An integrated Space Station ATCS model has been created with ten submodels representing five water loops, three ammonia loops, a Freon loop and a thermal submodel representing the air loop. The model, which has approximately 800 FLUINT lumps and 300 thermal nodes, is used to determine the interaction between the multiple fluid loops which comprise the Space Station ATCS. Several detailed models of the flow-through radiator subsystem of the Space Station ATCS have been developed. One model, which has approximately 70 FLUINT lumps and 340 thermal nodes, provides a representation of the ATCS low temperature radiator array with two fluid loops connected only by conduction through the radiator face sheet. The detailed models are used to determine parameters such as radiator fluid return temperature, fin efficiency, flow distribution and total heat rejection for the baseline design as well as proposed alternate designs. SINDA/FLUINT has also been used as a design tool for several systems using pressurized gasses. One model examined the pressurization and depressurization of the Space Station airlock under a variety of operating conditions including convection with the side walls and internal cooling. Another model predicted the performance of a new generation of manned maneuvering units. This model included high pressure gas depressurization, internal heat transfer and supersonic thruster equations. The results of both models were used to size components, such as the heaters and gas bottles and also to point to areas where hardware testing was needed.

Maintenance of a fully functional digestive system during hibernation in the European hamster, a food-storing hibernator.

PubMed

Weitten, Mathieu; Oudart, Hugues; Habold, Caroline

2016-03-01

Some small mammals limit energy expenditure during winter conditions through torpor bouts, which are characterized by a decrease in body temperature and metabolic rate. Individuals arise periodically from torpor to restore critical functions requiring euthermia. Although most of the species involved do not feed during hibernation and rely on body reserves to fulfil energy requirements (fat-storing species), others hoard food in a burrow (food-storing species) and can feed during interbout euthermy. Whereas fat-storing species undergo a marked atrophy of the digestive tract, food-storing species have to maintain a functional digestive system during hibernation. Our study aimed to evaluate the absorption capacities of a food-storing species, the European hamster, throughout the annual cycle. In vivo intestinal perfusions were conducted in different groups of hamsters (n=5) during the different life periods, namely before hibernation, in torpor, during interbout euthermy, and during summer rest. The triglyceride, non-esterified free fatty acid, starch, glucose and protein composition of the perfusate was evaluated before and after the 1h perfusion of a closed intestinal loop. Triglyceride, starch and protein hydrolysis rates were similar in hibernating (torpid and euthermic) and non-hibernating hamsters. Intestinal absorption of free fatty acid was also similar in all groups. However, glucose uptake rate was higher during hibernation than during the summer. In contrast with fat-storing species, the intestinal absorption capacities of food-storing species are fully maintained during hibernation to optimize nutrient assimilation during short interbout euthermy. In particular, glucose uptake rate is increased during hibernation to restore glycaemia and ensure glucose-dependent pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice

PubMed Central

Aslam, Mohamad F.; Frazer, David M.; Faria, Nuno; Bruggraber, Sylvaine F. A.; Wilkins, Sarah J.; Mirciov, Cornel; Powell, Jonathan J.; Anderson, Greg J.; Pereira, Dora I. A.

2014-01-01

The ferritin core is composed of fine nanoparticulate Fe3+ oxohydroxide, and we have developed a synthetic mimetic, nanoparticulate Fe3+ polyoxohydroxide (nanoFe3+). The aim of this study was to determine how dietary iron derived in this fashion is absorbed in the duodenum. Following a 4 wk run-in on an Fe-deficient diet, mice with intestinal-specific disruption of the Fpn-1 gene (Fpn-KO), or littermate wild-type (WT) controls, were supplemented with Fe2+ sulfate (FeSO4), nanoFe3+, or no added Fe for a further 4 wk. A control group was Fe sufficient throughout. Direct intestinal absorption of nanoFe3+ was investigated using isolated duodenal loops. Our data show that FeSO4 and nanoFe3+ are equally bioavailable in WT mice, and at wk 8 the mean ± sem hemoglobin increase was 18 ± 7 g/L in the FeSO4 group and 30 ± 5 g/L in the nanoFe3+ group. Oral iron failed to be utilized by Fpn-KO mice and was retained in enterocytes, irrespective of the iron source. In summary, although nanoFe3+ is taken up directly by the duodenum its homeostasis is under the normal regulatory control of dietary iron absorption, namely via ferroportin-dependent efflux from enterocytes, and thus offers potential as a novel oral iron supplement.—Aslam, M. F., Frazer, D. M., Faria, N., Bruggraber, S. F. A., Wilkins, S. J., Mirciov, C., Powell, J. J., Anderson, G. J., Pereira, D. I. A. Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice. PMID:24776745

Real-time Measurement of Epithelial Barrier Permeability in Human Intestinal Organoids.

PubMed

Hill, David R; Huang, Sha; Tsai, Yu-Hwai; Spence, Jason R; Young, Vincent B

2017-12-18

Advances in 3D culture of intestinal tissues obtained through biopsy or generated from pluripotent stem cells via directed differentiation, have resulted in sophisticated in vitro models of the intestinal mucosa. Leveraging these emerging model systems will require adaptation of tools and techniques developed for 2D culture systems and animals. Here, we describe a technique for measuring epithelial barrier permeability in human intestinal organoids in real-time. This is accomplished by microinjection of fluorescently-labeled dextran and imaging on an inverted microscope fitted with epifluorescent filters. Real-time measurement of the barrier permeability in intestinal organoids facilitates the generation of high-resolution temporal data in human intestinal epithelial tissue, although this technique can also be applied to fixed timepoint imaging approaches. This protocol is readily adaptable for the measurement of epithelial barrier permeability following exposure to pharmacologic agents, bacterial products or toxins, or live microorganisms. With minor modifications, this protocol can also serve as a general primer on microinjection of intestinal organoids and users may choose to supplement this protocol with additional or alternative downstream applications following microinjection.

Suppression of Heating of Coronal Loops Rooted in Opposite Polarity Sunspot Umbrae

NASA Technical Reports Server (NTRS)

Tiwari, Sanjiv K.; Thalmann, Julia K.; Moore, Ronald L.; Panesar, Navdeep K.; Winebarger, Amy R.

2016-01-01

EUV observations of active region (AR) coronae reveal the presence of loops at different temperatures. To understand the mechanisms that result in hotter or cooler loops, we study a typical bipolar AR, near solar disk center, which has moderate overall magnetic twist and at least one fully developed sunspot of each polarity. From AIA 193 and 94 Å images we identify many clearly discernible coronal loops that connect plage or a sunspot of one polarity to an opposite-­polarity plage region. The AIA 94 Å images show dim regions in the umbrae of the spots. To see which coronal loops are rooted in a dim umbral area, we performed a non-linear force-free field (NLFFF) modeling using photospheric vector magnetic field measurements obtained with the Heliosesmic Magnetic Imager (HMI) onboard SDO. The NLFFF model, validated by comparison of calculated model field lines with observed loops in AIA 193 and 94 Å, specifies the photospheric roots of the model field lines. Some model coronal magnetic field lines arch from the dim umbral area of the positive-polarity sunspot to the dim umbral area of a negative-polarity sunspot. Because these coronal loops are not visible in any of the coronal EUV and X-ray images of the AR, we conclude they are the coolest loops in the AR. This result suggests that the loops connecting opposite polarity umbrae are the least heated because the field in umbrae is so strong that the convective braiding of the field is strongly suppressed.

RELAP5-3D Modeling of Heat Transfer Components (Intermediate Heat Exchanger and Helical-Coil Steam Generator) for NGNP Application

DOE Office of Scientific and Technical Information (OSTI.GOV)

N. A. Anderson; P. Sabharwall

2014-01-01

The Next Generation Nuclear Plant project is aimed at the research and development of a helium-cooled high-temperature gas reactor that could generate both electricity and process heat for the production of hydrogen. The heat from the high-temperature primary loop must be transferred via an intermediate heat exchanger to a secondary loop. Using RELAP5-3D, a model was developed for two of the heat exchanger options a printed-circuit heat exchanger and a helical-coil steam generator. The RELAP5-3D models were used to simulate an exponential decrease in pressure over a 20 second period. The results of this loss of coolant analysis indicate thatmore » heat is initially transferred from the primary loop to the secondary loop, but after the decrease in pressure in the primary loop the heat is transferred from the secondary loop to the primary loop. A high-temperature gas reactor model should be developed and connected to the heat transfer component to simulate other transients.« less

The Presence or Absence of Intestinal Microbiota Affects Lipid Deposition and Related Genes Expression in Zebrafish (Danio rerio).

PubMed

Sheng, Yi; Ren, Hui; Limbu, Samwel M; Sun, Yuhong; Qiao, Fang; Zhai, Wanying; Du, Zhen-Yu; Zhang, Meiling

2018-01-01

Understanding how intestinal microbiota alters energy homeostasis and lipid metabolism is a critical process in energy balance and health. However, the exact role of intestinal microbiota in the regulation of lipid metabolism in fish remains unclear. Here, we used two zebrafish models (germ-free and antibiotics-treated zebrafish) to identify the role of intestinal microbiota in lipid metabolism. Conventional and germ-free zebrafish larvae were fed with egg yolk. Transmission electron microscopy was used to detect the presence of lipid droplets in the intestinal epithelium. The results showed that, microbiota increased lipid accumulation in the intestinal epithelium. The mRNA sequencing technology was used to assess genes expression level. We found majority of the differentially expressed genes were related to lipid metabolism. Due to the limitation of germ-free zebrafish larvae, antibiotics-treated zebrafish were also used to identify the relationship between the gut microbiota and the host lipid metabolism. Oil-red staining showed antibiotics-treated zebrafish had less intestinal lipid accumulation than control group. The mRNA expression of genes related to lipid metabolism in liver and intestine was also quantified by using real-time PCR. The results indicated that apoa4 , hsl , cox15 , slc2a1a , and lss were more related to intestinal bacteria in fish, while the influence of intestinal microbiota on the activity of fabp6 , acsl5 , cd36 , and gpat2 was different between the liver and intestine. This study identified several genes regulated by intestinal microbiota. Furthermore, the advantages and disadvantages of each model have been discussed. This study provides valuable information for exploring host-microbiota interactions in zebrafish in future.

Oral PEG 15-20 protects the intestine against radiation : role of lipid rafts.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valuckaite, V.; Zaborina, O.; Long, J.

Intestinal injury following abdominal radiation therapy or accidental exposure remains a significant clinical problem that can result in varying degrees of mucosal destruction such as ulceration, vascular sclerosis, intestinal wall fibrosis, loss of barrier function, and even lethal gut-derived sepsis. We determined the ability of a high-molecular-weight polyethylene glycol-based copolymer, PEG 15-20, to protect the intestine against the early and late effects of radiation in mice and rats and to determine its mechanism of action by examining cultured rat intestinal epithelia. Rats were exposed to fractionated radiation in an established model of intestinal injury, whereby an intestinal segment is surgicallymore » placed into the scrotum and radiated daily. Radiation injury score was decreased in a dose-dependent manner in rats gavaged with 0.5 or 2.0 g/kg per day of PEG 15-20 (n = 9-13/group, P < 0.005). Complementary studies were performed in a novel mouse model of abdominal radiation followed by intestinal inoculation with Pseudomonas aeruginosa (P. aeruginosa), a common pathogen that causes lethal gut-derived sepsis following radiation. Mice mortality was decreased by 40% in mice drinking 1% PEG 15-20 (n = 10/group, P < 0.001). Parallel studies were performed in cultured rat intestinal epithelial cells treated with PEG 15-20 before radiation. Results demonstrated that PEG 15-20 prevented radiation-induced intestinal injury in rats, prevented apoptosis and lethal sepsis attributable to P. aeruginosa in mice, and protected cultured intestinal epithelial cells from apoptosis and microbial adherence and possible invasion. PEG 15-20 appeared to exert its protective effect via its binding to lipid rafts by preventing their coalescence, a hallmark feature in intestinal epithelial cells exposed to radiation.« less

Anti-inflammatory Effects of Fungal Metabolites in Mouse Intestine as Revealed by In vitro Models

PubMed Central

Schreiber, Dominik; Marx, Lisa; Felix, Silke; Clasohm, Jasmin; Weyland, Maximilian; Schäfer, Maximilian; Klotz, Markus; Lilischkis, Rainer; Erkel, Gerhard; Schäfer, Karl-Herbert

2017-01-01

Inflammatory bowel diseases (IBD), which include Crohn's disease and ulcerative colitis, are chronic inflammatory disorders that can affect the whole gastrointestinal tract or the colonic mucosal layer. Current therapies aiming to suppress the exaggerated immune response in IBD largely rely on compounds with non-satisfying effects or side-effects. Therefore, new therapeutical options are needed. In the present study, we investigated the anti-inflammatory effects of the fungal metabolites, galiellalactone, and dehydrocurvularin in both an in vitro intestinal inflammation model, as well as in isolated myenteric plexus and enterocyte cells. Administration of a pro-inflammatory cytokine mix through the mesenteric artery of intestinal segments caused an up-regulation of inflammatory marker genes. Treatment of the murine intestinal segments with galiellalactone or dehydrocurvularin by application through the mesenteric artery significantly prevented the expression of pro-inflammatory marker genes on the mRNA and the protein level. Comparable to the results in the perfused intestine model, treatment of primary enteric nervous system (ENS) cells from the murine intestine with the fungal compounds reduced expression of cytokines such as IL-6, TNF-α, IL-1β, and inflammatory enzymes such as COX-2 and iNOS on mRNA and protein levels. Similar anti-inflammatory effects of the fungal metabolites were observed in the human colorectal adenocarcinoma cell line DLD-1 after stimulation with IFN-γ (10 ng/ml), TNF-α (10 ng/ml), and IL-1β (5 ng/ml). Our results show that the mesenterially perfused intestine model provides a reliable tool for the screening of new therapeutics with limited amounts of test compounds. Furthermore, we could characterize the anti-inflammatory effects of two novel active compounds, galiellalactone, and dehydrocurvularin which are interesting candidates for studies with chronic animal models of IBD. PMID:28824460

Modeling a Full Coronal Loop Observed with Hinode EIS and SDO AIA

NASA Technical Reports Server (NTRS)

Alexander, Caroline; Winebarger, Amy R.

2015-01-01

Physical parameters measured from an observation of a coronal loop from Gupta et al. (2015) using Hinode/EIS and SDO/AIA were used as input for the hydrodynamic, impulsively heating NRLSOFM 1-­d loop model. The model was run at eight different energy inputs and used the measured quantities of temperature (0.73 MK), density (10(sup 8.5)cm(sup -3) and minimum loop lifetime to evaluate the success of the model at recreating the observations. The loop was measured by us to have an unprojected length of 236 Mm and was assumed to be almost perpendicular to the solar surface (tilt of 3.5 degrees) and have a dipolar geometry. Our results show that two of our simulation runs (with input energies of 0.01 and 0.02 ergs cm(sup -3)S(sup -1) closely match the temperature/density combination exhibited by the loop observation. However, our simulated loops only remain in the temperature sensitive region of the Mg 278.4 Angstrom filter for 500 and 800 seconds respectively which is less than the 1200 seconds that the loop is observed for with EIS in order to make the temperature/density measurements over the loop's entire length. This leads us to conclude that impulsive heating of a single loop is not complex enough to explain this observation. Additional steady heating or a collection of additional strands along the line-­of-­sight would help to align the simulation with the observation.

Effects of enteral arginine supplementation on the structural intestinal adaptation in a rat model of short bowel syndrome.

PubMed

Sukhotnik, Igor; Lerner, Aaron; Sabo, Edmund; Krausz, Michael M; Siplovich, Leonardo; Coran, Arnold G; Mogilner, Jorge; Shiloni, Eitan

2003-07-01

The nitric oxide precursor L-arginine (ARG) has been shown to influence intestinal morphology and intestinal absorptive function. The purpose of the present study was to determine the effect of enteral ARG supplementation on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Thirty male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection, SBS rats underwent 75% small bowel resection, and SBS-ARG rats underwent bowel resection and were treated with ARG given in the drinking water (2%). Parameters of intestinal adaptation, enterocyte proliferation and enterocyte apoptosis were determined on day 14 following operation. We have demonstrated that SBS-ARG animals had a lower jejunal and ileal mucosal weight, jejunal mucosal DNA and protein, ileal mucosal protein, jejunal villus height, jejunal and ileal crypt depth, and enterocyte proliferation index and a greater enterocyte apoptosis compared to SBS untreated animals. We conclude that in a rat model of SBS enteral L-arginine inhibits structural intestinal adaptation. Possible mechanism for this effect may be decreased cell proliferation and increased cell apoptosis.

Use of a combination of in vitro models to investigate the impact of chlorpyrifos and inulin on the intestinal microbiota and the permeability of the intestinal mucosa.

PubMed

Réquilé, Marina; Gonzàlez Alvarez, Dubàn O; Delanaud, Stéphane; Rhazi, Larbi; Bach, Véronique; Depeint, Flore; Khorsi-Cauet, Hafida

2018-05-28

Dietary exposure to the organophosphorothionate pesticide chlorpyrifos (CPF) has been linked to dysbiosis of the gut microbiota. We therefore sought to investigate whether (i) CPF's impact extends to the intestinal barrier and (ii) the prebiotic inulin could prevent such an effect. In vitro models mimicking the intestinal environment (the SHIME®) and the intestinal mucosa (Caco-2/TC7 cells) were exposed to CPF. After the SHIME® had been exposed to CPF and/or inulin, we assessed the system's bacterial and metabolic profiles. Extracts from the SHIME®'s colon reactors were then transferred to Caco-2/TC7 cultures, and epithelial barrier integrity and function were assessed. We found that inulin co-treatment partially reversed CPF-induced dysbiosis and increased short-chain fatty acid production in the SHIME®. Furthermore, co-treatment impacted tight junction gene expression and inhibited pro-inflammatory signaling in the Caco-2/TC7 intestinal cell line. Whereas, an isolated in vitro assessment of CPF and inulin effects provides useful information on the mechanism of dysbiosis, combining two in vitro models increases the in vivo relevance.

Old drug new use--amoxapine and its metabolites as potent bacterial β-glucuronidase inhibitors for alleviating cancer drug toxicity.

PubMed

Kong, Ren; Liu, Timothy; Zhu, Xiaoping; Ahmad, Syed; Williams, Alfred L; Phan, Alexandria T; Zhao, Hong; Scott, John E; Yeh, Li-An; Wong, Stephen T C

2014-07-01

Irinotecan (CPT-11) induced diarrhea occurs frequently in patients with cancer and limits its usage. Bacteria β-glucuronidase (GUS) enzymes in intestines convert the nontoxic metabolite of CPT-11, SN-38G, to toxic SN-38, and finally lead to damage of intestinal epithelial cells and diarrhea. We previously reported amoxapine as a potent GUS inhibitor in vitro. To further understand the molecular mechanism of amoxapine and its potential for treatment of CPT-11-induced diarrhea, we studied the binding modes of amoxapine and its metabolites by docking and molecular dynamics simulation, and tested the in vivo efficacy on mice in combination with CPT-11. The binding of amoxapine, its metabolites, 7-hydroxyamoxapine and 8-hydroxyamoxapine, and a control drug loxapine with GUS was explored by computational protocols. The in vitro potencies of metabolites were measured by Escherichia coli GUS enzyme and cell-based assay. Low-dosage daily oral administration was designed to use along with CPT-11 to treat tumor-bearing mice. Computational modeling results indicated that amoxapine and its metabolites bound in the active site of GUS and satisfied critical pharmacophore features: aromatic features near bacterial loop residue F365' and hydrogen bond toward E413. Amoxapine and its metabolites were demonstrated as potent in vitro. Administration of low dosages of amoxapine with CPT-11 in mice achieved significant suppression of diarrhea and reduced tumor growth. Amoxapine has great clinical potential to be rapidly translated to human subjects for irinotecan-induced diarrhea. ©2014 American Association for Cancer Research.

Old drug new use - Amoxapine and its metabolites as potent bacterial β-glucuronidase inhibitors for alleviating cancer drug toxicity

PubMed Central

Kong, Ren; Liu, Timothy; Zhu, Xiaoping; Ahmad, Syed; Williams, Alfred L.; Phan, Alexandria T; Zhao, Hong; Scott, John E.; Yeh, Li-An; Wong, Stephen TC

2014-01-01

Purpose Irinotecan (CPT-11) induced diarrhea occurs frequently in cancer patients and limits its usage. Bacteria β-glucuronidase (GUS) enzymes in intestines convert the non-toxic metabolite of CPT-11, SN-38G, to toxic SN-38, and finally lead to damage of intestinal epithelial cells and diarrhea. We previously reported amoxapine as potent GUS inhibitor in vitro. To further understand the molecular mechanism of amoxapine and its potential for treatment of CPT-11 induced diarrhea, we studied the binding modes of amoxapine and its metabolites by docking and molecular dynamics simulation, and tested the in vivo efficacy on mice in combination with CPT-11. Experimental Design The binding of amoxapine, its metabolites, 7-hydroxyamoxapine and 8-hydroxyamoxapine, and a control drug loxapine with GUS was explored by computational protocols. The in vitro potencies of metabolites were measured by E. Coli GUS enzyme and cell-based assay. Low dosage daily oral administration was designed to use along with CPT-11 to treat tumor-bearing mice. Results Computational modeling results indicated that amoxapine and its metabolites bound in the active site of GUS and satisfied critical pharmacophore features: aromatic features near bacterial loop residue F365’ and hydrogen bond toward E413. Amoxapine and its metabolites were demonstrated as potent in vitro. Administration of low dosages of amoxapine with CPT-11 in mice achieved significant suppression of diarrhea and reduced tumor growth. Conclusions Amoxapine has great clinical potential to be rapidly translated to human subjects for irinotecan induced diarrhea. PMID:24780296

Intestinal permeability defects: Is it time to treat?

PubMed Central

Odenwald, Matthew A.; Turner, Jerrold R.

2013-01-01

An essential role of the intestinal epithelium is to separate luminal contents from the interstitium, a function primarily determined by the integrity of the epithelium and the tight junction that seals the paracellular space. Intestinal tight junctions are selectively-permeable, and intestinal permeability can be increased physiologically in response to luminal nutrients or pathologically by mucosal immune cells and cytokines, the enteric nervous system, and pathogens. Compromised intestinal barrier function is associated with an array of clinical conditions, both intestinal and systemic. While most available data are correlative, some studies support a model where cycles of increased intestinal permeability, intestinal immune activation, and subsequent immune-mediated barrier loss contribute to disease progression. This model is applicable to intestinal and systemic diseases. However, it has not been proven and both mechanistic and therapeutic studies are ongoing. Nevertheless, the correlation between increased intestinal permeability and disease has caught the attention of the public, leading to a rise in popularity of the diagnosis of “leaky gut syndrome,” which encompasses a range of systemic disorders. Proponents claim that barrier restoration will cure underlying disease, but this has not been demonstrated in clinical trials. Moreover, human and mouse studies show that intestinal barrier loss alone is insufficient to initiate disease. It is therefore uncertain if increased permeability in these patients is a cause or effect of the underlying disorder. Although drug targets that may mediate barrier restoration have been proposed, none have been proven effective. As such, current treatments for barrier dysfunction should target the underlying disease. PMID:23851019

A comprehensive model of the spatio-temporal stem cell and tissue organisation in the intestinal crypt.

PubMed

Buske, Peter; Galle, Jörg; Barker, Nick; Aust, Gabriela; Clevers, Hans; Loeffler, Markus

2011-01-06

We introduce a novel dynamic model of stem cell and tissue organisation in murine intestinal crypts. Integrating the molecular, cellular and tissue level of description, this model links a broad spectrum of experimental observations encompassing spatially confined cell proliferation, directed cell migration, multiple cell lineage decisions and clonal competition.Using computational simulations we demonstrate that the model is capable of quantitatively describing and predicting the dynamic behaviour of the intestinal tissue during steady state as well as after cell damage and following selective gain or loss of gene function manipulations affecting Wnt- and Notch-signalling. Our simulation results suggest that reversibility and flexibility of cellular decisions are key elements of robust tissue organisation of the intestine. We predict that the tissue should be able to fully recover after complete elimination of cellular subpopulations including subpopulations deemed to be functional stem cells. This challenges current views of tissue stem cell organisation.

Effects of sleeve gastrectomy with jejuno-jejunal or jejuno-ileal loop on glycolipid metabolism in diabetic rats

PubMed Central

Zhong, Ming-Wei; Liu, Shao-Zhuang; Zhang, Guang-Yong; Zhang, Xiang; Hu, San-Yuan

2016-01-01

AIM To explore the effect of sleeve gastrectomy (SG) with jejuno-jejunal or jejuno-ileal loop on glycolipid metabolism in diabetic rats. METHODS Diabetic rats, which were induced by high-fat diet (HFD), nicotinamide and low-dose streptozotocin, underwent sham operations, SG, SG with jejuno-ileal loop (SG-JI) and SG with jejuno-jejunal loop (SG-JJ) followed by postoperative HFD. Then, at the time points of baseline and 2, 12 and 24 wk postoperatively, we determined and compared several variables, including the area under the curve for the results of oral glucose tolerance test (AUCOGTT), serum levels of triglyceride, cholesterol and ghrelin in fasting state, homeostasis model assessment of insulin resistance (HOMA-IR), body weight, calorie intake, glucagon-like peptide (GLP)-1 and insulin secretions after glucose gavage at dose of 1 g/kg. RESULTS At 2 wk postoperatively, rats that underwent SG, SG-JJ and SG-JI, compared with sham-operated (SHAM) rats, demonstrated lower body weight, calorie intake and ghrelin (P < 0.05 vs SHAM), enhanced secretion of insulin and GLP-1 after glucose gavage (P < 0.05 vs SHAM), improved AUCOGTT, HOMA-IR, fasting serum triglyceride and cholesterol (AUCOGTT: 1616.9 ± 83.2, 837.4 ± 83.7, 874.9 ± 97.2 and 812.6 ± 81.9, P < 0.05 vs SHAM; HOMA-IR: 4.31 ± 0.54, 2.94 ± 0.22, 3.17 ± 0.37 and 3.41 ± 0.22, P < 0.05 vs SHAM; Triglyceride: 2.35 ± 0.17, 1.87 ± 0.23, 1.98 ± 0.30 and 2.04 ± 0.21 mmol/L, P < 0.05 vs SHAM; Cholesterol: 1.84 ± 0.21, 1.53 ± 0.20, 1.52 ± 0.20 and 1.46 ± 0.23 mmol/L). At 12 wk postoperatively, rats receiving SG-JJ and SG-JI had lower body weight, reduced levels of triglyceride and cholesterol and elevated level of GLP-1 compared to those receiving SG (P < 0.05 vs SG). At 24 wk after surgery, compared with SG, the advantage of SG-JJ and SG-JI for glucolipid metabolism was still evident (P < 0.05 vs SG). SG-JI had a better performance in lipid metabolism and GLP-1 secretion of rats than did SG-JJ. CONCLUSION SG combined with intestinal loop induces better glycolipid metabolism than simple SG, with the lipid metabolism being more improved with SG-JI compared to SG-JJ. PMID:27621579

Dislocation loop evolution during in-situ ion irradiation of model FeCrAl alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haley, Jack C.; Briggs, Samuel A.; Edmondson, Philip D.

Model FeCrAl alloys of Fe-10%Cr-5%Al, Fe-12%Cr-4.5%Al, Fe-15%Cr-4%Al, and Fe-18%Cr-3%Al (in wt %) were irradiated with 1 MeV Kr++ ions in-situ with transmission electron microscopy to a dose of 2.5 displacements per atom (dpa) at 320 °C. In all cases, the microstructural damage consisted of dislocation loops with ½< 111 > and <100 > Burgers vectors. The proportion of ½< 111 > dislocation loops varied from ~50% in the Fe-10%Cr-5%Al model alloy and the Fe-18Cr%-3%Al model alloy to a peak of ~80% in the model Fe-15%Cr-4.5%Al alloy. The dislocation loop volume density increased with dose for all alloys and showed signsmore » of approaching an upper limit. The total loop populations at 2.5 dpa had a slight (and possibly insignificant) decline as the chromium content was increased from 10 to 15 wt %, but the Fe-18%Cr-3%Al alloy had a dislocation loop population ~50% smaller than the other model alloys. As a result, the largest dislocation loops in each alloy had image sizes of close to 20 nm in the micrographs, and the median diameters for all alloys ranged from 6 to 8 nm. Nature analysis by the inside-outside method indicated most dislocation loops were interstitial type.« less

Dislocation loop evolution during in-situ ion irradiation of model FeCrAl alloys

DOE PAGES

Haley, Jack C.; Briggs, Samuel A.; Edmondson, Philip D.; ...

2017-07-06

Model FeCrAl alloys of Fe-10%Cr-5%Al, Fe-12%Cr-4.5%Al, Fe-15%Cr-4%Al, and Fe-18%Cr-3%Al (in wt %) were irradiated with 1 MeV Kr++ ions in-situ with transmission electron microscopy to a dose of 2.5 displacements per atom (dpa) at 320 °C. In all cases, the microstructural damage consisted of dislocation loops with ½< 111 > and <100 > Burgers vectors. The proportion of ½< 111 > dislocation loops varied from ~50% in the Fe-10%Cr-5%Al model alloy and the Fe-18Cr%-3%Al model alloy to a peak of ~80% in the model Fe-15%Cr-4.5%Al alloy. The dislocation loop volume density increased with dose for all alloys and showed signsmore » of approaching an upper limit. The total loop populations at 2.5 dpa had a slight (and possibly insignificant) decline as the chromium content was increased from 10 to 15 wt %, but the Fe-18%Cr-3%Al alloy had a dislocation loop population ~50% smaller than the other model alloys. As a result, the largest dislocation loops in each alloy had image sizes of close to 20 nm in the micrographs, and the median diameters for all alloys ranged from 6 to 8 nm. Nature analysis by the inside-outside method indicated most dislocation loops were interstitial type.« less

Design and verification of large-moment transmitter loops for geophysical applications

NASA Astrophysics Data System (ADS)

Sternberg, Ben K.; Dvorak, Steven L.; Feng, Wanjie

2017-01-01

In this paper we discuss the modeling, design and verification of large-moment transmitter (TX) loops for geophysical applications. We first develop two equivalent circuit models for TX loops. We show that the equivalent inductance can be predicted using one of two empirical formulas. The stray capacitance of the loop is then calculated using the measured self-resonant frequency and the loop inductance. We model the losses associated with both the skin effect and the dissipation factor in both of these equivalent circuits. We find that the two equivalent circuit models produce the same results provided that the dissipation factor is small. Next we compare the measured input impedances for three TX loops that were constructed with different wire configurations with the equivalent circuit model. We found excellent agreement between the measured and simulated results after adjusting the dissipation factor. Since the skin effect and dissipation factor yield good agreement with measurements, the proximity effect is negligible in the three TX loops that we tested. We found that the effects of the dissipation factor dominated those of the skin effect when the wires were relatively close together. When the wires were widely separated, then the skin effect was the dominant loss mechanism. We also found that loops with wider wire separations exhibited higher self-resonant frequencies and better high-frequency performance.

Chiral topological insulating phases from three-dimensional nodal loop semimetals

NASA Astrophysics Data System (ADS)

Li, Linhu; Yin, Chuanhao; Chen, Shu; Araujo, Miguel

We begin with a minimal model of three-dimensional nodal loop semimetals, and study the effect of anticommuting gap terms. The resulting topological insulating phases are protected by a chiral symmetry, and can be characterized by a winding number defined along the nodal loop. We illustrate the geometric relation between the nodal loop and the gap terms, which has a correspondence to the nodal loop winding number. We further investigate a lattice model and study its edge states under open boundary condition. The edge states hold Dirac cones with the same number as the summation of the winding numbers of each nodal loop in the first Brillouin zone.

A Culture-Behavior-Brain Loop Model of Human Development.

PubMed

Han, Shihui; Ma, Yina

2015-11-01

Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model. Copyright © 2015 Elsevier Ltd. All rights reserved.

