Scintigraphic measurement of regional gut transit in idiopathic constipation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stivland, T.; Camilleri, M.; Vassallo, M.
1991-07-01
In this study, total gut transit and regional colonic transit in patients with idiopathic constipation were measured scintigraphically. Eight patients with severe constipation were studied, none of whom had evidence of abnormal function of the pelvic floor. 99mTc-radiolabeled Amberlite resin particles with a mixed meal were used to assess gastric emptying and small bowel transit; similar particles labeled with 111In were ingested in a coated capsule that dispersed in the ileocecal region. These were used to quantify colonic transit. Five healthy volunteers were also studied. Two patients showed delayed gastric emptying and two had slow small bowel transit. Seven ofmore » the eight patients had slow colonic transit. In five, delay affected the whole colon (pancolonic inertia); in two, transit in the ascending and transverse colon was normal, but solids moved through the left colon slowly. Mean colonic transit was also measured using radiopaque markers; this technique identified the patients with slow transit, as shown by measurements of overall colonic transit by simultaneous scintigraphy. However, estimated transit through the ascending and transverse colons was considerably shorter by the radiopaque marker technique. In conclusion, idiopathic constipation is characterized by either exaggerated reservoir functions of the ascending and transverse colons and/or impairment of propulsive function in the descending colon. Particle size may influence the result of regional colonic transit tests. Transit delays in other parts of the gut suggest that, in some patients, the condition may be a more generalized motor dysfunction.« less
Quantitative measurement of feline colonic transit
DOE Office of Scientific and Technical Information (OSTI.GOV)
Krevsky, B.; Somers, M.B.; Maurer, A.H.
1988-10-01
Colonic transit scintigraphy, a method for quantitatively evaluating the movement of the fecal stream in vivo, was employed to evaluate colonic transit in the cat. Scintigraphy was performed in duplicate in five cats and repeated four times in one cat. After instillation of an 111In marker into the cecum through a surgically implanted silicone cecostomy tube, colonic movement of the instillate was quantitated for 24 h using gamma scintigraphy. Antegrade and retrograde motion of radionuclide was observed. The cecum and ascending colon emptied rapidly, with a half-emptying time of 1.68 +/- 0.56 h (mean +/- SE). After 24 h, 25.1more » +/- 5.2% of the activity remained in the transverse colon. The progression of the geometric center was initially rapid, followed later by a delayed phase. Geometric center reproducibility was found to be high when analyzed using simple linear regression (slope = 0.92; r = 0.73; P less than 0.01). Atropine (0.1 mg/kg im) was found to delay cecum and ascending colon emptying and delay progression of the geometric center. These results demonstrate both 1) the ability of colonic transit scintigraphy to detect changes in transit induced by pharmacological manipulation and 2) the fact that muscarinic blockade inhibits antegrade transit of the fecal stream. We conclude that feline colonic transit may be studied in a quantitative and reproducible manner with colonic transit scintigraphy.« less
Hasler, W. L.; May, K. P.; Wilson, L. A.; Van Natta, M.; Parkman, H. P.; Pasricha, P. J.; Koch, K. L.; Abell, T. L.; McCallum, R. W.; Nguyen, L. A.; Snape, W. J.; Sarosiek, I.; Clarke, J. O.; Farrugia, G.; Calles-Escandon, J.; Grover, M.; Tonascia, J.; Lee, L. A.; Miriel, L.; Hamilton, F. A.
2018-01-01
Background Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, etiology, and symptoms in patients undergoing gastric emptying testing. Methods A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms. Key Results Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04). Conclusions & Inferences Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities. PMID:28872760
Patterns of colonic transit in chronic idiopathic constipation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Krevsky, B.; Maurer, A.H.; Fisher, R.S.
1989-02-01
Rectosigmoid motility, anal manometry, and radiopaque marker studies have suggested the presence of several patterns of altered colonic transit in patients with chronic idiopathic constipation. Colonic transit scintigraphy was used to evaluate 23 constipated patients. After oral passage of a tube to the cecum, 50 microCi of /sup 111/In-diethylenetriaminepentaaceticacid (/sup 111/In-DTPA) were instilled, and abdominal images were obtained for 48 h with a gamma camera. The 95% confidence limit for the geometric center in normals at 24 h was used as a criterion to differentiate patients with colonic inertia from those with functional rectosigmoid obstruction. In patients with functional rectosigmoidmore » obstruction, colonic transit was essentially normal. In colonic inertia, transit was delayed in the cecum and ascending colon, hepatic flexure, and transverse colon. These two distinct patterns of colonic transit may have different pathogenetic and therapeutic implications.« less
MacDonald, A; Baxter, J N; Bessent, R G; Gray, H W; Finlay, I G
1997-08-01
Idiopathic slow transit constipation (ISTC) is considered to be a heterogeneous condition in which patients have varying sites and degrees of delayed gastrointestinal transit. The majority of patients have pancolonic disease, and colectomy with ileocolorectal anastomosis has been the mainstay of surgical treatment. Severe constipation following traumatic childbirth is now being recognized and this subgroup of patients may have delayed transit confined to the rectosigmoid colon. In theory, proximal transit in these patients should be normal. Gastric emptying was studied in patients with constipation following childbirth or ISTC and in controls. After an overnight fast, both patients and controls received breakfast, which consisted of cornflakes, sugar and milk. The liquid marker 111In-labelled di-ethylene tri-amine penta-acetic acid (DTPA) was added to the milk. A solid marker, 99mTc-labelled colloid, was impregnated on to paper and sealed with cellulose. The t1/2 for gastric emptying was calculated. Liquid phase emptying was normal in both constipation following childbirth and ISTC. Solid phase emptying was delayed significantly in ISTC compared with that in patients with constipation following childbirth and controls. In addition, half the patients with ISTC had delayed transit through the small bowel and proximal colon. Small bowel and colonic transit were normal in patients with constipation following childbirth. Patients with constipation following childbirth represent a distinct subgroup with normal proximal gastrointestinal function. Gastric emptying studies may be helpful in selecting patients for surgical management of severe constipation.
Pilot study of pyridostigmine in constipated patients with autonomic neuropathy.
Bharucha, Adil E; Low, Phillip A; Camilleri, Michael; Burton, Duane; Gehrking, Tonette L; Zinsmeister, Alan R
2008-08-01
The effects of cholinesterase inhibitors, which increase colonic motility in health, on chronic constipation are unknown. Our aims were to evaluate the efficacy of cholinesterase inhibitors for dysautonomia and chronic constipation and to assess whether acute effects could predict the long term response. In this single-blind study, 10 patients with autonomic neuropathy and constipation were treated with placebo (2 weeks), followed by an escalating dose of pyridostigmine to the maximum tolerated dose (i.e., 180-540 mg daily) for 6 weeks. Symptoms and gastrointestinal transit were assessed at 2 and 8 weeks. The acute effects of neostigmine on colonic transit and motility were also assessed. At baseline, 4, 6, and 3 patients had delayed gastric, small intestinal, and colonic transit respectively. Pyridostigmine was well tolerated in most patients, improved symptoms in 4 patients, and accelerated the geometric center for colonic transit at 24 h by > or =0.7 unit in 3 patients. The effects of i.v. neostigmine on colonic transit and compliance predicted (P < 0.05) the effects of pyridostigmine on colonic transit. Pyridostigmine improves colonic transit and symptoms in some patients with autonomic neuropathy and constipation. The motor response to neostigmine predicted the response to oral pyridostigmine.
The Wireless Motility Capsule: a One-Stop Shop for the Evaluation of GI Motility Disorders.
Saad, Richard J
2016-03-01
The wireless motility and pH capsule (WMC) provides an office-based test to simultaneously assess both regional and whole gut transit. Ingestion of this non-digestible capsule capable of measuring temperature, pH, and the pressure of its immediate surroundings allows for the measurement of gastric, small bowel, and colonic transit times in an ambulatory setting. Approved by the US Food and Drug Administration for the evaluation of suspected conditions of delayed gastric emptying and the evaluation of colonic transit in chronic idiopathic constipation, WMC should be considered in suspected gastrointestinal motility disorders as it provides a single study capable of simultaneously assessing for regional, multiregional, or generalized motility disorders. Specific indications for testing with the WMC should include the evaluation of suspect cases of gastroparesis, small bowel dysmotility, and slow transit constipation, as well as symptom syndromes suggestive of a multiregional or generalized gastrointestinal transit delay.
The Effect of DA-9701 in Opioid-induced Bowel Dysfunction of Guinea Pig.
Hussain, Zahid; Rhee, Kwang Won; Lee, Young Ju; Park, Hyojin
2016-07-30
Opioid induced bowel dysfunction (OIBD) is associated with decreased gastrointestinal (GI) propulsive activity due to intake of opioid analgesics. DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber has promising effects on GI motor function. Therefore, we aim to evaluate the prokinetic effects of DA-9701 in an OIBD model of guinea pig. The ileal and distal colon muscle contraction in presence of different doses of DA-9701, morphine, and combination (morphine + DA-9701) was measured by tissue bath study. The prokinetic effect of DA-9701 was assessed by charcoal transit and fecal pellet output assay in an OIBD model of guinea pig. DA-9701 significantly increased the amplitude and area under the curve of ileal muscle contraction, while there was insignificant effect on the distal colon compared to the control. The maximal amplitude of ileal muscle contraction was acquired at a concentration of 10 μg/mL of DA-9701. In contrast, morphine significantly decreased the amplitude of ileal and distal colon muscle contraction compared to the control. Morphine delayed both upper (P < 0.01) and lower (P < 0.05) GI transit, and delayed GI transit was restored by the administration of DA-9701. Morphine induced reduction of contractility was significantly ameliorated by addition of DA-9701 in both ileal and distal colon muscles. DA-9701 significantly increased the amplitude of contraction of the ileal muscle, however the distal colon muscle contraction was insignificant. Additionally, it restored delayed upper and lower GI transit in an OIBD model of guinea pig, and it might prove to be a useful candidate drug in a clinical trial for OIBD.
Pilot study of pyridostigmine in constipated patients with autonomic neuropathy
Bharucha, Adil E.; Camilleri, Michael; Burton, Duane; Low, Phillip A.; Gehrking, Tonette L.; Zinsmeister, Alan R.
2008-01-01
Background The effects of cholinesterase inhibitors, which increase colonic motility in health, on chronic constipation are unknown. Our aims were to evaluate the efficacy of cholinesterase inhibitors for dysautonomia and chronic constipation and to assess whether acute effects could predict the long term response. Methods In this single-blind study, 10 patients with autonomic neuropathy and constipation were treated with placebo (2 weeks), followed by an escalating dose of pyridostigmine to the maximum tolerated dose (i.e., 180–540 mg daily) for 6 weeks. Symptoms and gastrointestinal transit were assessed at 2 and 8 weeks. The acute effects of neostigmine on colonic transit and motility were also assessed. Results At baseline, 4, 6, and 3 patients had delayed gastric, small intestinal, and colonic transit respectively. Pyridostigmine was well tolerated in most patients, improved symptoms in 4 patients, and accelerated the geometric center for colonic transit at 24 h by ≥0.7 unit in 3 patients. The effects of i.v. neostigmine on colonic transit and compliance predicted (P < 0.05) the effects of pyridostigmine on colonic transit. Conclusions Pyridostigmine improves colonic transit and symptoms in some patients with autonomic neuropathy and constipation. The motor response to neostigmine predicted the response to oral pyridostigmine. PMID:18622640
Yu, Ting; Qian, Dong; Zheng, Yongping; Jiang, Ya; Wu, Ping; Lin, Lin
2016-01-01
Abstract The physiological mechanism of functional constipation (FC) includes defecatory disorders and delayed colon transit. About 18% to 68% constipated patients may have rectal hyposensitivity (RH). We performed this study to investigate the association between RH and functional defecatory disorder (FDD) as well as that between RH and delayed colon transit in FC patients. A total of 218 FC patients were enrolled. The constipation severity instrument (CSI) was used to assess constipation symptoms. High-resolution anorectal manometry (HR-ARM), defecography, balloon expulsion tests, and colon transit studies were performed for each patient. RH was defined as 1 or more sensory threshold pressures raised beyond the normal range based on HR-ARM. We investigated the association between RH and constipation symptoms, and the occurrence of FDD and delayed CTT. Ninety FDD patients completed the initial phase of biofeedback treatment (BFT). We investigated the association between RH and the effect of BFT. Totally 122 (56.0%) patients had RH. The total CSI (49.82 ± 1.09 vs 41.25 ± 1.55, P = 0.023) and obstructive defecation subscale scores (23.19 ± 0.69 vs 17.07 ± 0.90, P < 0.001) were significantly higher in RH than in non-RH patients. No significant difference was observed in slow transit symptoms (21.77 ± 0.72 vs 19.90 ± 0.85, P = 0.121) or abdominal pain (6.85 ± 2.61 vs 5.00 ± 1.04, P = 0.380). The frequency of prolonged CTT was not significantly different between RH and non-RH groups (54.1% vs 58.3%, P = 0.403). RH patients rated more occurrence of FDD (72.1% vs 53.1%, P = 0.014) and dysynergic defecation (79.8% vs 50.2%, P = 0.004) than non-RH patients, whereas no differences were seen for inadequate defecatory propulsion (59.2% vs 55.0%, P = 0.589). After BFT, the proportion of “no effect” was significantly higher in the RH group than in the non-RH group (22.4% vs 9.4%, P = 0.010). RH is associated with obstructive defecation symptoms and the occurrence of FDD. Further studies are needed to detect the mechanism of RH's effect on BFT and FC. PMID:27175697
Yu, Ting; Qian, Dong; Zheng, Yongping; Jiang, Ya; Wu, Ping; Lin, Lin
2016-05-01
The physiological mechanism of functional constipation (FC) includes defecatory disorders and delayed colon transit. About 18% to 68% constipated patients may have rectal hyposensitivity (RH). We performed this study to investigate the association between RH and functional defecatory disorder (FDD) as well as that between RH and delayed colon transit in FC patients.A total of 218 FC patients were enrolled. The constipation severity instrument (CSI) was used to assess constipation symptoms. High-resolution anorectal manometry (HR-ARM), defecography, balloon expulsion tests, and colon transit studies were performed for each patient. RH was defined as 1 or more sensory threshold pressures raised beyond the normal range based on HR-ARM. We investigated the association between RH and constipation symptoms, and the occurrence of FDD and delayed CTT. Ninety FDD patients completed the initial phase of biofeedback treatment (BFT). We investigated the association between RH and the effect of BFT.Totally 122 (56.0%) patients had RH. The total CSI (49.82 ± 1.09 vs 41.25 ± 1.55, P = 0.023) and obstructive defecation subscale scores (23.19 ± 0.69 vs 17.07 ± 0.90, P < 0.001) were significantly higher in RH than in non-RH patients. No significant difference was observed in slow transit symptoms (21.77 ± 0.72 vs 19.90 ± 0.85, P = 0.121) or abdominal pain (6.85 ± 2.61 vs 5.00 ± 1.04, P = 0.380). The frequency of prolonged CTT was not significantly different between RH and non-RH groups (54.1% vs 58.3%, P = 0.403). RH patients rated more occurrence of FDD (72.1% vs 53.1%, P = 0.014) and dysynergic defecation (79.8% vs 50.2%, P = 0.004) than non-RH patients, whereas no differences were seen for inadequate defecatory propulsion (59.2% vs 55.0%, P = 0.589). After BFT, the proportion of "no effect" was significantly higher in the RH group than in the non-RH group (22.4% vs 9.4%, P = 0.010).RH is associated with obstructive defecation symptoms and the occurrence of FDD. Further studies are needed to detect the mechanism of RH's effect on BFT and FC.
Rao, S S C; Coss-Adame, E; Valestin, J; Mysore, K
2012-01-01
There is scarce information regarding assessment of constipation in older subjects. We examined regional and whole-gut transit time (WGTT) with wireless motility capsule (WMC) and compared this with radioopaque markers (ROM) transit. 39 constipated and 11 healthy older subjects (≥ 65 years) ingested a ROM capsule and WMC, wore a data receiver and kept stool diaries for 5 days. WMC recordings were analyzed for colonic transit time (CTT), WGTT and gastric emptying time (GET). Radiographs obtained on day 5 assessed ROM transit. Results for each device were compared. The CTT (p = <0.0001), WGTT (p = <0.001) and GET (p = <0.04) as measured by WMC were all slower in constipated subjects compared to healthy subjects. ROM colonic transit was also slower (p = <0.007) in constipated compared to healthy subjects. The diagnostic utility for identifying subjects with constipation as assessed by receiver operating characteristics were similar; 0.85 (WMC) versus 0.73 (ROM). Device agreement for slow colonic transit was 88% with good correlation between WMC and ROM (CTT r=0.718, p=0.0001, WGTT r=0.693, p=0.0001). Slow transit constipation was identified in 28% with ROM and 32% with WMC. No adverse events were recorded. WMC is a safe and useful device that provides objective diagnosis of delayed colonic and whole gut transit in older constipated adults. It is a radiation-free, physiologic and ambulatory technique that provides additional diagnostic information than ROM. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Effect of Itopride Hydrochloride on the Ileal and Colonic Motility in Guinea Pig In Vitro
Lim, Hyun Chul; Kim, Young Gyun; Lim, Jung Hyun; Kim, Hee Sun
2008-01-01
Purpose Itopride hydrochloride (itopride) inhibits acetylcholinesterase (AChE) and antagonizes dopamine D2 receptor, and has been used as a gastroprokinetic agent. However, its prokinetic effect on the small bowel or colon has not yet been thoroughly investigated. The aim of this study was to investigate the effects of itopride on motor functions of the ileum and colon in guinea pigs. Materials and Methods The distal ileum was excised and the activity of peristaltic contraction was determined by measuring the amplitude and propagation velocity of peristaltic contraction. The distal colon was removed and connected to the chamber containing Krebs-Henseleit solution (K-H solution). Artificial fecal matter was inserted into the oral side of the lumen, and moved toward the anal side by intraluminal perfusion via peristaltic pump. Colonic transit times were measured by the time required for the artificial feces to move a total length of 10 cm with 2-cm intervals. Results In the ileum, itopride accelerated peristaltic velocity at higher dosage (10-10-10-6 M) whereas neostigmine accelerated it only with a lower dosage (10-10-10-9 M). Dopamine (10-8 M) decelerated the velocity that was recovered by itopride infusion. Itopride and neostigmine significantly shortened colonic transit at a higher dosage (10-10-10-6 M). Dopamine (10-8 M) delayed colonic transit time that was also recovered after infusion of itopride. Conclusion Itopride has prokinetic effects on both the ileum and colon, which are regulated through inhibitory effects on AChE and antagonistic effects on dopamine D2 receptor. PMID:18581598
Effect of itopride hydrochloride on the ileal and colonic motility in guinea pig in vitro.
Lim, Hyun Chul; Kim, Young Gyun; Lim, Jung Hyun; Kim, Hee Sun; Park, Hyojin
2008-06-30
Itopride hydrochloride (itopride) inhibits acetylcholinesterase (AChE) and antagonizes dopamine D(2) receptor, and has been used as a gastroprokinetic agent. However, its prokinetic effect on the small bowel or colon has not yet been thoroughly investigated. The aim of this study was to investigate the effects of itopride on motor functions of the ileum and colon in guinea pigs. The distal ileum was excised and the activity of peristaltic contraction was determined by measuring the amplitude and propagation velocity of peristaltic contraction. The distal colon was removed and connected to the chamber containing Krebs-Henseleit solution (K-H solution). Artificial fecal matter was inserted into the oral side of the lumen, and moved toward the anal side by intraluminal perfusion via peristaltic pump. Colonic transit times were measured by the time required for the artificial feces to move a total length of 10 cm with 2-cm intervals. In the ileum, itopride accelerated peristaltic velocity at higher dosage (10(-10)-10(-6) M) whereas neostigmine accelerated it only with a lower dosage (10(-10)-10(-9) M). Dopamine (10(-8) M) decelerated the velocity that was recovered by itopride infusion. Itopride and neostigmine significantly shortened colonic transit at a higher dosage (10(-10)-10(-6) M). Dopamine (10(-8) M) delayed colonic transit time that was also recovered after infusion of itopride. Itopride has prokinetic effects on both the ileum and colon, which are regulated through inhibitory effects on AChE and antagonistic effects on dopamine D(2) receptor.
Application of three-dimensional printing for colon targeted drug delivery systems
Charbe, Nitin B.; McCarron, Paul A.; Lane, Majella E.; Tambuwala, Murtaza M.
2017-01-01
Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems. PMID:28929046
Application of three-dimensional printing for colon targeted drug delivery systems.
Charbe, Nitin B; McCarron, Paul A; Lane, Majella E; Tambuwala, Murtaza M
2017-01-01
Orally administered solid dosage forms currently dominate over all other dosage forms and routes of administrations. However, human gastrointestinal tract (GIT) poses a number of obstacles to delivery of the drugs to the site of interest and absorption in the GIT. Pharmaceutical scientists worldwide have been interested in colon drug delivery for several decades, not only for the delivery of the drugs for the treatment of colonic diseases such as ulcerative colitis and colon cancer but also for delivery of therapeutic proteins and peptides for systemic absorption. Despite extensive research in the area of colon targeted drug delivery, we have not been able to come up with an effective way of delivering drugs to the colon. The current tablets designed for colon drug release depend on either pH-dependent or time-delayed release formulations. During ulcerative colitis the gastric transit time and colon pH-levels is constantly changing depending on whether the patient is having a relapse or under remission. Hence, the current drug delivery system to the colon is based on one-size-fits-all. Fails to effectively deliver the drugs locally to the colon for colonic diseases and delivery of therapeutic proteins and peptides for systemic absorption from the colon. Hence, to overcome the current issues associated with colon drug delivery, we need to provide the patients with personalized tablets which are specifically designed to match the individual's gastric transit time depending on the disease state. Three-dimensional (3D) printing (3DP) technology is getting cheaper by the day and bespoke manufacturing of 3D-printed tablets could provide the solutions in the form of personalized colon drug delivery system. This review provides a bird's eye view of applications and current advances in pharmaceutical 3DP with emphasis on the development of colon targeted drug delivery systems.
Suri, Jaspreet; Kataria, Rahul; Malik, Zubair; Parkman, Henry P; Schey, Ron
2018-05-01
Limited research exists regarding the relationship between small intestinal bacterial overgrowth (SIBO), small bowel transit (SBT), and colonic transit (CT). Furthermore, symptom analysis is limited between the subtypes of SIBO: hydrogen producing (H-SIBO) and methane producing (M-SIBO). The primary aims of this study are to: compare the SBT and CT in patients with a positive lactulose breath test (LBT) to those with a normal study; compare the SBT and CT among patients with H-SIBO or M-SIBO; compare the severity of symptoms in patients with a positive LBT to those with a normal study; compare the severity of symptoms among patients with H-SIBO or M-SIBO.A retrospective review was performed for 89 patients who underwent a LBT and whole gut transit scintigraphy (WGTS) between 2014 and 2016. Seventy-eight patients were included. WGTS evaluated gastric emptying, SBT (normal ≥40% radiotracer bolus accumulated at the ileocecal valve at 6 hours), and CT (normal geometric center of colonic activity = 1.6-7.0 at 24 hours, 4.0-7.0 at 48 hours, 6.2-7.0 at 72 hours; elevated geometric center indicates increased transit). We also had patients complete a pretest symptom survey to evaluate nausea, bloating, constipation, diarrhea, belching, and flatulence.A total of 78 patients (69 females, 9 males, mean age of 48 years, mean BMI of 25.9) were evaluated. Forty-seven patients had a positive LBT (H-SIBO 66%, M-SIBO 34%). Comparison of SBT among patients with a positive LBT to normal LBT revealed no significant difference (62.1% vs 58.6%, P = .63). The mean accumulated radiotracer was higher for H-SIBO compared to M-SIBO (71.5% vs 44.1%; P < .05). For CT, all SIBO patients had no significant difference in geometric centers of colonic activity at 24, 48, and 72 hours when compared to the normal group. When subtyping, H-SIBO had significantly higher geometric centers compared to the M-SIBO group at 24 hours (4.4 vs 3.1, P < .001), 48 hours (5.2 vs 3.8, P = .002), and at 72 hours (5.6 vs 4.3, P = .006). The symptom severity scores did not differ between the positive and normal LBT groups. A higher level of nausea was present in the H-SIBO group when compared to the M-SIBO group.Overall, the presence of SIBO does not affect SBT or CT at 24, 48, and 72 hours. However, when analyzing the subtypes, M-SIBO has significantly more delayed SBT and CT when compared to H-SIBO. These results suggest the presence of delayed motility in patients with high methane levels on LBT.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Spiller, R.C.; Brown, M.L.; Phillips, S.F.