ANALYSIS AND MODELING OF TWO FLARE LOOPS OBSERVED BY AIA AND EIS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Y.; Ding, M. D.; Qiu, J.

2012-10-10

We analyze and model an M1.0 flare observed by SDO/AIA and Hinode/EIS to investigate how flare loops are heated and evolve subsequently. The flare is composed of two distinctive loop systems observed in extreme ultraviolet (EUV) images. The UV 1600 A emission at the feet of these loops exhibits a rapid rise, followed by enhanced emission in different EUV channels observed by the Atmospheric Imaging Assembly (AIA) and the EUV Imaging Spectrometer (EIS). Such behavior is indicative of impulsive energy deposit and the subsequent response in overlying coronal loops that evolve through different temperatures. Using the method we recently developed,more » we infer empirical heating functions from the rapid rise of the UV light curves for the two loop systems, respectively, treating them as two big loops with cross-sectional area of 5'' by 5'', and compute the plasma evolution in the loops using the EBTEL model. We compute the synthetic EUV light curves, which, with the limitation of the model, reasonably agree with observed light curves obtained in multiple AIA channels and EIS lines: they show the same evolution trend and their magnitudes are comparable by within a factor of two. Furthermore, we also compare the computed mean enthalpy flow velocity with the Doppler shift measurements by EIS during the decay phase of the two loops. Our results suggest that the two different loops with different heating functions as inferred from their footpoint UV emission, combined with their different lengths as measured from imaging observations, give rise to different coronal plasma evolution patterns captured both in the model and in observations.« less

Simulating closed- and open-loop voluntary movement: a nonlinear control-systems approach.

PubMed

Davidson, Paul R; Jones, Richard D; Andreae, John H; Sirisena, Harsha R

2002-11-01

In many recent human motor control models, including feedback-error learning and adaptive model theory (AMT), feedback control is used to correct errors while an inverse model is simultaneously tuned to provide accurate feedforward control. This popular and appealing hypothesis, based on a combination of psychophysical observations and engineering considerations, predicts that once the tuning of the inverse model is complete the role of feedback control is limited to the correction of disturbances. This hypothesis was tested by looking at the open-loop behavior of the human motor system during adaptation. An experiment was carried out involving 20 normal adult subjects who learned a novel visuomotor relationship on a pursuit tracking task with a steering wheel for input. During learning, the response cursor was periodically blanked, removing all feedback about the external system (i.e., about the relationship between hand motion and response cursor motion). Open-loop behavior was not consistent with a progressive transfer from closed- to open-loop control. Our recently developed computational model of the brain--a novel nonlinear implementation of AMT--was able to reproduce the observed closed- and open-loop results. In contrast, other control-systems models exhibited only minimal feedback control following adaptation, leading to incorrect open-loop behavior. This is because our model continues to use feedback to control slow movements after adaptation is complete. This behavior enhances the internal stability of the inverse model. In summary, our computational model is currently the only motor control model able to accurately simulate the closed- and open-loop characteristics of the experimental response trajectories.

ORION Environmental Control and Life Support Systems Suit Loop and Pressure Control Analysis

NASA Technical Reports Server (NTRS)

Eckhardt, Brad; Conger, Bruce; Stambaugh, Imelda C.

2015-01-01

Under NASA's ORION Multi-Purpose Crew Vehicle (MPCV) Environmental Control and Life Support System (ECLSS) Project at Johnson Space Center's (JSC), the Crew and Thermal Systems Division has developed performance models of the air system using Thermal Desktop/FloCAD. The Thermal Desktop model includes an Air Revitalization System (ARS Loop), a Suit Loop, a Cabin Loop, and Pressure Control System (PCS) for supplying make-up gas (N2 and O2) to the Cabin and Suit Loop. The ARS and PCS are designed to maintain air quality at acceptable O2, CO2 and humidity levels as well as internal pressures in the vehicle Cabin and during suited operations. This effort required development of a suite of Thermal Desktop Orion ECLSS models to address the need for various simulation capabilities regarding ECLSS performance. An initial highly detailed model of the ARS Loop was developed in order to simulate rapid pressure transients (water hammer effects) within the ARS Loop caused by events such as cycling of the Pressurized Swing Adsorption (PSA) Beds and required high temporal resolution (small time steps) in the model during simulation. A second ECLSS model was developed to simulate events which occur over longer periods of time (over 30 minutes) where O2, CO2 and humidity levels, as well as internal pressures needed to be monitored in the cabin and for suited operations. Stand-alone models of the PCS and the Negative Pressure relief Valve (NPRV) were developed to study thermal effects within the PCS during emergency scenarios (Cabin Leak) and cabin pressurization during vehicle re-entry into Earth's atmosphere. Results from the Orion ECLSS models were used during Orion Delta-PDR (July, 2014) to address Key Design Requirements (KDR's) for Suit Loop operations for multiple mission scenarios.

Comparison of Two Coronal Magnetic Field Models to Reconstruct a Sigmoidal Solar Active Region with Coronal Loops

NASA Astrophysics Data System (ADS)

Duan, Aiying; Jiang, Chaowei; Hu, Qiang; Zhang, Huai; Gary, G. Allen; Wu, S. T.; Cao, Jinbin

2017-06-01

Magnetic field extrapolation is an important tool to study the three-dimensional (3D) solar coronal magnetic field, which is difficult to directly measure. Various analytic models and numerical codes exist, but their results often drastically differ. Thus, a critical comparison of the modeled magnetic field lines with the observed coronal loops is strongly required to establish the credibility of the model. Here we compare two different non-potential extrapolation codes, a nonlinear force-free field code (CESE-MHD-NLFFF) and a non-force-free field (NFFF) code, in modeling a solar active region (AR) that has a sigmoidal configuration just before a major flare erupted from the region. A 2D coronal-loop tracing and fitting method is employed to study the 3D misalignment angles between the extrapolated magnetic field lines and the EUV loops as imaged by SDO/AIA. It is found that the CESE-MHD-NLFFF code with preprocessed magnetogram performs the best, outputting a field that matches the coronal loops in the AR core imaged in AIA 94 Å with a misalignment angle of ˜10°. This suggests that the CESE-MHD-NLFFF code, even without using the information of the coronal loops in constraining the magnetic field, performs as good as some coronal-loop forward-fitting models. For the loops as imaged by AIA 171 Å in the outskirts of the AR, all the codes including the potential field give comparable results of the mean misalignment angle (˜30°). Thus, further improvement of the codes is needed for a better reconstruction of the long loops enveloping the core region.

Comparison of Two Coronal Magnetic Field Models to Reconstruct a Sigmoidal Solar Active Region with Coronal Loops

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duan, Aiying; Zhang, Huai; Jiang, Chaowei

Magnetic field extrapolation is an important tool to study the three-dimensional (3D) solar coronal magnetic field, which is difficult to directly measure. Various analytic models and numerical codes exist, but their results often drastically differ. Thus, a critical comparison of the modeled magnetic field lines with the observed coronal loops is strongly required to establish the credibility of the model. Here we compare two different non-potential extrapolation codes, a nonlinear force-free field code (CESE–MHD–NLFFF) and a non-force-free field (NFFF) code, in modeling a solar active region (AR) that has a sigmoidal configuration just before a major flare erupted from themore » region. A 2D coronal-loop tracing and fitting method is employed to study the 3D misalignment angles between the extrapolated magnetic field lines and the EUV loops as imaged by SDO /AIA. It is found that the CESE–MHD–NLFFF code with preprocessed magnetogram performs the best, outputting a field that matches the coronal loops in the AR core imaged in AIA 94 Å with a misalignment angle of ∼10°. This suggests that the CESE–MHD–NLFFF code, even without using the information of the coronal loops in constraining the magnetic field, performs as good as some coronal-loop forward-fitting models. For the loops as imaged by AIA 171 Å in the outskirts of the AR, all the codes including the potential field give comparable results of the mean misalignment angle (∼30°). Thus, further improvement of the codes is needed for a better reconstruction of the long loops enveloping the core region.« less

Intra-abdominal infection combined with intra-abdominal hypertension aggravates the intestinal mucosal barrier dysfunction.

PubMed

Li, Yuan; Ren, Jianan; Wu, Xiuwen; Li, Jieshou

2018-02-28

Some patients with intra-abdominal infection (IAI) may develop intra-abdominal hypertension (IAH) during treatment. The present study investigated the impact of IAI combined with IAH on the intestinal mucosal barrier in a rabbit model. Forty-eight New Zealand white rabbits were randomly divided into four groups: (i) IAI and IAH; (ii) IAI alone; (iii) IAH alone; and (iv) Control group. IAI model: cecal ligation and puncture for 48 h; IAH model: raised intra-abdominal pressure (IAP) of 20 mmHg for 4 h. Pathological changes in intestinal mucosa were confirmed by light and scanning electron microscopy. FITC-conjugated dextran (FITC-dextran) by gavage was used to measure intestinal mucosal permeability in plasma. Endotoxin, d-Lactate, and diamine oxidase (DAO) in plasma were measured to determine intestinal mucosal damage. Malonaldehyde (MDA), superoxide dismutase (SOD), and GSH in ileum tissues were measured to evaluate intestinal mucosal oxidation and reducing state. Histopathologic scores were significantly higher in the IAI and IAH group, followed by IAI alone, IAH alone, and the control group. FITC-dextran, d-Lactate, DAO, and endotoxin in plasma and MDA in ileum tissues had similar trends. GSH and SOD were significantly lowest the in IAI and IAH group. Occludin levels were lowest in the ileums of the IAI and IAH group. All differences were statistically significant ( P -values <0.001). IAI combined with IAH aggravates damage of the intestinal mucosal barrier in a rabbit model. The combined effects were significantly more severe compared with a single factor. IAI combined with IAH should be prevented and treated effectively. © 2018 The Author(s).

Milk with and without lactoferrin can influence intestinal damage in a pig model of malnutrition.

PubMed

Garas, Lydia C; Feltrin, Cristiano; Hamilton, M Kristina; Hagey, Jill V; Murray, James D; Bertolini, Luciana R; Bertolini, Marcelo; Raybould, Helen E; Maga, Elizabeth A

2016-02-01

Malnutrition remains a leading contributor to the morbidity and mortality of children under the age of five worldwide. However, the underlying mechanisms are not well understood necessitating an appropriate animal model to answer fundamental questions and conduct translational research into optimal interventions. One potential intervention is milk from livestock that more closely mimics human milk by increased levels of bioactive components that can promote a healthy intestinal epithelium. We tested the ability of cow milk and milk from transgenic cows expressing human lactoferrin at levels found in human milk (hLF milk) to mitigate the effects of malnutrition at the level of the intestine in a pig model of malnutrition. Weaned pigs (3 weeks old) were fed a protein and calorie restricted diet for five weeks, receiving cow, hLF or no milk supplementation daily from weeks 3-5. After three weeks, the restricted diet induced changes in growth, blood chemistry and intestinal structure including villous atrophy, increased ex vivo permeability and decreased expression of tight junction proteins. Addition of both cow and hLF milk to the diet increased growth rate and calcium and glucose levels while promoting growth of the intestinal epithelium. In the jejunum hLF milk restored intestinal morphology, reduced permeability and increased expression of anti-inflammatory IL-10. Overall, this pig model of malnutrition mimics salient aspects of the human condition and demonstrates that cow milk can stimulate the repair of damage to the intestinal epithelium caused by protein and calorie restriction with hLF milk improving this recovery to a greater extent.

Divergent Roles of Interferon-γ and Innate Lymphoid Cells in Innate and Adaptive Immune Cell-Mediated Intestinal Inflammation.

PubMed

Brasseit, Jennifer; Kwong Chung, Cheong K C; Noti, Mario; Zysset, Daniel; Hoheisel-Dickgreber, Nina; Genitsch, Vera; Corazza, Nadia; Mueller, Christoph

2018-01-01

Aberrant interferon gamma (IFNγ) expression is associated with the pathogenesis of numerous autoimmune- and inflammatory disorders, including inflammatory bowel diseases (IBD). However, the requirement of IFNγ for the pathogenesis of chronic intestinal inflammation remains controversial. The aim of this study was thus to investigate the role of IFNγ in experimental mouse models of innate and adaptive immune cell-mediated intestinal inflammation using genetically and microbiota-stabilized hosts. While we find that IFNγ drives acute intestinal inflammation in the anti-CD40 colitis model in an innate lymphoid cell (ILC)-dependent manner, IFNγ secreted by both transferred CD4 T cells and/or cells of the lymphopenic Rag1 -/- recipient mice was dispensable for CD4 T cell-mediated colitis. In the absence of IFNγ, intestinal inflammation in CD4 T cell recipient mice was associated with enhanced IL17 responses; consequently, targeting IL17 signaling in IFNγ-deficient mice reduced T cell-mediated colitis. Intriguingly, in contrast to the anti-CD40 model of colitis, depletion of ILC in the Rag1 -/- recipients of colitogenic CD4 T cells did not prevent induction of colonic inflammation. Together, our findings demonstrate that IFNγ represents an essential, or a redundant, pro-inflammatory cytokine for the induction of intestinal inflammation, depending on the experimental mouse model used and on the nature of the critical disease inducing immune cell populations involved.

Steady State Model for Solar Coronal Loops

NASA Astrophysics Data System (ADS)

Sugiyama, L.; Asgari-Targhi, M.

2017-12-01

Solar coronal loops on the surface of the sun provide background magnetic and plasma structures for the release of a significant amount of the sun's energy, through energetic solar flares and coronal mass ejections and more gradual processes. Understanding their steady states is the first step in understanding loop dynamics. A consistent MHD steady state model, for a curved magnetic flux rope that contains plasma, has been developed[1] for simple coronal loops with both ends anchored in the photosphere. Plasma pressure or current makes the loop unstable to expansion in major radius and must be balanced by external forces, such as the solar gravity. The MHD momentum equation has a well defined small parameter ordering in the loop inverse aspect ratio ɛ=a/Ro (minor/major radius). Different types of common coronal loops fall in different parameter regimes, determined by the relative values of the plasma beta β=po/(Bo2/2μo), the MHD gravity parameter Ĝ≡ga/vA2 (the gravitational acceleration g normalized to the minor radius a and shear Alfvén velocity vA), and ɛ. The largest possible gravity, Ĝ ɛ1β, corresponds to the largest loops because it reduces the plasma density at the top of the loop exponentially compared to its lower ends, reducing the downward gravitational force -ρĜ there. The thin loops that are ubiquitous in solar active regions have ``high'' beta, β ɛ1, for ɛ≃0.02, and fit the predicted model scalings. The thicker loops that can give rise to flares and CMEs have ``low'' beta, β ɛ2. Cool loops, such as solar filaments outside active regions, that have a central pressure lower than that of the surrounding corona would have the strongest stability against radial expansion. The model raises a number of questions about the connection of loops to the photosphere and the force-free nature of the magnetic field there. [1] L. Sugiyama, M. Asgari-Targhi, Phys. Plasmas 24, 022904 (2017).

Naringin, a natural dietary compound, prevents intestinal tumorigenesis in Apc (Min/+) mouse model.

PubMed

Zhang, Yu-Sheng; Li, Ye; Wang, Yan; Sun, Shi-Yue; Jiang, Tao; Li, Cong; Cui, Shu-Xiang; Qu, Xian-Jun

2016-05-01

Naringin is a natural dietary flavonoid compound. We aimed to evaluate the effects of naringin on intestinal tumorigenesis in the adenomatous polyposis coli multiple intestinal neoplasia (Apc (Min/+)) mouse model. Apc (Min/+) mice were given either naringin (150 mg/kg) or vehicle by p.o. gavage daily for 12 consecutive weeks. Mice were killed with ether, and blood samples were collected to assess the concentrations of IL-6 and PGE2. Total intestines were removed, and the number of polyps was examined. Tissue samples of intestinal polyps were subjected to the assays of histopathology, immunohistochemical analysis and Western blotting analysis. Apc (Min/+) mice fed with naringin developed less and smaller polyps in total intestines. Naringin prevented intestinal tumorigenesis without adverse effects. Histopathologic analysis revealed the reduction of dysplastic cells and dysplasia in the adenomatous polyps. The treatments' effects might arise from its anti-proliferation, induction of apoptosis and modulation of GSK-3β and APC/β-catenin signaling pathways. Naringin also exerted its effects on tumorigenesis through anti-chronic inflammation. Naringin prevented intestinal tumorigenesis likely through a collection of activities including anti-proliferation, induction of apoptosis, modulation of GSK-3β and APC/β-catenin pathways and anti-inflammation. Naringin is a potential chemopreventive agent for reducing the risk of colonic cancers.

Material Data Representation of Hysteresis Loops for Hastelloy X Using Artificial Neural Networks

NASA Technical Reports Server (NTRS)

Alam, Javed; Berke, Laszlo; Murthy, Pappu L. N.

1993-01-01

The artificial neural network (ANN) model proposed by Rumelhart, Hinton, and Williams is applied to develop a functional approximation of material data in the form of hysteresis loops from a nickel-base superalloy, Hastelloy X. Several different ANN configurations are used to model hysteresis loops at different cycles for this alloy. The ANN models were successful in reproducing the hysteresis loops used for its training. However, because of sharp bends at the two ends of hysteresis loops, a drift occurs at the corners of the loops where loading changes to unloading and vice versa (the sharp bends occurred when the stress-strain curves were reproduced by adding stress increments to the preceding values of the stresses). Therefore, it is possible only to reproduce half of the loading path. The generalization capability of the network was tested by using additional data for two other hysteresis loops at different cycles. The results were in good agreement. Also, the use of ANN led to a data compression ratio of approximately 22:1.

Experimental validation of a predicted feedback loop in the multi-oscillator clock of Arabidopsis thaliana

PubMed Central

Locke, James C W; Kozma-Bognár, László; Gould, Peter D; Fehér, Balázs; Kevei, Éva; Nagy, Ferenc; Turner, Matthew S; Hall, Anthony; Millar, Andrew J

2006-01-01

Our computational model of the circadian clock comprised the feedback loop between LATE ELONGATED HYPOCOTYL (LHY), CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and TIMING OF CAB EXPRESSION 1 (TOC1), and a predicted, interlocking feedback loop involving TOC1 and a hypothetical component Y. Experiments based on model predictions suggested GIGANTEA (GI) as a candidate for Y. We now extend the model to include a recently demonstrated feedback loop between the TOC1 homologues PSEUDO-RESPONSE REGULATOR 7 (PRR7), PRR9 and LHY and CCA1. This three-loop network explains the rhythmic phenotype of toc1 mutant alleles. Model predictions fit closely to new data on the gi;lhy;cca1 mutant, which confirm that GI is a major contributor to Y function. Analysis of the three-loop network suggests that the plant clock consists of morning and evening oscillators, coupled intracellularly, which may be analogous to coupled, morning and evening clock cells in Drosophila and the mouse. PMID:17102804

Closed-loop model identification of cooperative manipulators holding deformable objects

NASA Astrophysics Data System (ADS)

Alkathiri, A. A.; Akmeliawati, R.; Azlan, N. Z.

2017-11-01

This paper presents system identification to obtain the closed-loop models of a couple of cooperative manipulators in a system, which function to hold deformable objects. The system works using the master-slave principle. In other words, one of the manipulators is position-controlled through encoder feedback, while a force sensor gives feedback to the other force-controlled manipulator. Using the closed-loop input and output data, the closed-loop models, which are useful for model-based control design, are estimated. The criteria for model validation are a 95% fit between the measured and simulated output of the estimated models and residual analysis. The results show that for both position and force control respectively, the fits are 95.73% and 95.88%.

Using video modeling with substitutable loops to teach varied play to children with autism.

PubMed

Dupere, Sally; MacDonald, Rebecca P F; Ahearn, William H

2013-01-01

Children with autism often engage in repetitive play with little variation in the actions performed or items used. This study examined the use of video modeling with scripted substitutable loops on children's pretend play with trained and untrained characters. Three young children with autism were shown a video model of scripted toy play that included a substitutable loop that allowed various characters to perform the same actions and vocalizations. Three characters were modeled with the substitutable loop during training sessions, and 3 additional characters were present in the video but never modeled. Following video modeling, all the participants incorporated untrained characters into their play, but the extent to which they did so varied. © Society for the Experimental Analysis of Behavior.

Protective Effect of a Synbiotic against Multidrug-Resistant Acinetobacter baumannii in a Murine Infection Model

PubMed Central

Takahashi, Akira; Yuki, Norikatsu; Kaji, Rumi; Takahashi, Takuya; Nomoto, Koji

2016-01-01

This study investigated the ability of the probiotic Bifidobacterium breve strain Yakult (BbY) to protect against infection, as well as the potentiation of BbY activity by the synbiotic combination of BbY and prebiotic galactooligosaccharides (GOS). The study employed a mouse model of lethal intestinal multidrug-resistant Acinetobacter baumannii (MDRAb) infection. The endogenous intestinal microbiota was disrupted by the administration of multiple antibiotics, causing the loss of endogenous Bifidobacterium. Oral infection of these mice with MDRAb resulted in marked growth of this organism. Additional treatment of the infected mice with a sublethal dose of 5-fluorouracil (5-FU) induced systemic invasion by MDRAb and subsequent animal death. The continuous oral administration of BbY increased the survival rate and inhibited the intestinal growth and invasion by MDRAb in the infection model. Disruptions of the intestinal environment and barrier function in the infected mice were attenuated by BbY. Protection against the MDRAb infection was markedly potentiated by a synbiotic combination of BbY and GOS, although GOS by itself did not provide protection. Negative correlations were observed between intestinal MDRAb and BbY counts or acetic acid levels; positive correlations were observed between acetic acid levels and intestinal epithelium expression of tight-junction-related genes. These results demonstrated that the probiotic and synbiotic markedly potentiated protection against fatal intestinal infection caused by a multidrug-resistant bacterium. Probiotics and synbiotics are presumed to provide protection by compensation for the disrupted indigenous populations, thereby maintaining the intestinal environments and barrier functions otherwise targeted during opportunistic infection by MDRAb. PMID:26953197

Titanium Dioxide Nanoparticle Ingestion Alters Nutrient Absorption in an In Vitro Model of the Small Intestine

PubMed Central

Guo, Zhongyuan; Martucci, Nicole J.; Moreno-Olivas, Fabiola; Tako, Elad; Mahler, Gretchen J.

2017-01-01

Ingestion of titanium dioxide (TiO2) nanoparticles from products such as agricultural chemicals, processed food, and nutritional supplements is nearly unavoidable. The gastrointestinal tract serves as a critical interface between the body and the external environment, and is the site of essential nutrient absorption. The goal of this study was to examine the effects of ingesting the 30 nm TiO2 nanoparticles with an in vitro cell culture model of the small intestinal epithelium, and to determine how acute or chronic exposure to nano-TiO2 influences intestinal barrier function, reactive oxygen species generation, proinflammatory signaling, nutrient absorption (iron, zinc, fatty acids), and brush border membrane enzyme function (intestinal alkaline phosphatase). A Caco-2/HT29-MTX cell culture model was exposed to physiologically relevant doses of TiO2 nanoparticles for acute (four hours) or chronic (five days) time periods. Exposure to TiO2 nanoparticles significantly decreased intestinal barrier function following chronic exposure. Reactive oxygen species (ROS) generation, proinflammatory signaling, and intestinal alkaline phosphatase activity all showed increases in response to nano-TiO2. Iron, zinc, and fatty acid transport were significantly decreased following exposure to TiO2 nanoparticles. This is because nanoparticle exposure induced a decrease in absorptive microvilli in the intestinal epithelial cells. Nutrient transporter protein gene expression was also altered, suggesting that cells are working to regulate the transport mechanisms disturbed by nanoparticle ingestion. Overall, these results show that intestinal epithelial cells are affected at a functional level by physiologically relevant exposure to nanoparticles commonly ingested from food. PMID:28944308

[Magnetic closure for ileostomy (author's transl)].

PubMed

Loygue, J; Salmon, R; Bloch, P

1980-09-20

The Maclet magnetic stoma seal already used by the authors for colostomies was applied to the closure of permanent terminal ileostomies. A reservoir is constructed upstreams of the closure with the last loop of ileum, so that the faeces accumulate and can be evacuated by intermittence. Patients empty the reservoir by removing the cap which blocks the intestinal lumen and introducing a probe into it. The technique was used on 2 patients who had undergone total proctocolectomy for familial polyposis of the colon. One patient has now been followed up for 3 years and the other for 6 months. The perfect continence obtained by this method favourably compares with Kock's continent ileostomy.

The effect of vagotomy and drainage on the small bowel flora

PubMed Central

Browning, G. G.; Buchan, K. A.; Mackay, C.

1974-01-01

The incidence of small intestinal colonization in unoperated duodenal ulcer patients was low and similar to that in the normal population. The majority of patients seven to 10 days following truncal vagotomy and drainage were colonized whereas none of a control group of patients following simple closure of a perforated duodenal ulcer was colonized. In patients with pyloroplasty, this high incidence fell to control levels on average 18 months postoperatively, but in patients with a gastro-jejunostomy, the incidence remained raised probably due to the presence of the afferent loop. Only two patients developed episodic diarrhoea and there was no obvious association with small bowel colonization. PMID:4820640

Enzyme-linked immunosorbent assay for Escherichia coli heat-stable enterotoxin type II.

PubMed Central

Handl, C; Rönnberg, B; Nilsson, B; Olsson, E; Jonsson, H; Flock, J I

1988-01-01

The gene for Escherichia coli heat-stable enterotoxin type II (STII) was fused to the genes for protein A from Staphylococcus aureus and beta-galactosidase in two different expression systems. Antibodies raised in rabbits against the protein A-STII fusion protein recognized the beta-galactosidase-STII fusion protein. The latter fusion protein was used as the immobilized antigen in an enzyme-linked immunosorbent assay (ELISA) for detection of STII. The correlation between the results of the ELISA and the intestinal loop test in piglets was 95%, suggesting that the ELISA can be used to reliably detect STII. Images PMID:3049659

Hemoptysis due to pulmonary pseudosequestration secondary to gastro-pulmonary fistula after a revisional bariatric operation.

PubMed

Santacruz, Carlos Cerdán; Rodríguez, María Conde; Sánchez-Pernaute, Andrés; García, Antonio José Torres

2014-10-01

We report the case of a patient with a history of a complicated revisional bariatric operation who developed a lung pseudosequestration secondary to a gastro-pulmonary fistula. As the patient presented with recurrent hemoptysis, she was initially submitted to embolization of the aberrant vessels and later to a definite operation, which consisted on a diversion of the gastric fistula into a Roux-en-Y intestinal loop. It is an exceptional case about late complications of bariatric surgery, and it underlines the importance of discarding these complications even when the clinical manifestations affect another anatomic region different from the operated abdomen.

Hemoptysis due to pulmonary pseudosequestration secondary to gastro-pulmonary fistula after a revisional bariatric operation

PubMed Central

Santacruz, Carlos Cerdán; Rodríguez, María Conde; Sánchez-Pernaute, Andrés; García, Antonio José Torres

2014-01-01

We report the case of a patient with a history of a complicated revisional bariatric operation who developed a lung pseudosequestration secondary to a gastro-pulmonary fistula. As the patient presented with recurrent hemoptysis, she was initially submitted to embolization of the aberrant vessels and later to a definite operation, which consisted on a diversion of the gastric fistula into a Roux-en-Y intestinal loop. It is an exceptional case about late complications of bariatric surgery, and it underlines the importance of discarding these complications even when the clinical manifestations affect another anatomic region different from the operated abdomen. PMID:25276245

Management of ingested magnets in children.

PubMed

Hussain, Sunny Z; Bousvaros, Athos; Gilger, Mark; Mamula, Petar; Gupta, Sandeep; Kramer, Robert; Noel, R Adam

2012-09-01

We describe a comprehensive algorithm for the management of ingested rare-earth magnets in children. These newer and smaller neodymium magnets sold as adult toys are much stronger than the traditional magnets, and can attract each other with formidable forces. If >1 magnet is swallowed at the same time, or a magnet is co-ingested with another metallic object, the loops of intestine can be squeezed between them resulting in bowel damage including perforations. An algorithm that uses the number of magnets ingested, location of magnets, and the timing of ingestion before intervention helps to delineate the roles of the pediatric gastroenterologists and surgeons in the management of these cases.

[Fetal meconium pseudocyst secondary to in utero perforation of colon transversum and meconium peritonitis].

PubMed

Markov, D; Jekova, N; Ivanov, St; Diavolov, V; Brankov, O

2011-01-01

Fetal bowel intrauterine perforation causes sterile inflammation of the peritoneum, known as meconium peritonitis. In some cases the perforation closes spontaneously, thus forming a meconium pseudocyst between the intestinal loops and the omentum. Meconium peritonitis, complicated by pseudocyst formation, should always be considered when a fetal abdominal mass with diverse echogenicity and hyperechogenic calcifications is observed on prenatal ultrasound. Usually, this is associated with ascites and/or polyhydramnios. The differential diagnosis necessitates exclusion of all other fetal abdominal tumors. We present a case report of meconium pseudocyst diagnosed prenatally at 32 weeks of gestation which was successfully treated by surgery after birth.

Introduction to Loop Heat Pipes

NASA Technical Reports Server (NTRS)

Ku, Jentung

2015-01-01

This is the presentation file for the short course Introduction to Loop Heat Pipes, to be conducted at the 2015 Thermal Fluids and Analysis Workshop, August 3-7, 2015, Silver Spring, Maryland. This course will discuss operating principles and performance characteristics of a loop heat pipe. Topics include: 1) pressure profiles in the loop; 2) loop operating temperature; 3) operating temperature control; 4) loop startup; 4) loop shutdown; 5) loop transient behaviors; 6) sizing of loop components and determination of fluid inventory; 7) analytical modeling; 8) examples of flight applications; and 9) recent LHP developments.

Prediction of protein loop conformations using multiscale modeling methods with physical energy scoring functions.

PubMed

Olson, Mark A; Feig, Michael; Brooks, Charles L

2008-04-15

This article examines ab initio methods for the prediction of protein loops by a computational strategy of multiscale conformational sampling and physical energy scoring functions. Our approach consists of initial sampling of loop conformations from lattice-based low-resolution models followed by refinement using all-atom simulations. To allow enhanced conformational sampling, the replica exchange method was implemented. Physical energy functions based on CHARMM19 and CHARMM22 parameterizations with generalized Born (GB) solvent models were applied in scoring loop conformations extracted from the lattice simulations and, in the case of all-atom simulations, the ensemble of conformations were generated and scored with these models. Predictions are reported for 25 loop segments, each eight residues long and taken from a diverse set of 22 protein structures. We find that the simulations generally sampled conformations with low global root-mean-square-deviation (RMSD) for loop backbone coordinates from the known structures, whereas clustering conformations in RMSD space and scoring detected less favorable loop structures. Specifically, the lattice simulations sampled basins that exhibited an average global RMSD of 2.21 +/- 1.42 A, whereas clustering and scoring the loop conformations determined an RMSD of 3.72 +/- 1.91 A. Using CHARMM19/GB to refine the lattice conformations improved the sampling RMSD to 1.57 +/- 0.98 A and detection to 2.58 +/- 1.48 A. We found that further improvement could be gained from extending the upper temperature in the all-atom refinement from 400 to 800 K, where the results typically yield a reduction of approximately 1 A or greater in the RMSD of the detected loop. Overall, CHARMM19 with a simple pairwise GB solvent model is more efficient at sampling low-RMSD loop basins than CHARMM22 with a higher-resolution modified analytical GB model; however, the latter simulation method provides a more accurate description of the all-atom energy surface, yet demands a much greater computational cost. (c) 2007 Wiley Periodicals, Inc.