Emptying of the terminal ileum was assessed in 15 healthy humans by injecting technetium 99m-diethyltriaminopentaacetic acid into the bowel through a multilumen orocolonic tube. The subsequent arrival of isotope in the colon was quantified by gamma-scintigraphy and colonic filling curves were obtained. Studies were performed during fasting (n = 5) cnd 2.5 h after either a low residue meal (n = 5) or a meal made high in residue (n = 5) by adding 4 g of guar. The time for 50% of the isotope to reach the colon (T50) was significantly accelerated after both meals, being 72 +/- 15more » min for the high residue meal and 62 +/- 8 min for the low residue meal, compared with 183 +/- 37 min (p less than 0.01) in the 5 fasting subjects. Although the addition of guar did not alter T50 significantly, it did cause a significant fall in the rate of colonic filling, implying increased isotope dilution. Delay at the ileocolonic junction, as shown by plateaus in the middle of the colonic filling curves, was uncommon. Hold-up was significant in only 2 of 10 postprandial and 2 of 5 fasting studies. Rates of ileocolonic transit could not be related to either a mean ileal motility index or the occurrence of specific ileal motor patterns immediately proximal to the ileocolonic junction. Fasting ileocolonic transit was characteristically erratic but could not be related to interdigestive migrating motor complexes, which were rarely observed in the last 60 cm of ileum. We conclude that ileocolonic transit in humans is related to the rate at which material accumulates in the ileum, being rapid postprandially and slow and erratic during fasting. This method yields consistent results and could be used to define further factors that influence ileocolonic inflow.« less
Croaker, G D H; Pearce, R; Li, J; Nahon, I; Javaid, A; Kecskes, Z
2007-12-01
We hypothesise that constipated children would be more likely to come from a socially deprived background. We also hypothesise that a percentage of children with resistant constipation would have a congenital gut motility problem that might be recognised at birth, and that some of these would have slow transit constipation that could be recognised on nuclear transit study. One hundred and forty children with a constipation related diagnosis were seen in the last 4 years, and were reviewed as a retrospective audit. Twenty-six children who were felt likely to have a congenital cause for their constipation were offered nuclear colon transit study to search for slow transit constipation. One hundred and forty children from the constipation clinic were reviewed. There were 67 females (47.9%) and 73 males (52.1%), a sex ratio near equality. The mean age at presentation was 5.38 years. Forty-one percent were formally discharged, 36% were lost to follow up, and 23% are still being seen. There was a highly significant tendency for these children to have delayed passage of meconium, as compared normal newborns (P < 0.001). Twenty-six children were considered for possible transit study, and 14 were performed. Four of these were normal, seven showed hold up in the recto-sigmoid, and three showed more proximal slow transit. Two of these probably have non ISTC diagnoses. Social class seems similar to the general population on the criterion employed. Delayed passage of meconium in this group was significantly more frequent than in the general population, but only one of the group seems likely to have truly idiopathic slow transit constipation, and he did not have delayed passage of meconium. There is no evidence for an effect of social class in this population. Idiopathic slow transit constipation itself is rare.
[Fiber intake and colonic transit time in functional constipated patients].
Lopes, Adriana Cruz; Victoria, Carlos Roberto
2008-01-01
Patients with functional constipation presenting no response to treatment using fibers supplement represents important clinical issue. To evaluate the relations among the amount of ingested fiber, the constipation intensity and the colonic transit time in patients with functional constipation. We evaluated 30 patients, presenting no response to treatment using fibers supplement, and 18 healthy volunteers conducting individual inquiry into fibers intake, constipation intensity and the total and segmental colonic transit evaluation using radiopaque markers. In the constipated, despite the good level of fiber intake (26.3 +/- 12.9 g, constipated x 9.3 +/- 5,2 g, control), the symptoms of constipation was serious (score = 21.3 +/- 4.07). Mean total colonic transit was 58.8h. The colonic transit was slower in the constipated group (41.0 +/- 22.8 hours, constipated x 21.8 +/- 18.5h, control). In constipated patients with slow colonic transit (>58.8h) there were colonic inertia (eight), outlet constipation (one) and slow transit in left colon (one), and among constipated patients with normal colonic transit (<58.8h), there were isolated slow transit, in the right colon (nine), left colon (three) and in the rectosigmoid segment (eight). There were no relation among the amount of ingested fiber, constipation intensity and the colon transit. In the functional constipation the gravity of symptoms does not depend only on the dietary fibers intake, which is not the only responsible for the differences in the colonic transit. The colonic transit can differentiate normal from constipated patients and, among them, those with altered transit that demand approaches distinct of fiber supplementation.
Effects of morphine and naloxone on feline colonic transit
DOE Office of Scientific and Technical Information (OSTI.GOV)
Krevsky, B.; Libster, B.; Maurer, A.H.
1989-01-01
The effects of endogenous and exogenous opioid substances on feline colonic transit were evaluated using colonic transit scintigraphy. Naloxone accelerated emptying of the cecum and ascending colon, and filling of the transverse colon. Endogenous opioid peptides thus appear to play a significant role in the regulation of colonic transit. At a moderate dose of morphine cecum and ascending colon transit was accelerated, while at a larger dose morphine had no effect. Since naloxone, a relatively nonspecific opioid antagonist, and morphine, a principally mu opioid receptor agonist, both accelerate proximal colonic transit, a decelerating role for at least one of themore » other opioid receptors is inferred.« less
Di Stefano, Michele; Mengoli, Caterina; Bergonzi, Manuela; Klersy, Catherine; Pagani, Elisabetta; Miceli, Emanuela; Corazza, Gino Roberto
2015-06-01
The role of colonic methane production in functional bowel disorders is still uncertain. In small samples of irritable bowel syndrome (IBS) patients, it was shown that methane breath excretion correlates with clinical presentation and delayed gastrointestinal transit time. The aim of this study was to evaluate the relationship between intestinal production and breath excretion of CH4 and to correlate CH4 production with the presence and the severity of symptoms, in a large cohort of IBS patients and in a group of healthy volunteers. A group of 103 IBS patients and a group of 28 healthy volunteers were enrolled. The presence and severity of symptoms and gastrointestinal transit were evaluated in all subjects, who underwent breath H2/CH4 measurement for 7 h after lactulose to identify breath excretors of these gases; H2 and CH4 were also measured in rectal samples to identify colonic producers. Cumulative H2 and CH4 excretion and production were evaluated by the area under the time-concentration curve calculation (AUC). In IBS patients, CH4 was detected in rectal samples in 48 patients (47%), but only 27 of them (26% of the 103 enrolled patients) excreted this gas with breath. In CH4 producers, the prevalence and severity of symptoms and gastrointestinal transit time were not significantly different with respect to non-producers. IBS subtypes were homogeneously represented in CH4 producers and in non-producers. Healthy volunteers, compared with IBS patients, showed a significantly lower prevalence of CH4 excretion, whereas no difference was found in the prevalence of colonic CH4 production; moreover, in healthy volunteers compared with IBS, CH4 breath excretion and CH4 production were not different in quantitative terms. Our data show that colonic CH4 production is not associated with clinical presentation in IBS patients and does not correlate with symptom severity or with gastrointestinal transit time. Clinical inferences based on breath CH4 excretion should undergo an in-depth revision, as this method is not a good marker of CH4 colonic production.
Fried, David; Gomez-Suarez, Roberto A.; Leinninger, Gina M.; Sévigny, Jean; Parpura, Vladimir; Gulbransen, Brian D.
2014-01-01
Background & Aims In the enteric nervous system, neurotransmitters initiate changes in Ca2+ (Ca2+ responses) in glia, but it is not clear how this process affects intestinal function. We investigated whether Ca2+-mediated responses in enteric glial are required to maintain gastrointestinal function. Methods We used in situ Ca2+ imaging to monitor glial Ca2+ responses, which were manipulated with pharmacologic agents or via glia-specific disruption of the gene encoding connexin-43 (Cx43) (hGFAP::creERT2+/−/Cx43f/f mice). Gastrointestinal function was assessed based on pellet output, total gut transit, colonic bead expulsion, and muscle tension recordings. Proteins were localized and quantified by immunohistochemistry, immunoblot, and reverse transcription PCR analyses. Results Ca2+ responses in enteric glia of mice were mediated by Cx43 hemichannels. Cx43 immunoreactivity was confined to enteric glia within the myenteric plexus of the mouse colon; the Cx43 inhibitors carbenoxolone and 43Gap26 inhibited the ability of enteric glia to propagate Ca2+ responses. In vivo attenuation of Ca2+ responses in the enteric glial network slowed gut transit overall and delayed colonic transit—these changes are also observed during normal aging. Altered motility with increasing age was associated with reduced glial Ca2+-mediated responses and changes in glial expression of Cx43 mRNA and protein. Conclusions Ca2+-mediated responses in enteric glia regulate gastrointestinal function in mice. Altered intercellular signaling between enteric glia and neurons might contribute to motility disorders. PMID:24211490
Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut.
Roager, Henrik M; Hansen, Lea B S; Bahl, Martin I; Frandsen, Henrik L; Carvalho, Vera; Gøbel, Rikke J; Dalgaard, Marlene D; Plichta, Damian R; Sparholt, Morten H; Vestergaard, Henrik; Hansen, Torben; Sicheritz-Pontén, Thomas; Nielsen, H Bjørn; Pedersen, Oluf; Lauritzen, Lotte; Kristensen, Mette; Gupta, Ramneek; Licht, Tine R
2016-06-27
Little is known about how colonic transit time relates to human colonic metabolism and its importance for host health, although a firm stool consistency, a proxy for a long colonic transit time, has recently been positively associated with gut microbial richness. Here, we show that colonic transit time in humans, assessed using radio-opaque markers, is associated with overall gut microbial composition, diversity and metabolism. We find that a long colonic transit time associates with high microbial richness and is accompanied by a shift in colonic metabolism from carbohydrate fermentation to protein catabolism as reflected by higher urinary levels of potentially deleterious protein-derived metabolites. Additionally, shorter colonic transit time correlates with metabolites possibly reflecting increased renewal of the colonic mucosa. Together, this suggests that a high gut microbial richness does not per se imply a healthy gut microbial ecosystem and points at colonic transit time as a highly important factor to consider in microbiome and metabolomics studies.
Keshtgar, Alireza S; Ward, Harry C; Clayden, Graham S
2013-04-01
Chronic idiopathic constipation (IC) is a common problem in children. We hypothesised that hypertonicity and overactivity of the internal anal sphincter (IAS) contributed to childhood IC. This was a prospective study of children who were admitted for investigation and treatment of chronic constipation at the gastrointestinal motility clinic in Guy's and St. Thomas' Hospital, NHS Foundation Trust, London. All children had a colonic transit marker study followed by anorectal manometry and anal endosonography under ketamine anesthesia. We used a validated symptom severity (SS) score questionnaire for assessment of constipation and fecal incontinence on admission to hospital and during follow-up for 12months. The SS score of 0 was the best and 65 the worst. Of 92 children, 57 were male and median (range) age was 8.46years (3.35-14.97). Duration of symptoms was 4.7years (0.3-13). Soiling was present in 88 (96%) patients, delay in defecation of once every 2 to 3days or less frequently in 86 (93%) and a palpable fecaloma (megarectum) on abdominal examination in 76 (83%). 42 children had 'fecal impaction' requiring disimpaction of stool from the rectum under general anesthesia and 50 had 'no impaction'. The median IAS resting pressure was within the normal range measuring 55mm Hg (25-107) and median amplitude and frequency of the IAS contractions were 10mm Hg (2.0-58) and 17cycles per min (5.0-34), respectively. The median IAS thickness was 0.93mm (0.5-2.0). There was no correlation between amplitude and frequency of anorectal contractions and anal sphincter resting pressure. The mean right colonic transit time was 8.55 (standard deviation ±13.22) h, left colonic transit time was 11.51h (±13.21), rectosigmoid transit time was 25.91h (±18.89) and total colonic transit time was 45.97h (±17.69). The anal sphincter resting pressure is normal in children with chronic IC. Increased frequency and amplitude of IAS contractions seen in these patients do not cause raised anal sphincter resting pressure or obstructive defecation. Further studies should be done to investigate the role of external anal sphincter dysfunction in pathophysiology of childhood constipation and fecal incontinence. Copyright © 2013 Elsevier Inc. All rights reserved.
Parthasarathy, Gopanandan; Chen, Jun; Chen, Xianfeng; Chia, Nicholas; O'Connor, Helen M.; Wolf, Patricia G.; Gaskins, H. Rex; Bharucha, Adil E.
2015-01-01
Background & Aims In fecal samples from patients with chronic constipation, the microbiota differs from that of healthy subjects. However, the profiles of fecal microbiota only partially replicate those of the mucosal microbiota. It is not clear whether these differences are caused by variations in diet or colonic transit, or are associated with methane production (measured by breath tests). We compared the colonic mucosal and fecal microbiota in patients with chronic constipation and in healthy subjects to investigate the relationships between microbiota and other parameters. Methods Sigmoid colonic mucosal and fecal microbiota samples were collected from 25 healthy women (controls) and 25 women with chronic constipation and evaluated by 16S ribosomal RNA gene sequencing (average of 49,186 reads/sample). We assessed associations between microbiota (overall composition and operational taxonomic units) and demographic variables, diet, constipation status, colonic transit, and methane production (measured in breath samples after oral lactulose intake). Results Fourteen patients with chronic constipation had slow colonic transit. The profile of the colonic mucosal microbiota differed between constipated patients and controls (P<.05). The overall composition of the colonic mucosal microbiota was associated with constipation, independent of colonic transit (P<.05) and discriminated between patients with constipation and controls with 94% accuracy. Genera from Bacteroidetes were more abundant in the colonic mucosal microbiota of patients with constipation. The profile of the fecal microbiota was associated with colonic transit before adjusting for constipation, age, body mass index, and diet; genera from Firmicutes (Faecalibacterium, Lactococcus, and Roseburia) correlated with faster colonic transit. Methane production was associated with the composition of the fecal microbiota, but not with constipation or colonic transit. Conclusions After adjusting for diet and colonic transit, the profile of the microbiota in the colonic mucosa could discriminate patients with constipation from healthy individuals. The profile of the fecal microbiota was associated with colonic transit and methane production (measured in breath), but not constipation. PMID:26460205
Parthasarathy, Gopanandan; Chen, Jun; Chen, Xianfeng; Chia, Nicholas; O'Connor, Helen M; Wolf, Patricia G; Gaskins, H Rex; Bharucha, Adil E
2016-02-01
In fecal samples from patients with chronic constipation, the microbiota differs from that of healthy subjects. However, the profiles of fecal microbiota only partially replicate those of the mucosal microbiota. It is not clear whether these differences are caused by variations in diet or colonic transit, or are associated with methane production (measured by breath tests). We compared the colonic mucosal and fecal microbiota in patients with chronic constipation and in healthy subjects to investigate the relationships between microbiota and other parameters. Sigmoid colonic mucosal and fecal microbiota samples were collected from 25 healthy women (controls) and 25 women with chronic constipation and evaluated by 16S ribosomal RNA gene sequencing (average, 49,186 reads/sample). We assessed associations between microbiota (overall composition and operational taxonomic units) and demographic variables, diet, constipation status, colonic transit, and methane production (measured in breath samples after oral lactulose intake). Fourteen patients with chronic constipation had slow colonic transit. The profile of the colonic mucosal microbiota differed between constipated patients and controls (P < .05). The overall composition of the colonic mucosal microbiota was associated with constipation, independent of colonic transit (P < .05), and discriminated between patients with constipation and controls with 94% accuracy. Genera from Bacteroidetes were more abundant in the colonic mucosal microbiota of patients with constipation. The profile of the fecal microbiota was associated with colonic transit before adjusting for constipation, age, body mass index, and diet; genera from Firmicutes (Faecalibacterium, Lactococcus, and Roseburia) correlated with faster colonic transit. Methane production was associated with the composition of the fecal microbiota, but not with constipation or colonic transit. After adjusting for diet and colonic transit, the profile of the microbiota in the colonic mucosa could discriminate patients with constipation from healthy individuals. The profile of the fecal microbiota was associated with colonic transit and methane production (measured in breath), but not constipation. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.
Lee, Min Jung; Cho, Kang Hun; Park, Hyun Min; Sung, Hyun Jung; Choi, Sunghak; Im, Weonbin
2014-07-15
DA-6886, the gastrointestinal prokinetic benzamide derivative is a novel 5-HT4 receptor agonist being developed for the treatment of constipation-predominant irritable bowel syndrome (IBS-C). The purpose of this study was to characterize in vitro and in vivo pharmacological profile of DA-6886. We used various receptor binding assay, cAMP accumulation assay, organ bath experiment and colonic transit assay in normal and chemically constipated mice. DA-6886 exhibited high affinity and selectivity to human 5-HT4 receptor splice variants, with mean pKi of 7.1, 7.5, 7.9 for the human 5-HT4a, 5-HT4b and 5-HT4d, respectively. By contrast, DA-6886 did not show significant affinity for several receptors including dopamine D2 receptor, other 5-HT receptors except for 5-HT2B receptor (pKi value of 6.2). The affinity for 5-HT4 receptor was translated into functional agonist activity in Cos-7 cells expressing 5-HT4 receptor splice variants. Furthermore, DA-6886 induced relaxation of the rat oesophagus preparation (pEC50 value of 7.4) in a 5-HT4 receptor antagonist-sensitive manner. The evaluation of DA-6886 in CHO cells expressing hERG channels revealed that it inhibited hERG channel current with an pIC50 value of 4.3, indicating that the compound was 1000-fold more selective for the 5-HT4 receptor over hERG channels. In the normal ICR mice, oral administration of DA-6886 (0.4 and 2mg/kg) resulted in marked stimulation of colonic transit. Furthermore, in the loperamide-induced constipation mouse model, 2mg/kg of DA-6886 significantly improved the delay of colonic transit, similar to 10mg/kg of tegaserod. Taken together, DA-6886 is a highly potent and selective 5-HT4 receptor agonist to accelerate colonic transit in mice, which might be therapeutic agent having a favorable safety profile in the treatment of gastrointestinal motor disorders such as IBS-C and chronic constipation. Copyright © 2014 Elsevier B.V. All rights reserved.
Hebert, Jeffrey J; Taylor, Andrew J; Winter, Thomas C
2006-11-01
The objective of our study was to assess the efficacy of a new positive oral contrast agent's ability to reach the colon during CT evaluation of acute appendicitis. Eighty adult emergency department patients who underwent abdominal CT to evaluate for appendicitis were studied. Forty patients received the department's standard dose of 1,600 mL of a water-iodinated contrast mixture (ratio of 2 mL of iodinated contrast material to 100 mL of water) with a standard delay time of 2-2.5 hours from the beginning of contrast medium ingestion. Forty patients were given a new oral contrast mixture of 1,000 mL of polyethylene glycol (PEG) mixed with 30 mL of iodinated contrast agent, and the examination was conducted only 1 hour from inception of contrast administration. Examinations were reviewed for the presence of contrast medium in the cecum and the presence of appendicitis or other abdominal abnormality. Thirty-eight of 40 patients in the PEG group had contrast medium in the colon at 1 hour after contrast administration, 20 of whom had surgically confirmed cases of appendicitis. In five other patients in that group, another cause to explain the patient's complaints was identified on imaging. Only 18 of the 40 patients who received the standard oral preparation had contrast material present in the cecum. Eleven patients in that group had confirmed appendicitis, and four others had another abnormal finding detected at CT. There was a significant difference in the success of contrast medium transit to the colon with these two agents (p < 0.0001). The use of an oral contrast agent composed of PEG and iodinated contrast material provided a marked improvement in oral agent transit to the colon even in patients with intraabdominal inflammation.
Almeida, Sintia; Legembre, Patrick; Edmond, Valérie; Azevedo, Vasco; Miyoshi, Anderson; Even, Sergine; Taieb, Frédéric; Arlot-Bonnemains, Yannick; Le Loir, Yves; Berkova, Nadia
2013-01-01
Staphylococcus aureus is a highly versatile, opportunistic pathogen and the etiological agent of a wide range of infections in humans and warm-blooded animals. The epithelial surface is its principal site of colonization and infection. In this work, we investigated the cytopathic effect of S. aureus strains from human and animal origins and their ability to affect the host cell cycle in human HeLa and bovine MAC-T epithelial cell lines. S. aureus invasion slowed down cell proliferation and induced a cytopathic effect, resulting in the enlargement of host cells. A dramatic decrease in the number of mitotic cells was observed in the infected cultures. Flow cytometry analysis revealed an S. aureus-induced delay in the G2/M phase transition in synchronous HeLa cells. This delay required the presence of live S. aureus since the addition of the heat-killed bacteria did not alter the cell cycle. The results of Western blot experiments showed that the G2/M transition delay was associated with the accumulation of inactive cyclin-dependent kinase Cdk1, a key inducer of mitosis entry, and with the accumulation of unphosphorylated histone H3, which was correlated with a reduction of the mitotic cell number. Analysis of S. aureus proliferation in asynchronous, G1- and G2-phase-enriched HeLa cells showed that the G2 phase was preferential for bacterial infective efficiency, suggesting that the G2 phase delay may be used by S. aureus for propagation within the host. Taken together, our results divulge the potential of S. aureus in the subversion of key cellular processes such as cell cycle progression, and shed light on the biological significance of S. aureus-induced host cell cycle alteration. PMID:23717407
Su, Andrew; Gandhy, Rita; Barlow, Carrolee; Triadafilopoulos, George
2016-01-01
Background The aetiology of constipation in Parkinson's disease remains poorly understood. Defaecatory dyssynergia, anal sphincter spasticity and slow transit constipation may, individually or collectively, play a role. Aims In this retrospective cohort analysis of patients with Parkinson's disease and chronic constipation, we determined the utility of high-resolution anorectal manometry, balloon expulsion and wireless motility capsule testing in defining the underlying aetiology for constipation. Methods In this retrospective cohort study, consecutive patients with Parkinson's disease and chronic constipation underwent clinical assessment, manometry with balloon expulsion and wireless motility capsule testing using standard protocols. Results We studied 66 patients fulfilling Rome IV criteria for functional constipation. Most patients (89%) had abnormal manometry, exhibiting various types of defaecatory dyssynergia (mostly types II and IV), abnormal balloon expulsion, diminished rectal sensation and, in some, lacking rectoanal inhibitory reflex. 62% exhibited colonic transit delay by wireless motility capsule study, while 57% had combined manometric and transit abnormalities, suggesting of overlap constipation. Symptoms of infrequent defaecation, straining and incomplete evacuation were not discriminatory. There was a relationship between constipation scores and colonic transit times (p=0.01); Parkinson's disease scores and duration were not correlated with either the manometric or transit findings. Faecal incontinence was seen in 26% of the patients. Conclusions Chronic constipation in patients with Parkinson's disease may reflect pelvic floor dyssynergia, slow transit constipation or both, and may be associated with faecal incontinence, suggesting both motor and autonomic dysfunction. Anorectal manometry and wireless motility capsule testing are useful in the assessment of these patients. PMID:27843572
Asian motility studies in irritable bowel syndrome.
Lee, Oh Young
2010-04-01
Altered motility remains one of the important pathophysiologic factors in patients with irritable bowel syndrome (IBS) who commonly complain of abdominal pain and stool changes such as diarrhea and constipation. The prevalence of IBS has increased among Asian populations these days. Gastrointestinal (GI) physiology may vary between Asian and Western populations because of differences in diets, socio-cultural backgrounds, and genetic factors. The characteristics and differences of GI dysmotility in Asian IBS patients were reviewed. MEDLINE search work was performed including following terms, 'IBS,' 'motility,' 'transit time,' 'esophageal motility,' 'gastric motility,' 'small intestinal motility,' 'colonic motility,' 'anorectal function,' and 'gallbladder motility' and over 100 articles were categorized under 'esophagus,' 'stomach,' 'small intestine,' 'colon,' 'anorectum,' 'gallbladder,' 'transit,' 'motor pattern,' and 'effect of stressors.' Delayed gastric emptying, slow tansit in constipation predominant IBS patients, rapid transit in diarrhea predominant IBS patients, accelerated motility responses to various stressors such as meals, mental stress, or corticotrophin releasing hormones, and altered rectal compliance and altered rectal accomodation were reported in many Asian studies regarding IBS. Many conflicting results were found among these studies and there are still controversies to conclude these as unique features of Asian IBS patients. Multinational and multicenter studies are needed to be performed vigorously in order to elaborate characteristics as well as differences of altered motililty in Asian patients with IBS.
Zhu, D; Chen, S; Yao, S K; Li, Y M; Chen, S X
2018-06-12
Objective: To establish a canine model of slow transit constipation (STC), and to test the changes in defecation, gastrointestinal transit time and pathology sections. Methods: Baseline information was measured in 8 beagle dogs, and these dogs were randomly divided into the control group and the model group. The dogs in model group were given a diet of canned meat, as well as a combination of compound diphenoxylate and alosetron hydrochloride for 5 weeks. Dogs in control group were given normal diet with no special intervention. Stool frequency and consistency were observed and recorded daily, and the gastrointestinal transit time (GITT) were measured every week. All animals underwent the midline laparotomy and the colonic tissues were taken from the rectosigmoid colon, then investigated by light microscopy, electron microscopy, and immunohistochemistry to evaluate changes of protein gene product 9.5(PGP9.5), synaptophysin and c-kit between two groups. Results: 8 beagle dogs underwent all experiment items successfully.Both of the stool frequency and scores of stool consistency decreased in model group( F =6.568, P =0.043; F =25.954, P =0.002). GITT delayed in model group( F =42.573, P =0.001). After 5 weeks of intervention, in the model group, the myenteric neurons and interstitial cells of Cajal showed damage such as swelling of mitochondria under electron microscopy, and both of the PGP9.5 and synaptophysin integrated option density of rectosigmoid colon were decreased ( t =3.471, P =0.013; t =2.506, P =0.046)under immunohistochemistry. The c-kit integrated option density showed no statistically significant differences between two groups( t =1.709, P =0.138). Conclusions: The canine model of STC which was consistent with clinical symptoms and pathological changes was successfully established, and it can be used to observe and evaluate the therapeutic effect of electrical stimulation, surgery and so on.