Defining new criteria for selection of cell-based intestinal models using publicly available databases

PubMed Central

2012-01-01

Background The criteria for choosing relevant cell lines among a vast panel of available intestinal-derived lines exhibiting a wide range of functional properties are still ill-defined. The objective of this study was, therefore, to establish objective criteria for choosing relevant cell lines to assess their appropriateness as tumor models as well as for drug absorption studies. Results We made use of publicly available expression signatures and cell based functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium. We have compared a panel of intestinal cell lines with patient-derived normal and tumor epithelium and classified them according to traits relating to oncogenic pathway activity, epithelial-mesenchymal transition (EMT) and stemness, migratory properties, proliferative activity, transporter expression profiles and chemosensitivity. For example, SW480 represent an EMT-high, migratory phenotype and scored highest in terms of signatures associated to worse overall survival and higher risk of recurrence based on patient derived databases. On the other hand, differentiated HT29 and T84 cells showed gene expression patterns closest to tumor bulk derived cells. Regarding drug absorption, we confirmed that differentiated Caco-2 cells are the model of choice for active uptake studies in the small intestine. Regarding chemosensitivity we were unable to confirm a recently proposed association of chemo-resistance with EMT traits. However, a novel signature was identified through mining of NCI60 GI50 values that allowed to rank the panel of intestinal cell lines according to their drug responsiveness to commonly used chemotherapeutics. Conclusions This study presents a straightforward strategy to exploit publicly available gene expression data to guide the choice of cell-based models. While this approach does not overcome the major limitations of such models, introducing a rank order of selected features may allow selecting model cell lines that are more adapted and pertinent to the addressed biological question. PMID:22726358

Similarity Metrics for Closed Loop Dynamic Systems

NASA Technical Reports Server (NTRS)

Whorton, Mark S.; Yang, Lee C.; Bedrossian, Naz; Hall, Robert A.

2008-01-01

To what extent and in what ways can two closed-loop dynamic systems be said to be "similar?" This question arises in a wide range of dynamic systems modeling and control system design applications. For example, bounds on error models are fundamental to the controller optimization with modern control design methods. Metrics such as the structured singular value are direct measures of the degree to which properties such as stability or performance are maintained in the presence of specified uncertainties or variations in the plant model. Similarly, controls-related areas such as system identification, model reduction, and experimental model validation employ measures of similarity between multiple realizations of a dynamic system. Each area has its tools and approaches, with each tool more or less suited for one application or the other. Similarity in the context of closed-loop model validation via flight test is subtly different from error measures in the typical controls oriented application. Whereas similarity in a robust control context relates to plant variation and the attendant affect on stability and performance, in this context similarity metrics are sought that assess the relevance of a dynamic system test for the purpose of validating the stability and performance of a "similar" dynamic system. Similarity in the context of system identification is much more relevant than are robust control analogies in that errors between one dynamic system (the test article) and another (the nominal "design" model) are sought for the purpose of bounding the validity of a model for control design and analysis. Yet system identification typically involves open-loop plant models which are independent of the control system (with the exception of limited developments in closed-loop system identification which is nonetheless focused on obtaining open-loop plant models from closed-loop data). Moreover the objectives of system identification are not the same as a flight test and hence system identification error metrics are not directly relevant. In applications such as launch vehicles where the open loop plant is unstable it is similarity of the closed-loop system dynamics of a flight test that are relevant.

The two and three-loop matter bispectrum in perturbation theories

NASA Astrophysics Data System (ADS)

Lazanu, Andrei; Liguori, Michele

2018-04-01

We evaluate for the first time the dark matter bispectrum of large-scale structure at two loops in the Standard Perturbation Theory and at three loops in the Renormalised Perturbation Theory (MPTBREEZE formalism), removing in each case the leading divergences in the integrals in order to make them infrared-safe. We show that the Standard Perturbation Theory at two loops can be employed to model the matter bispectrum further into the quasi-nonlinear regime compared to the one loop, up to kmax ~ 0.1 h/Mpc at z = 0, but without reaching a high level of accuracy. In the case of the MPTBREEZE method, we show that its bispectra decay at smaller and smaller scales with increasing loop order, but with smaller improvements decreases with loop order. At three loops, this model predicts the bispectrum accurately up to scales kmax ~ 0.17 h/Mpc at z = 0 and kmax ~ 0.24 h/Mpc at z = 1.

Intestinal tract is an important organ for lowering serum uric acid in rats

PubMed Central

Gao, Zhiyi; Li, Yue; Gao, Tao; Duan, Jinlian; Yang, Rong; Dong, Xianxiang; Zhang, Lumei

2017-01-01

The kidney was recognized as a dominant organ for uric acid excretion. The main aim of the study demonstrated intestinal tract was an even more important organ for serum uric acid (SUA) lowering. Sprague-Dawley rats were treated normally or with antibiotics, uric acid, adenine, or inosine of the same molar dose orally or intraperitoneally for 5 days. Rat’s intestinal tract was equally divided into 20 segments except the cecum. Uric acid in serum and intestinal segment juice was assayed. Total RNA in the initial intestinal tract and at the end ileum was extracted and sequenced. Protein expression of xanthine dehydrogenase (XDH) and urate oxidase (UOX) was tested by Western blot analysis. The effect of oral UOX in lowering SUA was investigated in model rats treated with adenine and an inhibitor of uric oxidase for 5 days. SUA in the normal rats was 20.93±6.98 μg/ml, and total uric acid in the intestinal juice was 308.27±16.37 μg, which is two times more than the total SUA. The uric acid was very low in stomach juice, and attained maximum in the juice of the first segment (duodenum) and then declined all the way till the intestinal end. The level of uric acid in the initial intestinal tissue was very high, where XDH and most of the proteins associated with bicarbonate secretion were up-regulated. In addition, SUA was decreased by oral UOX in model rats. The results suggested that intestinal juice was an important pool for uric acid, and intestinal tract was an important organ for SUA lowering. The uric acid distribution was associated with uric acid synthesis and secretion in the upper intestinal tract, and reclamation in the lower. PMID:29267361

A Model for Developing Clinical Analytics Capacity: Closing the Loops on Outcomes to Optimize Quality.

PubMed

Eggert, Corinne; Moselle, Kenneth; Protti, Denis; Sanders, Dale

2017-01-01

Closed Loop Analytics© is receiving growing interest in healthcare as a term referring to information technology, local data and clinical analytics working together to generate evidence for improvement. The Closed Loop Analytics model consists of three loops corresponding to the decision-making levels of an organization and the associated data within each loop - Patients, Protocols, and Populations. The authors propose that each of these levels should utilize the same ecosystem of electronic health record (EHR) and enterprise data warehouse (EDW) enabled data, in a closed-loop fashion, with that data being repackaged and delivered to suit the analytic and decision support needs of each level, in support of better outcomes.

Comparison between two models of energy balance in coronal loops

NASA Astrophysics Data System (ADS)

Mac Cormack, C.; López Fuentes, M.; Vásquez, A. M.; Nuevo, F. A.; Frazin, R. A.; Landi, E.

2017-10-01

In this work we compare two models to analyze the energy balance along coronal magnetic loops. For the first stationary model we deduce an expression of the energy balance along the loops expressed in terms of quantities provided by the combination of differential emission measure tomography (DEMT) applied to EUV images time series and potential extrapolations of the coronal magnetic field. The second applied model is a 0D hydrodynamic model that provides the evolution of the average properties of the coronal plasma along the loops, using as input parameters the loop length and the heating rate obtained with the first model. We compare the models for two Carrington rotations (CR) corresponding to different periods of activity: CR 2081, corresponding to a period of minimum activity observed with the Extreme Ultraviolet Imager (EUVI) on board of the Solar Terrestrial Relations Observatory (STEREO), and CR 2099, corresponding to a period of activity increase observed with the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamics Observatory (SDO). The results of the models are consistent for both rotations.

Potential of Lactobacillus plantarum CCFM639 in Protecting against Aluminum Toxicity Mediated by Intestinal Barrier Function and Oxidative Stress.

PubMed

Yu, Leilei; Zhai, Qixiao; Tian, Fengwei; Liu, Xiaoming; Wang, Gang; Zhao, Jianxin; Zhang, Hao; Narbad, Arjan; Chen, Wei

2016-12-02

Aluminum (Al) is a ubiquitous metal that can seriously harm the health of animals and humans. In our previous study, we demonstrated that Lactobacillus plantarum CCFM639 can decrease Al burden in the tissues of mice by inhibiting intestinal Al absorption. The main aim of the present research was to investigate whether the protection by the strain is also associated with enhancement of the intestinal barrier, alleviation of oxidative stress and modulation of the inflammatory response. In an in vitro cell model, two protection modes (intervention and therapy) were examined and the results indicated that L. plantarum CCFM639 alleviated Al-induced cytotoxicity. In a mouse model, L. plantarum CCFM639 treatment was found to significantly alleviate oxidative stress in the intestinal tract, regulate the function of the intestinal mucosal immune system, restore the integrity of tight junction proteins and maintain intestinal permeability. These results suggest that in addition to Al sequestration, L. plantarum CCFM639 can also inhibit Al absorption by protecting the intestinal barrier, alleviating Al-induced oxidative stress and inflammatory response. Therefore, L. plantarum CCFM639 has the potential to be a dietary supplement ingredient that provides protection against Al-induced gut injury.

Targeting of GLUT1-GLUT5 chimeric proteins in the polarized cell line Caco-2.

PubMed

Inukai, K; Takata, K; Asano, T; Katagiri, H; Ishihara, H; Nakazaki, M; Fukushima, Y; Yazaki, Y; Kikuchi, M; Oka, Y

1997-04-01

Caco-2, a human differentiated intestinal epithelial cell line, is a promising model for investigating the mechanism of polarized targeting of apical and basolateral membrane proteins. We stably transfected rat GLUT5 cDNA and rabbit GLUT1 cDNA into Caco-2 cells with an expression vector. Immunohistochemical study revealed that the GLUT5 protein expressed was localized at apical membranes and that the GLUT1 expressed was present primarily in the basolateral membranes of cells grown on permeable support. Next, to investigate the domain responsible for determining apical vs. basolateral sorting in glucose transporters, we prepared several GLUT1-GLUT5 chimeric cDNAs and transfected them into Caco-2 cells. A GLUT1 [N terminus approximately sixth transmembrane domain (TM6)]-GLUT5 [intracellular loop (IL) approximately C terminus] chimera was observed exclusively at the apical membrane, while GLUT1 (N terminus approximately IL)-GLUT5 (TM7 approximately C terminus) and GLUT1 (N terminus approximately TM12)-GLUT5 (C-terminal domain) chimeras were observed mainly at the basolateral membrane, a localization similar to that of GLUT1. Moreover, using a recombinant adenovirus expression system, we expressed a GLUT5 (N terminus approximately TM6)-GLUT1(IL)-GLUT5(TM7 approximately C-terminus) chimera, which was observed at the basolateral membrane. Based on these results, the C-terminal domain does not determine isoform-specific targeting of GLUT1 and GLUT5. Rather, it is the intracellular loop in glucose transporters that appears to play a pivotal role in apical-basolateral sorting signals in Caco-2 cells.

Evaluation of BW942C, a novel antidiarrheal agent, against enterotoxins of Escherichia coli and Vibrio cholerae.

PubMed Central

Morgan, D R; Sellin, J; Gutierrez, L; DuPont, H L; Wood, L V

1985-01-01

BW942C, an enkephalin-like pentapeptide with anti-diarrheal activity, was tested against crude toxins of Escherichia coli and Vibrio cholerae in the Y-1 adrenal cell assay, rabbit ileal loop assay, and suckling mouse assay. The effects of BW942C on in vitro ion transport were measured in rabbit ileum mounted in Ussing chambers. In vitro, BW942C decreased basal short-circuit current (2.26 and 3.15 mueq cm-2 h-1 in experimental samples and controls, respectively; n = 7, P less than 0.05) and increased basal net Cl absorption (1.59 and 0.50 mueq cm-2 h-1 in experimental samples and controls, respectively; P less than 0.025). Net Na absorption was also increased, but not significantly. BW942C did not block the secretory response to a maximal dose of purified heat-stable toxin. BW942C directly enhanced intestinal fluid absorption. In the Y-1 adrenal cell assay, 5 mg of BW942C per ml inhibited the cytopathic effect caused by cholera toxin or heat-labile enterotoxin of E. coli. In the rabbit ileal loop assay, E. coli heat-stable toxin, E. coli heat-labile enterotoxin, and cholera toxin were inhibited 35 to 70% by administration of BW942C. With the suckling mouse model, the fluid accumulation caused by E. coli heat-stable toxin was ablated by prior treatment with BW942C. The drug is currently being evaluated in patients with acute secretory diarrhea to determine its effect on clinical symptoms. PMID:3838969

Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

PubMed Central

Onal, Ozkan; Yetisir, Fahri; Sarer, A. Ebru Salman; Zeybek, N. Dilara; Onal, C. Oztug; Yurekli, Banu; Celik, H. Tugrul; Sirma, Ayse; Kılıc, Mehmet

2015-01-01

Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH-Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented intestine from ischemia reperfusion injury. It is thought that the therapeutic effect of ozone is associated with increase in antioxidant enzymes and protection of cells from oxidation and inflammation. PMID:26161005

Enthalpy-Based Thermal Evolution of Loops: II. Improvements to the Model

NASA Technical Reports Server (NTRS)

Cargill, P. J.; Bradshaw, S. J.; Klimchuk, J. A.

2011-01-01

This paper further develops the zero-dimensional (0D) hydrodynamic coronal loop model "Enthalpy-based Thermal Evolution of Loops" (EBTEL) originally proposed by Klimchuk et al (2008), which studies the plasma response to evolving coronal heating. It has typically been applied to impulsive heating events. The basis of EBTEL is the modelling of mass exchange between the corona and transition region and chromosphere in response to heating variations, with the key parameter being the ratio of transition region to coronal radiation. We develop new models for this parameter that now include gravitational stratification and a physically motivated approach to radiative cooling. A number of examples are presented, including nanoflares in short and long loops, and a small flare. It is found that while the evolution of the loop temperature is rather insensitive to the details of the model, accurate tracking of the density requires the inclusion of our new features. In particular, we are able to now obtain highly over-dense loops in the late cooling phase and decreases to the coronal density arising due to stratification. The 0D results are compared to a 1D hydro code (Hydrad). The agreement is acceptable, with the exception of the flare case where some versions of Hydrad can give significantly lower densities. This is attributed to the method used to model the chromosphere in a flare. EBTEL is suitable for general use as a tool for (a) quick-look results of loop evolution in response to a given heating function and (b) situations where the modelling of hundreds or thousands of elemental loops is needed. A single run takes a few seconds on a contemporary laptop.

Feedback control laws for highly maneuverable aircraft

NASA Technical Reports Server (NTRS)

Garrard, William L.; Balas, Gary J.

1994-01-01

During the first half of the year, the investigators concentrated their efforts on completing the design of control laws for the longitudinal axis of the HARV. During the second half of the year they concentrated on the synthesis of control laws for the lateral-directional axes. The longitudinal control law design efforts can be briefly summarized as follows. Longitudinal control laws were developed for the HARV using mu synthesis design techniques coupled with dynamic inversion. An inner loop dynamic inversion controller was used to simplify the system dynamics by eliminating the aerodynamic nonlinearities and inertial cross coupling. Models of the errors resulting from uncertainties in the principal longitudinal aerodynamic terms were developed and included in the model of the HARV with the inner loop dynamic inversion controller. This resulted in an inner loop transfer function model which was an integrator with the modeling errors characterized as uncertainties in gain and phase. Outer loop controllers were then designed using mu synthesis to provide robustness to these modeling errors and give desired response to pilot inputs. Both pitch rate and angle of attack command following systems were designed. The following tasks have been accomplished for the lateral-directional controllers: inner and outer loop dynamic inversion controllers have been designed; an error model based on a linearized perturbation model of the inner loop system was derived; controllers for the inner loop system have been designed, using classical techniques, that control roll rate and Dutch roll response; the inner loop dynamic inversion and classical controllers have been implemented on the six degree of freedom simulation; and lateral-directional control allocation scheme has been developed based on minimizing required control effort.

A Dynamic Model of Sustainment Investment

DTIC Science & Technology

2015-02-01

Sustainment System Dynamics Model 11 Figure 7: Core Structure of Sustainment Work 12 Figure 8: Bandwagon Effect Loop 13 Figure 9: Limits to Growth Loop 14...Dynamics Model sustainment capacity sustainment performance gap Bandwagon Effect R1 Limits to Growth B1 S Work Smarter B3 Work Bigger B2 desired...which is of concern primarily when using the model as a vehicle for research. Figure 8 depicts a reinforcing loop called the “ Bandwagon Effect

Low-energy effective action in two-dimensional SQED: a two-loop analysis

NASA Astrophysics Data System (ADS)

Samsonov, I. B.

2017-07-01

We study two-loop quantum corrections to the low-energy effective actions in N=(2,2) and N=(4,4) SQED on the Coulomb branch. In the latter model, the low-energy effective action is described by a generalized Kähler potential which depends on both chiral and twisted chiral superfields. We demonstrate that this generalized Kähler potential is one-loop exact and corresponds to the N=(4,4) sigma-model with torsion presented by Roček, Schoutens and Sevrin [1]. In the N=(2,2) SQED, the effective Kähler potential is not protected against higher-loop quantum corrections. The two-loop quantum corrections to this potential and the corresponding sigma-model metric are explicitly found.

Evaluation of Effects and Effectiveness of Various α and β Angulations for Three Different Loop Made of Stainless Steel Arch Wires - A FEM Study.

PubMed

Kamisetty, Supradeep Kumar; N, Raghuveer; N, Rajavikram; N, Chakrapani; Dwaragesh; Praven

2014-07-01

Evaluations on retraction loop designs have been limited to describe the force systems applied to the buccal surfaces of the tooth that can be in different planes resulting undesirable effects, needing corrective action in future. By initially understanding these effects, modifications to the loop design can essentially counteract the undesired affects. To deter-mine Moments & M/F ratios produced by different gabling in the three retraction loops (Tear drop loop, T-loop, Open vertical loop) and movement of the anterior teeth and posterior teeth) of the maxillary arch in an extraction model, on activation of three retraction loops by1 mm. A PC with Quad core processor, 8GB RAM, 1TB storage space and Graphic Accelerator was used. Computer Software: ANSYS Version11, PRO/ENGINEER was used in the study. The first step is modeling, done by using Pro/Engineer software and for creating a model the CT scan data is required. The maxilla with teeth of a patient is scanned at various sections at regular intervals of 0.5 mm. These scanned images are then imported into Pro/E software to various offset planes. Once imported, the software can do an automatic meshing and establishes contact automatically. When angulations increases intrusive or extrusive movements and movements in horizontal direction of crown tip and root tip increases. All values of T-loop are more than Teardrop loop and less than Open vertical loop. FEM study concludes that Teardrop loop with 10-20(α-β) combination is preferred for Group A anchorage.

Analysis of a first order phase locked loop in the presence of Gaussian noise

NASA Technical Reports Server (NTRS)

Blasche, P. R.

1977-01-01

A first-order digital phase locked loop is analyzed by application of a Markov chain model. Steady state loop error probabilities, phase standard deviation, and mean loop transient times are determined for various input signal to noise ratios. Results for direct loop simulation are presented for comparison.

The incidence of complications associated with loop duodeno-ileostomy after single-anastomosis duodenal switch procedures among 1328 patients: a multicenter experience.

PubMed

Surve, Amit; Cottam, Daniel; Sanchez-Pernaute, Andres; Torres, Antonio; Roller, Joshua; Kwon, Yong; Mourot, Joshua; Schniederjan, Bleu; Neichoy, Bo; Enochs, Paul; Tyner, Michael; Bruce, Jon; Bovard, Scott; Roslin, Mitchell; Jawad, Muhammad; Teixeira, Andre; Srikanth, Myur; Free, Jason; Zaveri, Hinali; Pilati, David; Bull, Jamie; Belnap, LeGrand; Richards, Christina; Medlin, Walter; Moon, Rena; Cottam, Austin; Sabrudin, Sarah; Cottam, Samuel; Dhorepatil, Aneesh

2018-02-02

The single-anastomosis duodenal switch procedure is a type of duodenal switch that involves a loop anastomosis rather than traditional Roux-en-Y reconstruction. To date, there have been no multicenter studies looking at the complications associated with post-pyloric loop reconstruction. The aim of the study was to report the incidence of complications associated with loop duodeno-ileostomy (DI) following single-anastomosis duodenal switch (SADS) procedures. Mixed of private and teaching facilities. The medical records of 1328 patients who underwent primary SADS procedure (single-anastomosis duodeno-ileal bypass with sleeve gastrectomy or stomach intestinal pylorus-sparing surgery) by 17 surgeons from 3 countries (United States, Spain, and Australia) at 9 centers over a 6-year period were retrospectively reviewed, and their results were compared with articles in the literature. Mean preoperative body mass index was 51.6 kg/m 2 . Of 1328 patients, 123 patients received a linear stapled duodeno-ileostomy (DI) and 1205 patients a hand-sewn DI. In the overall series, the anastomotic leak, ulcer, and bile reflux occurred in .6% (9/1328), .1% (2/1328), and .1% (2/1328), respectively. None of our patients experienced volvulus at the DI or an internal hernia. Overall, 5 patients (.3%) (3/123 [2.4%] with linear stapled DI versus 2/1205 [.1%] with hand-sewn DI [P<.05]) experienced stricture at the DI in this series. The overall incidence of complications associated with loop DI was lower than the reported incidence of anastomotic complications after Roux-en-Y gastric bypass and biliopancreatic diversion with duodenal switch. SADS procedures may cause much fewer anastomotic complications compared with Roux-en-Y gastric bypass and biliopancreatic diversion with duodenal switch. Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Ostomy-related complications after emergent abdominal surgery: a 2-year follow-up study.

PubMed

Lindholm, Elisabet; Persson, Eva; Carlsson, Eva; Hallén, Anne-Marie; Fingren, Jeanette; Berndtsson, Ina

2013-01-01

The aim of this study was to prospectively evaluate ostomy-related complications and describe ostomy configuration in patients undergoing acute abdominal surgery. The study sample comprised 144 patients with a median age of 67 years (IOR: 53.5-78 years) who underwent an intestinal ostomy as part of an acute abdominal surgical procedure. The research setting was the surgical and gynecological clinics at the Sahlgrenska University Hospital in Gothenburg, Sweden. Ostomy configuration, diameter, height, and the presence of stomal and peristomal complications were assessed by a WOC nurse 1 to 2 times while in hospital, once at the ostomy outpatient clinic 2 weeks after discharge, and at 3, 6, 12, and 24 months following ostomy creation. The types of ostomies evaluated were end colostomy (58%), end ileostomy (18%), loop ileostomy (17%), and loop colostomy (7%). Most stomal or peristomal complications occurred within 1 year after surgery (31 of 57; 54.4%). Necrosis, separation, and stenosis were most common in patients with an end colostomy. Peristomal skin complications occurred in 45% of subjects during the first 6 months after surgery. The ostomy's diameter decreased significantly during the hospital course and over the first 2 weeks following hospital discharge in patients with end colostomy (P< .0001), end ileostomy (P< .0081), loop ileostomy (P= .008), and loop colostomy (ns). Patients with a low ostomy had peristomal skin problems ranging between 21% and 57% over this time period. The frequency of using a pouching system that incorporated convexity was highest in the case of loop ileostomy, used in 67% at 6 months. During the first 2 weeks after discharge, the physical configuration of the ostomy evolves and the pouching system must be frequently adjusted by a WOC nurse. Stomal and peristomal complications are prevalent during the first 2 postoperative years and especially during the first 6 months.

Glucose Transport into Everted Sacks of Intestine of Mice: A Model for the Study of Active Transport.

ERIC Educational Resources Information Center

Deyrup-Olsen, Ingrith; Linder, Alison R.

1979-01-01

Described is a laboratory procedure which uses the small intestines of mice as models for the transport of glucose and other solutes. Demonstrations are suitable for either introductory or advanced physiology courses. (RE)

2D MHD AND 1D HD MODELS OF A SOLAR FLARE—A COMPREHENSIVE COMPARISON OF THE RESULTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Falewicz, R.; Rudawy, P.; Murawski, K.

Without any doubt, solar flaring loops possess a multithread internal structure that is poorly resolved, and there are no means to observe heating episodes and thermodynamic evolution of the individual threads. These limitations cause fundamental problems in numerical modeling of flaring loops, such as selection of a structure and a number of threads, and an implementation of a proper model of the energy deposition process. A set of one-dimensional (1D) hydrodynamic and two-dimensional (2D) magnetohydrodynamic models of a flaring loop are developed to compare energy redistribution and plasma dynamics in the course of a prototypical solar flare. Basic parameters ofmore » the modeled loop are set according to the progenitor M1.8 flare recorded in AR 10126 on 2002 September 20 between 09:21 UT and 09:50 UT. The nonideal 1D models include thermal conduction and radiative losses of the optically thin plasma as energy-loss mechanisms, while the nonideal 2D models take into account viscosity and thermal conduction as energy-loss mechanisms only. The 2D models have a continuous distribution of the parameters of the plasma across the loop and are powered by varying in time and space along and across the loop heating flux. We show that such 2D models are an extreme borderline case of a multithread internal structure of the flaring loop, with a filling factor equal to 1. Nevertheless, these simple models ensure the general correctness of the obtained results and can be adopted as a correct approximation of the real flaring structures.« less

Intestinal stem cells and their defining niche.

PubMed

Tan, David Wei-Min; Barker, Nick

2014-01-01

The intestinal epithelium is a classic example of a rapidly self-renewing tissue fueled by dedicated resident stem cells. These stem cells reside at the crypt base, generating committed progeny that mature into the various functional epithelial lineages while following a rapid migratory path toward the villi. Two models of intestinal stem cell location were proposed half a century ago and data have been presented in support of both models, dividing the scientific community. Molecular markers have been identified and validated using new techniques such as in vivo lineage tracing and ex vivo organoid culture. The intestinal stem cell niche comprises both epithelial cells, in particular the Paneth cell, and the stromal compartment, where cell-associated ligands and soluble factors regulate stem cell behavior. This review highlights the recent advances in identifying and characterizing the intestinal stem cells and their defining niche. © 2014 Elsevier Inc. All rights reserved.

Hemosuccus Pancreaticus following a Puestow Procedure in a Patient with Chronic Pancreatitis

PubMed Central

Okamoto, Hirotaka; Miura, Kazuo; Fujii, Hideki

2011-01-01

Hemosuccus pancreaticus is an unusual cause of gastrointestinal bleeding that occurs as a complication of chronic or acute pancreatitis. We report a case of extremely acute-onset hemosuccus pancreaticus occurring in a patient with chronic pancreatitis over a long-term follow-up after a Puestow procedure (side-to-side pancreaticojejunostomy). The patient was admitted to our hospital due to severe anemia and tarry stools indicative of gastrointestinal bleeding. Emergent endoscopy, including gastrointestinal fiberscopy and colon fiberscopy, showed no abnormal findings. Abdominal contrast-enhanced computed tomography and hemorrhagic scintigraphy did not detect a hemorrhagic lesion. Although interventional radiology was considered for diagnosis and treatment, conservative therapy seemed sufficient to affect hemostasis. Two weeks later, however, acute intestinal bleeding with hemodynamic shock occurred, and exploration was performed without delay. Intraoperative endoscopy through an incision of the reconstructed jejunal loop in the close proximal end revealed a site of active bleeding from the side-to-side anastomotic pancreatic duct. Following a longitudinal incision of the jejunal loop, a bleeding point was sutured and ligated on direct inspection. The patient showed a good postoperative course. PMID:21960948

Hemosuccus Pancreaticus following a Puestow Procedure in a Patient with Chronic Pancreatitis.

PubMed

Okamoto, Hirotaka; Miura, Kazuo; Fujii, Hideki

2011-05-01

Hemosuccus pancreaticus is an unusual cause of gastrointestinal bleeding that occurs as a complication of chronic or acute pancreatitis. We report a case of extremely acute-onset hemosuccus pancreaticus occurring in a patient with chronic pancreatitis over a long-term follow-up after a Puestow procedure (side-to-side pancreaticojejunostomy). The patient was admitted to our hospital due to severe anemia and tarry stools indicative of gastrointestinal bleeding. Emergent endoscopy, including gastrointestinal fiberscopy and colon fiberscopy, showed no abnormal findings. Abdominal contrast-enhanced computed tomography and hemorrhagic scintigraphy did not detect a hemorrhagic lesion. Although interventional radiology was considered for diagnosis and treatment, conservative therapy seemed sufficient to affect hemostasis. Two weeks later, however, acute intestinal bleeding with hemodynamic shock occurred, and exploration was performed without delay. Intraoperative endoscopy through an incision of the reconstructed jejunal loop in the close proximal end revealed a site of active bleeding from the side-to-side anastomotic pancreatic duct. Following a longitudinal incision of the jejunal loop, a bleeding point was sutured and ligated on direct inspection. The patient showed a good postoperative course.

A novel model for simultaneous study of neointestinal regeneration and intestinal adaptation.

PubMed

Jwo, Shyh-Chuan; Tang, Shye-Jye; Chen, Jim-Ray; Chiang, Kun-Chun; Huang, Ting-Shou; Chen, Huang-Yang

2013-01-01

The use of autologous grafts, fabricated from tissue-engineered neointestine, to enhance insufficient compensation of intestinal adaptation for severe short bowel syndrome is a compelling idea. Unfortunately, current approaches and knowledge for neointestinal regeneration, unlike intestinal adaptation, are still unsatisfactory. Thus, we have designed a novel model of intestinal adaptation with simultaneous neointestinal regeneration and evaluated its feasibility for future basic research and clinical application. Fifty male Sprague-Dawley rats weighing 250-350 g underwent this procedure and sacrificed at 4, 8, and 12 weeks postoperatively. Spatiotemporal analyses were carried out by gross, histology, and DNA/protein quantification. Three rats died of operative complications. In early experiments, the use of hard silicone stent as tissue scaffold in 11 rats was unsatisfactory for neointestinal regeneration. In later experiments, when a soft silastic tube was used, the success rate increased up to 90.9%. Further analyses revealed that no neointestine developed without donor intestine; regenerated lengths of mucosa and muscle were positively related to time postsurgery but independent of donor length with 0.5 or 1 cm. Other parameters of neointestinal regeneration or intestinal adaptation showed no relationship to both time postsurgery and donor length. In conclusion, this is a potentially important model for investigators searching for solutions to short bowel syndrome. © 2013 by the Wound Healing Society.

Topological insulating phases from two-dimensional nodal loop semimetals

NASA Astrophysics Data System (ADS)

Li, Linhu; Araújo, Miguel A. N.

2016-10-01

Starting from a minimal model for a two-dimensional nodal loop semimetal, we study the effect of chiral mass gap terms. The resulting Dirac loop anomalous Hall insulator's Chern number is the phase-winding number of the mass gap terms on the loop. We provide simple lattice models, analyze the topological phases, and generalize a previous index characterizing topological transitions. The responses of the Dirac loop anomalous Hall and quantum spin Hall insulators to a magnetic field's vector potential are also studied both in weak- and strong-field regimes, as well as the edge states in a ribbon geometry.

Using causal loop diagrams for the initialization of stakeholder engagement in soil salinity management in agricultural watersheds in developing countries: a case study in the Rechna Doab watershed, Pakistan.

PubMed

Inam, Azhar; Adamowski, Jan; Halbe, Johannes; Prasher, Shiv

2015-04-01

Over the course of the last twenty years, participatory modeling has increasingly been advocated as an integral component of integrated, adaptive, and collaborative water resources management. However, issues of high cost, time, and expertise are significant hurdles to the widespread adoption of participatory modeling in many developing countries. In this study, a step-wise method to initialize the involvement of key stakeholders in the development of qualitative system dynamics models (i.e. causal loop diagrams) is presented. The proposed approach is designed to overcome the challenges of low expertise, time and financial resources that have hampered previous participatory modeling efforts in developing countries. The methodological framework was applied in a case study of soil salinity management in the Rechna Doab region of Pakistan, with a focus on the application of qualitative modeling through stakeholder-built causal loop diagrams to address soil salinity problems in the basin. Individual causal loop diagrams were developed by key stakeholder groups, following which an overall group causal loop diagram of the entire system was built based on the individual causal loop diagrams to form a holistic qualitative model of the whole system. The case study demonstrates the usefulness of the proposed approach, based on using causal loop diagrams in initiating stakeholder involvement in the participatory model building process. In addition, the results point to social-economic aspects of soil salinity that have not been considered by other modeling studies to date. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparisons of a Constrained Least Squares Model versus Human-in-the-Loop for Spectral Unmixing to Determine Material Type of GEO Debris

NASA Technical Reports Server (NTRS)

Abercromby, Kira J.; Rapp, Jason; Bedard, Donald; Seitzer, Patrick; Cardona, Tommaso; Cowardin, Heather; Barker, Ed; Lederer, Susan

2013-01-01

Constrained Linear Least Squares model is generally more accurate than the "human-in-the-loop". However, "human-in-the-loop" can remove materials that make no sense. The speed of the model in determining a "first cut" at the material ID makes it a viable option for spectral unmixing of debris objects.