Correlation between colonic secretion and colonic motility in rats: Role of ghrelin
Huang, Hsien-Hao; Ting, Ching-Heng; Syu, Yu-Fong; Chang, Shi-Chuan; Chen, Chih-Yen
2016-01-01
AIM To explore the relationship between colonic secretory function and colonic motility. METHODS Using a rat model chronically implanted with intracerebroventricular (ICV) and cecal catheters, we validated the correlation between colonic secretion and colonic motor functions, as well as the role of ICV injection volume. RESULTS Compared to saline controls (5 μL/rat), ICV acyl ghrelin at 1 nmol/5 μL enhanced the total fecal weight, accelerated the colonic transit time, and increased the fecal pellet output during the first hour post-injection, while ICV des-acyl ghrelin at 1 nmol/5 μL only accelerated the colonic transit time. These stimulatory effects on colonic motility and/or secretion from acyl ghrelin and des-acyl ghrelin disappeared when the ICV injection volume increased to 10 μL compared with saline controls (10 μL/rat). Additionally, the ICV injection of 10 μL of saline significantly shortened the colonic transit time compared with the ICV injection of 5 μL of saline. The total fecal weight during the first hour post-injection correlated with the colonic transit time and fecal pellet output after the ICV injection of acyl ghrelin (1 nmol/5 μL), whereas the total fecal weight during the first hour post-injection correlated with the fecal pellet output but not the colonic transit time after the ICV injection of des-acyl ghrelin (1 nmol/5 μL). CONCLUSION Colonic secretion does not always correlate with colonic motility in response to different colonic stimulations. Acyl ghrelin stimulates colonic secretion. PMID:28028362
Tough, IR; Forbes, S; Tolhurst, R; Ellis, M; Herzog, H; Bornstein, JC; Cox, HM
2011-01-01
BACKGROUND AND PURPOSE Peptide YY (PYY) and neuropeptide Y (NPY) activate Y receptors, targets under consideration as treatments for diarrhoea and other intestinal disorders. We investigated the gastrointestinal consequences of selective PYY or NPY ablation on mucosal ion transport, smooth muscle activity and transit using wild-type, single and double peptide knockout mice, comparing mucosal responses with those from human colon. EXPERIMENTAL APPROACH Mucosae were pretreated with a Y1 (BIBO3304) or Y2 (BIIE0246) receptor antagonist and changes in short-circuit current recorded. Colonic transit and colonic migrating motor complexes (CMMCs) were assessed in vitro and upper gastrointestinal and colonic transit measured in vivo. KEY RESULTS Y receptor antagonists revealed tonic Y1 and Y2 receptor-mediated antisecretory effects in human and wild-type mouse colon mucosae. In both, Y1 tone was epithelial while Y2 tone was neuronal. Y1 tone was reduced 90% in PYY−/− mucosa but unchanged in NPY−/− tissue. Y2 tone was partially reduced in NPY−/− or PYY−/− mucosae and abolished in tetrodotoxin-pretreated PYY−/− tissue. Y1 and Y2 tone were absent in NPYPYY−/− tissue. Colonic transit was inhibited by Y1 blockade and increased by Y2 antagonism indicating tonic Y1 excitation and Y2 inhibition respectively. Upper GI transit was increased in PYY−/− mice only. Y2 blockade reduced CMMC frequency in isolated mouse colon. CONCLUSIONS AND IMPLICATIONS Endogenous PYY and NPY induced significant mucosal antisecretory tone mediated by Y1 and Y2 receptors, via similar mechanisms in human and mouse colon mucosa. Both peptides contributed to tonic Y2-receptor-mediated inhibition of colonic transit in vitro but only PYY attenuated upper GI transit. PMID:21457230
Reichardt, François; Chassaing, Benoit; Nezami, Behtash Ghazi; Li, Ge; Tabatabavakili, Sahar; Mwangi, Simon; Uppal, Karan; Liang, Bill; Vijay-Kumar, Matam; Jones, Dean; Gewirtz, Andrew T; Srinivasan, Shanthi
2017-03-01
A high-fat diet (60% kcal from fat) is associated with motility disorders inducing constipation and loss of nitrergic myenteric neurons in the proximal colon. Gut microbiota dysbiosis, which occurs in response to HFD, contributes to endotoxaemia. High levels of lipopolysaccharide lead to apoptosis in cultured myenteric neurons that express Toll-like receptor 4 (TLR4). Consumption of a Western diet (WD) (35% kcal from fat) for 6 weeks leads to gut microbiota dysbiosis associated with altered bacterial metabolites and increased levels of plasma free fatty acids. These disorders precede the nitrergic myenteric cell loss observed in the proximal colon. Mice lacking TLR4 did not exhibit WD-induced myenteric cell loss and dysmotility. Lipopolysaccharide-induced in vitro enteric neurodegeneration requires the presence of palmitate and may be a result of enhanced NO production. The present study highlights the critical role of plasma saturated free fatty acids that are abundant in the WD with respect to driving enteric neuropathy and colonic dysmotility. The consumption of a high-fat diet (HFD) is associated with myenteric neurodegeneration, which in turn is associated with delayed colonic transit and constipation. We examined the hypothesis that an inherent increase in plasma free fatty acids (FFA) in the HFD together with an HFD-induced alteration in gut microbiota contributes to the pathophysiology of these disorders. C57BL/6 mice were fed a Western diet (WD) (35% kcal from fat enriched in palmitate) or a purified regular diet (16.9% kcal from fat) for 3, 6, 9 and 12 weeks. Gut microbiota dysbiosis was investigated by fecal lipopolysaccharide (LPS) measurement and metabolomics (linear trap quadrupole-Fourier transform mass spectrometer) analysis. Plasma FFA and LPS levels were assessed, in addition to colonic and ileal nitrergic myenteric neuron quantifications and motility. Compared to regular diet-fed control mice, WD-fed mice gained significantly more weight without blood glucose alteration. Dysbiosis was exhibited after 6 weeks of feeding, as reflected by increased fecal LPS and bacterial metabolites and concomitant higher plasma FFA. The numbers of nitrergic myenteric neurons were reduced in the proximal colon after 9 and 12 weeks of WD and this was also associated with delayed colonic transit. WD-fed Toll-like receptor 4 (TLR4) -/- mice did not exhibit myenteric cell loss or dysmotility. Finally, LPS (0.5-2 ng·ml -1 ) and palmitate (20 and 30 μm) acted synergistically to induce neuronal cell death in vitro, which was prevented by the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester. In conclusion, WD-feeding results in increased levels of FFA and microbiota that, even in absence of hyperglycaemia or overt endotoxaemia, synergistically induce TLR4-mediated neurodegeneration and dysmotility. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
Interpretation of Overall Colonic Transit in Defecation Disorders in Males and Females
Shin, Andrea; Camilleri, Michael; Nadeau, Ashley; Nullens, Sara; Rhee, Jong Chul; Jeong, In Du; Burton, Duane D.
2013-01-01
Background There is little information regarding gender-specific measurements of colonic transit and anorectal function in patients with defecation disorders (DD). Aim To compare overall colonic transit by gender in DD. Methods In 407 patients with constipation due to DD diagnosed by a single gastroenterologist (1994– 2012), DD was characterized by anorectal manometry, balloon expulsion test, and colonic transit by scintigraphy. The primary endpoint was overall colonic transit (geometric center, GC) at 24hours (GC24). Effects of gender in DD on colonic transit, and comparison with transit in 208 healthy controls were assessed by Mann-Whitney rank sum test. Secondary endpoints were maximum anal resting (ARP) and squeeze (ASP) pressures. We also tested association of the physiological endpoints among DD females by pregnancy history and among DD patients by colectomy history. Results The DD patients were 67 males (M) and 340 females (F). Significant differences by gender in DD patients were observed in GC24 (median: M: 2.2; F: 1.8; p=0.01), ARP (median: M: 87.8mmHg; F: 82.4mmHg; p=0.04), and ASP (median: M: 182.4mmHg; F: 128.7mmHg; p<0.001). GC24 was slower in DD compared to same gender healthy controls. GC24 did not differ among DD females by pregnancy history. Anorectal functions and upper GI transit did not differ among DD patients by colectomy history. Conclusions Patients with DD have slower colonic transit compared to gender-matched controls. Among DD patients, males have higher ARP and ASP, and females have slower colonic transit. Although the clinical significance of these differences may be unclear, findings suggest that interpretation of these tests in suspected DD should be based on same gender control data. PMID:23406422
Miranda, E; Arroyo, A; Ronda, J M; Muñoz, J L; Alonso, C; Martínez-Peñuelas, F; Martí-Viaño, J L
2007-01-01
Blunt abdominal trauma can damage the intestinal vasculature and may occasionally lead to delayed intestinal perforation, associated with a combined rate of morbidity and mortality of 25%. The diagnosis of such complications is hindered by sedation in critical patients, however, and morbimortality in this population is therefore higher. We report the case of a man with multiple injuries admitted to the intensive care unit, where delayed perforations of the sigmoid colon and cecum were diagnosed. The management of blunt abdominal trauma is reviewed and the possible causes, diagnostic approaches, and treatment options for colon injuries are discussed.
An unusual white blood cell scan in a child with inflammatory bowel disease: a case report.
Porn, U; Howman-Giles, R; O'Loughlin, E; Uren, R; Chaitow, J
2000-10-01
Technetium-99m-labeled leukocyte (WBC) imaging is a valuable screening method for inflammatory bowel disease, especially in children, because of its high rate of sensitivity, low cost, and ease of preparation. A 14-year-old girl is described who had juvenile arthritis and iritis complicated by inflammatory bowel disease. She was examined for recurrent abdominal pain. A Tc-99m stannous colloid WBC scan was performed, and tracer accumulation was seen in the small bowel in the region of the distal ileum on the initial 1-hour image. Delayed imaging at 3 hours also revealed tracer accumulation in the cecum and ascending colon, which was not seen on the early image. A biopsy of the colon during endoscopy showed no evidence of active inflammation in the colon. The small bowel was not seen. Computed tomography revealed changes suggestive of inflammatory bowel disease in the distal ileum. The appearance on the WBC study was most likely a result of inflammatory bowel disease involving the distal ileum, with transit of luminal activity into the large bowel.
CPT-11-Induced Delayed Diarrhea Develops via Reduced Aquaporin-3 Expression in the Colon
Kon, Risako; Tsubota, Yuika; Minami, Moe; Kato, Saki; Matsunaga, Yukari; Kimura, Hiroshi; Murakami, Yuta; Fujikawa, Tetsuya; Sakurai, Ryoya; Tomimoto, Rei; Machida, Yoshiaki; Ikarashi, Nobutomo; Sugiyama, Kiyoshi
2018-01-01
While irinotecan (CPT-11) has a potent anti-cancer effect, it also causes serious diarrhea as an adverse reaction. In this study, we analyzed the pathogenic mechanism of CPT-11-induced delayed diarrhea by focusing on water channel aquaporin-3 (AQP3) in the colon. When rats received CPT-11, the expression level of AQP3 was reduced during severe diarrhea. It was found that the expression levels of inflammatory cytokines and the loss of crypt cells were increased in the colon when CPT-11 was administered. When celecoxib, an anti-inflammatory drug, was concomitantly administered, both the diarrhea and the reduced expression of AQP3 induced by CPT-11 were suppressed. The inflammation in the rat colon during diarrhea was caused via activated macrophage by CPT-11. These results showed that when CPT-11 is administered, the expression level of AQP3 in the colon is reduced, resulting in delayed diarrhea by preventing water transport from the intestinal tract. It was also suggested that the reduced expression of AQP3 might be due to the inflammation that occurs following the loss of colonic crypt cells and to the damage caused by the direct activation of macrophages by CPT-11. Therefore, it was considered that anti-inflammatory drugs that suppress the reduction of AQP3 expression could prevent CPT-11-induced delayed diarrhea. PMID:29316651
CPT-11-Induced Delayed Diarrhea Develops via Reduced Aquaporin-3 Expression in the Colon.
Kon, Risako; Tsubota, Yuika; Minami, Moe; Kato, Saki; Matsunaga, Yukari; Kimura, Hiroshi; Murakami, Yuta; Fujikawa, Tetsuya; Sakurai, Ryoya; Tomimoto, Rei; Machida, Yoshiaki; Ikarashi, Nobutomo; Sugiyama, Kiyoshi
2018-01-06
While irinotecan (CPT-11) has a potent anti-cancer effect, it also causes serious diarrhea as an adverse reaction. In this study, we analyzed the pathogenic mechanism of CPT-11-induced delayed diarrhea by focusing on water channel aquaporin-3 (AQP3) in the colon. When rats received CPT-11, the expression level of AQP3 was reduced during severe diarrhea. It was found that the expression levels of inflammatory cytokines and the loss of crypt cells were increased in the colon when CPT-11 was administered. When celecoxib, an anti-inflammatory drug, was concomitantly administered, both the diarrhea and the reduced expression of AQP3 induced by CPT-11 were suppressed. The inflammation in the rat colon during diarrhea was caused via activated macrophage by CPT-11. These results showed that when CPT-11 is administered, the expression level of AQP3 in the colon is reduced, resulting in delayed diarrhea by preventing water transport from the intestinal tract. It was also suggested that the reduced expression of AQP3 might be due to the inflammation that occurs following the loss of colonic crypt cells and to the damage caused by the direct activation of macrophages by CPT-11. Therefore, it was considered that anti-inflammatory drugs that suppress the reduction of AQP3 expression could prevent CPT-11-induced delayed diarrhea.