Optimization of micro-fabricated porous membranes for intestinal epithelial cell culture and in vitro modeling of the human intestinal barrier

NASA Astrophysics Data System (ADS)

Nair Gourikutty Sajay, Bhuvanendran; Yin, Chiam Su; Ramadan, Qasem

2017-12-01

In vitro modeling of organs could provide a controlled platform for studying physiological events and has great potential in the field of pharmaceutical development. Here, we describe the characterization of in vitro modeling of the human intestinal barrier mimicked using silicon porous membranes as a substrate. To mimic an intestinal in vivo setup as closely as possible, a porous substrate is required in a dynamic environment for the cells to grow rather than a static setup with an impermeable surface such as a petri dish. In this study, we focus on the detailed characterization of Caco-2 cells cultured on a silicon membrane with different pore sizes as well as the effect of dynamic fluid flow on the model. The porous silicon membrane together with continuous perfusion of liquid applying shear stress on the cells enhances the differentiation of polarized cells by providing access to the both their basal and apical surfaces. Membranes with pore sizes of 0.5-3 µm were used and a shear stress of ~0.03 dyne cm-2 was created by applying a low flow rate of 20 nl s-1. By providing these optimized conditions, cells were able to differentiate with columnar morphology, which developed microvilli structures on their apical side and tight junctions between adjacent cells like those in a healthy human intestinal barrier. In this setup, it is possible to study the important cellular functions of the intestine such as transport, absorption and secretion, and thus this model has great potential in drug screening.

In vitro enteroid-derived three-dimensional tissue model of human small intestinal epithelium with innate immune responses.

PubMed

Chen, Ying; Zhou, Wenda; Roh, Terrence; Estes, Mary K; Kaplan, David L

2017-01-01

There is a need for functional in vitro 3D human intestine systems that can bridge the gap between conventional cell culture studies and human trials. The successful engineering in vitro of human intestinal tissues relies on the use of the appropriate cell sources, biomimetic scaffolds, and 3D culture conditions to support vital organ functions. We previously established a compartmentalized scaffold consisting of a hollow space within a porous bulk matrix, in which a functional and physiologically relevant intestinal epithelium system was generated using intestinal cell lines. In this study, we adopt the 3D scaffold system for the cultivation of stem cell-derived human small intestinal enteriods (HIEs) to engineer an in vitro 3D model of a nonstransformed human small intestinal epithelium. Characterization of tissue properties revealed a mature HIE-derived epithelium displaying four major terminally differentiated epithelial cell types (enterocytes, Goblet cells, Paneth cells, enteroendocrine cells), with tight junction formation, microvilli polarization, digestive enzyme secretion, and low oxygen tension in the lumen. Moreover, the tissue model demonstrates significant antibacterial responses to E. coli infection, as evidenced by the significant upregulation of genes involved in the innate immune response. Importantly, many of these genes are activated in human patients with inflammatory bowel disease (IBD), implicating the potential application of the 3D stem-cell derived epithelium for the in vitro study of host-microbe-pathogen interplay and IBD pathogenesis.

Improving predicted protein loop structure ranking using a Pareto-optimality consensus method.

PubMed

Li, Yaohang; Rata, Ionel; Chiu, See-wing; Jakobsson, Eric

2010-07-20

Accurate protein loop structure models are important to understand functions of many proteins. Identifying the native or near-native models by distinguishing them from the misfolded ones is a critical step in protein loop structure prediction. We have developed a Pareto Optimal Consensus (POC) method, which is a consensus model ranking approach to integrate multiple knowledge- or physics-based scoring functions. The procedure of identifying the models of best quality in a model set includes: 1) identifying the models at the Pareto optimal front with respect to a set of scoring functions, and 2) ranking them based on the fuzzy dominance relationship to the rest of the models. We apply the POC method to a large number of decoy sets for loops of 4- to 12-residue in length using a functional space composed of several carefully-selected scoring functions: Rosetta, DOPE, DDFIRE, OPLS-AA, and a triplet backbone dihedral potential developed in our lab. Our computational results show that the sets of Pareto-optimal decoys, which are typically composed of approximately 20% or less of the overall decoys in a set, have a good coverage of the best or near-best decoys in more than 99% of the loop targets. Compared to the individual scoring function yielding best selection accuracy in the decoy sets, the POC method yields 23%, 37%, and 64% less false positives in distinguishing the native conformation, indentifying a near-native model (RMSD < 0.5A from the native) as top-ranked, and selecting at least one near-native model in the top-5-ranked models, respectively. Similar effectiveness of the POC method is also found in the decoy sets from membrane protein loops. Furthermore, the POC method outperforms the other popularly-used consensus strategies in model ranking, such as rank-by-number, rank-by-rank, rank-by-vote, and regression-based methods. By integrating multiple knowledge- and physics-based scoring functions based on Pareto optimality and fuzzy dominance, the POC method is effective in distinguishing the best loop models from the other ones within a loop model set.

Improving predicted protein loop structure ranking using a Pareto-optimality consensus method

PubMed Central

2010-01-01

Background Accurate protein loop structure models are important to understand functions of many proteins. Identifying the native or near-native models by distinguishing them from the misfolded ones is a critical step in protein loop structure prediction. Results We have developed a Pareto Optimal Consensus (POC) method, which is a consensus model ranking approach to integrate multiple knowledge- or physics-based scoring functions. The procedure of identifying the models of best quality in a model set includes: 1) identifying the models at the Pareto optimal front with respect to a set of scoring functions, and 2) ranking them based on the fuzzy dominance relationship to the rest of the models. We apply the POC method to a large number of decoy sets for loops of 4- to 12-residue in length using a functional space composed of several carefully-selected scoring functions: Rosetta, DOPE, DDFIRE, OPLS-AA, and a triplet backbone dihedral potential developed in our lab. Our computational results show that the sets of Pareto-optimal decoys, which are typically composed of ~20% or less of the overall decoys in a set, have a good coverage of the best or near-best decoys in more than 99% of the loop targets. Compared to the individual scoring function yielding best selection accuracy in the decoy sets, the POC method yields 23%, 37%, and 64% less false positives in distinguishing the native conformation, indentifying a near-native model (RMSD < 0.5A from the native) as top-ranked, and selecting at least one near-native model in the top-5-ranked models, respectively. Similar effectiveness of the POC method is also found in the decoy sets from membrane protein loops. Furthermore, the POC method outperforms the other popularly-used consensus strategies in model ranking, such as rank-by-number, rank-by-rank, rank-by-vote, and regression-based methods. Conclusions By integrating multiple knowledge- and physics-based scoring functions based on Pareto optimality and fuzzy dominance, the POC method is effective in distinguishing the best loop models from the other ones within a loop model set. PMID:20642859

Atomistic modeling of shock-induced void collapse in copper

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davila, L P; Erhart, P; Bringa, E M

2005-03-09

Nonequilibrium molecular dynamics (MD) simulations show that shock-induced void collapse in copper occurs by emission of shear loops. These loops carry away the vacancies which comprise the void. The growth of the loops continues even after they collide and form sessile junctions, creating a hardened region around the collapsing void. The scenario seen in our simulations differs from current models that assume that prismatic loop emission is responsible for void collapse. We propose a new dislocation-based model that gives excellent agreement with the stress threshold found in the MD simulations for void collapse as a function of void radius.

Closing the loop: modelling of heart failure progression from health to end-stage using a meta-analysis of left ventricular pressure-volume loops.

PubMed

Warriner, David R; Brown, Alistair G; Varma, Susheel; Sheridan, Paul J; Lawford, Patricia; Hose, David R; Al-Mohammad, Abdallah; Shi, Yubing

2014-01-01

The American Heart Association (AHA)/American College of Cardiology (ACC) guidelines for the classification of heart failure (HF) are descriptive but lack precise and objective measures which would assist in categorising such patients. Our aim was two fold, firstly to demonstrate quantitatively the progression of HF through each stage using a meta-analysis of existing left ventricular (LV) pressure-volume (PV) loop data and secondly use the LV PV loop data to create stage specific HF models. A literature search yielded 31 papers with PV data, representing over 200 patients in different stages of HF. The raw pressure and volume data were extracted from the papers using a digitising software package and the means were calculated. The data demonstrated that, as HF progressed, stroke volume (SV), ejection fraction (EF%) decreased while LV volumes increased. A 2-element lumped parameter model was employed to model the mean loops and the error was calculated between the loops, demonstrating close fit between the loops. The only parameter that was consistently and statistically different across all the stages was the elastance (Emax). For the first time, the authors have created a visual and quantitative representation of the AHA/ACC stages of LVSD-HF, from normal to end-stage. The study demonstrates that robust, load-independent and reproducible parameters, such as elastance, can be used to categorise and model HF, complementing the existing classification. The modelled PV loops establish previously unknown physiological parameters for each AHA/ACC stage of LVSD-HF, such as LV elastance and highlight that it this parameter alone, in lumped parameter models, that determines the severity of HF. Such information will enable cardiovascular modellers with an interest in HF, to create more accurate models of the heart as it fails.

Interactions Between the Intestinal Microbiome and Liver Diseases

PubMed Central

Schnabl, Bernd; Brenner, David A.

2014-01-01

The human intestine harbors a diverse community of microbes that promote metabolism and digestion in their symbiotic relationship with the host. Disturbance of its homeostasis can result in disease. We review factors that disrupt intestinal homeostasis and contribute to non-alcoholic fatty liver disease (NAFLD), steatohepatitis (NASH), alcoholic liver disease, and cirrhosis. Liver disease has long been associated with qualitative and quantitative (overgrowth) dysbiotic changes in the intestinal microbiota. Extrinsic factors, such as the Western diet and alcohol, contribute to these changes. Dysbiosis results in intestinal inflammation, a breakdown of the intestinal barrier, and translocation of microbial products in animal models. However, the contribution of the intestinal microbiome to liver disease goes beyond simple translocation of bacterial products that promote hepatic injury and inflammation. Microbial metabolites produced in a dysbiotic intestinal environment and host factors are equally important in the pathogenesis of liver disease. We review how the combination of liver insult and disruptions in intestinal homeostasis contribute to liver disease. PMID:24440671

Quantitation of small intestinal permeability during normal human drug absorption

PubMed Central

2013-01-01

Background Understanding the quantitative relationship between a drug’s physical chemical properties and its rate of intestinal absorption (QSAR) is critical for selecting candidate drugs. Because of limited experimental human small intestinal permeability data, approximate surrogates such as the fraction absorbed or Caco-2 permeability are used, both of which have limitations. Methods Given the blood concentration following an oral and intravenous dose, the time course of intestinal absorption in humans was determined by deconvolution and related to the intestinal permeability by the use of a new 3 parameter model function (“Averaged Model” (AM)). The theoretical validity of this AM model was evaluated by comparing it to the standard diffusion-convection model (DC). This analysis was applied to 90 drugs using previously published data. Only drugs that were administered in oral solution form to fasting subjects were considered so that the rate of gastric emptying was approximately known. All the calculations are carried out using the freely available routine PKQuest Java (http://www.pkquest.com) which has an easy to use, simple interface. Results Theoretically, the AM permeability provides an accurate estimate of the intestinal DC permeability for solutes whose absorption ranges from 1% to 99%. The experimental human AM permeabilities determined by deconvolution are similar to those determined by direct human jejunal perfusion. The small intestinal pH varies with position and the results are interpreted in terms of the pH dependent octanol partition. The permeability versus partition relations are presented separately for the uncharged, basic, acidic and charged solutes. The small uncharged solutes caffeine, acetaminophen and antipyrine have very high permeabilities (about 20 x 10-4 cm/sec) corresponding to an unstirred layer of only 45 μm. The weak acid aspirin also has a large AM permeability despite its low octanol partition at pH 7.4, suggesting that it is nearly completely absorbed in the first part of the intestine where the pH is about 5.4. Conclusions The AM deconvolution method provides an accurate estimate of the human intestinal permeability. The results for these 90 drugs should provide a useful benchmark for evaluating QSAR models. PMID:23800230

New class of two-loop neutrino mass models with distinguishable phenomenology

NASA Astrophysics Data System (ADS)

Cao, Qing-Hong; Chen, Shao-Long; Ma, Ernest; Yan, Bin; Zhang, Dong-Ming

2018-04-01

We discuss a new class of neutrino mass models generated in two loops, and explore specifically three new physics scenarios: (A) doubly charged scalar, (B) dark matter, and (C) leptoquark and diquark, which are verifiable at the 14 TeV LHC Run-II. We point out how the different Higgs insertions will distinguish our two-loop topology with others if the new particles in the loop are in the simplest representations of the SM gauge group.

Gross morphology and histology of the alimentary tract of the convict cichlid Amatitlania nigrofasciata.

PubMed

Hopperdietzel, C; Hirschberg, R M; Hünigen, H; Wolter, J; Richardson, K; Plendl, J

2014-11-01

The primary objectives of this study were to document the macroscopic and histological structure of the alimentary tract (AT) of the convict cichlid Amatitlania nigrofasciata, because there are no data available for this omnivorous freshwater fish of the family Cichlidae. The morphology of the AT of A. nigrofasciata resembles that of related species. While having morphological criteria of the AT typical of most omnivorous fishes, such as a blind sac stomach and medium length intestine, A. nigrofasciata also has some structural peculiarities: the oesophagus is lined by a uniform stratified squamous epithelial layer with interspersed goblet cells along its entire length. Additionally, it has well-developed layers of the tunica muscularis including muscle fibre bundles that ascend into its mucosal folds. Occasionally, taste buds are present. In the transitional area between oesophagus and stomach, a prominent torus-like closure device is present. The mucosa of the stomach cannot be divided into different regions according to mucosal and morphological properties. The simple pattern of intestinal loops of A. nigrofasciata has few variations, irrespective of sex, mass and length of the individual fish. The first segment of the intestine is characterized by the largest mucososerosal ratio and the most complex mucosal surface architecture. A distinction of midgut and hindgut was not possible in A. nigrofasciata due to lack of defining structural components as described for other fish species. © 2014 The Fisheries Society of the British Isles.

Pilot study of bipolar radiofrequency-induced anastomotic thermofusion-exploration of therapy parameters ex vivo.

PubMed

Winter, Hanno; Holmer, Christoph; Buhr, Heinz-Johannes; Lindner, Gerd; Lauster, Roland; Kraft, Marc; Ritz, Jörg-Peter

2010-01-01

Vessel sealing has been well-established in surgical practice in recent years. Bipolar radiofrequency-induced thermofusion (BIRTH) of intestinal tissue might replace traditionally used staples or sutures in the near future. In this experimental study, the influence of compressive pressure, fusion temperature, and duration of heating on the quality of intestinal anastomosis was investigated to obtain the relevant major parameters for the in vivo use of this system. An experimental setup for a closed-loop temperature-controlled bipolar radiofrequency-induced thermofusion of porcine intestinal tissue was developed. Twenty-four colon samples were harvested from nine different Saalower-Kräuter pigs and then anastomosed altering compressive pressure on five different levels to explore its influence on anastomotic bursting pressure. The anastomotic bursting strength depends on the compressive pressure applied to the colonic fusion site. An optimal interval of compressive pressure (CP = 1.125 N/mm(2)) in respect of a high amount of burst pressure was detected. A correlation (r = 0.54, p = 0.015) of burst pressure to delta compression indicated that increasing colonic wall thickness probably strengthens the anastomotic fusion. This study is a first step to enlighten the major parameters of tissue fusion, though effects and interactions of various main parameters of bipolar radiofrequency-induced thermofusion of colonic tissue remain unclear. Further studies exploring the main effects and interactions of tissue and process parameters to the quality of the fusion site have to follow.

A Looping-Based Model for Quenching Repression

PubMed Central

Pollak, Yaroslav; Goldberg, Sarah; Amit, Roee

2017-01-01

We model the regulatory role of proteins bound to looped DNA using a simulation in which dsDNA is represented as a self-avoiding chain, and proteins as spherical protrusions. We simulate long self-avoiding chains using a sequential importance sampling Monte-Carlo algorithm, and compute the probabilities for chain looping with and without a protrusion. We find that a protrusion near one of the chain’s termini reduces the probability of looping, even for chains much longer than the protrusion–chain-terminus distance. This effect increases with protrusion size, and decreases with protrusion-terminus distance. The reduced probability of looping can be explained via an eclipse-like model, which provides a novel inhibitory mechanism. We test the eclipse model on two possible transcription-factor occupancy states of the D. melanogaster eve 3/7 enhancer, and show that it provides a possible explanation for the experimentally-observed eve stripe 3 and 7 expression patterns. PMID:28085884

Radiation-induced changes in intestinal and tissue-nonspecific alkaline phosphatase: implications for recovery after radiation therapy.

PubMed

Rentea, Rebecca M; Lam, Vy; Biesterveld, Ben; Fredrich, Katherine M; Callison, Jennifer; Fish, Brian L; Baker, John E; Komorowski, Richard; Gourlay, David M; Otterson, Mary F

2016-10-01

Exogenous replacement of depleted enterocyte intestinal alkaline phosphatase (IAP) decreases intestinal injury in models of colitis. We determined whether radiation-induced intestinal injury could be mitigated by oral IAP supplementation and the impact on tissue-nonspecific AP. WAG/RjjCmcr rats (n = 5 per group) received lower hemibody irradiation (13 Gy) followed by daily gavage with phosphate-buffered saline or IAP (40 U/kg/d) for 4 days. Real-time polymerase chain reaction, AP activity, and microbiota analysis were performed on intestine. Lipopolysaccharide and cytokine analysis was performed on serum. Data were expressed as a mean ± SEM with P greater than .05 considered significant. Intestine of irradiated animals demonstrates lower hemibody irradiation and is associated with upregulation of tissue-nonspecific AP, downregulation of IAP, decreased AP activity, and altered composition of the intestinal microbiome. Supplemental IAP after radiation may be beneficial in mitigating intestinal radiation syndrome as evidenced by improved histologic injury, decreased acute intestinal inflammation, and normalization of intestinal microbiome. Copyright © 2016 Elsevier Inc. All rights reserved.

Prom1 Function in Development, Intestinal Inflammation, and Intestinal Tumorigenesis

PubMed Central

Karim, Baktiar O.; Rhee, Ki-Jong; Liu, Guosheng; Yun, Kyuson; Brant, Steven R.

2014-01-01

Prom1/CD133 has been identified in colorectal, hepatocellular, and pancreatic cancer as a cancer stem cell marker and has been used as such to predict colon cancer recurrence in humans. Its potential molecular function as well as its role as a marker of intestinal regeneration is still not fully known. We evaluated the role of Prom1 in intestinal regeneration in inflammatory bowel disease (IBD), determined the function of Prom1, and characterized the effect of a lack of Prom1 on intestinal tumor formation in animal models. Our results suggest that Apc mutations lead to an increase in Prom1 expressing cells in the intestinal crypt stem cell compartment and in early intestinal adenomas. Also, Prom1 knockout mice are more susceptible to intestinal tumor formation. We conclude that Prom1 likely plays a role in regulating intestinal homeostasis and that these results clearly illustrate the role of Prom1 in intestinal regeneration. We further conclude that Prom1 may provide a novel therapeutic target for patients with gastrointestinal conditions such as IBD, short bowel syndrome, and colorectal cancer. PMID:25452936

Selectivity of antagonists for the Cys-loop native receptors for ACh, 5-HT and GABA in guinea-pig myenteric neurons.

PubMed

Juárez, E H; Ochoa-Cortés, F; Miranda-Morales, M; Espinosa-Luna, R; Montaño, L M; Barajas-López, C

2014-01-01

The three most common Cys-loop receptors expressed by myenteric neurons are nACh, 5-HT3 and GABAA . To investigate the function of these proteins researchers have used channel inhibitors such as hexamethonium (antagonist of nACh receptors), ondansetron (antagonist of 5-HT3 receptors), picrotoxin and bicuculline (both antagonists of GABAA receptors). The aim of this study was to investigate the specificity of these inhibitors on Cys-loop receptors of primary cultured neurons obtained from the guinea-pig small intestine. The whole-cell configuration of the patch clamp techniques was used to record membrane currents induced by ACh (IACh ), 5-HT (I5-HT ) and GABA (IGABA ) in the absence and the presence of various concentrations of hexamethonium, ondansetron, picrotoxin or bicuculline. The three Cys-loop receptors present in enteric neurons are expressed independently and they do not cross-desensitized. Hexamethonium inhibited IACh without affecting I5-HT and IGABA . Ondansetron inhibited I5-HT and also IACh but did not affect IGABA . Picrotoxin and bicuculline inhibited I5-HT , IACh and IGABA with different potency, being the lowest potency on 5-HT3 receptors. All these inhibitory effects were concentration dependent and reversible. Our observations showed that except for hexamethonium, all other inhibitors used here show different degrees of selectivity, which has to be considered when these antagonists are used in experimental studies aimed to investigate the functions of these receptors. In particular, in tissues expressing nACh receptors because these are the targets of all other inhibitors used here. The low potency of picrotoxin and bicuculline to inhibit 5-HT3 receptors suggests that these receptors are heteromeric proteins. © 2013 John Wiley & Sons Ltd.

Towards predictive models of the human gut microbiome

PubMed Central

2014-01-01

The intestinal microbiota is an ecosystem susceptible to external perturbations such as dietary changes and antibiotic therapies. Mathematical models of microbial communities could be of great value in the rational design of microbiota-tailoring diets and therapies. Here, we discuss how advances in another field, engineering of microbial communities for wastewater treatment bioreactors, could inspire development of mechanistic mathematical models of the gut microbiota. We review the current state-of-the-art in bioreactor modeling and current efforts in modeling the intestinal microbiota. Mathematical modeling could benefit greatly from the deluge of data emerging from metagenomic studies, but data-driven approaches such as network inference that aim to predict microbiome dynamics without explicit mechanistic knowledge seem better suited to model these data. Finally, we discuss how the integration of microbiome shotgun sequencing and metabolic modeling approaches such as flux balance analysis may fulfill the promise of a mechanistic model of the intestinal microbiota. PMID:24727124

Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut

PubMed Central

Ganguli, Kriston; Collado, Maria Carmen; Rautava, Jaana; Lu, Lei; Satokari, Reetta; von Ossowski, Ingemar; Reunanen, Justus; de Vos, Willem M.; Palva, Airi; Isolauri, Erika; Salminen, Seppo; Walker, W. Allan; Rautava, Samuli

2015-01-01

Background Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models. Methods TNF-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR. Results Live L. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression. Conclusion The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human intestinal epithelial cells and directly modulates intestinal epithelial cell innate immune gene expression. PMID:25580735

Distinguishing between the Permeability Relationships with Absorption and Metabolism To Improve BCS and BDDCS Predictions in Early Drug Discovery

PubMed Central

2015-01-01

The biopharmaceutics classification system (BCS) and biopharmaceutics drug distribution classification system (BDDCS) are complementary classification systems that can improve, simplify, and accelerate drug discovery, development, and regulatory processes. Drug permeability has been widely accepted as a screening tool for determining intestinal absorption via the BCS during the drug development and regulatory approval processes. Currently, predicting clinically significant drug interactions during drug development is a known challenge for industry and regulatory agencies. The BDDCS, a modification of BCS that utilizes drug metabolism instead of intestinal permeability, predicts drug disposition and potential drug–drug interactions in the intestine, the liver, and most recently the brain. Although correlations between BCS and BDDCS have been observed with drug permeability rates, discrepancies have been noted in drug classifications between the two systems utilizing different permeability models, which are accepted as surrogate models for demonstrating human intestinal permeability by the FDA. Here, we recommend the most applicable permeability models for improving the prediction of BCS and BDDCS classifications. We demonstrate that the passive transcellular permeability rate, characterized by means of permeability models that are deficient in transporter expression and paracellular junctions (e.g., PAMPA and Caco-2), will most accurately predict BDDCS metabolism. These systems will inaccurately predict BCS classifications for drugs that particularly are substrates of highly expressed intestinal transporters. Moreover, in this latter case, a system more representative of complete human intestinal permeability is needed to accurately predict BCS absorption. PMID:24628254

Intestinal Enteroids Model Guanylate Cyclase C-Dependent Secretion Induced by Heat-Stable Enterotoxins.

PubMed

Pattison, Amanda M; Blomain, Erik S; Merlino, Dante J; Wang, Fang; Crissey, Mary Ann S; Kraft, Crystal L; Rappaport, Jeff A; Snook, Adam E; Lynch, John P; Waldman, Scott A

2016-10-01

Enterotoxigenic Escherichia coli (ETEC) causes ∼20% of the acute infectious diarrhea (AID) episodes worldwide, often by producing heat-stable enterotoxins (STs), which are peptides structurally homologous to paracrine hormones of the intestinal guanylate cyclase C (GUCY2C) receptor. While molecular mechanisms mediating ST-induced intestinal secretion have been defined, advancements in therapeutics have been hampered for decades by the paucity of disease models that integrate molecular and functional endpoints amenable to high-throughput screening. Here, we reveal that mouse and human intestinal enteroids in three-dimensional ex vivo cultures express the components of the GUCY2C secretory signaling axis. ST and its structural analog, linaclotide, an FDA-approved oral secretagog, induced fluid accumulation quantified simultaneously in scores of enteroid lumens, recapitulating ETEC-induced intestinal secretion. Enteroid secretion depended on canonical molecular signaling events responsible for ETEC-induced diarrhea, including cyclic GMP (cGMP) produced by GUCY2C, activation of cGMP-dependent protein kinase (PKG), and opening of the cystic fibrosis transmembrane conductance regulator (CFTR). Importantly, pharmacological inhibition of CFTR abrogated enteroid fluid secretion, providing proof of concept for the utility of this model to screen antidiarrheal agents. Intestinal enteroids offer a unique model, integrating the GUCY2C signaling axis and luminal fluid secretion, to explore the pathophysiology of, and develop platforms for, high-throughput drug screening to identify novel compounds to prevent and treat ETEC diarrheal disease. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Distinguishing between the permeability relationships with absorption and metabolism to improve BCS and BDDCS predictions in early drug discovery.

PubMed

Larregieu, Caroline A; Benet, Leslie Z

2014-04-07

The biopharmaceutics classification system (BCS) and biopharmaceutics drug distribution classification system (BDDCS) are complementary classification systems that can improve, simplify, and accelerate drug discovery, development, and regulatory processes. Drug permeability has been widely accepted as a screening tool for determining intestinal absorption via the BCS during the drug development and regulatory approval processes. Currently, predicting clinically significant drug interactions during drug development is a known challenge for industry and regulatory agencies. The BDDCS, a modification of BCS that utilizes drug metabolism instead of intestinal permeability, predicts drug disposition and potential drug-drug interactions in the intestine, the liver, and most recently the brain. Although correlations between BCS and BDDCS have been observed with drug permeability rates, discrepancies have been noted in drug classifications between the two systems utilizing different permeability models, which are accepted as surrogate models for demonstrating human intestinal permeability by the FDA. Here, we recommend the most applicable permeability models for improving the prediction of BCS and BDDCS classifications. We demonstrate that the passive transcellular permeability rate, characterized by means of permeability models that are deficient in transporter expression and paracellular junctions (e.g., PAMPA and Caco-2), will most accurately predict BDDCS metabolism. These systems will inaccurately predict BCS classifications for drugs that particularly are substrates of highly expressed intestinal transporters. Moreover, in this latter case, a system more representative of complete human intestinal permeability is needed to accurately predict BCS absorption.

Herbal prescription Chang'an II repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome

PubMed Central

Wang, Feng-yun; Su, Min; Zheng, Yong-qiu; Wang, Xiao-ge; Kang, Nan; Chen, Ting; Zhu, En-lin; Bian, Zhao-xiang; Tang, Xu-dong

2015-01-01

Aim: The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. Methods: A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g·kg−1·d−1, ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4+ and CD8+ cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. Results: PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4+/CD8+ cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4+/CD8+ cell ratio and expression of IL-1β and IL-4. Conclusion: Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects. PMID:25960135

Herbal prescription Chang'an II repairs intestinal mucosal barrier in rats with post-inflammation irritable bowel syndrome.

PubMed

Wang, Feng-yun; Su, Min; Zheng, Yong-qiu; Wang, Xiao-ge; Kang, Nan; Chen, Ting; Zhu, En-lin; Bian, Zhao-xiang; Tang, Xu-dong

2015-06-01

The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g · kg(-1) · d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4(+) and CD8(+) cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL-1β and IL-4. Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.

Age-related increases in F344 rat intestine microsomal quercetin glucuronidation

USDA-ARS?s Scientific Manuscript database

The objective of this study was to establish the extent age modifies intestinal quercetin glucuronidation capacity. Pooled microsomal fractions of three equidistant small intestine (SI) segments from 4, 12, 18, and 28 mo male F344 rats (n=8/group) were employed to model the enzyme kinetics of UDP-gl...

Cytological and Morphological Analyses Reveal Distinct Features of Intestinal Development during Xenopus tropicalis Metamorphosis

PubMed Central

Matsuura, Kazuo; Shi, Yun-Bo

2012-01-01

Background The formation and/or maturation of adult organs in vertebrates often takes place during postembryonic development, a period around birth in mammals when thyroid hormone (T3) levels are high. The T3-dependent anuran metamorphosis serves as a model to study postembryonic development. Studies on the remodeling of the intestine during Xenopus (X.) laevis metamorphosis have shown that the development of the adult intestine involves de novo formation of adult stem cells in a process controlled by T3. On the other hand, X. tropicalis, highly related to X. laevis, offers a number of advantages for studying developmental mechanisms, especially at genome-wide level, over X. laevis, largely due to its shorter life cycle and sequenced genome. To establish X. tropicalis intestinal metamorphosis as a model for adult organogenesis, we analyzed the morphological and cytological changes in X. tropicalis intestine during metamorphosis. Methodology/Principal Findings We observed that in X. tropicalis, the premetamorphic intestine was made of mainly a monolayer of larval epithelial cells surrounded by little connective tissue except in the single epithelial fold, the typhlosole. During metamorphosis, the larval epithelium degenerates and adult epithelium develops to form a multi-folded structure with elaborate connective tissue and muscles. Interestingly, typhlosole, which is likely critical for adult epithelial development, is present along the entire length of the small intestine in premetamorphic tadpoles, in contrast to X. laevis, where it is present only in the anterior 1/3. T3-treatment induces intestinal remodeling, including the shortening of the intestine and the typhlosole, just like in X. laevis. Conclusions/Significance Our observations indicate that the intestine undergoes similar metamorphic changes in X. laevis and X. tropicalis, making it possible to use the large amount of information available on X. laevis intestinal metamorphosis and the genome sequence information and genetic advantages of X. tropicalis to dissect the pathways governing adult intestinal development. PMID:23071801

Transmural Intestinal Wall Permeability in Severe Ischemia after Enteral Protease Inhibition

PubMed Central

Altshuler, Angelina E.; Lamadrid, Itze; Li, Diana; Ma, Stephanie R.; Kurre, Leena; Schmid-Schönbein, Geert W.; Penn, Alexander H.

2014-01-01

In intestinal ischemia, inflammatory mediators in the small intestine's lumen such as food byproducts, bacteria, and digestive enzymes leak into the peritoneal space, lymph, and circulation, but the mechanisms by which the intestinal wall permeability initially increases are not well defined. We hypothesize that wall protease activity (independent of luminal proteases) and apoptosis contribute to the increased transmural permeability of the intestine's wall in an acutely ischemic small intestine. To model intestinal ischemia, the proximal jejunum to the distal ileum in the rat was excised, the lumen was rapidly flushed with saline to remove luminal contents, sectioned into equal length segments, and filled with a tracer (fluorescein) in saline, glucose, or protease inhibitors. The transmural fluorescein transport was determined over 2 hours. Villi structure and epithelial junctional proteins were analyzed. After ischemia, there was increased transmural permeability, loss of villi structure, and destruction of epithelial proteins. Supplementation with luminal glucose preserved the epithelium and significantly attenuated permeability and villi damage. Matrix metalloproteinase (MMP) inhibitors (doxycycline, GM 6001), and serine protease inhibitor (tranexamic acid) in the lumen, significantly reduced the fluorescein transport compared to saline for 90 min of ischemia. Based on these results, we tested in an in-vivo model of hemorrhagic shock (90 min 30 mmHg, 3 hours observation) for intestinal lesion formation. Single enteral interventions (saline, glucose, tranexamic acid) did not prevent intestinal lesions, while the combination of enteral glucose and tranexamic acid prevented lesion formation after hemorrhagic shock. The results suggest that apoptotic and protease mediated breakdown cause increased permeability and damage to the intestinal wall. Metabolic support in the lumen of an ischemic intestine with glucose reduces the transport from the lumen across the wall and enteral proteolytic inhibition attenuates tissue breakdown. These combined interventions ameliorate lesion formation in the small intestine after hemorrhagic shock. PMID:24805256

Time-course evaluation of intestinal structural disorders in a porcine model of intra-abdominal hypertension by mechanical intestinal obstruction

PubMed Central

Sánchez-Margallo, Francisco M.; Candanosa-Aranda, Irma Eugenia; Malbrain, Manu L. N. G.; Wise, Robert

2018-01-01

Background A mechanical intestinal obstruction (MIO) can generate intraabdominal hypertension (IAH) that is life threatening. The intestines are very sensitive to IAH since the low splanchnic perfusion causes intestinal hypoxia, local acidosis and bacterial translocations. This may lead to acute intestinal distress syndrome (AIDS). The identification of intestinal injuries during IAH and its correlation with clinical parameters as the abdominal perfusion pressure (APP), the gastric intramucosal pH (pHi) and lactic acid (Lc) are still unknown. This study aimed to evaluate the sequence of intestinal histopathological findings in an MIO model and to analyze potential relationships with parameters currently used in clinical practice (APP, pHi and Lc). Material and methods Twenty pigs were divided into three groups: a control group (n = 5) and two experimental groups with 20 mmHg (G1, n = 10) and 30 mmHg (G2, n = 5) of IAH by MIO. The pressures were maintained for 3 hours, except in 5 animals in G1 where it was maintained for 5 hours. The APP, pHi and LA were recorded and biopsies of the terminal ileum were taken every 30 minutes in all groups. The intestinal damage was graded according to the Park Score. Results Intestinal injuries were found in 42.9% of pigs in the experimental groups. The lesions were independent of the level and duration of IAH. Although APP and pHi were slightly lower in injured animals (I +) of G1 and G2, there were no significant differences among those uninjured (I-). Lc was significantly increased in all I+ pigs from the onset of IAH. Conclusion The IAH by MIO causes intestinal lesions from the first 30 minutes with concurrent decreases in APP and pHi and increases in Lc. Lc could be the best clinical parameter related to intestinal damages with a clear difference between I + and I- animals. PMID:29357386

Plant STAND P-loop NTPases: a current perspective of genome distribution, evolution, and function : Plant STAND P-loop NTPases: genomic organization, evolution, and molecular mechanism models contribute broadly to plant pathogen defense.

PubMed

Arya, Preeti; Acharya, Vishal

2018-02-01

STAND P-loop NTPase is the common weapon used by plant and other organisms from all three kingdoms of life to defend themselves against pathogen invasion. The purpose of this study is to review comprehensively the latest finding of plant STAND P-loop NTPase related to their genomic distribution, evolution, and their mechanism of action. Earlier, the plant STAND P-loop NTPase known to be comprised of only NBS-LRRs/AP-ATPase/NB-ARC ATPase. However, recent finding suggests that genome of early green plants comprised of two types of STAND P-loop NTPases: (1) mammalian NACHT NTPases and (2) NBS-LRRs. Moreover, YchF (unconventional G protein and members of P-loop NTPase) subfamily has been reported to be exceptionally involved in biotic stress (in case of Oryza sativa), thereby a novel member of STAND P-loop NTPase in green plants. The lineage-specific expansion and genome duplication events are responsible for abundance of plant STAND P-loop NTPases; where "moderate tandem and low segmental duplication" trajectory followed in majority of plant species with few exception (equal contribution of tandem and segmental duplication). Since the past decades, systematic research is being investigated into NBS-LRR function supported the direct recognition of pathogen or pathogen effectors by the latest models proposed via 'integrated decoy' or 'sensor domains' model. Here, we integrate the recently published findings together with the previous literature on the genomic distribution, evolution, and distinct models proposed for functional molecular mechanism of plant STAND P-loop NTPases.

Toward a Quantitative Comparison of Magnetic Field Extrapolations and Observed Coronal Loops

NASA Astrophysics Data System (ADS)

Warren, Harry P.; Crump, Nicholas A.; Ugarte-Urra, Ignacio; Sun, Xudong; Aschwanden, Markus J.; Wiegelmann, Thomas

2018-06-01

It is widely believed that loops observed in the solar atmosphere trace out magnetic field lines. However, the degree to which magnetic field extrapolations yield field lines that actually do follow loops has yet to be studied systematically. In this paper, we apply three different extrapolation techniques—a simple potential model, a nonlinear force-free (NLFF) model based on photospheric vector data, and an NLFF model based on forward fitting magnetic sources with vertical currents—to 15 active regions that span a wide range of magnetic conditions. We use a distance metric to assess how well each of these models is able to match field lines to the 12202 loops traced in coronal images. These distances are typically 1″–2″. We also compute the misalignment angle between each traced loop and the local magnetic field vector, and find values of 5°–12°. We find that the NLFF models generally outperform the potential extrapolation on these metrics, although the differences between the different extrapolations are relatively small. The methodology that we employ for this study suggests a number of ways that both the extrapolations and loop identification can be improved.

Application of cosmic-ray shock theories to the Cygnus Loop - an alternative model

NASA Astrophysics Data System (ADS)

Boulares, Ahmed; Cox, Donald P.

1988-10-01

Steady state cosmic-ray shock models are investigated in light of observations of the Cygnus Loop supernova remnant. In this work the authors find that the model of Völk, Drury, and McKenzie, in which the plasma waves are generated by the streaming instability of the cosmic rays and are dissipated into the gas, can be made consistent with some observed characteristics of Cygnus Loop shocks. The waves heat the gas substantially in the cosmic-ray precursor, in addition to the usual heating in the (possibly weak) gas shock. The model is used to deduce upstream densities and shock velocities using known quantities for Cygnus Loop shocks. Compared to the usual pure gas shock interpretation, it is found that lower densities and approximately 3 times higher velocities are required. If the cosmic-ray models are valid, this could significantly alter our understanding of the Cygnus Loop's distance and age and of the energy released during the initial explosion.

Closed Loop System Identification with Genetic Algorithms

NASA Technical Reports Server (NTRS)

Whorton, Mark S.

2004-01-01

High performance control design for a flexible space structure is challenging since high fidelity plant models are di.cult to obtain a priori. Uncertainty in the control design models typically require a very robust, low performance control design which must be tuned on-orbit to achieve the required performance. Closed loop system identi.cation is often required to obtain a multivariable open loop plant model based on closed-loop response data. In order to provide an accurate initial plant model to guarantee convergence for standard local optimization methods, this paper presents a global parameter optimization method using genetic algorithms. A minimal representation of the state space dynamics is employed to mitigate the non-uniqueness and over-parameterization of general state space realizations. This control-relevant system identi.cation procedure stresses the joint nature of the system identi.cation and control design problem by seeking to obtain a model that minimizes the di.erence between the predicted and actual closed-loop performance.

Two-loop mass splittings in electroweak multiplets: Winos and minimal dark matter

NASA Astrophysics Data System (ADS)

McKay, James; Scott, Pat

2018-03-01

The radiatively-induced splitting of masses in electroweak multiplets is relevant for both collider phenomenology and dark matter. Precision two-loop corrections of O (MeV ) to the triplet mass splitting in the wino limit of the minimal supersymmetric standard model can affect particle lifetimes by up to 40%. We improve on previous two-loop self-energy calculations for the wino model by obtaining consistent input parameters to the calculation via two-loop renormalization-group running, and including the effect of finite light quark masses. We also present the first two-loop calculation of the mass splitting in an electroweak fermionic quintuplet, corresponding to the viable form of minimal dark matter (MDM). We place significant constraints on the lifetimes of the charged and doubly-charged fermions in this model. We find that the two-loop mass splittings in the MDM quintuplet are not constant in the large-mass limit, as might naively be expected from the triplet calculation. This is due to the influence of the additional heavy fermions in loop corrections to the gauge boson propagators.

Simple way to calculate a UV-finite one-loop quantum energy in the Randall-Sundrum model

NASA Astrophysics Data System (ADS)

Altshuler, Boris L.

2017-04-01

The surprising simplicity of Barvinsky-Nesterov or equivalently Gelfand-Yaglom methods of calculation of quantum determinants permits us to obtain compact expressions for a UV-finite difference of one-loop quantum energies for two arbitrary values of the parameter of the double-trace asymptotic boundary conditions. This result generalizes the Gubser and Mitra calculation for the particular case of difference of "regular" and "irregular" one-loop energies in the one-brane Randall-Sundrum model. The approach developed in the paper also allows us to get "in one line" the one-loop quantum energies in the two-brane Randall-Sundrum model. The relationship between "one-loop" expressions corresponding to the mixed Robin and to double-trace asymptotic boundary conditions is traced.

Phase structure of the Polyakov-quark-meson model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaefer, B.-J.; Pawlowski, J. M.; Wambach, J.

2007-10-01

The relation between the deconfinement and chiral phase transition is explored in the framework of a Polyakov-loop-extended two-flavor quark-meson (PQM) model. In this model the Polyakov loop dynamics is represented by a background temporal gauge field which also couples to the quarks. As a novelty an explicit quark chemical potential and N{sub f}-dependence in the Polyakov loop potential is proposed by using renormalization group arguments. The behavior of the Polyakov loop as well as the chiral condensate as function of temperature and quark chemical potential is obtained by minimizing the grand canonical thermodynamic potential of the system. The effect ofmore » the Polyakov loop dynamics on the chiral phase diagram and on several thermodynamic bulk quantities is presented.« less

A simplified dynamic model of the T700 turboshaft engine

NASA Technical Reports Server (NTRS)

Duyar, Ahmet; Gu, Zhen; Litt, Jonathan S.

1992-01-01

A simplified open-loop dynamic model of the T700 turboshaft engine, valid within the normal operating range of the engine, is developed. This model is obtained by linking linear state space models obtained at different engine operating points. Each linear model is developed from a detailed nonlinear engine simulation using a multivariable system identification and realization method. The simplified model may be used with a model-based real time diagnostic scheme for fault detection and diagnostics, as well as for open loop engine dynamics studies and closed loop control analysis utilizing a user generated control law.

Comparative analysis of the intestinal flora in type 2 diabetes and nondiabetic mice

PubMed Central

Horie, Masanori; Miura, Takamasa; Hirakata, Satomi; Hosoyama, Akira; Sugino, Sakiko; Umeno, Aya; Murotomi, Kazutoshi; Yoshida, Yasukazu; Koike, Taisuke

2017-01-01

A relationship between type 2 diabetes mellitus (T2DM) and intestinal flora has been suggested since development of analysis technology for intestinal flora. An animal model of T2DM is important for investigation of T2DM. Although there are some animal models of T2DM, a comparison of the intestinal flora of healthy animals with that of T2DM animals has not yet been reported. The intestinal flora of Tsumura Suzuki Obese Diabetes (TSOD) mice was compared with that of Tsumura, Suzuki, Non Obesity (TSNO) mice in the present study. The TSOD mice showed typical type 2 diabetes symptoms, which were high-fat diet-independent. The TSOD and the TSNO mouse models were derived from the same strain, ddY. In this study, we compared the intestinal flora of TSOD mice with that if TSNO mice at 5 and 12 weeks of age. We determined that that the number of operational taxonomic units (OTUs) was significantly higher in the cecum of TSOD mice than in that of TSNO mice. The intestinal flora of the cecum and that of the feces were similar between the TSNO and the TSOD strains. The dominant bacteria in the cecum and feces were of the phyla Firmicutes and Bacteroidetes. However, the content of some bacterial species varied between the two strains. The percentage of Lactobacillus spp. within the general intestinal flora was higher in TSOD mice than in TSNO mice. In contrast, the percentages of order Bacteroidales and family Lachnospiraceae were higher in TSNO mice than in TSOD mice. Some species were observed only in TSOD mice, such as genera Turicibacter and SMB53 (family Clostridiaceae), the percentage of which were 3.8% and 2.0%, respectively. Although further analysis of the metabolism of the individual bacteria in the intestinal flora is essential, genera Turicibacter and SMB53 may be important for the abnormal metabolism of type 2 diabetes. PMID:28701620

Comparative analysis of the intestinal flora in type 2 diabetes and nondiabetic mice.

PubMed

Horie, Masanori; Miura, Takamasa; Hirakata, Satomi; Hosoyama, Akira; Sugino, Sakiko; Umeno, Aya; Murotomi, Kazutoshi; Yoshida, Yasukazu; Koike, Taisuke

2017-10-30

A relationship between type 2 diabetes mellitus (T2DM) and intestinal flora has been suggested since development of analysis technology for intestinal flora. An animal model of T2DM is important for investigation of T2DM. Although there are some animal models of T2DM, a comparison of the intestinal flora of healthy animals with that of T2DM animals has not yet been reported. The intestinal flora of Tsumura Suzuki Obese Diabetes (TSOD) mice was compared with that of Tsumura, Suzuki, Non Obesity (TSNO) mice in the present study. The TSOD mice showed typical type 2 diabetes symptoms, which were high-fat diet-independent. The TSOD and the TSNO mouse models were derived from the same strain, ddY. In this study, we compared the intestinal flora of TSOD mice with that if TSNO mice at 5 and 12 weeks of age. We determined that that the number of operational taxonomic units (OTUs) was significantly higher in the cecum of TSOD mice than in that of TSNO mice. The intestinal flora of the cecum and that of the feces were similar between the TSNO and the TSOD strains. The dominant bacteria in the cecum and feces were of the phyla Firmicutes and Bacteroidetes. However, the content of some bacterial species varied between the two strains. The percentage of Lactobacillus spp. within the general intestinal flora was higher in TSOD mice than in TSNO mice. In contrast, the percentages of order Bacteroidales and family Lachnospiraceae were higher in TSNO mice than in TSOD mice. Some species were observed only in TSOD mice, such as genera Turicibacter and SMB53 (family Clostridiaceae), the percentage of which were 3.8% and 2.0%, respectively. Although further analysis of the metabolism of the individual bacteria in the intestinal flora is essential, genera Turicibacter and SMB53 may be important for the abnormal metabolism of type 2 diabetes.

Precision-cut rat, mouse, and human intestinal slices as novel models for the early-onset of intestinal fibrosis.

PubMed

Pham, Bao Tung; van Haaften, Wouter Tobias; Oosterhuis, Dorenda; Nieken, Judith; de Graaf, Inge Anne Maria; Olinga, Peter

2015-04-01

Intestinal fibrosis (IF) is a major complication of inflammatory bowel disease. IF research is limited by the lack of relevant in vitro and in vivo models. We evaluated precision-cut intestinal slices (PCIS) prepared from human, rat, and mouse intestine as ex vivo models mimicking the early-onset of (human) IF. Precision-cut intestinal slices prepared from human (h), rat (r), and mouse (m) jejunum, were incubated up to 72 h, the viability of PCIS was assessed by ATP content and morphology, and the gene expression of several fibrosis markers was determined. The viability of rPCIS decreased after 24 h of incubation, whereas mPCIS and hPCIS were viable up to 72 h of culturing. Furthermore, during this period, gene expression of heat shock protein 47 and plasminogen activator inhibitor 1 increased in all PCIS in addition to augmented expression of synaptophysin in hPCIS, fibronectin (Fn2) and TGF-β1 in rPCIS, and Fn2 and connective tissue growth factor (Ctgf) in mPCIS. Addition of TGF-β1 to rPCIS or mPCIS induced the gene expression of the fibrosis markers Pro-collagen1a1, Fn2, and Ctgf in both species. However, none of the fibrosis markers was further elevated in hPCIS. We successfully developed a novel ex vivo model that can mimic the early-onset of fibrosis in the intestine using human, rat, and mouse PCIS. Furthermore, in rat and mouse PCIS, TGF-β1 was able to even further increase the gene expression of fibrosis markers. This indicates that PCIS can be used as a model for the early-onset of IF. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

HOW GAS-DYNAMIC FLARE MODELS POWERED BY PETSCHEK RECONNECTION DIFFER FROM THOSE WITH AD HOC ENERGY SOURCES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Longcope, D. W.; Klimchuk, J. A.

Aspects of solar flare dynamics, such as chromospheric evaporation and flare light curves, have long been studied using one-dimensional models of plasma dynamics inside a static flare loop, subjected to some energy input. While extremely successful at explaining the observed characteristics of flares, all such models so far have specified energy input ad hoc, rather than deriving it self-consistently. There is broad consensus that flares are powered by magnetic energy released through reconnection. Recent work has generalized Petschek’s basic reconnection scenario, topological change followed by field line retraction and shock heating, to permit its inclusion in a one-dimensional flare loop model. Heremore » we compare the gas dynamics driven by retraction and shocking to those from more conventional static loop models energized by ad hoc source terms. We find significant differences during the first minute, when retraction leads to larger kinetic energies and produces higher densities at the loop top, while ad hoc heating tends to rarify the loop top. The loop-top density concentration is related to the slow magnetosonic shock, characteristic of Petschek’s model, but persists beyond the retraction phase occurring in the outflow jet. This offers an explanation for observed loop-top sources of X-ray and EUV emission, with advantages over that provided by ad hoc heating scenarios. The cooling phases of the two models are, however, notably similar to one another, suggesting that observations at that stage will yield little information on the nature of energy input.« less

Human Intestinal Enteroids: a New Model To Study Human Rotavirus Infection, Host Restriction, and Pathophysiology

PubMed Central

Saxena, Kapil; Blutt, Sarah E.; Ettayebi, Khalil; Zeng, Xi-Lei; Broughman, James R.; Crawford, Sue E.; Karandikar, Umesh C.; Sastri, Narayan P.; Conner, Margaret E.; Opekun, Antone R.; Graham, David Y.; Qureshi, Waqar; Sherman, Vadim; Foulke-Abel, Jennifer; In, Julie; Kovbasnjuk, Olga; Zachos, Nicholas C.; Donowitz, Mark

2015-01-01

ABSTRACT Human gastrointestinal tract research is limited by the paucity of in vitro intestinal cell models that recapitulate the cellular diversity and complex functions of human physiology and disease pathology. Human intestinal enteroid (HIE) cultures contain multiple intestinal epithelial cell types that comprise the intestinal epithelium (enterocytes and goblet, enteroendocrine, and Paneth cells) and are physiologically active based on responses to agonists. We evaluated these nontransformed, three-dimensional HIE cultures as models for pathogenic infections in the small intestine by examining whether HIEs from different regions of the small intestine from different patients are susceptible to human rotavirus (HRV) infection. Little is known about HRVs, as they generally replicate poorly in transformed cell lines, and host range restriction prevents their replication in many animal models, whereas many animal rotaviruses (ARVs) exhibit a broader host range and replicate in mice. Using HRVs, including the Rotarix RV1 vaccine strain, and ARVs, we evaluated host susceptibility, virus production, and cellular responses of HIEs. HRVs infect at higher rates and grow to higher titers than do ARVs. HRVs infect differentiated enterocytes and enteroendocrine cells, and viroplasms and lipid droplets are induced. Heterogeneity in replication was seen in HIEs from different patients. HRV infection and RV enterotoxin treatment of HIEs caused physiological lumenal expansion detected by time-lapse microscopy, recapitulating one of the hallmarks of rotavirus-induced diarrhea. These results demonstrate that HIEs are a novel pathophysiological model that will allow the study of HRV biology, including host restriction, cell type restriction, and virus-induced fluid secretion. IMPORTANCE Our research establishes HIEs as nontransformed cell culture models to understand human intestinal physiology and pathophysiology and the epithelial response, including host restriction of gastrointestinal infections such as HRV infection. HRVs remain a major worldwide cause of diarrhea-associated morbidity and mortality in children ≤5 years of age. Current in vitro models of rotavirus infection rely primarily on the use of animal rotaviruses because HRV growth is limited in most transformed cell lines and animal models. We demonstrate that HIEs are novel, cellularly diverse, and physiologically relevant epithelial cell cultures that recapitulate in vivo properties of HRV infection. HIEs will allow the study of HRV biology, including human host-pathogen and live, attenuated vaccine interactions; host and cell type restriction; virus-induced fluid secretion; cell-cell communication within the epithelium; and the epithelial response to infection in cultures from genetically diverse individuals. Finally, drug therapies to prevent/treat diarrheal disease can be tested in these physiologically active cultures. PMID:26446608

Activation of intestinal Cl- secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator.

PubMed

Bijvelds, Marcel J C; Bot, Alice G M; Escher, Johanna C; De Jonge, Hugo R

2009-09-01

Lubiprostone alleviates constipation by stimulating intestinal fluid secretion, purportedly through activation of ClC-2-type Cl(-) channels. Intestinal obstruction is also a recurrent cause of distress in cystic fibrosis (CF) patients, caused by loss of CF transmembrane conductance regulator (CFTR) Cl(-) channel activity. Because ClC-2 recruitment might be beneficial to CF patients, we investigated lubiprostone's mode of action. Cl(-) transport was measured in an Ussing chamber, in 3 model systems: (1) T84 colonocytes, (2) intestinal epithelium of wild-type and CF mice, and (3) intestinal epithelium of CF patients and controls. In T84 monolayers, lubiprostone induced a robust secretory response. Selective permeabilization of the basolateral plasma membrane revealed that lubiprostone activated an apical Cl(-) conductance. The lubiprostone response was attenuated by H89, an inhibitor of the cAMP-dependent protein kinase, and lubiprostone precluded responsiveness to the cAMP agonist forskolin. CFTR blockage by CFTRinh172, but not ClC-2 blockage by CdCl(2), inhibited the lubiprostone response. Lubiprostone induced a CdCl(2)-insensitive secretory response in mouse intestine, but failed to induce intestinal Cl(-) secretion in Cftr-null mice. Correspondingly, lubiprostone induced a secretory response in human intestinal epithelium, but not in tissue of CF patients. The EP(4)-type prostanoid receptor antagonist L-161,982 blocked the lubiprostone response in all 3 models studied. In T84 cells, lubiprostone induced a rise in cAMP levels that was sensitive to EP(4)-receptor blockage. Lubiprostone enhances intestinal Cl(-) and fluid secretion via prostanoid receptor signaling, triggering activation of CFTR. Therefore, it is of limited use for treatment of CF-related intestinal disease.

The Duration of Energy Deposition on Unresolved Flaring Loops in the Solar Corona

NASA Astrophysics Data System (ADS)

Reep, Jeffrey W.; Polito, Vanessa; Warren, Harry P.; Crump, Nicholas A.

2018-04-01

Solar flares form and release energy across a large number of magnetic loops. The global parameters of flares, such as the total energy released, duration, physical size, etc., are routinely measured, and the hydrodynamics of a coronal loop subjected to intense heating have been extensively studied. It is not clear, however, how many loops comprise a flare, nor how the total energy is partitioned between them. In this work, we employ a hydrodynamic model to better understand the energy partition by synthesizing Si IV and Fe XXI line emission and comparing to observations of these lines with the Interface Region Imaging Spectrograph (IRIS). We find that the observed temporal evolution of the Doppler shifts holds important information on the heating duration. To demonstrate this, we first examine a single loop model, and find that the properties of chromospheric evaporation seen in Fe XXI can be reproduced by loops heated for long durations, while persistent redshifts seen in Si IV cannot be reproduced by any single loop model. We then examine a multithreaded model, assuming both a fixed heating duration on all loops and a distribution of heating durations. For a fixed heating duration, we find that durations of 100–200 s do a fair job of reproducing both the red- and blueshifts, while a distribution of durations, with a median of about 50–100 s, does a better job. Finally, we compare our simulations directly to observations of an M-class flare seen by IRIS, and find good agreement between the modeled and observed values given these constraints.

Loops determine the mechanical properties of mitotic chromosomes

NASA Astrophysics Data System (ADS)

Zhang, Yang; Heermann, Dieter W.

2013-03-01

In mitosis, chromosomes undergo a condensation into highly compacted, rod-like objects. Many models have been put forward for the higher-order organization of mitotic chromosomes including radial loop and hierarchical folding models. Additionally, mechanical properties of mitotic chromosomes under different conditions were measured. However, the internal organization of mitotic chromosomes still remains unclear. Here we present a polymer model for mitotic chromosomes and show how chromatin loops play a major role for their mechanical properties. The key assumption of the model is the ability of the chromatin fibre to dynamically form loops with the help of binding proteins. Our results show that looping leads to a tight compaction and significantly increases the bending rigidity of chromosomes. Moreover, our qualitative prediction of the force elongation behaviour is close to experimental findings. This indicates that the internal structure of mitotic chromosomes is based on self-organization of the chromatin fibre. We also demonstrate how number and size of loops have a strong influence on the mechanical properties. We suggest that changes in the mechanical characteristics of chromosomes can be explained by an altered internal loop structure. YZ gratefully appreciates funding by the German National Academic Foundation (Studienstiftung des deutschen Volkes) and support by the Heidelberg Graduate School for Mathematical and Computational Methods in the Sciences (HGS MathComp).

A Simple Model for the Evolution of Multi-Stranded Coronal Loops

NASA Technical Reports Server (NTRS)

Fuentes, M. C. Lopez; Klimchuk, J. A.

2010-01-01

We develop and analyze a simple cellular automaton (CA) model that reproduces the main properties of the evolution of soft X-ray coronal loops. We are motivated by the observation that these loops evolve in three distinguishable phases that suggest the development, maintainance, and decay of a self-organized system. The model is based on the idea that loops are made of elemental strands that are heated by the relaxation of magnetic stress in the form of nanoflares. In this vision, usually called "the Parker conjecture" (Parker 1988), the origin of stress is the displacement of the strand footpoints due to photospheric convective motions. Modeling the response and evolution of the plasma we obtain synthetic light curves that have the same characteristic properties (intensity, fluctuations, and timescales) as the observed cases. We study the dependence of these properties on the model parameters and find scaling laws that can be used as observational predictions of the model. We discuss the implications of our results for the interpretation of recent loop observations in different wavelengths. Subject headings: Sun: corona - Sun: flares - Sun: magnetic topology - Sun: X-rays, gamma rays

The food processing contaminant glyoxal promotes tumour growth in the multiple intestinal neoplasia (Min) mouse model.

PubMed

Svendsen, Camilla; Høie, Anja Hortemo; Alexander, Jan; Murkovic, Michael; Husøy, Trine

2016-08-01

Glyoxal is formed endogenously and at a higher rate in the case of hyperglycemia. Glyoxal is also a food processing contaminant and has been shown to be mutagenic and genotoxic in vitro. The tumourigenic potential of glyoxal was investigated using the multiple intestinal neoplasia (Min) mouse model, which spontaneously develops intestinal tumours and is susceptible to intestinal carcinogens. C57BL/6J females were mated with Min males. Four days after mating and throughout gestation and lactation, the pregnant dams were exposed to glyoxal through drinking water (0.0125%, 0.025%, 0.05%, 0.1%) or regular tap water. Female and male offspring were housed separately from PND21 and continued with the same treatment. One group were only exposed to 0.1% glyoxal from postnatal day (PND) 21. There was no difference in the number of intestinal tumours between control and treatment groups. However, exposure to 0.1% glyoxal starting in utero and at PND21 caused a significant increase in tumour size in the small intestine for male and female mice in comparison with respective control groups. This study suggests that glyoxal has tumour growth promoting properties in the small intestine in Min mice. Copyright © 2016 Norwegian Institute of Public Health. Published by Elsevier Ltd.. All rights reserved.

Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation

PubMed Central

Kechele, Daniel O.; Blue, R. Eric; Zwarycz, Bailey; Espenschied, Scott T.; Mah, Amanda T.; Siegel, Marni B.; Perou, Charles M.; Ding, Shengli; Magness, Scott T.; Lund, P. Kay

2017-01-01

Orphan GPCRs provide an opportunity to identify potential pharmacological targets, yet their expression patterns and physiological functions remain challenging to elucidate. Here, we have used a genetically engineered knockin reporter mouse to map the expression pattern of the Gpr182 during development and adulthood. We observed that Gpr182 is expressed at the crypt base throughout the small intestine, where it is enriched in crypt base columnar stem cells, one of the most active stem cell populations in the body. Gpr182 knockdown had no effect on homeostatic intestinal proliferation in vivo, but led to marked increases in proliferation during intestinal regeneration following irradiation-induced injury. In the ApcMin mouse model, which forms spontaneous intestinal adenomas, reductions in Gpr182 led to more adenomas and decreased survival. Loss of Gpr182 enhanced organoid growth efficiency ex vivo in an EGF-dependent manner. Gpr182 reduction led to increased activation of ERK1/2 in basal and challenge models, demonstrating a potential role for this orphan GPCR in regulating the proliferative capacity of the intestine. Importantly, GPR182 expression was profoundly reduced in numerous human carcinomas, including colon adenocarcinoma. Together, these results implicate Gpr182 as a negative regulator of intestinal MAPK signaling–induced proliferation, particularly during regeneration and adenoma formation. PMID:28094771

Potential of Lactobacillus plantarum CCFM639 in Protecting against Aluminum Toxicity Mediated by Intestinal Barrier Function and Oxidative Stress

PubMed Central

Yu, Leilei; Zhai, Qixiao; Tian, Fengwei; Liu, Xiaoming; Wang, Gang; Zhao, Jianxin; Zhang, Hao; Narbad, Arjan; Chen, Wei

2016-01-01

Aluminum (Al) is a ubiquitous metal that can seriously harm the health of animals and humans. In our previous study, we demonstrated that Lactobacillus plantarum CCFM639 can decrease Al burden in the tissues of mice by inhibiting intestinal Al absorption. The main aim of the present research was to investigate whether the protection by the strain is also associated with enhancement of the intestinal barrier, alleviation of oxidative stress and modulation of the inflammatory response. In an in vitro cell model, two protection modes (intervention and therapy) were examined and the results indicated that L. plantarum CCFM639 alleviated Al-induced cytotoxicity. In a mouse model, L. plantarum CCFM639 treatment was found to significantly alleviate oxidative stress in the intestinal tract, regulate the function of the intestinal mucosal immune system, restore the integrity of tight junction proteins and maintain intestinal permeability. These results suggest that in addition to Al sequestration, L. plantarum CCFM639 can also inhibit Al absorption by protecting the intestinal barrier, alleviating Al-induced oxidative stress and inflammatory response. Therefore, L. plantarum CCFM639 has the potential to be a dietary supplement ingredient that provides protection against Al-induced gut injury. PMID:27918411

Intestinal anti-inflammatory effects of total alkaloid extract from Fumaria capreolata in the DNBS model of mice colitis and intestinal epithelial CMT93 cells.