Yik, Yee Ian; Cain, Timothy M; Tudball, Coral F; Cook, David J; Southwell, Bridget R; Hutson, John M
2011-07-01
Nuclear transit studies (NTS) allow us to follow transit through the stomach and the small and large intestines. We identified children with chronic constipation with rapid proximal colonic transit and characterized their clinical features. We reviewed NTS from 1998 to 2009 to identify patients with chronic constipation and rapid proximal colonic transit, defined as greater than 25% of tracer beyond hepatic flexure at 6 hour and/or greater than 25% of tracer beyond end of descending colon at 24 hour. This was correlated with clinical symptoms and outcome from patient records. Five hundred twenty children with chronic constipation underwent investigation by NTS, and 64 (12%) were identified with rapid proximal colonic transit. The clinical history, symptoms, and outcome in 55 of 64 available for analysis frequently showed family history of allergy (10.9%) and symptoms associated with food allergy/intolerance: abdominal pain (80%), anal fissure (27.3%), and other allergic symptoms (43.6%). Eighteen children were treated with dietary exclusion, with resolution of symptoms in 9 (50%). Some children with intractable chronic constipation have rapid proximal colonic transit, have symptoms consistent with possible food allergy/intolerance, and may respond to dietary exclusion. The NTS can identify these patients with rapid proximal transit that may be secondary to food intolerance. Copyright © 2011 Elsevier Inc. All rights reserved.
Van Os, E C; Zins, B J; Sandborn, W J; Mays, D C; Tremaine, W J; Mahoney, D W; Zinsmeister, A R; Lipsky, J J
1996-01-01
BACKGROUND: 6-Mercaptopurine and its prodrug azathioprine are effective medications for refractory inflammatory bowel disease. However, use of these drugs has been limited by concerns about their toxicity. Colonic delivery of azathioprine may reduce its systemic bioavailability and limit toxicity. AIM: To determine the bioavailability of 6-mercaptopurine after administration of azathioprine via three colonic delivery formulations. METHODS: Twenty four healthy human subjects each received 50 mg of azathioprine by one of four delivery formulations (each n = 6): oral; delayed release oral; hydrophobic rectal foam; and hydrophilic rectal foam. All subjects also received a 50 mg dose of intravenous azathioprine during a separate study period. Plasma concentrations of 6-mercaptopurine were determined by high pressure liquid chromatography. RESULTS: The bioavailabilities of 6-mercaptopurine after colonic azathioprine administration via delayed release oral, hydrophobic rectal foam, and hydrophilic rectal foam (7%, 5%, 1%; respectively) were significantly lower than the bioavailability of 6-mercaptopurine after oral azathioprine administration (47%) by Wilcoxon rank sum pairwise comparison. CONCLUSIONS: Azathioprine delivered to the colon by delayed release oral and rectal foam formulations considerably reduced systemic 6-mercaptopurine bioavailability. The therapeutic potential of these colonic delivery methods, which can potentially limit toxicity by local delivery of high doses of azathioprine, should be investigated in patients with inflammatory bowel disease. PMID:8881811
Colonic transit in soccer players.
Sesboüé, B; Arhan, P; Devroede, G; Lecointe-Besançon, I; Congard, P; Bouchoucha, M; Fabre, J
1995-04-01
To evaluate the effects of exercise on colonic function, we measured total and segmental transit times in 11 male soccer players and nine male radiology student technicians. Diet was kept constant in all subjects, who maintained their normal activities. For the soccer players, normal activities included 15 h of training and one match each week. Transit times were measured with radioopaque markers, using the multiple-ingestion, single-radiograph technique. No overall difference in large bowel transit was observed between the two groups. Right colon transit was considerably slower in the soccer players, whereas left colon and rectal transit were slightly accelerated. We conclude that an intensive sport activity only modifies regional differences in large bowel function. This may be of importance in extreme conditions, such as those experienced by marathon runners. Data should be obtained before prescribing exercise to treat constipation.
Buddingh, K Tim; Herngreen, Thomas; Haringsma, Jelle; van der Zwet, Wil C; Vleggaar, Frank P; Breumelhof, Ronald; Ter Borg, Frank
2011-06-01
Delayed hemorrhage is an infrequent, but serious complication of colonoscopic polypectomy. Large size is the only polyp-related factor that has been unequivocally proven to increase the risk of delayed bleeding. It has been suggested that location in the right hemi-colon is also a risk factor. The objective of this study was to determine whether polyp location is an independent risk factor for delayed post-polypectomy hemorrhage. A retrospective case-control study was conducted in two university hospitals and two community hospitals. Thirty-nine cases and 117 controls were identified. In multivariate analysis, size and location were found to be independent polyp-related risk factors for delayed type hemorrhage. The risk increased by 13% for every 1 mm increase in polyp diameter (odds ratio (OR) 1.13, 95% confidence interval (CI) 1.05-1.20, P<0.001). Polyps located in the right hemi-colon had an OR of 4.67 (1.88-11.61, P=0.001) for delayed hemorrhage. Polyps in the cecum seemed to be especially at high risk in univariate analysis (OR 13.82, 95% CI 2.66-71.73), but this could not be assessed in multivariate analysis as the number of cases was too small. Polyp type (sessile or pedunculated) was not a risk factor. Polyp location in the right hemi-colon seems to be an independent and substantial risk factor for delayed post-polypectomy hemorrhage. A low threshold for preventive hemostatic measures is advised when removing polyps from this region.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yeoh, Eric K., E-mail: eric.yeoh@health.sa.gov.a; Bartholomeusz, Dylan L.; Holloway, Richard H.
2010-11-01
Purpose: To evaluate the role of colonic motility in the pathogenesis of anorectal symptoms and dysfunction after radiotherapy (RT) for carcinoma of the prostate. Patients and Methods: Thirty-eight patients, median age 71 (range, 50-81) years with localized prostate carcinoma randomized to one of two radiation dose schedules underwent colonic transit scintigraphy and assessment of anorectal symptoms (questionnaire), anorectal function (manometry), and anal sphincteric morphology (endoanal ultrasound) before and at 1 month and 1 year after RT. Results: Whole and distal colonic transit increased 1 month after RT, with faster distal colonic transit only persisting at 1 year. Frequency and urgencymore » of defecation, fecal incontinence, and rectal bleeding increased 1 month after RT and persisted at 1 year. Basal anal pressures remained unchanged, but progressive reductions occurred in anal squeeze pressures and responses to increased intra-abdominal pressure. Rectal compliance decreased progressively in the patients, although no changes in anorectal sensory function ensued. Radiotherapy had no effect on the morphology of the internal and external anal sphincters. Distal colonic retention was weakly related to rectal compliance at 1 month, but both faster colonic transit and reduced rectal compliance were more frequent with increased fecal urgency. At 1 year, a weak inverse relationship existed between colonic half-clearance time and frequency of defecation, although both faster whole-colonic transit and reduced rectal compliance occurred more often with increased stool frequency. Conclusion: Colonic dysmotility contributes to anorectal dysfunction after RT for carcinoma of the prostate. This has implications for improving the management of anorectal radiation sequelae.« less
Vattimo, A; Burroni, L; Bertelli, P; Messina, M; Meucci, D; Tota, G
1993-12-01
Serial colon scintigraphy using 111In-DTPA (2 MBq) given orally was performed in 39 children referred for constipation, and the total and segmental colon transit times were measured. The bowel movements during the study were recorded and the intervals between defecations (ID) were calculated. This method proved able to identify children with normal colon morphology (no. = 32) and those with dolichocolon (no. = 7). Normal children were not included for ethical reasons and we used the normal range determined by others using x-ray methods (29 +/- 4 hours). Total and segmental colon transit times were found to be prolonged in all children with dolichocolon (TC: 113.55 +/- 41.20 hours; RC: 39.85 +/- 26.39 hours; LC: 43.05 +/- 18.30 hours; RS: 30.66 +/- 26.89 hours). In the group of children with a normal colon shape, 13 presented total and segmental colon transit times within the referred normal value (TC: 27.79 +/- 4.10 hours; RC: 9.11 +/- 2.53 hours; LC: 9.80 +/- 3.50 hours; RS: 8.88 +/- 4.09 hours) and normal bowel function (ID: 23.37 +/- 5.93 hours). In the remaining children, 5 presented prolonged retention in the rectum (RS: 53.36 +/- 29.66 hours), and 14 a prolonged transit time in all segments. A good correlation was found between the transit time and bowel function. From the point of view of radiation dosimetry, the most heavily irradiated organs were the lower large intestine and the ovaries, and the level of radiation burden depended on the colon transit time. We can conclude that the described method results safe, accurate and fully diagnostic.
Isolated colonic inertia is not usually the cause of chronic constipation.
Ragg, J; McDonald, R; Hompes, R; Jones, O M; Cunningham, C; Lindsey, I
2011-11-01
Chronic constipation is classified as outlet obstruction, colonic inertia or both. We aimed to determine the incidence of isolated colonic inertia in chronic constipation and to study symptom pattern in those with prolonged colonic transit time. Chronic constipation patients were classified radiologically by surgeon-reported defaecating proctography and transit study into four groups: isolated outlet obstruction, isolated colonic inertia, outlet obstruction plus colonic inertia, or normal. Symptom patterns were defined as stool infrequency (twice weekly or less) or frequent unsuccessful evacuations (more than twice weekly). Of 541 patients with chronic constipation, 289 (53%) were classified as isolated outlet obstruction, 26 (5%) as isolated colonic inertia, 159 (29%) as outlet obstruction plus colonic inertia and 67 (12%) as normal. Of 448 patients (83%) with outlet obstruction, 35% had additional colonic inertia. Only 14% of those with prolonged colonic transit time had isolated colonic inertia. Frequent unsuccessful evacuations rather than stool infrequency was the commonest symptom pattern in all three disease groups (isolated outlet obstruction 86%, isolated colonic inertia 54% and outlet obstruction plus colonic inertia 63%). Isolated colonic inertia is an unusual cause of chronic constipation. Most patients with colonic inertia have associated outlet obstruction. These data question the clinical significance of isolated colonic inertia. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.
Theodore, Lindsay N; Hagedorn, Elliott J; Cortes, Mauricio; Natsuhara, Kelsey; Liu, Sarah Y; Perlin, Julie R; Yang, Song; Daily, Madeleine L; Zon, Leonard I; North, Trista E
2017-05-09
Hematopoietic stem/progenitor cells (HSPCs) are formed during ontogeny from hemogenic endothelium in the ventral wall of the dorsal aorta (VDA). Critically, the cellular mechanism(s) allowing HSPC egress and migration to secondary niches are incompletely understood. Matrix metalloproteinases (MMPs) are inflammation-responsive proteins that regulate extracellular matrix (ECM) remodeling, cellular interactions, and signaling. Here, inhibition of vascular-associated Mmp2 function caused accumulation of fibronectin-rich ECM, retention of runx1/cmyb + HSPCs in the VDA, and delayed caudal hematopoietic tissue (CHT) colonization; these defects were absent in fibronectin mutants, indicating that Mmp2 facilitates endothelial-to-hematopoietic transition via ECM remodeling. In contrast, Mmp9 was dispensable for HSPC budding, being instead required for proper colonization of secondary niches. Significantly, these migration defects were mimicked by overexpression and blocked by knockdown of C-X-C motif chemokine-12 (cxcl12), suggesting that Mmp9 controls CHT homeostasis through chemokine regulation. Our findings indicate Mmp2 and Mmp9 play distinct but complementary roles in developmental HSPC production and migration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Sloots, C E J; Felt-Bersma, R J F
2002-02-01
Colon transit time measurement with radio-opaque markers is a method of studying the passage of luminal contents throughout the colon. Overall colonic transit time (CTT), as well as segmental transit times [right (RTT), left (LTT) and rectosigmoid (RSTT)], can be calculated. We hypothesize that CTT is influenced by faecal impaction when the rectum is emptied infrequently. The aim of this study is to investigate the effect of bowel cleansing on colonic transit time in patients with chronic constipation. In 25 women (age 41 years; range 20-65 years) with constipation according to Thompson criteria, CTT measurement was performed in an unprepared situation and repeated after cleansing with 4 L of Klean-Prepreg. Ten healthy female volunteers (age 41 years; range 27-57 years) were used as controls. In constipated patients, CTT decreased from a median 70 h (range 10-130 h) to 48 h (5-94 h) in the cleansed state (P < 0.001). A shortening of transit time was found in all three segments. In 10 patients with slow transit (ST) (CTT > 86 h), CTT decreased from 110 h (range 94-130) to 86 (38-94) (P < 0.001). Five of the 10 patients with ST before bowel cleansing had a CTT below 86 h after cleansing. In female controls, uncleansed CTT and RSTT shortened from 39 h (23 to 62) and 17 h (8-29) to 29 h (17-48) and 10 h (0-20) after bowel cleansing (P=0.058 and P=0.046). Colonic intraluminal contents have a substantial effect on colonic transit. In female controls, bowel cleansing shortened rectosigmoid transit. Women with constipation had faster transit in the cleansed state, however, the distribution of markers was not altered. Despite the effect of bowel cleansing on CTT, it seems unnecessary to prepare the bowel in clinical practice because the differentiation of patients between slow transit constipation and outlet obstruction is not changed. However, because in an infrequent defecation pattern, the influence of faecal impaction is considerable, CTT should be applied with care for critical clinical decisions in the treatment of constipation.