PubMed

Bribi, Noureddine; Algieri, Francesca; Rodriguez-Nogales, Alba; Vezza, Teresa; Garrido-Mesa, Jose; Utrilla, María Pilar; Del Mar Contreras, María; Maiza, Fadila; Segura-Carretero, Antonio; Rodriguez-Cabezas, Maria Elena; Gálvez, Julio

2016-08-15

Fumaria capreolata L. (Papaveraceae) is a botanical drug used in North Africa for its gastro-intestinal and anti-inflammatory properties. It is characterized for the presence of several alkaloids that could be responsible for some of its effects, including an immunomodulatory activity. To test in vivo the intestinal anti-inflammatory properties of the total alkaloid fraction extracted from the aerial parts of F. capreolata (AFC), and to evaluate its effects on an intestinal epithelial cell line. AFC was chemically characterized by liquid chromatography coupled to diode array detection and high resolution mass spectrometry. Different doses of AFC (25, 50 and 100mg/kg) were assayed in the DNBS model of experimental colitis in mice, and the colonic damage was evaluated both histologically and biochemically. In addition, in vitro experiments were performed with this alkaloid fraction on the mouse intestinal epithelial cell line CMT93 stimulated with LPS. The chemical analysis of AFC revealed the presence of 23 alkaloids, being the most abundants stylopine, protopine and coptisine. Oral administration of AFC produced a significant inhibition of the release and the expression of IL-6 and TNF-α in the colonic tissue. It also suppressed in vivo the transcription of other pro-inflammatory mediators such as IL-1β, iNOS, IL-12 and IL-17. Furthermore, AFC showed an immunomodulatory effect in vitro since it was able to inhibit the mRNA expression of IL-6, TNF-α and ICAM-1. Moreover, the beneficial effect of AFC in the colitic mice could also be associated with the normalization of the expression of MUC-2 and ZO-1, which are important for the intestinal epithelial integrity. The present study suggests that AFC, containing 1.3% of stylopine and 0.9% of protopine, significantly exerted intestinal anti-inflammatory effects in an experimental model of mouse colitis. This fact could be related to a modulation of the intestinal immune response and a restoration of the intestinal epithelial function. Copyright © 2016 Elsevier GmbH. All rights reserved.

Nitrogen metabolism of the intestine during digestion in a teleost fish, the plainfin midshipman (Porichthys notatus).

PubMed

Bucking, Carol; LeMoine, Christophe M R; Craig, Paul M; Walsh, Patrick J

2013-08-01

Digestion affects nitrogen metabolism in fish, as both exogenous and endogenous proteins and amino acids are catabolized, liberating ammonia in the process. Here we present a model of local detoxification of ammonia by the intestinal tissue of the plainfin midshipman (Porichthys notatus) during digestion, resulting in an increase in urea excretion of gastrointestinal origin. Corroborating evidence indicated whole-animal ammonia and urea excretion increased following feeding, and ammonia levels within the lumen of the midshipman intestine increased to high levels (1.8±0.4 μmol N g(-1)). We propose that this ammonia entered the enterocytes and was detoxified to urea via the ornithine-urea cycle (O-UC) enzymes, as evidenced by a 1.5- to 2.9-fold post-prandial increase in glutamine synthetase activity (0.14±0.05 and 0.28±0.02 μmol min(-1) g(-1) versus 0.41±0.03 μmol min(-1) g(-1)) and an 8.7-fold increase in carbamoyl phosphate synthetase III activity (0.3±1.2 versus 2.6±0.4 nmol min(-1) g(-1)). Furthermore, digestion increased urea production by isolated gastrointestinal tissue 1.7-fold, supporting our hypothesis that intestinal tissue synthesizes urea in response to feeding. We further propose that the intestinal urea may have been excreted into the intestinal lumen via an apical urea transporter as visualized using immunohistochemistry. A portion of the urea was then excreted to the environment along with the feces, resulting in the observed increase in urea excretion, while another portion may have been used by intestinal ureolytic bacteria. Overall, we propose that P. notatus produces urea within the enterocytes via a functional O-UC, which is then excreted into the intestinal lumen. Our model of intestinal nitrogen metabolism does not appear to be universal as we were unab le to activate the O-UC in the intestine of fed rainbow trout. However, literature values suggest that multiple fish species could follow this model.

Altered expression of intestinal duodenal cytochrome b and divalent metal transporter 1 might be associated with cardio-renal anemia syndrome.

PubMed

Naito, Yoshiro; Sawada, Hisashi; Oboshi, Makiko; Okuno, Keisuke; Yasumura, Seiki; Okuhara, Yoshitaka; Eguchi, Akiyo; Nishimura, Koichi; Soyama, Yuko; Asakura, Masanori; Ishihara, Masaharu; Tsujino, Takeshi; Masuyama, Tohru

2017-11-01

The interaction among heart failure (HF), chronic kidney disease (CKD), and anemia is called cardio-renal anemia syndrome. The mechanism of anemia in cardio-renal anemia syndrome is complex and remains completely unknown. We have previously reported that impaired intestinal iron transporters may contribute to the mechanism of anemia in HF using in vivo HF model rats. In this study, we assessed intestinal iron transporters in CKD model rats to investigate the association of intestinal iron transporters in the mechanism of cardio-renal anemia syndrome. CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. Sham-operated rats served as a control. After 24-week surgery, CKD rats exhibited normocytic normochromic anemia and normal serum erythropoietin levels despite of anemia. Serum iron levels were decreased in CKD rats compared with the controls. Of interest, intestinal expression of critical iron importers, such as duodenal cytochrome b (Dcyt-b) and divalent metal transporter 1 (DMT-1), was decreased in CKD rats compared with the controls. On the other hand, intestinal expression of ferroportin, an intestinal iron exporter, was not different in the control and CKD groups. Moreover, hepatic expression of hepcidin, a regulator of iron homeostasis, did not differ between the control and CKD groups. These results suggest that impaired intestinal expression of Dcyt-b and DMT-1 might be associated with the reduction of an iron uptake in CKD. Taken together, impaired these intestinal iron transporters may become a novel therapeutic target for cardio-renal anemia syndrome.

Performance Analysis of Digital Tracking Loops for Telemetry Ranging Applications

NASA Astrophysics Data System (ADS)

Vilnrotter, V.; Hamkins, J.; Xie, H.; Ashrafi, S.

2015-08-01

In this article, we analyze mathematical models of digital loops used to track the phase and timing of communications and navigation signals. The limits on the accuracy of phase and timing estimates play a critical role in the accuracy achievable in telemetry ranging applications. We describe in detail a practical algorithm to compute the loop parameters for discrete update (DU) and continuous update (CU) loop formulations, and we show that a simple power-series approximation to the DU model is valid over a large range of time-bandwidth product . Several numerical examples compare the estimation error variance of the DU and CU models to each other and to Cramer-Rao lower bounds. Finally, the results are applied to the problem of ranging, by evaluating the performance of a phase-locked loop designed to track a typical ambiguity-resolving pseudonoise (PN) code received and demodulated at the spacecraft on the uplink part of the two-way ranging link, and a data transition tracking loop (DTTL) on the downlink part.

Barrier tunneling of the loop-nodal semimetal in the hyperhoneycomb lattice

NASA Astrophysics Data System (ADS)

Guan, Ji-Huan; Zhang, Yan-Yang; Lu, Wei-Er; Xia, Yang; Li, Shu-Shen

2018-05-01

We theoretically investigate the barrier tunneling in the 3D model of the hyperhoneycomb lattice, which is a nodal-line semimetal with a Dirac loop at zero energy. In the presence of a rectangular potential, the scattering amplitudes for different injecting states around the nodal loop are calculated, by using analytical treatments of the effective model, as well as numerical simulations of the tight binding model. In the low energy regime, states with remarkable transmissions are only concentrated in a small range around the loop plane. When the momentum of the injecting electron is coplanar with the nodal loop, nearly perfect transmissions can occur for a large range of injecting azimuthal angles if the potential is not high. For higher potential energies, the transmission shows a resonant oscillation with the potential, but still with peaks being perfect transmissions that do not decay with the potential width. These strikingly robust transports of the loop-nodal semimetal can be approximately explained by a momentum dependent Dirac Hamiltonian.

Effect of threonine on secretory immune system using a chicken intestinal ex vivo model with lipopolysaccharide challenge

USDA-ARS?s Scientific Manuscript database

Secretory IgA (sIgA) and its transcytosis receptor, polymeric immunoglobulin receptor (pIgR), along with mucus, form the first lines of intestinal defense. Threonine (Thr) is a major constituent component of intestinal mucins and IgA, which are highly secreted under lipopolysaccharide (LPS) induced ...

A new in vitro model using small intestinal epithelial cells to enhance infection of Cryptosporidium parvum

EPA Science Inventory

To better understand and study the infection of the protozoan parasite Cryptosporidium parvum, a more sensitive in vitro assay is required. In vivo, this parasite infects the epithelial cells of the microvilli layer in the small intestine. While cell infection models using colon,...

Closed loop models for analyzing the effects of simulator characteristics. [digital simulation of human operators

NASA Technical Reports Server (NTRS)

Baron, S.; Muralidharan, R.; Kleinman, D. L.

1978-01-01

The optimal control model of the human operator is used to develop closed loop models for analyzing the effects of (digital) simulator characteristics on predicted performance and/or workload. Two approaches are considered: the first utilizes a continuous approximation to the discrete simulation in conjunction with the standard optimal control model; the second involves a more exact discrete description of the simulator in a closed loop multirate simulation in which the optimal control model simulates the pilot. Both models predict that simulator characteristics can have significant effects on performance and workload.

Computational Model of a Positive BDNF Feedback Loop in Hippocampal Neurons Following Inhibitory Avoidance Training

ERIC Educational Resources Information Center

Zhang, Yili; Smolen, Paul; Alberini, Cristina M.; Baxter, Douglas A.; Byrne, John H.

2016-01-01

Inhibitory avoidance (IA) training in rodents initiates a molecular cascade within hippocampal neurons. This cascade contributes to the transition of short- to long-term memory (i.e., consolidation). Here, a differential equation-based model was developed to describe a positive feedback loop within this molecular cascade. The feedback loop begins…

Intestinal ischemia-reperfusion suppresses biliary excretion of hepatic organic anion transporting polypeptides substrate.

PubMed

Maruyama, Hajime; Ogura, Jiro; Fujikawa, Asuka; Terada, Yusuke; Tsujimoto, Takashi; Koizumi, Takahiro; Kuwayama, Kaori; Kobayashi, Masaki; Yamaguchi, Hiroaki; Iseki, Ken

2013-01-01

Intestinal ischemia-reperfusion (I/R) causes gut dysfunction and promotes multi-organ failure. The liver and kidney can be affected by multi-organ failure after intestinal I/R. Organic anion transporting polypeptides (OATPs) and organic anion transporters (OATs) are recognized in a broad spectrum from endogenous compounds to xenobiotics, including clinically important drugs. Therefore, it is important for understanding the pharmacokinetics to obtain evidence of alterations in OATPs and OATs expression and transport activities. In the present study, we investigated the expression of rat Oatps and Oats after intestinal I/R. We used intestinal ischemia-reperfusion (I/R) model rats. Real-time PCR and Western blotting were used to assess mRNA and protein expression levels. Plasma concentration and biliary excretion of sulfobromophthalein (BSP), which is used as a model compound of organic anion drugs, were measured after intravenous administration in intestinal I/R rats. Although Oat1 and Oat3 mRNA levels were not altered in the kidney, Oatp1a1, Oatp1b2 and Oatp2b1 mRNA levels in the liver were significantly decreased at 1-6 h after intestinal I/R. Moreover, Oatp1a1 and Oatp2b1 protein expression levels were decreased at 1 h after intestinal I/R. Plasma concentration of BSP, which is a typical substrate of Oatps, in intestinal I/R rats reperfused 1 h was increased than that in sham-operated rats. Moreover, the area under the concentration-time curve (AUC₀₋₉₀) in intestinal I/R rats reperfused 1 h was significantly increased than that in sham-operated rats. The total clearance (CL(tot)) and the biliary clearance (CL(bile)) in intestinal I/R rats reperfused 1 h were significantly decreased than those in sham-operated rats. Oatp1a1 and Oatp2b1 expression levels are decreased by intestinal I/R. The decreases in these transporters cause alteration of pharmacokinetics of organic anion compound. The newly found influence of intestinal I/R on the expression and function of Oatps may be a key to perform appropriate drug therapy.

Biorelevant media resistant co-culture model mimicking permeability of human intestine.

PubMed

Antoine, Delphine; Pellequer, Yann; Tempesta, Camille; Lorscheidt, Stefan; Kettel, Bernadette; Tamaddon, Lana; Jannin, Vincent; Demarne, Frédéric; Lamprecht, Alf; Béduneau, Arnaud

2015-03-15

Cell culture models are currently used to predict absorption pattern of new compounds and formulations in the human gastro-intestinal tract (GIT). One major drawback is the lack of relevant apical incubation fluids allowing mimicking luminal conditions in the GIT. Here, we suggest a culture model compatible with biorelevant media, namely Fasted State Simulated Intestinal Fluid (FaSSIF) and Fed State Simulated Intestinal Fluid (FeSSIF). Co-culture was set up from Caco-2 and mucus-secreting HT29-MTX cells using an original seeding procedure. Viability and cytotoxicity assays were performed following incubation of FeSSIF and FaSSIF with co-culture. Influence of biorelevant fluids on paracellular permeability or transporter proteins were also evaluated. Results were compared with Caco-2 and HT29-MTX monocultures. While Caco-2 viability was strongly affected with FeSSIF, no toxic effect was detected for the co-cultures in terms of viability and lactate dehydrogenase release. The addition of FeSSIF to the basolateral compartment of the co-culture induced cytotoxic effects which suggested the apical mucus barrier being cell protective. In contrast to FeSSIF, FaSSIF induced a slight increase of the paracellular transport and both tested media inhibited partially the P-gp-mediated efflux in the co-culture. Additionally, the absorptive transport of propranolol hydrochloride, a lipophilic β-blocker, was strongly affected by biorelevant fluids. This study demonstrated the compatibility of the Caco-2/HT29-MTX model with some of the current biorelevant media. Combining biorelevant intestinal fluids with features such as mucus secretion, adjustable paracellular and P-gp mediated transports, is a step forward to more realistic in-vitro models of the human intestine. Copyright © 2015. Published by Elsevier B.V.

A new therapeutic association to manage relapsing experimental colitis: Doxycycline plus Saccharomyces boulardii.

PubMed

Garrido-Mesa, José; Algieri, Francesca; Rodriguez-Nogales, Alba; Utrilla, Maria Pilar; Rodriguez-Cabezas, Maria Elena; Zarzuelo, Antonio; Ocete, Maria Angeles; Garrido-Mesa, Natividad; Galvez, Julio

2015-07-01

Immunomodulatory antibiotics have been proposed for the treatment of multifactorial conditions such as inflammatory bowel disease. Probiotics are able to attenuate intestinal inflammation, being considered as safe when chronically administered. The aim of the study was to evaluate the anti-inflammatory effects of doxycycline, a tetracycline with immunomodulatory properties, alone and in association with the probiotic Saccharomyces boulardii CNCMI-745. Doxycycline was assayed both in vitro (Caco-2 epithelial cells and RAW 264.7 macrophages) and in vivo, in the trinitrobenzenesulfonic acid (TNBS) model of rat colitis and the dextran sodium sulfate (DSS) model of mouse colitis. In addition, the anti-inflammatory effect of the association of doxycycline and the probiotic was evaluated in vitro and in vivo in a DSS model of reactivated colitis in mice. Doxycycline displayed immunomodulatory activity in vitro, reducing IL-8 production by intestinal epithelial cells and nitric oxide by macrophages. Doxycycline administration to TNBS-colitic rats (5, 10 and 25 mg/kg) ameliorated the intestinal inflammatory process, being its efficacy comparable to that previously showed by minocycline. Doxycycline treatment was also effective in reducing acute intestinal inflammation in the DSS model of mouse colitis. The association of doxycycline and S. boulardii helped managing colitis in a reactivated model of colitis, by reducing intestinal inflammation and accelerating the recovery and attenuating the relapse. This was evidenced by a reduced disease activity index, colonic tissue damage and expression of inflammatory mediators. This study confirms the intestinal anti-inflammatory activity of doxycycline and supports the potential use of its therapeutic association with S. boulardii for the treatment of inflammatory bowel diseases, in which doxycycline is used to induce remission and long term probiotic administration helps to prevent the relapses. Copyright © 2015 Elsevier Ltd. All rights reserved.

An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse.

PubMed

Pagano, Ester; Capasso, Raffaele; Piscitelli, Fabiana; Romano, Barbara; Parisi, Olga A; Finizio, Stefania; Lauritano, Anna; Marzo, Vincenzo Di; Izzo, Angelo A; Borrelli, Francesca

2016-01-01

Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for "CBD botanical drug substance," on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage - after the inflammatory insult (curative protocol). The amounts of CBD in the colon, brain, and liver after the oral treatments were measured by high-performance liquid chromatography coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice) in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion) or orally (only at one dose). In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse

PubMed Central

Pagano, Ester; Capasso, Raffaele; Piscitelli, Fabiana; Romano, Barbara; Parisi, Olga A.; Finizio, Stefania; Lauritano, Anna; Marzo, Vincenzo Di; Izzo, Angelo A.; Borrelli, Francesca

2016-01-01

Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for “CBD botanical drug substance,” on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage – after the inflammatory insult (curative protocol). The amounts of CBD in the colon, brain, and liver after the oral treatments were measured by high-performance liquid chromatography coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice) in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion) or orally (only at one dose). In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment. PMID:27757083

Experimental research on anchoring force in intestine for the motion of capsule robot.

PubMed

Chen, Wenwen; Ke, Quan; He, Shu; Luo, Weijie; Ji, Xing Chun; Yan, Guozheng

2013-07-01

Multiple research groups are currently attempting to develop less-invasive robotic capsule endoscopes (RCEs) with better outcomes for enteroscopic procedures. Understanding the biomechanical response of the bowel to RCE is crucial for optimizing the design of these devices. For this reason, this study aims to develop an analytical model to predict the anchoring force of the model when travelling through the intestine. Previous work has developed, characterized and tested the frictional characteristics of the intestine with microgroove structures that had different surface contours. This work tested basic anchoring force characteristics with custom-built testers and clamping mechanism dummies to analyse the robot clamping movement (which is vital to improving movement efficiency). Balloon-shaped and leg-based clamping mechanisms were developed, which were found to have variable anchoring forces from 0.01 N to 1.2 N. After analysing the experimental results it was found that: (a) robot weight does not play a major role in anchoring force; (b) an increase in anchoring force corresponded to an increase in diameter of the clamping mechanism; and (c) textured contact surfaces effectively increased friction. These results could be explained by the biomechanical response of the intestine, friction and mucoadhesion characteristics of the small intestine material. With these factors considered, a model was developed for determining anchoring force in the small intestine.

Effect of N-acetylcysteine on microcirculation of mucosa in rat ileum in a model of intestinal inflammation.

PubMed

Ruh, Joachim; Schmidt, Eduard; Vogel, Frank

2003-05-01

Oxygen radicals are formed by the endothelium and blood cells and have specific functions in various organs systems. On the level of the microcirculation, oxygen radicals take part in the regulation of the leukocyte-endothelial interaction. The involvement of oxygen radicals has previously been found in conditions such as sepsis, ischemia-reperfusion, and inflammation. Indomethacin is a clinically applied nonsteroidal antiphlogistic, and in previous studies in the rat, it has been found to induce an inflammatory reaction in the small intestine characterized by edema and reddening of the intestinal epithelium, ulceration, and dysregulation in the intestinal-epithelial barrier function. In the present study, we investigated the effect of N-acetylcysteine on erythrocyte velocity and the arteriolar diameter of the main arteriole in single villi, thus providing insight in the perfusion of the mucosa in indomethacin-induced intestinal inflammation. N-Acetylcysteine is known to inactivate superoxide and its precursors. Therefore, we used N-acetylcysteine to investigate whether superoxide and its precursors participate in the regulation of blood supply to single villi in this animal model. We found that indomethacin induced an increase in villous perfusion that was significantly reduced by N-acetylcysteine, indicating that superoxide and its precursors may participate in the regulation of blood supply to the mucosa in this animal model of intestinal inflammation.

Blood and small intestine cell kinetics under radiation exposures: Mathematical modeling

NASA Astrophysics Data System (ADS)

Smirnova, Olga

Biophysical models, which describe the dynamics of vital body systems (namely, hematopoiesis and small intestinal epithelium) in mammals exposed to acute and chronic radiation, are developed. These models, based on conventional biological theories, are realized as the systems of nonlinear differential equations. Their variables and constant parameters have real biological meaning, that provides successful identification and verification of the models in hand. The explanation of a number of radiobiological effects, including those of the low-level long-term exposures, is proposed proceeding from the modeling results. It is proved that the predictions the models agree with the respective experimental data at both qualitative and quantitative levels. All this testifies to the efficiency of employment of the developed models in investigation and prediction of radiation effects on the hematopoietic and small intestinal epithelium systems, that can be used for the radiation risk assessment in the long-term space missions such as lunar colony and Mars voyage.

Development and Validation of an in vitro Experimental GastroIntestinal Dialysis Model with Colon Phase to Study the Availability and Colonic Metabolisation of Polyphenolic Compounds.

PubMed

Breynaert, Annelies; Bosscher, Douwina; Kahnt, Ariane; Claeys, Magda; Cos, Paul; Pieters, Luc; Hermans, Nina

2015-08-01

The biological effects of polyphenols depend on their mechanism of action in the body. This is affected by bioconversion by colon microbiota and absorption of colonic metabolites. We developed and validated an in vitro continuous flow dialysis model with colon phase (GastroIntestinal dialysis model with colon phase) to study the gastrointestinal metabolism and absorption of phenolic food constituents. Chlorogenic acid was used as model compound. The physiological conditions during gastrointestinal digestion were mimicked. A continuous flow dialysis system simulated the one-way absorption by passive diffusion from lumen to mucosa. The colon phase was developed using pooled faecal suspensions. Several methodological aspects including implementation of an anaerobic environment, adapted Wilkins Chalgren broth medium, 1.10(8) CFU/mL bacteria suspension as inoculum, pH adaptation to 5.8 and implementation of the dialysis system were conducted. Validation of the GastroIntestinal dialysis model with colon phase system showed a good recovery and precision (CV < 16 %). Availability of chlorogenic acid in the small intestinal phase (37 ± 3 %) of the GastroIntestinal dialysis model with colon phase is comparable with in vivo studies on ileostomy patients. In the colon phase, the human faecal microbiota deconjugated chlorogenic acid to caffeic acid, 3,4-dihydroxyphenyl propionic acid, 4-hydroxybenzoic acid, 3- or 4-hydroxyphenyl acetic acid, 2-methoxy-4-methylphenol and 3-phenylpropionic acid. The GastroIntestinal dialysis model with colon phase is a new, reliable gastrointestinal simulation system. It permits a fast and easy way to predict the availability of complex secondary metabolites, and to detect metabolites in an early stage after digestion. Isolation and identification of these metabolites may be used as references for in vivo bioavailability experiments and for investigating their bioactivity in in vitro experiments. Georg Thieme Verlag KG Stuttgart · New York.

Two-phase Heating in Flaring Loops

NASA Astrophysics Data System (ADS)

Zhu, Chunming; Qiu, Jiong; Longcope, Dana W.

2018-03-01

We analyze and model a C5.7 two-ribbon solar flare observed by the Solar Dynamics Observatory, Hinode, and GOES on 2011 December 26. The flare is made of many loops formed and heated successively over one and half hours, and their footpoints are brightened in the UV 1600 Å before enhanced soft X-ray and EUV missions are observed in flare loops. Assuming that anchored at each brightened UV pixel is a half flaring loop, we identify more than 6700 half flaring loops, and infer the heating rate of each loop from the UV light curve at the footpoint. In each half loop, the heating rate consists of two phases: intense impulsive heating followed by a low-rate heating that is persistent for more than 20 minutes. Using these heating rates, we simulate the evolution of their coronal temperatures and densities with the model of the “enthalpy-based thermal evolution of loops.” In the model, suppression of thermal conduction is also considered. This model successfully reproduces total soft X-ray and EUV light curves observed in 15 passbands by four instruments GOES, AIA, XRT, and EVE. In this flare, a total energy of 4.9 × 1030 erg is required to heat the corona, around 40% of this energy is in the slow-heating phase. About two-fifths of the total energy used to heat the corona is radiated by the coronal plasmas, and the other three fifth transported to the lower atmosphere by thermal conduction.

Modeling gene regulatory network motifs using statecharts

PubMed Central

2012-01-01

Background Gene regulatory networks are widely used by biologists to describe the interactions among genes, proteins and other components at the intra-cellular level. Recently, a great effort has been devoted to give gene regulatory networks a formal semantics based on existing computational frameworks. For this purpose, we consider Statecharts, which are a modular, hierarchical and executable formal model widely used to represent software systems. We use Statecharts for modeling small and recurring patterns of interactions in gene regulatory networks, called motifs. Results We present an improved method for modeling gene regulatory network motifs using Statecharts and we describe the successful modeling of several motifs, including those which could not be modeled or whose models could not be distinguished using the method of a previous proposal. We model motifs in an easy and intuitive way by taking advantage of the visual features of Statecharts. Our modeling approach is able to simulate some interesting temporal properties of gene regulatory network motifs: the delay in the activation and the deactivation of the "output" gene in the coherent type-1 feedforward loop, the pulse in the incoherent type-1 feedforward loop, the bistability nature of double positive and double negative feedback loops, the oscillatory behavior of the negative feedback loop, and the "lock-in" effect of positive autoregulation. Conclusions We present a Statecharts-based approach for the modeling of gene regulatory network motifs in biological systems. The basic motifs used to build more complex networks (that is, simple regulation, reciprocal regulation, feedback loop, feedforward loop, and autoregulation) can be faithfully described and their temporal dynamics can be analyzed. PMID:22536967

PAF-Myc-Controlled Cell Stemness Is Required for Intestinal Regeneration and Tumorigenesis.

PubMed

Kim, Moon Jong; Xia, Bo; Suh, Han Na; Lee, Sung Ho; Jun, Sohee; Lien, Esther M; Zhang, Jie; Chen, Kaifu; Park, Jae-Il

2018-03-12

The underlying mechanisms of how self-renewing cells are controlled in regenerating tissues and cancer remain ambiguous. PCNA-associated factor (PAF) modulates DNA repair via PCNA. Also, PAF hyperactivates Wnt/β-catenin signaling independently of PCNA interaction. We found that PAF is expressed in intestinal stem and progenitor cells (ISCs and IPCs) and markedly upregulated during intestinal regeneration and tumorigenesis. Whereas PAF is dispensable for intestinal homeostasis, upon radiation injury, genetic ablation of PAF impairs intestinal regeneration along with the severe loss of ISCs and Myc expression. Mechanistically, PAF conditionally occupies and transactivates the c-Myc promoter, which induces the expansion of ISCs/IPCs during intestinal regeneration. In mouse models, PAF knockout inhibits Apc inactivation-driven intestinal tumorigenesis with reduced tumor cell stemness and suppressed Wnt/β-catenin signaling activity, supported by transcriptome profiling. Collectively, our results unveil that the PAF-Myc signaling axis is indispensable for intestinal regeneration and tumorigenesis by positively regulating self-renewing cells. Copyright © 2018 Elsevier Inc. All rights reserved.

Stem cell-derived human intestinal organoids as an infection model for rotaviruses.

PubMed

Finkbeiner, Stacy R; Zeng, Xi-Lei; Utama, Budi; Atmar, Robert L; Shroyer, Noah F; Estes, Mary K

2012-01-01

Directed differentiation of stem cell lines into intestine-like tissue called induced human intestinal organoids (iHIOs) is now possible (J. R. Spence, C. N. Mayhew, S. A. Rankin, M. F. Kuhar, J. E. Vallance, K. Tolle, E. E. Hoskins, V. V. Kalinichenko, S. I. Wells, A. M. Zorn, N. F. Shroyer, and J. M. Wells, Nature 470:105-109, 2011). We tested iHIOs as a new model to cultivate and study fecal viruses. Protocols for infection of iHIOs with a laboratory strain of rotavirus, simian SA11, were developed. Proof-of-principle analyses showed that iHIOs support replication of a gastrointestinal virus, rotavirus, on the basis of detection of nonstructural viral proteins (nonstructural protein 4 [NSP4] and NSP2) by immunofluorescence, increased levels of viral RNA by quantitative reverse transcription-PCR (qRT-PCR), and production of infectious progeny virus. iHIOs were also shown to support replication of 12/13 clinical rotavirus isolates directly from stool samples. An unexpected finding was the detection of rotavirus infection not only in the epithelial cells but also in the mesenchymal cell population of the iHIOs. This work demonstrates that iHIOs offer a promising new model to study rotaviruses and other gastrointestinal viruses. Gastrointestinal viral infections are a major cause of illness and death in children and adults. The ability to fully understand how viruses interact with human intestinal cells in order to cause disease has been hampered by insufficient methods for growing many gastrointestinal viruses in the laboratory. Induced human intestinal organoids (iHIOs) are a promising new model for generating intestine-like tissue. This is the first report of a study using iHIOs to cultivate any microorganism, in this case, an enteric virus. The evidence that both laboratory and clinical rotavirus isolates can replicate in iHIOs suggests that this model would be useful not only for studies of rotaviruses but also potentially of other infectious agents. Furthermore, detection of rotavirus proteins in unexpected cell types highlights the promise of this system to reveal new questions about pathogenesis that have not been previously recognized or investigated in other intestinal cell culture models.

[Study on intestinal absorption features of oligosaccharides in Morinda officinalis How. with sigle-pass perfusion].

PubMed

Deng, Shao-Dong; Zhang, Peng; Lin, Li; Xiao, Feng-Xia; Lin, Jing-Ran

2015-01-01

To study the in situ intestinal absorption of five oligosaccharides contained in Morinda officinalis How. (sucrose, kestose, nystose, 1F-Fructofuranosyinystose and Bajijiasu). The absorption of the five oligosaccharides in small intestine (duodenum, jejunum and ileum) and colon of rats and their contents were investigated by using in situ single-pass perfusion model and HPLC-ELSD. The effects of drug concentration, pH in perfusate and P-glycoprotein inhibitor on the intestinal absorption were investigated to define the intestinal absorption mechanism of the five oligosaccharides in rats. According to the results, all of the five oligosaccharides were absorbed in the whole intestine, and their absorption rates were affected by the pH of the perfusion solution, drug concentration and intestinal segments. Verapamil Hydrochloride could significantly increase the absorptive amount of sucrose and Bajijiasu, suggesting sucrose and Bajijiasu are P-gp's substrate. The five oligosaccharides are absorbed mainly through passive diffusion in the intestinal segments, without saturated absorption. They are absorbed well in all intestines and mainly in duodenum and jejunum.

Predictive models of radiative neutrino masses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Julio, J., E-mail: julio@lipi.go.id

2016-06-21

We discuss two models of radiative neutrino mass generation. The first model features one–loop Zee model with Z{sub 4} symmetry. The second model is the two–loop neutrino mass model with singly- and doubly-charged scalars. These two models fit neutrino oscillation data well and predict some interesting rates for lepton flavor violation processes.

Study on the effects of microencapsulated Lactobacillus delbrueckii on the mouse intestinal flora.

PubMed

Sun, Qingshen; Shi, Yue; Wang, Fuying; Han, Dequan; Lei, Hong; Zhao, Yao; Sun, Quan

2015-01-01

To evaluate the protective effects of microencapsulation on Lactobacillus delbrueckii by random, parallel experimental design. Lincomycin hydrochloride-induced intestinal malfunction mouse model was successfully established; then the L. delbrueckii microcapsule was given to the mouse. The clinical behaviour, number of intestinal flora, mucous IgA content in small intestine, IgG and IL-2 level in peripheral blood were monitored. The histological sections were also prepared. The L. delbrueckii microcapsule could have more probiotic effects as indicated by higher bifidobacterium number in cecal contents. The sIgA content in microcapsule treated group was significantly higher than that in non-encapsulated L. delbrueckii treated group (p < 0.05). Intestine pathological damage of the L. delbrueckii microcapsule-treated group showed obvious restoration. The L. delbrueckii microcapsules could relieve the intestinal tissue pathological damage and play an important role in curing antibiotic-induced intestinal flora dysfunction.

Cardiac looping may be driven by compressive loads resulting from unequal growth of the heart and pericardial cavity. Observations on a physical simulation model

PubMed Central

Bayraktar, Meriç; Männer, Jörg

2014-01-01

The transformation of the straight embryonic heart tube into a helically wound loop is named cardiac looping. Such looping is regarded as an essential process in cardiac morphogenesis since it brings the building blocks of the developing heart into an approximation of their definitive topographical relationships. During the past two decades, a large number of genes have been identified which play important roles in cardiac looping. However, how genetic information is physically translated into the dynamic form changes of the looping heart is still poorly understood. The oldest hypothesis of cardiac looping mechanics attributes the form changes of the heart loop (ventral bending → simple helical coiling → complex helical coiling) to compressive loads resulting from growth differences between the heart and the pericardial cavity. In the present study, we have tested the physical plausibility of this hypothesis, which we call the growth-induced buckling hypothesis, for the first time. Using a physical simulation model, we show that growth-induced buckling of a straight elastic rod within the confined space of a hemispherical cavity can generate the same sequence of form changes as observed in the looping embryonic heart. Our simulation experiments have furthermore shown that, under bilaterally symmetric conditions, growth-induced buckling generates left- and right-handed helices (D-/L-loops) in a 1:1 ratio, while even subtle left- or rightward displacements of the caudal end of the elastic rod at the pre-buckling state are sufficient to direct the buckling process toward the generation of only D- or L-loops, respectively. Our data are discussed with respect to observations made in biological “models.” We conclude that compressive loads resulting from unequal growth of the heart and pericardial cavity play important roles in cardiac looping. Asymmetric positioning of the venous heart pole may direct these forces toward a biased generation of D- or L-loops. PMID:24772086

Systematic review: microbial dysbiosis and nonalcoholic fatty liver disease.

PubMed

Wieland, A; Frank, D N; Harnke, B; Bambha, K

2015-11-01

The human intestinal microbiota is a key regulator of host metabolic and immune functions and alterations in the microbiome ('dysbiosis') have been implicated in several human diseases. Because of the anatomical links between the intestines and the liver, dysbiosis may also disrupt hepatic function and thereby contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). To perform a comprehensive review of the medical literature investigating associations between intestinal dysbiosis and NAFLD, with a particular emphasis on studies that characterise the microbiome in NAFLD. We conducted a search of PubMed, Embase, and Web of Science using multiple search terms including: 'NAFLD, NASH, fatty liver, steatohepatitis' combined with 'metagenome, microbiom*, microbiota*, fecal flora, intestinal flora, gut bacteria'. Results were manually reviewed and studies selected based on relevance to intestinal microbiota and NAFLD. We also included studies that addressed potential mechanistic models of pathways linking the dysbiosis to NAFLD. Nine studies (five human and four animal models) were identified in our search that assessed associations between specific intestinal microbiota composition and NAFLD. We reviewed and summarised the results of additional investigations that more broadly addressed the mechanisms by which the microbiome may impact NAFLD pathogenesis. Investigations in humans and animals demonstrate associations between intestinal dysbiosis and NAFLD; however, causality has not been proven and mechanistic links require further delineation. As the field of microbiome research matures in techniques and study design, more detailed insights into NAFLD pathogenesis and its associations with the intestinal microbiota will be elucidated. © 2015 John Wiley & Sons Ltd.

Mosapride Stabilizes Intestinal Microbiota to Reduce Bacterial Translocation and Endotoxemia in CCl4-Induced Cirrhotic Rats.

PubMed

Xu, Hong; Xiong, Jingfang; Xu, Jianjun; Li, Shuiming; Zhou, Yang; Chen, Dongya; Cai, Xinjun; Ping, Jian; Deng, Min; Chen, Jianyong

2017-10-01

Impaired intestinal motility may lead to the disruption of gut microbiota equilibrium, which in turn facilitates bacterial translocation (BT) and endotoxemia in cirrhosis. We evaluated the influence of mosapride, a prokinetic agent, on BT and DNA fingerprints of gut microbiota in cirrhotic rats. A rat model of cirrhosis was set up via subcutaneous injection of carbon tetrachloride (CCl 4 ). The portal pressure, liver and intestinal damage, plasma endotoxin, BT, and intestinal transit rate (ITR) of cirrhotic rats were determined. Fecal DNA fingerprints were obtained by ERIC-PCR. The expressions of tight junction proteins were evaluated by western blotting. Mosapride treatment to cirrhotic rats significantly reduced the plasma endotoxin level and incidence of BT, accompanied by increased ITR. Cirrhotic rats (including those treated with mosapride) suffered from BT exhibited significantly lower ITR than those who are free of BT. Pearson coefficient indicated a significant and negative correlation between the plasma endotoxin level and ITR. The genomic fingerprints of intestinal microbiota from the three groups fell into three distinctive clusters. In the mosapride-treated group, Shannon's index was remarkably increased compared to the model group. Significantly positive correlation was detected between Shannon's index and ITR. Mosapride did not improve hepatic and intestinal damages and ileal expressions of occludin and ZO-1. Mosapride significantly increases intestinal motility in cirrhotic rats, thus to recover the disordered intestinal microbiota, finally resulting in decreased plasma endotoxin and BT.

Preservation of the gut by preoperative carbohydrate loading improves postoperative food intake.

PubMed

Luttikhold, Joanna; Oosting, Annemarie; van den Braak, Claudia C M; van Norren, Klaske; Rijna, Herman; van Leeuwen, Paul A M; Bouritius, Hetty

2013-08-01

A carbohydrate (CHO) drink given preoperatively changes the fasted state into a fed state. The ESPEN guidelines for perioperative care include preoperative CHO loading and re-establishment of oral feeding as early as possible after surgery. An intestinal ischaemia reperfusion (IR) animal model was used to investigate whether preoperative CHO loading increases spontaneous postoperative food intake, intestinal barrier function and the catabolic response. Male Wistar rats (n = 65) were subjected to 16 h fasting with ad libitum water and: A) sham laparotomy (Sham fasted, n = 24); B) intestinal ischaemia (IR fasted, n = 27); and C) intestinal ischaemia with preoperatively access to a CHO drink (IR CHO, n = 14). Spontaneous food intake, intestinal barrier function, insulin sensitivity, intestinal motility and plasma amino acids were measured after surgery. The IR CHO animals started eating significantly earlier and also ate significantly more than the IR fasted animals. Furthermore, preoperative CHO loading improved the intestinal barrier function, functional enterocyte metabolic mass measured by citrulline and reduced muscle protein catabolism, as indicated by normalization of the biomarker 3-methylhistidine. Preoperative CHO loading improves food intake, preserves the GI function and reduces the catabolic response in an IR animal model. These findings suggest that preoperative CHO loading preserves the intestinal function in order to accelerate recovery and food intake. If this effect is caused by overcoming the fasted state or CHO loading remains unclear. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Differential Transmission of HIV Traversing Fetal Oral/Intestinal Epithelia and Adult Oral Epithelia

PubMed Central

Herrera, Rossana; Veluppillai, Piri; Greenspan, Deborah; Soros, Vanessa; Greene, Warner C.; Levy, Jay A.; Palefsky, Joel M.

2012-01-01

While human immunodeficiency virus (HIV) transmission through the adult oral route is rare, mother-to-child transmission (MTCT) through the neonatal/infant oral and/or gastrointestinal route is common. To study the mechanisms of cell-free and cell-associated HIV transmission across adult oral and neonatal/infant oral/intestinal epithelia, we established ex vivo organ tissue model systems of adult and fetal origin. Given the similarity of neonatal and fetal oral epithelia with respect to epithelial stratification and density of HIV-susceptible immune cells, we used fetal oral the epithelium as a model for neonatal/infant oral epithelium. We found that cell-free HIV traversed fetal oral and intestinal epithelia and infected HIV-susceptible CD4+ T lymphocytes, Langerhans/dendritic cells, and macrophages. To study the penetration of cell-associated virus into fetal oral and intestinal epithelia, HIV-infected macrophages and lymphocytes were added to the surfaces of fetal oral and intestinal epithelia. HIV-infected macrophages, but not lymphocytes, transmigrated across fetal oral epithelia. HIV-infected macrophages and, to a lesser extent, lymphocytes transmigrated across fetal intestinal epithelia. In contrast to the fetal oral/intestinal epithelia, cell-free HIV transmigration through adult oral epithelia was inefficient and virions did not infect intraepithelial and subepithelial HIV-susceptible cells. In addition, HIV-infected macrophages and lymphocytes did not transmigrate through intact adult oral epithelia. Transmigration of cell-free and cell-associated HIV across the fetal oral/intestinal mucosal epithelium may serve as an initial mechanism for HIV MTCT. PMID:22205732

Unmixing Magnetic Hysteresis Loops

NASA Astrophysics Data System (ADS)

Heslop, D.; Roberts, A. P.

2012-04-01

Magnetic hysteresis loops provide important information in rock and environmental magnetic studies. Natural samples often contain an assemblage of magnetic particles composed of components with different origins. Each component potentially carries important environmental information. Hysteresis loops, however, provide information concerning the bulk magnetic assemblage, which makes it difficult to isolate the specific contributions from different sources. For complex mineral assemblages an unmixing strategy with which to separate hysteresis loops into their component parts is therefore essential. Previous methods to unmix hysteresis data have aimed at separating individual loops into their constituent parts using libraries of type-curves thought to correspond to specific mineral types. We demonstrate an alternative approach, which rather than decomposing a single loop into monomineralic contributions, examines a collection of loops to determine their constituent source materials. These source materials may themselves be mineral mixtures, but they provide a genetically meaningful decomposition of a magnetic assemblage in terms of the processes that controlled its formation. We show how an empirically derived hysteresis mixing space can be created, without resorting to type-curves, based on the co-variation within a collection of measured loops. Physically realistic end-members, which respect the expected behaviour and symmetries of hysteresis loops, can then be extracted from the mixing space. These end-members allow the measured loops to be described as a combination of invariant parts that are assumed to represent the different sources in the mixing model. Particular attention is paid to model selection and estimating the complexity of the mixing model, specifically, how many end-members should be included. We demonstrate application of this approach using lake sediments from Butte Valley, northern California. Our method successfully separates the hysteresis loops into sources with a variety of terrigenous and authigenic origins.

Application of cosmic-ray shock theories to the Cygnus Loop - An alternative model

NASA Technical Reports Server (NTRS)

Boulares, Ahmed; Cox, Donald P.

1988-01-01

Steady state cosmic-ray shock models are investigated here in the light of observations of the Cygnus Loop supernova remnant. The predicted downstream temperature is derived for each model. The Cygnus Loop data and the application of the models to them, including wave dissipation, are presented. Heating rate and ionization fraction structures are provided along with an estimate of the cosmic-ray diffusion coefficient. It is found that the model of Voelk, Drury, and McKenzie (1984), in which the plasma waves are generated by the streaming instability of the cosmic rays and are dissipated into the gas, can be made consistent with some observed characteristics of the Cygnus Loop shocks. The model is used to deduce upstream densities and shock velocities and, compared to the usual pure gas shock interpretation, it is found that lower densities and approximately three times higher velocities are required.

The microbial fermentation characteristics depend on both carbohydrate source and heat processing: a model experiment with ileo-cannulated pigs.

PubMed

Nielsen, Tina Skau; Jørgensen, Henry; Knudsen, Knud Erik Bach; Lærke, Helle Nygaard

2017-11-01

The effects of carbohydrate (CHO) source and processing (extrusion cooking) on large intestinal fermentation products were studied in ileo-cannulated pigs as a model for humans. Pigs were fed diets containing barley, pea or a mixture of potato starch:wheat bran (PSWB) either raw or extrusion cooked. Extrusion cooking reduced the amount of starch fermented in the large intestine by 52-96% depending on the CHO source and the total pool of butyrate in the distal small intestine + large intestine by on average 60% across diets. Overall, extrusion cooking caused a shift in the composition of short-chain fatty acids (SCFA) produced towards more acetate and less propionate and butyrate. The CHO source and processing highly affected the fermentation characteristics and extrusion cooking generally reduced large intestinal fermentation and resulted in a less desirable composition of the fermentation products. The latter outcome is non-conducive to a healthy large intestinal environment and its resulting metabolic health.

Dysregulated LIGHT expression on T cells mediates intestinal inflammation and contributes to IgA nephropathy

PubMed Central

Wang, Jing; Anders, Robert A.; Wu, Qiang; Peng, Dacheng; Cho, Judy H.; Sun, Yonglian; Karaliukas, Reda; Kang, Hyung-Sik; Turner, Jerrold R.; Fu, Yang-Xin

2004-01-01

Whether and how T cells contribute to the pathogenesis of immunoglobulin A nephropathy (IgAN) has not been well defined. Here, we explore a murine model that spontaneously develops T cell–mediated intestinal inflammation accompanied by pathological features similar to those of human IgAN. Intestinal inflammation mediated by LIGHT, a ligand for lymphotoxin β receptor (LTβR), not only stimulates IgA overproduction in the gut but also results in defective IgA transportation into the gut lumen, causing a dramatic increase in serum polymeric IgA. Engagement of LTβR by LIGHT is essential for both intestinal inflammation and hyperserum IgA syndrome in our LIGHT transgenic model. Impressively, the majority of patients with inflammatory bowel disease showed increased IgA-producing cells in the gut, elevated serum IgA levels, and severe hematuria, a hallmark of IgAN. These observations indicate the critical contributions of dysregulated LIGHT expression and intestinal inflammation to the pathogenesis of IgAN. PMID:15067315

The formation of intestinal organoids in a hanging drop culture.

PubMed

Panek, Malgorzata; Grabacka, Maja; Pierzchalska, Malgorzata

2018-01-25

Recently organoids have become widely used in vitro models of many tissue and organs. These type of structures, originated from embryonic or adult mammalian intestines, are called "mini guts". They organize spontaneously when intestinal crypts or stem cells are embedded in the extracellular matrix proteins preparation scaffold (Matrigel). This approach has some disadvantages, as Matrigel is undefined (the concentrations of growth factors and other biologically active components in it may vary from batch to batch), difficult to handle and expensive. Here we show that the organoids derived from chicken embryo intestine are formed in a hanging drop without embedding, providing an attractive alternative for currently used protocols. Using this technique we obtained compact structures composed of contiguous organoids, which were generally similar to chicken organoids cultured in Matrigel in terms of morphology and expression of intestinal epithelial markers. Due to the simplicity, high reproducibility and throughput capacity of hanging drop technique our model may be applied in various studies concerning the gut biology.

3D stromal tissue equivalent affects intestinal epithelium morphogenesis in vitro.

PubMed

De Gregorio, Vincenza; Imparato, Giorgia; Urciuolo, Francesco; Netti, Paolo A

2018-04-01

Current in vitro models of human intestine commonly fail to mimic the complex intestinal functions and features required for drug development and disease research. Here, we deeply investigate the interaction existing between epithelium and the underneath stroma, and its role in the epithelium morphogenesis. We cultured human intestinal subepithelial myofibroblasts (ISEMFs) in two different 3D configurations: 3D-collagen gel equivalent (3D-CGE) and 3D cell-synthetized stromal equivalent (3D-CSSE). The 3D-CGEs were obtained by means of the traditional collagen-based cell technique and the 3D-CSSE were obtained by bottom-up tissue engineering strategy. The biophysical properties of both 3D models with regard to cell growth and composition (via histological analysis, immunofluorescence, and multiphoton imaging) were assessed. Then, human colorectal adenocarcinoma cell line (CaCo-2) was cultured on both the 3D constructs in order to produce the intestinal model. We identified higher levels of matrix-associated proteins from ISEMFs cultured in 3D-CSSE compared to 3D-CGE. Furthermore, multiphoton investigation revealed differences in the collagen network architecture in both models. At last, the more physiologically relevant stromal environment of the 3D-CSSE drove the CaCo-2 cell differentiation toward the four different type of intestinal epithelial cells (absorptive, mucus-secretory, enteroendocrine, and Paneth) phenotype and promotes, in contrast to the 3D-CGE, the production of the basement membrane. Taken together, these results highlight a fundamental role of the 3D stromal environment in addressing a correct epithelium morphogenesis as well as epithelial-stromal interface establishment. © 2017 Wiley Periodicals, Inc.

Near-Native Protein Loop Sampling Using Nonparametric Density Estimation Accommodating Sparcity

PubMed Central

Day, Ryan; Lennox, Kristin P.; Sukhanov, Paul; Dahl, David B.; Vannucci, Marina; Tsai, Jerry

2011-01-01

Unlike the core structural elements of a protein like regular secondary structure, template based modeling (TBM) has difficulty with loop regions due to their variability in sequence and structure as well as the sparse sampling from a limited number of homologous templates. We present a novel, knowledge-based method for loop sampling that leverages homologous torsion angle information to estimate a continuous joint backbone dihedral angle density at each loop position. The φ,ψ distributions are estimated via a Dirichlet process mixture of hidden Markov models (DPM-HMM). Models are quickly generated based on samples from these distributions and were enriched using an end-to-end distance filter. The performance of the DPM-HMM method was evaluated against a diverse test set in a leave-one-out approach. Candidates as low as 0.45 Å RMSD and with a worst case of 3.66 Å were produced. For the canonical loops like the immunoglobulin complementarity-determining regions (mean RMSD <2.0 Å), the DPM-HMM method performs as well or better than the best templates, demonstrating that our automated method recaptures these canonical loops without inclusion of any IgG specific terms or manual intervention. In cases with poor or few good templates (mean RMSD >7.0 Å), this sampling method produces a population of loop structures to around 3.66 Å for loops up to 17 residues. In a direct test of sampling to the Loopy algorithm, our method demonstrates the ability to sample nearer native structures for both the canonical CDRH1 and non-canonical CDRH3 loops. Lastly, in the realistic test conditions of the CASP9 experiment, successful application of DPM-HMM for 90 loops from 45 TBM targets shows the general applicability of our sampling method in loop modeling problem. These results demonstrate that our DPM-HMM produces an advantage by consistently sampling near native loop structure. The software used in this analysis is available for download at http://www.stat.tamu.edu/~dahl/software/cortorgles/. PMID:22028638

Dislocation loop models for the high temperature creep of Al-5.5 at.% Mg alloy

DOE Office of Scientific and Technical Information (OSTI.GOV)

An, S.U.; Blum, W.

1995-04-15

The Al-5.5 at.% Mg alloy is a typical class I type solution hardened material. The dislocation loop models proposed by Orlova and Cadek and by Mills et al., respectively are widely applied models in describing the high temperature creep behavior of the Al-5.5 at.% Mg alloy. These models, however, are in conflict in explaining dislocation loop theory. Orlova and Cadek suggest that in class I solution hardened alloys screw dislocations are relatively easier to migrate because they are subject to a smaller resistance in motion than edge dislocations. Consequently, the migration rate of screw dislocations is higher than that ofmore » edge dislocations. However, since dislocation loops are composed of both screw and edge components, the overall migration rate of screw dislocations are reduced by that of the edge component. Mills et al. on the contrary, used a different dislocation loop model. As the loop grows while it moves, it takes on the shape of an ellipsoid due to the unbalance in growth rate, the score segment moving much easier than the edge. Therefore, as shown in the results of the stress reduction tests, rapid elastic ({Delta} {var_epsilon}{sub el}) and anelastic contraction ({Delta} {var_epsilon}{sub an}) occur simultaneously directly after stress reduction. During the movement of the dislocation loop, the screw component hence becomes severely curved, while the edge component retains a straight line. This has been proved through dislocation structure observations by TEM.« less

N -loop running should be combined with N -loop matching

NASA Astrophysics Data System (ADS)

Braathen, Johannes; Goodsell, Mark D.; Krauss, Manuel E.; Opferkuch, Toby; Staub, Florian

2018-01-01

We investigate the high-scale behavior of Higgs sectors beyond the Standard Model, pointing out that the proper matching of the quartic couplings before applying the renormalization group equations (RGEs) is of crucial importance for reliable predictions at larger energy scales. In particular, the common practice of leading-order parameters in the RGE evolution is insufficient to make precise statements on a given model's UV behavior, typically resulting in uncertainties of many orders of magnitude. We argue that, before applying N -loop RGEs, a matching should even be performed at N -loop order in contrast to common lore. We show both analytical and numerical results where the impact is sizable for three minimal extensions of the Standard Model: a singlet extension, a second Higgs doublet and finally vector-like quarks. We highlight that the known two-loop RGEs tend to moderate the running of their one-loop counterparts, typically delaying the appearance of Landau poles. For the addition of vector-like quarks we show that the complete two-loop matching and RGE evolution hints at a stabilization of the electroweak vacuum at high energies, in contrast to results in the literature.

EXPLAINING INVERTED-TEMPERATURE LOOPS IN THE QUIET SOLAR CORONA WITH MAGNETOHYDRODYNAMIC WAVE-MODE CONVERSION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schiff, Avery J.; Cranmer, Steven R.

Coronal loops trace out bipolar, arch-like magnetic fields above the Sun’s surface. Recent measurements that combine rotational tomography, extreme-ultraviolet imaging, and potential-field extrapolation have shown the existence of large loops with inverted-temperature profiles, i.e., loops for which the apex temperature is a local minimum, not a maximum. These “down loops” appear to exist primarily in equatorial quiet regions near solar minimum. We simulate both these and the more prevalent large-scale “up loops” by modeling coronal heating as a time-steady superposition of (1) dissipation of incompressible Alfvén wave turbulence and (2) dissipation of compressive waves formed by mode conversion from themore » initial population of Alfvén waves. We found that when a large percentage (>99%) of the Alfvén waves undergo this conversion, heating is greatly concentrated at the footpoints and stable “down loops” are created. In some cases we found loops with three maxima that are also gravitationally stable. Models that agree with the tomographic temperature data exhibit higher gas pressures for “down loops” than for “up loops,” which is consistent with observations. These models also show a narrow range of Alfvén wave amplitudes: 3 to 6 km s{sup -1} at the coronal base. This is low in comparison to typical observed amplitudes of 20–30 km s{sup -1} in bright X-ray loops. However, the large-scale loops we model are believed to compose a weaker diffuse background that fills much of the volume of the corona. By constraining the physics of loops that underlie quiescent streamers, we hope to better understand the formation of the slow solar wind.« less

Development of a new physics-based internal coordinate mechanics force field and its application to protein loop modeling.

PubMed

Arnautova, Yelena A; Abagyan, Ruben A; Totrov, Maxim

2011-02-01

We report the development of internal coordinate mechanics force field (ICMFF), new force field parameterized using a combination of experimental data for crystals of small molecules and quantum mechanics calculations. The main features of ICMFF include: (a) parameterization for the dielectric constant relevant to the condensed state (ε = 2) instead of vacuum, (b) an improved description of hydrogen-bond interactions using duplicate sets of van der Waals parameters for heavy atom-hydrogen interactions, and (c) improved backbone covalent geometry and energetics achieved using novel backbone torsional potentials and inclusion of the bond angles at the C(α) atoms into the internal variable set. The performance of ICMFF was evaluated through loop modeling simulations for 4-13 residue loops. ICMFF was combined with a solvent-accessible surface area solvation model optimized using a large set of loop decoys. Conformational sampling was carried out using the biased probability Monte Carlo method. Average/median backbone root-mean-square deviations of the lowest energy conformations from the native structures were 0.25/0.21 Å for four residues loops, 0.84/0.46 Å for eight residue loops, and 1.16/0.73 Å for 12 residue loops. To our knowledge, these results are significantly better than or comparable with those reported to date for any loop modeling method that does not take crystal packing into account. Moreover, the accuracy of our method is on par with the best previously reported results obtained considering the crystal environment. We attribute this success to the high accuracy of the new ICM force field achieved by meticulous parameterization, to the optimized solvent model, and the efficiency of the search method. © 2010 Wiley-Liss, Inc.

Formation of intestinal atresias in the Fgfr2IIIb-/- mice is not associated with defects in notochord development or alterations in Shh expression.

PubMed

Reeder, Amy L; Botham, Robert A; Franco, Marta; Zaremba, Krzysztof M; Nichol, Peter F

2012-09-01

The etiology of intestinal atresia remains elusive but has been ascribed to a number of possible events including in utero vascular accidents, failure of recanalization of the intestinal lumen, and mechanical compression. Another such event that has been postulated to be a cause in atresia formation is disruption in notochord development. This hypothesis arose from clinical observations of notochord abnormalities in patients with intestinal atresias as well as abnormal notochord development observed in a pharmacologic animal model of intestinal atresia. Atresias in this model result from in utero exposure to Adriamycin, wherein notochord defects were noted in up to 80% of embryos that manifested intestinal atresias. Embryos with notochord abnormalities were observed to have ectopic expression of Sonic Hedgehog (Shh), which in turn was postulated to be causative in atresia formation. We were interested in determining whether disruptions in notochord development or Shh expression occurred in an established genetic model of intestinal atresia and used the fibroblast growth factor receptor 2IIIb homozygous mutant (Fgfr2IIIb-/-) mouse model. These embryos develop colonic atresias (100% penetrance) and duodenal atresias (42% penetrance). Wild-type and Fgfr2IIIb-/- mouse embryos were harvested at embryonic day (E) 10.5, E11.5, E12.5, and E13.5. Whole-mount in situ hybridization was performed on E10.5 embryos for Shh. Embryos at each time point were harvested and sectioned for hematoxylin-eosin staining. Sections were photographed specifically for the notochord and resulting images reconstructed in 3-D using Amira software. Colons were isolated from wild-type and Fgfr2IIIb-/- embryos at E10.5, then cultured for 48 hours in Matrigel with FGF10 in the presence or absence of exogenous Shh protein. Explants were harvested, fixed in formalin, and photographed. Fgfr2IIIb-/- mouse embryos exhibit no disruptions in Shh expression at E10.5, when the first events in atresia formation are known to occur. Three-dimensional reconstructions failed to demonstrate any anatomical disruptions in the notochord by discontinuity or excessive branching. Culture of wild-type intestines in the presence of Shh failed to induce atresia formation in either the duodenum or colon. Cultured Fgfr2IIIb-/- intestines developed atresias of the colon in either the presence or absence of Shh protein. Although disruptions in notochord development can be associated with intestinal atresia formation, in the Fgfr2IIIb-/- genetic animal model neither disruptions in notochord development nor the presence of exogenous Shh protein are causative in the formation of these defects. Copyright © 2012 Elsevier Inc. All rights reserved.

Formation of Intestinal Atresias in the Fgfr2IIIb−/− Mice is not Associated with Defects in Notochord Development or Alterations in Shh Expression

PubMed Central

Reader, Amy L.; Botham, Robert A.; Franco, Marta; Zaremba, Krzysztof M.; Nichol, Peter F.

2012-01-01

Purpose The etiology of intestinal atresia remains elusive but has been ascribed to a number of possible events including in utero vascular accidents, failure of recanalization of the intestinal lumen and mechanical compression. Another such event that has been postulated to be a cause in atresia formation is disruption in notochord development. This hypothesis arose from clinical observations of notochord abnormalities in patients with intestinal atresias as well as abnormal notochord development observed in a pharmacological animal model of intestinal atresia. Atresias in this model result from in utero exposure to Adriamycin, wherein notochord defects were noted in up to 80% of embryos that manifested intestinal atresias. Embryos with notochord abnormalities were observed to have ectopic expression of Sonic Hedgehog (Shh) which in turn was postulated to be causative in atresia formation. We were interested in determining whether disruptions in notochord development or Shh expression occurred in an established genetic model of intestinal atresia and utilized the Fibroblast Growth Factor Receptor 2IIIb homozygous mutant (Fgfr2IIIb−/−) mouse model. These embryos develop colonic atresias (100% penetrance) and duodenal atresias (42% penetrance). Methods Wild-type and Fgfr2IIIb−/− mouse embryos were harvested at E10.5, E11.5, E12.5 and E13.5. Whole mount in situ hybridization was performed on E10.5 embryos for Shh. Embryos at each time point were harvested and sectioned for H&E staining. Sections were photographed specifically for the notochord and resulting images reconstructed in 3-D using Amira software. Colons were isolated from wild-type and Fgfr2IIIb−/− embryos at E10.5, then cultured for 48 hours in matrigel with FGF10 in the presence or absence of exogenous SHH protein. Explants were harvested, fixed in formalin and photographed. Results Fgfr2IIIb−/− mouse embryos exhibit no disruptions in Shh expression at E10.5, when the first events in atresia formation are known to occur. Three-dimensional reconstructions failed to demonstrate any anatomical disruptions in the notochord by discontinuity or excessive branching. Culture of wild-type intestines in the presence of Shh failed to induce atresia formation in either the duodenum or colon. Cultured Fgfr2IIIb−/− intestines developed atresias of the colon in either the presence, or absence, of Shh protein. Conclusions Although disruptions in notochord development can be associated with intestinal atresia formation, in the Fgfr2IIIb−/− genetic animal model neither disruptions in notochord development nor the presence of exogenous Shh protein are causative in the formation of these defects. PMID:22572615

CLOSED-FIELD CORONAL HEATING DRIVEN BY WAVE TURBULENCE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Downs, Cooper; Lionello, Roberto; Mikić, Zoran

To simulate the energy balance of coronal plasmas on macroscopic scales, we often require the specification of the coronal heating mechanism in some functional form. To go beyond empirical formulations and to build a more physically motivated heating function, we investigate the wave-turbulence-driven (WTD) phenomenology for the heating of closed coronal loops. Our implementation is designed to capture the large-scale propagation, reflection, and dissipation of wave turbulence along a loop. The parameter space of this model is explored by solving the coupled WTD and hydrodynamic evolution in 1D for an idealized loop. The relevance to a range of solar conditionsmore » is also established by computing solutions for over one hundred loops extracted from a realistic 3D coronal field. Due to the implicit dependence of the WTD heating model on loop geometry and plasma properties along the loop and at the footpoints, we find that this model can significantly reduce the number of free parameters when compared to traditional empirical heating models, and still robustly describe a broad range of quiet-Sun and active region conditions. The importance of the self-reflection term in producing relatively short heating scale heights and thermal nonequilibrium cycles is also discussed.« less

Thermal stability of static coronal loops: Part 1: Effects of boundary conditions

NASA Technical Reports Server (NTRS)

Antiochos, S. K.; Shoub, E. C.; An, C. H.; Emslie, A. G.

1985-01-01

The linear stability of static coronal-loop models undergoing thermal perturbations was investigated. The effect of conditions at the loop base on the stability properties of the models was considered in detail. The question of appropriate boundary conditions at the loop base was considered and it was concluded that the most physical assumptions are that the temperature and density (or pressure) perturbations vanish there. However, if the base is taken to be sufficiently deep in the chromosphere, either several chromospheric scale heights or several coronal loop lengths in depth, then the effect of the boundary conditions on loop stability becomes negligible so that all physically acceptable conditions are equally appropriate. For example, one could as well assume that the velocity vanishes at the base. The growth rates and eigenmodes of static models in which gravity is neglected and in which the coronal heating is a relatively simple function, either constant per-unit mass or per-unit volume were calculated. It was found that all such models are unstable with a growth rate of the order of the coronal cooling time. The physical implications of these results for the solar corona and transition region are discussed.

Closed-field Coronal Heating Driven by Wave Turbulence

NASA Astrophysics Data System (ADS)

Downs, Cooper; Lionello, Roberto; Mikić, Zoran; Linker, Jon A.; Velli, Marco

2016-12-01

To simulate the energy balance of coronal plasmas on macroscopic scales, we often require the specification of the coronal heating mechanism in some functional form. To go beyond empirical formulations and to build a more physically motivated heating function, we investigate the wave-turbulence-driven (WTD) phenomenology for the heating of closed coronal loops. Our implementation is designed to capture the large-scale propagation, reflection, and dissipation of wave turbulence along a loop. The parameter space of this model is explored by solving the coupled WTD and hydrodynamic evolution in 1D for an idealized loop. The relevance to a range of solar conditions is also established by computing solutions for over one hundred loops extracted from a realistic 3D coronal field. Due to the implicit dependence of the WTD heating model on loop geometry and plasma properties along the loop and at the footpoints, we find that this model can significantly reduce the number of free parameters when compared to traditional empirical heating models, and still robustly describe a broad range of quiet-Sun and active region conditions. The importance of the self-reflection term in producing relatively short heating scale heights and thermal nonequilibrium cycles is also discussed.