Ge, Xiaolong; Ding, Chao; Zhao, Wei; Xu, Lizhi; Tian, Hongliang; Gong, Jianfeng; Zhu, Minsheng; Li, Jieshou; Li, Ning
2017-01-13
The gastrointestinal motility is affected by gut microbiota and the relationship between them has become a hot topic. However, mechanisms of microbiota in regulating motility have not been well defined. We thus investigated the effect of microbiota depletion by antibiotics on gastrointestinal motility, colonic serotonin levels, and bile acids metabolism. After 4 weeks with antibiotics treatments, gastrointestinal and colon transit, defecation frequency, water content, and other fecal parameters were measured and analyzed in both wild-type and antibiotics-treated mice, respectively. Contractility of smooth muscle, serotonin levels, and bile acids levels in wild-type and antibiotics-treated mice were also analyzed. After antibiotics treatment, the richness and diversity of intestinal microbiota decreased significantly, and the fecal of mice had less output (P < 0.01), more water content (P < 0.01), and longer pellet length (P < 0.01). Antibiotics treatment in mice also resulted in delayed gastrointestinal and colonic motility (P < 0.05), and inhibition of phasic contractions of longitudinal muscle from isolated proximal colon (P < 0.01). In antibiotics-treated mice, serotonin, tryptophan hydroxylase 1, and secondary bile acids levels were decreased. Gut microbiota play an important role in the regulation of intestinal bile acids and serotonin metabolism, which could probably contribute to the association between gut microbiota and gastrointestinal motility as intermediates.
Increasing butyrate concentration in the distal colon by accelerating intestinal transit
Lewis, S; Heaton, K
1997-01-01
Background—Populations at low risk of colonic cancer consume large amounts of fibre and starch and pass acid, bulky stools. One short chain fatty acid (SCFA), butyrate, is the colon's main energy source and inhibits malignant transformation in vitro. Aim—To test the hypothesis that altering colonic transit rate alters colonic pH and the SCFA content of the stools. Patients—Thirteen healthy adults recruited by advertisement. Methods—Volunteers consumed, in turn, wheat bran, senna and loperamide, each for nine days with a two week washout period between study periods, dietary intake being unchanged. Before, and in the last four days of each intervention, whole gut transit time (WGTT), defaecation frequency, stool form, stool β-glucuronidase activity, stool pH, stool SCFA concentrations and intracolonic pH (using a radiotelemetry capsule for continuous monitoring) were assessed. Results—WGTT decreased, stool output and frequency increased with wheat bran and senna, vice versa with loperamide. The pH was similar in the distal colon and stool. Distal colonic pH fell with wheat bran and senna and tended to increase with loperamide. Faecal SCFA concentrations, including butyrate, increased with senna and fell with loperamide. With wheat bran the changes were non-significant, possibly because of the short duration of the study. Baseline WGTT correlated with faecal SCFA concentration (r=−0.511, p=0.001), with faecal butyrate (r=−0.577, p<0.001) and with distal colonic pH (r=0.359, p=0.029). Conclusion—Bowel transit rate is a determinant of stool SCFA concentration including butyrate and distal colonic pH. This may explain the inter-relations between colonic cancer, dietary fibre intake, stool output, and stool pH. Keywords: bowel cancer; colonic pH; fibre; intestinal transit; pH; short chain fatty acids PMID:9301506
Tatebe, Leah Carey; Jennings, Andrew; Tatebe, Ken; Handy, Alexandra; Prajapati, Purvi; Smith, Michael; Do, Tai; Ogola, Gerald O; Gandhi, Rajesh R; Duane, Therese M; Luk, Stephen; Petrey, Laura Bruce
2017-04-01
Delayed colonic anastomosis after damage control laparotomy (DCL) is an alternative to colostomies during a single laparotomy (SL) in high-risk patients. However, literature suggests increased colonic leak rates up to 27% with DCL, and various reported risk factors. We evaluated our regional experience to determine if delayed colonic anastomosis was associated with worse outcomes. A multicenter retrospective cohort study was performed across three Level I trauma centers encompassing traumatic colon injuries from January 2006 through June 2014. Patients with rectal injuries or mortality within 24 hours were excluded. Patient and injury characteristics, complications, and interventions were compared between SL and DCL groups. Regional readmission data were utilized to capture complications within 6 months of index trauma. Of 267 patients, 69% had penetrating injuries, 21% underwent DCL, and the mortality rate was 4.9%. Overall, 176 received primary repair (26 in DCL), 90 had resection and anastomosis (28 in DCL), and 26 had a stoma created (10 end colostomies and 2 loop ileostomies in DCL). Thirty-five of 56 DCL patients had definitive colonic repair subsequent to their index operation. DCL patients were more likely to be hypotensive; require more resuscitation; and suffer acute kidney injury, pneumonia, adult respiratory distress syndrome, and death. Five enteric leaks (1.9%) and three enterocutaneous fistulas (ECF, 1.1%) were identified, proportionately distributed between DCL and SL (p = 1.00, p = 0.51). No difference was seen in intraperitoneal abscesses (p = 0.13) or surgical site infections (SSI, p = 0.70) between cohorts. Among SL patients, pancreas injuries portended an increased risk of intraperitoneal abscesses (p = 0.0002), as did liver injuries in DCL patients (p = 0.06). DCL was not associated with increased enteric leaks, ECF, SSI, or intraperitoneal abscesses despite nearly two-thirds having delayed repair. Despite this being a multicenter study, it is underpowered, and a prospective trial would better demonstrate risks of DCL in colon trauma. Therapeutic study, level IV.
Central apelin mediates stress-induced gastrointestinal motor dysfunction in rats.
Bülbül, Mehmet; İzgüt-Uysal, V Nimet; Sinen, Osman; Birsen, İlknur; Tanrıöver, Gamze
2016-02-15
Apelin, an endogenous ligand for APJ receptor, has been reported to be upregulated in paraventricular nucleus (PVN) following stress. Central apelin is known to stimulate release of corticotropin-releasing factor (CRF) via APJ receptor. We tested the hypothesis that stress-induced gastrointestinal (GI) dysfunction is mediated by central apelin. We also assessed the effect of exogenous apelin on GI motility under nonstressed (NS) conditions in conscious rats. Prior to solid gastric emptying (GE) and colon transit (CT) measurements, APJ receptor antagonist F13A was centrally administered under NS conditions and following acute stress (AS), chronic homotypic stress (CHS), and chronic heterotypic stress (CHeS). Plasma corticosterone was assayed. Strain gage transducers were implanted on serosal surfaces of antrum and distal colon to record postprandial motility. Stress exposure induced coexpression of c-Fos and apelin in hypothalamic PVN. Enhanced hypothalamic apelin and CRF levels in microdialysates were detected following AS and CHeS, which were negatively and positively correlated with GE and CT, respectively. Central F13A administration abolished delayed GE and accelerated CT induced by AS and CHeS. Central apelin-13 administration increased the plasma corticosterone and inhibited GE and CT by attenuating antral and colonic contractions. The inhibitory effect elicited by apelin-13 was abolished by central pretreatment of CRF antagonist CRF9-41 in antrum, but not in distal colon. Central endogenous apelin mediates stress-induced changes in gastric and colonic motor functions through APJ receptor. The inhibitory effects of central exogenous apelin-13 on GI motility appear to be partly CRF dependent. Apelin-13 inhibits colon motor functions through a CRF-independent pathway. Copyright © 2016 the American Physiological Society.
[Determination of total and segmental colonic transit time in constipated children].
Zhang, Shu-cheng; Wang, Wei-lin; Bai, Yu-zuo; Yuan, Zheng-wei; Wang, Wei
2003-03-01
To determine the total and segmental colonic transit time of normal Chinese children and to explore its value in constipation in children. The subjects involved in this study were divided into 2 groups. One group was control, which had 33 healthy children (21 males and 12 females) aged 2 - 13 years (mean 5 years). The other was constipation group, which had 25 patients (15 males and 10 females) aged 3 - 14 years (mean 7 years) with constipation according to Benninga's criteria. Written informed consent was obtained from the parents of each subject. In this study the simplified method of radio opaque markers was used to determine the total gastrointestinal transit time and segmental colonic transit time of the normal and constipated children, and in part of these patients X-ray defecography was also used. The total gastrointestinal transit time (TGITT), right colonic transit time (RCTT), left colonic transit time (LCTT) and rectosigmoid colonic transit time (RSTT) of the normal children were 28.7 +/- 7.7 h, 7.5 +/- 3.2 h, 6.5 +/- 3.8 h and 13.4 +/- 5.6 h, respectively. In the constipated children, the TGITT, LCTT and RSTT were significantly longer than those in controls (92.2 +/- 55.5 h vs 28.7 +/- 7.7 h, P < 0.001; 16.9 +/- 12.6 h vs 6.5 +/- 3.8 h, P < 0.01; 61.5 +/- 29.0 h vs 13.4 +/- 5.6 h, P < 0.001), while the RCTT had no significant difference. X-ray defecography demonstrated one rectocele, one perineal descent syndrome and one puborectal muscle syndrome, respectively. The TGITT, RCTT, LCTT and RSTT of the normal children were 28.7 +/- 7.7 h, 7.5 +/- 3.2 h, 6.5 +/- 3.8 h and 13.4 +/- 5.6 h, respectively. With the segmental colonic transit time, constipation can be divided into four types: slow-transit constipation, outlet obstruction, mixed type and normal transit constipation. X-ray defecography can demonstrate the anatomical or dynamic abnormalities within the anorectal area, with which constipation can be further divided into different subtypes, and combined use of the gastrointestinal transit time and X-ray defecography is of clinical importance in exploration of etiology of constipation.
Sharma, Abhinav; Kumar, Bimlesh; Singh, Sachin Kumar; Gulati, Monica; Vaidya, Yogyata; Rathee, Harish; Ghai, Deepak; Malik, Adil Hussain; Yadav, Ankit Kumar; Maharshi, Peddi; Bawa, Palak; Rajesh, Sarvi Yadav; Sharma, Parth; Pandey, Narendra Kumar; Mohanta, Souvik
2018-01-01
Polysaccharide based delivery systems have been successfully used to target drugs to colon. In some recent reports, the superiority of concomitant administration of probiotics with such systems has been established. However, the pharmacokinetics of such symbiotic therapy remain unexplored hitherto. This study deciphers the pharmacokinetic parameters of guar gum based colon targeted spheroids of sulfasalazine with co-administration of probiotics in experimental rats. Thirty rats were divided into five groups using Latin square design. These were subjected to treatment with delayed release formulation, uncoated spheroids, coated spheroid and coated spheroids along with probiotics. In case of delayed release formulation, negligible presence of sulfasalazine in plasma was observed in first 2h, followed by significant increase in sulfasalazine concentration after 3h. Higher plasma concentrations of sulfasalazine were detected for uncoated spheroids with and without probiotics. Negligible release of drug upto 5h and delayed Tmax in case of guar-gum coated sulfasalazine spheroids with or without probiotics clearly indicated successful formulation of colon targeted spheroids. Further, for coated spheroids (both with and without probiotics), the value of Tmax is found to be significantly higher than those with the other treatments. Colon targeted spheroids were therefore, found to reduce absorption of drug which, in turn, is expected to reduce the side effects as only local action in colon is required for treatment of colitis. This is the first report on pharmacokinetic study of a colon targeted delivery system co-administered with probiotics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Bharucha, Adil E; Low, Phillip; Camilleri, Michael; Veil, Erica; Burton, Duane; Kudva, Yogish; Shah, Pankaj; Gehrking, Tonette; Zinsmeister, Alan R
2014-01-01
Objectives Chronic constipation in diabetes mellitus is associated with colonic motor dysfunction and is managed with laxatives. Cholinesterase inhibitors increase colonic motility. This study evaluated the effects of a cholinesterase inhibitor on gastrointestinal and colonic transit and bowel function in diabetic patients with constipation. Design After a 9-day baseline period, 30 patients (mean±SEM age 50±2 years) with diabetes mellitus (18 type 1, 12 type 2) and chronic constipation without defaecatory disorder were randomised to oral placebo or pyridostigmine, starting with 60 mg three times a day, increasing by 60 mg every third day up to the maximum tolerated dose or 120 mg three times a day; this dose was maintained for 7 days. Gastrointestinal and colonic transit (assessed by scintigraphy) and bowel function were evaluated at baseline and the final 3 and 7 days of treatment, respectively. Treatment effects were compared using analysis of covariance, with gender, body mass index and baseline colonic transit as covariates. Results 19 patients (63%) had moderate or severe autonomic dysfunction; 16 (53%) had diabetic retinopathy. 14 of 16 patients randomised to pyridostigmine tolerated 360 mg daily; two patients took 180 mg daily. Compared with placebo (mean±SEM 1.98±0.17 (baseline), 1.84±0.16 (treatment)), pyridostigmine accelerated (1.96±0.18 (baseline), 2.45±0.2 units (treatment), p<0.01) overall colonic transit at 24 h, but not gastric emptying or small-intestinal transit. Treatment effects on stool frequency, consistency and ease of passage were significant (p≤0.04). Cholinergic side effects were somewhat more common with pyridostigmine (p=0.14) than with placebo. Conclusions Cholinesterase inhibition with oral pyridostigmine accelerates colonic transit and improves bowel function in diabetic patients with chronic constipation. Clinical trial registration number TrialRegNo (NCT 00276406). PMID:22677718
DOE Office of Scientific and Technical Information (OSTI.GOV)
Smart, R.C.; McLean, R.G.; Gaston-Parry, D.