Universality, twisted fans, and the Ising model. [Renormalization, two-loop calculations, scale

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dash, J.W.; Harrington, S.J.

1975-06-24

Critical exponents are evaluated for the Ising model using universality in the form of ''twisted fans'' previously introduced in Reggeon field theory. The universality is with respect to scales induced through renormalization. Exact twists are obtained at ..beta.. = 0 in one loop for D = 2,3 with ..nu.. = 0.75 and 0.60 respectively. In two loops one obtains ..nu.. approximately 1.32 and 0.68. No twists are obtained for eta, however. The results for the standard two loop calculations are also presented as functions of a scale.

Antisymmetric Wilson loops in N = 4 SYM beyond the planar limit

NASA Astrophysics Data System (ADS)

Gordon, James

2018-01-01

We study the 1/2 -BPS circular Wilson loop in the totally antisymmetric representation of the gauge group in N = 4 supersymmetric Yang-Mills. This observable is captured by a Gaussian matrix model with appropriate insertion. We compute the first 1 /N correction at leading order in 't Hooft coupling by means of the matrix model loop equations. Disagreement with the 1-loop effective action of the holographically dual D5-brane suggests the need to account for gravitational backreaction on the string theory side.

Loop-quantum-gravity vertex amplitude.

PubMed

Engle, Jonathan; Pereira, Roberto; Rovelli, Carlo

2007-10-19

Spin foam models are hoped to provide the dynamics of loop-quantum gravity. However, the most popular of these, the Barrett-Crane model, does not have the good boundary state space and there are indications that it fails to yield good low-energy n-point functions. We present an alternative dynamics that can be derived as a quantization of a Regge discretization of Euclidean general relativity, where second class constraints are imposed weakly. Its state space matches the SO(3) loop gravity one and it yields an SO(4)-covariant vertex amplitude for Euclidean loop gravity.

Current Hypothesis for the Relationship between Dietary Rice Bran Intake, the Intestinal Microbiota and Colorectal Cancer Prevention.

PubMed

So, Winnie K W; Law, Bernard M H; Law, Patrick T W; Chan, Carmen W H; Chair, Sek Ying

2016-09-15

Globally, colorectal cancer (CRC) is the third most common form of cancer. The development of effective chemopreventive strategies to reduce CRC incidence is therefore of paramount importance. Over the past decade, research has indicated the potential of rice bran, a byproduct of rice milling, in CRC chemoprevention. This was recently suggested to be partly attributable to modification in the composition of intestinal microbiota when rice bran was ingested. Indeed, previous studies have reported changes in the population size of certain bacterial species, or microbial dysbiosis, in the intestines of CRC patients and animal models. Rice bran intake was shown to reverse such changes through the manipulation of the population of health-promoting bacteria in the intestine. The present review first provides an overview of evidence on the link between microbial dysbiosis and CRC carcinogenesis and describes the molecular events associated with that link. Thereafter, there is a summary of current data on the effect of rice bran intake on the composition of intestinal microbiota in human and animal models. The article also highlights the need for further studies on the inter-relationship between rice bran intake, the composition of intestinal microbiota and CRC prevention.

Current Hypothesis for the Relationship between Dietary Rice Bran Intake, the Intestinal Microbiota and Colorectal Cancer Prevention

PubMed Central

So, Winnie K. W.; Law, Bernard M. H.; Law, Patrick T. W.; Chan, Carmen W. H.; Chair, Sek Ying

2016-01-01

Globally, colorectal cancer (CRC) is the third most common form of cancer. The development of effective chemopreventive strategies to reduce CRC incidence is therefore of paramount importance. Over the past decade, research has indicated the potential of rice bran, a byproduct of rice milling, in CRC chemoprevention. This was recently suggested to be partly attributable to modification in the composition of intestinal microbiota when rice bran was ingested. Indeed, previous studies have reported changes in the population size of certain bacterial species, or microbial dysbiosis, in the intestines of CRC patients and animal models. Rice bran intake was shown to reverse such changes through the manipulation of the population of health-promoting bacteria in the intestine. The present review first provides an overview of evidence on the link between microbial dysbiosis and CRC carcinogenesis and describes the molecular events associated with that link. Thereafter, there is a summary of current data on the effect of rice bran intake on the composition of intestinal microbiota in human and animal models. The article also highlights the need for further studies on the inter-relationship between rice bran intake, the composition of intestinal microbiota and CRC prevention. PMID:27649240

Breast Milk Enhances Growth of Enteroids: An Ex Vivo Model of Cell Proliferation.

PubMed

Lanik, Wyatt E; Xu, Lily; Luke, Cliff J; Hu, Elise Z; Agrawal, Pranjal; Liu, Victoria S; Kumar, Rajesh; Bolock, Alexa M; Ma, Congrong; Good, Misty

2018-02-15

Human small intestinal enteroids are derived from the crypts and when grown in a stem cell niche contain all of the epithelial cell types. The ability to establish human enteroid ex vivo culture systems are important to model intestinal pathophysiology and to study the particular cellular responses involved. In recent years, enteroids from mice and humans are being cultured, passaged, and banked away for future use in several laboratories across the world. This enteroid platform can be used to test the effects of various treatments and drugs and what effects are exerted on different cell types in the intestine. Here, a protocol for establishing primary stem cell-derived small intestinal enteroids derived from neonatal mice and premature human intestine is provided. Moreover, this enteroid culture system was utilized to test the effects of species-specific breast milk. Mouse breast milk can be obtained efficiently using a modified human breast pump and expressed mouse milk can then be used for further research experiments. We now demonstrate the effects of expressed mouse, human, and donor breast milk on the growth and proliferation of enteroids derived from neonatal mice or premature human small intestine.

A random-walk/giant-loop model for interphase chromosomes.

PubMed Central

Sachs, R K; van den Engh, G; Trask, B; Yokota, H; Hearst, J E

1995-01-01

Fluorescence in situ hybridization data on distances between defined genomic sequences are used to construct a quantitative model for the overall geometric structure of a human chromosome. We suggest that the large-scale geometry during the G0/G1 part of the cell cycle may consist of flexible chromatin loops, averaging approximately 3 million bp, with a random-walk backbone. A fully explicit, three-parametric polymer model of this random-walk/giant-loop structure can account well for the data. More general models consistent with the data are briefly discussed. PMID:7708711

Alternative functional in vitro models of human intestinal epithelia

PubMed Central

Kauffman, Amanda L.; Gyurdieva, Alexandra V.; Mabus, John R.; Ferguson, Chrissa; Yan, Zhengyin; Hornby, Pamela J.

2013-01-01

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 compared 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, intestinal organogenesis 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 (Pgp) 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. PMID:23847534

Alternative functional in vitro models of human intestinal epithelia.

PubMed

Kauffman, Amanda L; Gyurdieva, Alexandra V; Mabus, John R; Ferguson, Chrissa; Yan, Zhengyin; Hornby, Pamela J

2013-01-01

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 compared 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, intestinal organogenesis 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 (Pgp) 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.

A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures

DTIC Science & Technology

2016-08-01

Acronyms and Symbols ARA Applied Research Associates, Inc. ARS Acute radiation syndrome d Days DE Differential Evolution DTRA Defense Threat...04-08-2016 Technical Report A Mathematical Model of the Human Small Intestine Following Acute Radiation and Burn Exposures HDTRA1...epithelial cells to acute radiation alone. The model has been modified for improved radiation response, and an addition to the model allows for thermal injury

Numerical models of laser fusion of intestinal tissues.

PubMed

Pearce, John A

2009-01-01

Numerical models of continuous wave Tm:YAG thermal fusion in rat intestinal tissues were compared to experiment. Optical and thermal FDM models that included tissue damage based on Arrhenius kinetics were used to predict birefringence loss in collagen as the standard of comparison. The models also predicted collagen shrinkage, jellification and water loss. The inclusion of variable optical and thermal properties is essential to achieve favorable agreement between predicted and measured damage boundaries.

Blowhole colostomy for the urgent management of distal large bowel obstruction.

PubMed

Kasten, Kevin R; Midura, Emily F; Davis, Bradley R; Rafferty, Janice F; Paquette, Ian M

2014-05-01

Complete obstruction of the distal colon or rectum often presents as a surgical emergency. This study evaluated the efficacy of blowhole colostomy versus transverse loop colostomy for the emergent management of distal large intestinal obstruction. Retrospective chart review of all colostomy procedures (CPT 44320) performed for complete distal large bowel obstruction during the past 6 y in a university hospital practice was undertaken. Blowhole was compared with loop colostomy with a primary endpoint of successful colonic decompression. One hundred forty-one patients underwent colostomy creation during the study period. Of these, 61 were completed for acute obstruction of the distal colon or rectum (19 blowhole versus 42 loop colostomy). No differences between study groups were seen in age, gender, body mass index, malnutrition, American Society of Anesthesiology class, time to liquid or regular diet, 30-d or inhospital mortality, or rates of complications. Patients undergoing blowhole colostomy had significantly higher cecal diameters at diagnosis (9.14 versus 7.31 cm, P = 0.0035). Operative time was shorter in blowhole procedures (43 versus 51 min, P = 0.017). Postoperative length of stay was significantly shorter for blowhole colostomy (6 versus 8 d, P = 0.014). The primary endpoint of successful colonic decompression was met in all colostomy patients. Diverting blowhole colostomy is a safe, quick, and effective procedure for the urgent management of distal colonic obstruction associated with obstipation and massive distention. Copyright © 2014 Elsevier Inc. All rights reserved.

Acute surgical abdomen due to phytobezoar-induced ileal obstruction.

PubMed

Salemis, Nikolaos S; Panagiotopoulos, Nikolaos; Sdoukos, Nikolaos; Niakas, Evangelos

2013-01-01

Phytobezoar-induced small bowel obstruction is an uncommon clinical entity accounting for 2-4.8% of all mechanical intestinal obstructions. In addition, presentation with features of acute surgical abdomen is extremely rare, accounting for only 1% of the patients. The aim of this report is to present a very rare case of a phytobezoar-induced small bowel obstruction in a male patient who presented with acute surgical abdomen. A correct preoperative diagnosis was made based on the patient's history and characteristic imaging features on the emergency computed tomography (CT) scan. A 55-year-old man with previous gastrectomy presented with typical manifestations of acute abdomen. CT scan demonstrated dilatated small bowel loops and an intraluminal ileal mass with a mottled appearance. At exploratory laparotomy, a phytobezoar was found impacted in the terminal ileum and was removed through an enterotomy. Phytobezoar should be considered in patients with previous gastric outlet surgery who present with bowel obstruction and features of acute surgical abdomen. The presence of a well-defined intraluminal mass with a mottled gas pattern on emergency CT scan is suggestive of an intestinal phytobezoar. Copyright © 2013 Elsevier Inc. All rights reserved.

Clostridium perfringens Enterotoxin: Action, Genetics, and Translational Applications

PubMed Central

Freedman, John C.; Shrestha, Archana; McClane, Bruce A.

2016-01-01

Clostridium perfringens enterotoxin (CPE) is responsible for causing the gastrointestinal symptoms of several C. perfringens food- and nonfood-borne human gastrointestinal diseases. The enterotoxin gene (cpe) is located on either the chromosome (for most C. perfringens type A food poisoning strains) or large conjugative plasmids (for the remaining type A food poisoning and most, if not all, other CPE-producing strains). In all CPE-positive strains, the cpe gene is strongly associated with insertion sequences that may help to assist its mobilization and spread. During disease, CPE is produced when C. perfringens sporulates in the intestines, a process involving several sporulation-specific alternative sigma factors. The action of CPE starts with its binding to claudin receptors to form a small complex; those small complexes then oligomerize to create a hexameric prepore on the membrane surface. Beta hairpin loops from the CPE molecules in the prepore assemble into a beta barrel that inserts into the membrane to form an active pore that enhances calcium influx, causing cell death. This cell death results in intestinal damage that causes fluid and electrolyte loss. CPE is now being explored for translational applications including cancer therapy/diagnosis, drug delivery, and vaccination. PMID:26999202

MDL-1, a growth- and tumor-suppressor, slows aging and prevents germline hyperplasia and hypertrophy in C. elegans

PubMed Central

Riesen, Michèle; Feyst, Inna; Rattanavirotkul, Nattaphong; Ezcurra, Marina; Tullet, Jennifer M.A.; Papatheodorou, Irene; Ziehm, Matthias; Au, Catherine; Gilliat, Ann F.; Hellberg, Josephine; Thornton, Janet M.; Gems, David

2014-01-01

In C. elegans, increased lifespan in daf-2 insulin/IGF-1 receptor mutants is accompanied by up-regulation of the MDL-1 Mad basic helix-loop-helix leucine zipper transcription factor. Here we describe the role of mdl-1 in C. elegans germline proliferation and aging. The deletion allele mdl-1(tm311) shortened lifespan, and did so significantly more so in long-lived daf-2 mutants implying that mdl-1(+) contributes to effects of daf-2 on lifespan. mdl-1 mutant hermaphrodites also lay increased numbers of unfertilized oocytes. During aging, unfertilized oocytes in the uterus develop into tumors, whose development was accelerated by mdl-1(tm311). Opposite phenotypes were seen in daf-2 mutants, i.e. mdl-1 and daf-2 mutant germlines are hyperplastic and hypoplastic, respectively. Thus, MDL-1, like its mammalian orthologs, is an inhibitor of cell proliferation and growth that slows progression of an age-related pathology in C. elegans (uterine tumors). In addition, intestine-limited rescue of mdl-1 increased lifespan but not to wild type levels. Thus, mdl-1 likely acts both in the intestine and the germline to influence age-related mortality. PMID:24531613

REVIEWS OF TOPICAL PROBLEMS: Coronal magnetic loops

NASA Astrophysics Data System (ADS)

Zaitsev, Valerii V.; Stepanov, Alexander V.

2008-11-01

The goal of this review is to outline some new ideas in the physics of coronal magnetic loops, the fundamental structural elements of the atmospheres of the Sun and flaring stars, which are involved in phenomena such as stellar coronal heating, flare energy release, charged particle acceleration, and the modulation of optical, radio, and X-ray emissions. The Alfvén-Carlqvist view of a coronal loop as an equivalent electric circuit allows a good physical understanding of loop processes. Describing coronal loops as MHD-resonators explains various ways in which flaring emissions from the Sun and stars are modulated, whereas modeling them by magnetic mirror traps allows one to describe the dynamics and emission of high-energy particles. Based on these approaches, loop plasma and fast particle parameters are obtained and models for flare energy release and stellar corona heating are developed.

Digital simulation of hybrid loop operation in RFI backgrounds.

NASA Technical Reports Server (NTRS)

Ziemer, R. E.; Nelson, D. R.

1972-01-01

A digital computer model for Monte-Carlo simulation of an imperfect second-order hybrid phase-locked loop (PLL) operating in radio-frequency interference (RFI) and Gaussian noise backgrounds has been developed. Characterization of hybrid loop performance in terms of cycle slipping statistics and phase error variance, through computer simulation, indicates that the hybrid loop has desirable performance characteristics in RFI backgrounds over the conventional PLL or the costas loop.

Intestinal Translocation of Clinical Isolates of Vancomycin-Resistant Enterococcus faecalis and ESBL-Producing Escherichia coli in a Rat Model of Bacterial Colonization and Liver Ischemia/Reperfusion Injury

PubMed Central

van der Heijden, Karin M.; van der Heijden, Inneke M.; Galvao, Flavio H.; Lopes, Camila G.; Costa, Silvia F.; Abdala, Edson; D’Albuquerque, Luiz A.; Levin, Anna S.

2014-01-01

The objectives of this study were to develop a rat model of gastrointestinal colonization with vancomycin-resistant Enterococcus faecalis (VRE) and extended-spectrum beta-lactamase (ESBL)-producing E. coli and to evaluate intestinal translocation to blood and tissues after total and partial hepatic ischemia. Methods - We developed a model of rat colonization with VRE and ESBL-E coli. Then we studied four groups of colonized rats: Group I (with hepatic pedicle occlusion causing complete liver ischemia and intestinal stasis); Group II (with partial liver ischemia without intestinal stasis); Group III (surgical manipulation without hepatic ischemia or intestinal stasis); Group IV (anesthetized without surgical manipulation). After sacrifice, portal and systemic blood, large intestine, small intestine, spleen, liver, lungs, and cervical and mesenteric lymph nodes were cultured. Endotoxin concentrations in portal and systemic blood were determined. Results – The best inocula were: VRE: 2.4×1010 cfu and ESBL-E. coli: 1.12×1010 cfu. The best results occurred 24 hours after inoculation and antibiotic doses of 750 µg/mL of water for vancomycin and 2.1 mg/mL for ceftriaxone. There was a significantly higher proportion of positive cultures for ESBL-E. coli in the lungs in Groups I, II and III when compared with Group IV (67%; 60%; 75% and 13%, respectively; p:0.04). VRE growth was more frequent in mesenteric lymph nodes for Groups I (67%) and III (38%) than for Groups II (13%) and IV (none) (p:0.002). LPS was significantly higher in systemic blood of Group I (9.761±13.804 EU/mL−p:0.01). No differences for endotoxin occurred in portal blood. Conclusion –We developed a model of rats colonized with resistant bacteria useful to study intestinal translocation. Translocation occurred in surgical procedures with and without hepatic ischemia-reperfusion and probably occurred via the bloodstream. Translocation was probably lymphatic in the ischemia-reperfusion groups. Systemic blood endotoxin levels were higher in the group with complete hepatic ischemia. PMID:25255079

Numerical simulations of loops heated to solar flare temperatures. III - Asymmetrical heating

NASA Technical Reports Server (NTRS)

Cheng, C.-C.; Doschek, G. A.; Karpen, J. T.

1984-01-01

A numerical model is defined for asymmetric full solar flare loop heating and comparisons are made with observational data. The Dynamic Flux Tube Model is used to describe the heating process in terms of one-dimensional, two fluid conservation equations of mass, energy and momentum. An adaptive grid allows for the downward movement of the transition region caused by an advancing conduction front. A loop 20,000 km long is considered, along with a flare heating system and the hydrodynamic evolution of the loop. The model was applied to generating line profiles and spatial X-ray and UV line distributions, which were compared with SMM, P78-1 and Hintori data for Fe, Ca and Mg spectra. Little agreement was obtained, and it is suggested that flares be treated as multi-loop phenomena. Finally, it is concluded that chromospheric evaporation is not an effective mechanism for generating the soft X-ray bursts associated with flares.

Modelling a solar flare from X-ray, UV, and radio observations

NASA Astrophysics Data System (ADS)

Chiuderi Drago, F.; Monsignori Fossi, B. C.

1991-03-01

A slowly evolving, flaring loop was observed by the UVSP, XRP, and HXIS instruments onboard SMM on June 10, 1980. Simultaneous radio observations from Toyokawa (Japan) are also available. The SMM instruments have an angular resolution ranging from 3 to 30 arcsec by which the loop structure may be determined. It appears that these observations cannot be accounted for by a single loop model even assuming a variable temperature and pressure. The additional presence of a hot and tenuous isothermal plasma is necessary to explain the harder emission (HXIS). X-ray and UV data are used to fit the differential emission measure as a function of temperature and a model of the flare is deduced, which is then checked against radio data. An estimate of the heating function along the loop and of the total energy content of the loop is also given.

Agent-based model of fecal microbial transplant effect on bile acid metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection.

PubMed

Peer, Xavier; An, Gary

2014-10-01

Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the C. difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, fecal microbial transplant. The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with the goal of personalized medicine.

Agent-based model of Fecal Microbial Transplant effect on Bile Acid Metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection

PubMed Central

Peer, Xavier; An, Gary

2014-01-01

Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the Clostridium difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, Fecal Microbial Transplant (FMT). The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with the goal of personalized medicine. PMID:25168489

Contrasting Ecological Processes and Functional Compositions Between Intestinal Bacterial Community in Healthy and Diseased Shrimp.

PubMed

Zhu, Jinyong; Dai, Wenfang; Qiu, Qiongfen; Dong, Chunming; Zhang, Jinjie; Xiong, Jinbo

2016-11-01

Intestinal bacterial communities play a pivotal role in promoting host health; therefore, the disruption of intestinal bacterial homeostasis could result in disease. However, the effect of the occurrences of disease on intestinal bacterial community assembly remains unclear. To address this gap, we compared the multifaceted ecological differences in maintaining intestinal bacterial community assembly between healthy and diseased shrimps. The neutral model analysis shows that the relative importance of neutral processes decreases when disease occurs. This pattern is further corroborated by the ecosphere null model, revealing that the bacterial community assembly of diseased samples is dominated by stochastic processes. In addition, the occurrence of shrimp disease reduces the complexity and cooperative activities of species-to-species interactions. The keystone taxa affiliated with Alphaproteobacteria and Actinobacteria in healthy shrimp gut shift to Gammaproteobacteria species in diseased shrimp. Changes in intestinal bacterial communities significantly alter biological functions in shrimp. Within a given metabolic pathway, the pattern of enrichment or decrease between healthy and deceased shrimp is correlated with its functional effects. We propose that stressed shrimp are more prone to invasion by alien strains (evidenced by more stochastic assembly and higher migration rate in diseased shrimp), which, in turn, disrupts the cooperative activity among resident species. These findings greatly aid our understanding of the underlying mechanisms that govern shrimp intestinal community assembly between health statuses.

Anti-inflammatory and antioxidant effects of infliximab in a rat model of intestinal ischemia/reperfusion injury.

PubMed

Pergel, Ahmet; Kanter, Mehmet; Yucel, Ahmet Fikret; Aydin, Ibrahim; Erboga, Mustafa; Guzel, Ahmet

2012-11-01

The aim of this study was to investigate the possible protective effects of infliximab on oxidative stress, cell proliferation and apoptosis in the rat intestinal mucosa after ischemia/reperfusion (I/R). A total of 30 male Wistar albino rats were divided into three groups: sham, I/R and I/R+ infliximab; each group comprised 10 animals. Sham group animals underwent laparotomy without I/R injury. I/R groups after undergoing laparotomy, 1 hour of superior mesenteric artery ligation occurred, which was followed by 1 hour of reperfusion. In the infliximab group, 3 days before I/R, infliximab (3 mg/kg) was administered intravenously. All animals were killed at the end of reperfusion and intestinal tissues samples were obtained for biochemical and histopathological investigation in all groups. To date, no biochemical and histopathological changes have been reported regarding intestinal I/R injury in rats due to infliximab treatment. Infliximab treatment significantly decreased the elevated tissue malondialdehyde levels and increased reduced superoxide dismutase and glutathione peroxidase enzyme activities in intestinal tissues samples. I/R caused severe histopathological injury including mucosal erosions, inflammatory cell infiltration, necrosis, hemorrhage, and villous congestion. Infliximab treatment significantly attenuated the severity of intestinal I/R injury, inhibiting I/R-induced apoptosis, and cell proliferation. Because of its anti-inflammatory and antioxidant effects, infliximab pretreatment may have protective effects on the experimental intestinal I/R model of rats.

In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury

PubMed Central

Rannou, Emilie; François, Agnès; Toullec, Aurore; Guipaud, Olivier; Buard, Valérie; Tarlet, Georges; Mintet, Elodie; Jaillet, Cyprien; Iruela-Arispe, Maria Luisa; Benderitter, Marc; Sabourin, Jean-Christophe; Milliat, Fabien

2015-01-01

The pathophysiological mechanism involved in side effects of radiation therapy, and especially the role of the endothelium remains unclear. Previous results showed that plasminogen activator inhibitor-type 1 (PAI-1) contributes to radiation-induced intestinal injury and suggested that this role could be driven by an endothelium-dependent mechanism. We investigated whether endothelial-specific PAI-1 deletion could affect radiation-induced intestinal injury. We created a mouse model with a specific deletion of PAI-1 in the endothelium (PAI-1KOendo) by a Cre-LoxP system. In a model of radiation enteropathy, survival and intestinal radiation injury were followed as well as intestinal gene transcriptional profile and inflammatory cells intestinal infiltration. Irradiated PAI-1KOendo mice exhibited increased survival, reduced acute enteritis severity and attenuated late fibrosis compared with irradiated PAI-1flx/flx mice. Double E-cadherin/TUNEL labeling confirmed a reduced epithelial cell apoptosis in irradiated PAI-1KOendo. High-throughput gene expression combined with bioinformatic analyses revealed a putative involvement of macrophages. We observed a decrease in CD68+cells in irradiated intestinal tissues from PAI-1KOendo mice as well as modifications associated with M1/M2 polarization. This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis. PMID:26510580

Characteristics of locomotion efficiency of an expanding-extending robotic endoscope in the intestinal environment.

PubMed

He, Shu; Yan, Guozheng; Wang, Zhiwu; Gao, Jinyang; Yang, Kai

2015-07-01

Robotic endoscopes with locomotion ability are among the most promising alternatives to traditional endoscopes; the locomotion ability is an important factor when evaluating the performance of the robot. This article describes the research on the characteristics of an expanding-extending robotic endoscope's locomotion efficiency in real intestine and explores an approach to improve the locomotion ability in this environment. In the article, the robot's locomotion efficiency was first calculated according to its gait in the gut, and the reasons for step losses were analyzed. Next, dynamical models of the robot and the intestine were built to calculate the step losses caused by failed anchoring and intestinal compression/extension. Based on the models and the calculation results, methods for reducing step losses were proposed. Finally, a series of ex vivo experiments were carried out, and the actual locomotion efficiency of the robot was analyzed on the basis of the theoretical models. In the experiment, on a level platform, the locomotion efficiency of the robot varied between 34.2% and 63.7%; the speed of the robot varied between 0.62 and 1.29 mm/s. The robot's efficiency when climbing a sloping intestine was also tested and analyzed. The proposed theoretical models and experimental results provide a good reference for improving the design of robotic endoscopy. © IMechE 2015.

On the physical Hilbert space of loop quantum cosmology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noui, Karim; Perez, Alejandro; Vandersloot, Kevin

2005-02-15

In this paper we present a model of Riemannian loop quantum cosmology with a self-adjoint quantum scalar constraint. The physical Hilbert space is constructed using refined algebraic quantization. When matter is included in the form of a cosmological constant, the model is exactly solvable and we show explicitly that the physical Hilbert space is separable, consisting of a single physical state. We extend the model to the Lorentzian sector and discuss important implications for standard loop quantum cosmology.

Hydrogen maser frequency standard computer model for automatic cavity tuning servo simulations

NASA Technical Reports Server (NTRS)

Potter, P. D.; Finnie, C.

1978-01-01

A computer model of the JPL hydrogen maser frequency standard was developed. This model allows frequency stability data to be generated, as a function of various maser parameters, many orders of magnitude faster than these data can be obtained by experimental test. In particular, the maser performance as a function of the various automatic tuning servo parameters may be readily determined. Areas of discussion include noise sources, first-order autotuner loop, second-order autotuner loop, and a comparison of the loops.

Thermal Vacuum Test of GLAS Propylene Loop Heat Pipe Development Model

NASA Technical Reports Server (NTRS)

Baker, Charles; Butler, Dan; Ku, Jentung; Kaya, Tarik; Nikitkin, Michael

2000-01-01

This paper presents viewgraphs on Thermal Vacuum Tests of the GLAS (Geoscience Laser Altimeter System) Propylene Loop Heat Pipe Development Model. The topics include: 1) Flight LHP System (Laser); 2) Test Design and Objectives; 3) DM (Development Model) LHP (Loop Heat Pipe) Test Design; 4) Starter Heater and Coupling Blocks; 5) CC Control Heaters and PRT; 6) Heater Plates (Shown in Reflux Mode); 7) Startup Tests; 8) CC Control Heater Power Tests for CC Temperature Control; and 9) Control Temperature Stability.

Hepatic and intestinal glucuronidation of mono(2-ethylhexyl) phthalate, an active metabolite of di(2-ethylhexyl) phthalate, in humans, dogs, rats, and mice: an in vitro analysis using microsomal fractions.

PubMed

Hanioka, Nobumitsu; Isobe, Takashi; Kinashi, Yu; Tanaka-Kagawa, Toshiko; Jinno, Hideto

2016-07-01

Mono(2-ethylhexyl) phthalate (MEHP) is an active metabolite of di(2-ethylhexyl) phthalate (DEHP) and has endocrine-disrupting effects. MEHP is metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in mammals. In the present study, the hepatic and intestinal glucuronidation of MEHP in humans, dogs, rats, and mice was examined in an in vitro system using microsomal fractions. The kinetics of MEHP glucuronidation by liver microsomes followed the Michaelis-Menten model for humans and dogs, and the biphasic model for rats and mice. The K m and V max values of human liver microsomes were 110 µM and 5.8 nmol/min/mg protein, respectively. The kinetics of intestinal microsomes followed the biphasic model for humans, dogs, and mice, and the Michaelis-Menten model for rats. The K m and V max values of human intestinal microsomes were 5.6 µM and 0.40 nmol/min/mg protein, respectively, for the high-affinity phase, and 430 µM and 0.70 nmol/min/mg protein, respectively, for the low-affinity phase. The relative levels of V max estimated by Eadie-Hofstee plots were dogs (2.0) > mice (1.4) > rats (1.0) ≈ humans (1.0) for liver microsomes, and mice (8.5) > dogs (4.1) > rats (3.1) > humans (1.0) for intestinal microsomes. The percentages of the V max values of intestinal microsomes to liver microsomes were mice (120 %) > rats (57 %) > dogs (39 %) > humans (19 %). These results suggest that the metabolic abilities of UGT enzymes expressed in the liver and intestine toward MEHP markedly differed among species, and imply that these species differences are strongly associated with the toxicity of DEHP.

Radiofrequency-induced small bowel thermofusion: an ex vivo study of intestinal seal adequacy using mechanical and imaging modalities.

PubMed

Arya, Shobhit; Hadjievangelou, Nancy; Lei, Su; Kudo, Hiromi; Goldin, Robert D; Darzi, Ara W; Elson, Daniel S; Hanna, George B

2013-09-01

Bipolar radiofrequency (RF) induced tissue fusion is believed to have the potential to seal and anastomose intestinal tissue thereby providing an alternative to current techniques which are associated with technical and functional complications. This study examines the mechanical and cellular effects of RF energy and varying compressive pressures when applied to create ex vivo intestinal seals. A total of 299 mucosa-to-mucosa fusions were formed on ex vivo porcine small bowel segments using a prototype bipolar RF device powered by a closed-loop, feedback-controlled RF generator. Compressive pressures were increased at 0.05 MPa intervals from 0.00 to 0.49 MPa and RF energy was applied for a set time period to achieve bowel tissue fusion. Seal strength was subsequently assessed using burst pressure and tensile strength testing, whilst morphological changes were determined through light microscopy. To further identify the subcellular tissue changes that occur as a result of RF energy application, the collagen matrix in the fused area of a single bowel segment sealed at an optimal pressure was examined using transmission electron microscopy (TEM). An optimal applied compressive pressure range was observed between 0.10 and 0.25 MPa. Light microscopy demonstrated a step change between fused and unfused tissues but was ineffective in distinguishing between pressure levels once tissues were sealed. Non uniform collagen damage was observed in the sealed tissue area using TEM, with some areas showing complete collagen denaturation and others showing none, despite the seal being complete. This finding has not been described previously in RF-fused tissue and may have implications for in vivo healing. This study shows that both bipolar RF energy and optimal compressive pressures are needed to create strong intestinal seals. This finding suggests that RF fusion technology can be effectively applied for bowel sealing and may lead to the development of novel anastomosis tools.