1991-09-01
In 11 normal subjects and 11 patients with a clinical diagnosis of constipation, oral 131I-cellulose and 111In-DTPA were compared simultaneously as tracers for radionuclide colon transit scintigraphy. Visual assessment of the images revealed no differences between tracers. Quantitation was performed using total and segmental percent retention and the derived value of clearance half-time. In addition, profiles of the activity distribution along the length of the colon were generated and the mean position of the activity in the colon calculated. For all indices, the results were similar in both normal subjects and constipated patients when comparing tracers, although marked differences weremore » present between normal subjects and constipated patients for each tracer. Indium-111-DTPA was easy to administer and dosimetry was more acceptable than for 131I-cellulose, especially in constipated patients. It is concluded that 111In-DTPA is the preferred tracer for oral colon transit scintigraphy.« less
Biochemical Association of Metabolic Profile and Microbiome in Chronic Pressure Ulcer Wounds
Ammons, Mary Cloud B.; Morrissey, Kathryn; Tripet, Brian P.; Van Leuven, James T.; Han, Anne; Lazarus, Gerald S.; Zenilman, Jonathan M.; Stewart, Philip S.; James, Garth A.; Copié, Valérie
2015-01-01
Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR) spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment. PMID:25978400
Variability of gastrointestinal transit in healthy women and men.
Degen, L P; Phillips, S F
1996-01-01
BACKGROUND AND AIMS: Measurements of gastrointestinal transit are made in clinical and research gastroenterology, yet their intrinsic variability is not well characterised. In particular, an influence of hormones on transit has been proposed as the basis for gastrointestinal symptoms that vary with the menstrual cycle. Our aims were to quantify individual differences in transit during the menstrual cycle in healthy women and to compare these with the intrinsic variability in healthy men. METHODS: On two occasions, whole gut transit was assessed scintigraphically and colonic transit quantified by radio-opaque markers. Thirty two healthy volunteers (12 women, 20 men) were studied, women during the follicular and luteal phases, men twice within a similar four week period. Diets and exercise were standardised prior to and during both studies. RESULTS: Colonic transit was significantly faster in men, and postlag gastric emptying was also more rapid; other indices of regional transit were not different between the sexes. Total colonic transit time was equally well reflected by the scintigraphic and radio-opaque marker methods. Important intraindividual differences were noted in both sexes. The variances in our samples predicted an 80% chance of detecting (with 95% confidence) a mean effect of menstrual hormones on transit that was in the same range as the intrinsic variation in men. CONCLUSIONS: Colonic transit was faster in men than in women. Although group means in the two studies were almost identical, single assessments of transit in subjects sometimes exhibited considerable variability, implying broad biological variations. Given this intrinsic variability, the influence of menstrual hormones on gastrointestinal transit must be small and of doubtful clinical significance. PMID:8977347
Huang, Hsien-Hao; Chen, Liang-Yu; Doong, Ming-Luen; Chang, Shi-Chuan; Chen, Chih-Yen
2017-01-01
Acyl ghrelin-induced intake depends on hypothalamic neuropeptide Y and agouti-related protein (AgRP) neurotransmitters. Intracerebroventricular (ICV) injection of AgRP increases feeding through competitive antagonism at melanocortin receptors. ICV administration of α-melanocyte stimulating hormone (α-MSH), a natural antagonist of AgRP, may modulate the acyl ghrelin-induced orexigenic effect. This study aimed to investigate the modulating effect of α-MSH on the central acyl ghrelin-induced food intake, gastrointestinal motility, and colonic secretion in rats. We examined the effects of α-MSH and acyl ghrelin on food intake, gastric emptying, small intestinal transit, colonic motility, and secretion in conscious rats with a chronic implant of ICV catheters. ICV injection of O - n -octanoylated ghrelin (0.1 nmol/rat) significantly increased the cumulative food intake up to 8 h ( P <0.01), enhanced non-nutrient semi-liquid gastric emptying ( P <0.001), increased the geometric center and running percentage of small intestinal transit ( P <0.001), accelerated colonic transit time ( P <0.05), and increased fecal pellet output ( P <0.01) and total fecal weight ( P <0.01). Pretreatment with ICV injection of α-MSH (1.0 and 2.0 nmol/rat) attenuated the acyl ghrelin-induced hyperphagic effect, fecal pellet output, and total fecal weight, while higher dose of α-MSH (2.0 nmol/rat) attenuated the increase in the geometric center of small intestinal transit ( P <0.01). However, neither dose of α-MSH altered acyl ghrelin-stimulated gastroprokinetic effect, increase in the running percentage of small intestinal transit, nor accelerated colonic transit time. α-MSH is involved in central acyl ghrelin-elicited feeding, small intestinal transit, fecal pellet output, and fecal weight. α-MSH does not affect central acyl ghrelin-induced acceleration of gastric emptying and colonic transit time in rats.
Transabdominal electrical stimulation (TES) for the treatment of slow-transit constipation (STC).
Hutson, John M; Dughetti, Lauren; Stathopoulos, Lefteris; Southwell, Bridget R
2015-05-01
Slow-transit constipation (STC) is a newly described subtype of intractable constipation in children which we originally identified with deficiency of substance P in axons supplying the proximal colonic muscle. When nuclear transit studies became available, the patients were found to have slow proximal colonic transit, and responded to antegrade enemas. Using the appendicostomy, we found that there was reduced frequency in propagating sequences throughout the colon. We began testing whether transcutaneous electrical stimulation (TES) could improve motility and symptoms, and over several trials have now shown that TES is remarkably effective in treating children with STC, with long-lasting effects. TES holds promise for treating STC, as well as a range of gastrointestinal motility disorders.
Spada, Cristiano; Riccioni, Maria Elena; Costamagna, Guido
2007-07-01
Small bowel capsule endoscopy represents a significant advance in the investigation of the small bowel, allowing direct visualization of this section of the gastrointestinal system. More recently, new video capsules have been released, specifically designed to investigate the esophagus and the colon. In June 2006, Given Imaging Ltd received marketing clearance from the US FDA for the Rapid Access Real-Time (RT) and Rapid Access software. The Rapid Access RT is a handheld device that enables real-time viewing during capsule endoscopy procedures. To date, the clinical benefits of this device are unknown as studies on the Rapid Access RT system have not yet been published. However, it appears that the Rapid Access RT system may reduce the examination and reading time, and may impact significantly in cases where it is important to know the precise localization of the capsule (during PillCam ESO ingestion procedures, PillCam Colon examinations or when delayed gastric transit is suspected) or in case of severe gastrointestinal bleeding (when a therapeutic procedure is required urgently).
Kirchhoff, K N; Hauffe, T; Stelbrink, B; Albrecht, C; Wilke, T
2017-08-01
Species richness in freshwater bony fishes depends on two main processes: the transition into and the diversification within freshwater habitats. In contrast to bony fishes, only few cartilaginous fishes, mostly stingrays (Myliobatoidei), were able to colonize fresh water. Respective transition processes have been mainly assessed from a physiological and morphological perspective, indicating that the freshwater lifestyle is strongly limited by the ability to perform osmoregulatory adaptations. However, the transition history and the effect of physiological constraints on the diversification in stingrays remain poorly understood. Herein, we estimated the geographic pathways of freshwater colonization and inferred the mode of habitat transitions. Further, we assessed habitat-related speciation rates in a time-calibrated phylogenetic framework to understand factors driving the transition of stingrays into and the diversification within fresh water. Using South American and Southeast Asian freshwater taxa as model organisms, we found one independent freshwater colonization event by stingrays in South America and at least three in Southeast Asia. We revealed that vicariant processes most likely caused freshwater transition during the time of major marine incursions. The habitat transition rates indicate that brackish water species switch preferably back into marine than forth into freshwater habitats. Moreover, our results showed significantly lower diversification rates in brackish water lineages, whereas freshwater and marine lineages exhibit similar rates. Thus, brackish water habitats may have functioned as evolutionary bottlenecks for the colonization of fresh water by stingrays, probably because of the higher variability of environmental conditions in brackish water. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.
Stimulatory action of itopride hydrochloride on colonic motor activity in vitro and in vivo.
Tsubouchi, Tadashi; Saito, Takaharu; Mizutani, Fujie; Yamauchi, Toshie; Iwanaga, Yuji
2003-08-01
We investigated the effects of itopride hydrochloride (itopride, N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide hydrochloride), a gastroprokinetic agent, on the colonic motor activity in vitro and in vivo, in comparison with benzamides, cisapride hydrate (cisapride), and mosapride citrate (mosapride). Itopride stimulated both peristaltic and segmental motility induced by applying intraluminal pressure to the isolated guinea pig colon. Although cisapride and mosapride enhanced the segmental motility, they markedly reduced the peristaltic motility. In conscious dogs with implanted strain gauge force transducers, itopride stimulated contractile activity in the gastrointestinal tract from the stomach to the colon. Cisapride stimulated contractile activity in the gastric antrum, ileum, and ascending colon. Mosapride stimulated contractile activity only in the gastric antrum and ileum. In guinea pigs and rats, itopride accelerated colonic luminal transit. On the other hand, cisapride and mosapride failed to enhance colonic transit. These results demonstrate that itopride has a stimulatory action on colonic peristalsis, propelling colonic luminal contents, different from that of cisapride and mosapride. Therefore, itopride may be a useful drug for the treatment of functional bowel disorders such as functional constipation.
NASA Astrophysics Data System (ADS)
Corrado, Raffaele; Cherubini, Anna Maria; Pennetta, Cecilia
2015-05-01
In this work we study the effect of two different ecological mechanisms on the desertification transition in arid or semi-arid ecosystems, modeled by a stochastic cellular automaton. Namely we consider the role of the facilitation mechanism, i.e. the local positive effects of plants on their neighborhood and of colonization factors, such as seed production, survival and germination probabilities. Within the model, the strength of these two mechanisms is determined by the parameters f and b, respectively controlling the rates of the recovery and colonization processes. In particular we focus on the full desertification transition occurring at increasing value of the mortality rate m and we discuss how the values of f and b affect the critical mortality mc , the critical exponents β and γσ‧, determining the power-law scaling of the average vegetation density and of the root-mean-square deviation of the density fluctuations, and the character of the transition: continuous or abrupt. We show that mc strongly depends on both f and b, a dependence which accounts for the higher resilience of the ecosystems to external stresses as a consequence of an increased effectiveness of positive feedback effects. On the other hand, concerning the value of the exponents and the character of the transition, our results point out that both these features are unaffected by changes in the strength of the local facilitation. Viceversa, we show that an increase of the colonization factor b significantly modifies the values of the exponents and the order of the transition, changing a continuous transition into an abrupt one. We explain these results in terms of the different range of the interactions characterizing facilitation and colonization mechanisms.
Song, Jun; Yin, Jieyun; Xu, Xiaohong; Chen, Jiande
2015-01-01
To systemically explore effects of large dose of lubiprostone on gastrointestinal (GI) transit and contractions and its safety in dogs. 12 healthy dogs were studied. 6 dogs were operated to receive duodenal cannula and colon cannula and the other 6 dogs received gastric cannula. Lubiprostone was orally administrated at a dose of 24 µg or 48 µg 1 hr prior to the experiments. Gastric emptying (GE) of solids and small bowel transit were evaluated by collecting the effluents from the duodenal cannula and from the colon cannula. Gastric accommodation was measured by barostat. Gastric and intestinal contractions were by manometry. Colon transit was by X-ray pictures. 1) Lubiprostone 48 µg not 24 µg accelerated GE. Atropine could block the effect; 2) Average motility index (MI) of gastric antrum in lubiprostone 48 µg session was significantly higher in both fasting state (P = 0.01) and fed state (P = 0.03). Gastric accommodation was not significantly different; 3) Lubiprostone 48 µg accelerated small bowel and colon transit. Atropine could block the effect on small bowel transit; 4) Lubiprostone 48 µg increased postprandial small bowel MI (P = 0.0008) and colon MI (P = 0.002). 5) No other adverse effects except for diarrhea were observed. Acute administration of lubiprostone at a dose of 48 µg accelerates GI motility and enhances GI contractions in the postprandial state. The findings suggest that lubiprostone may have an indirect prokinetic effects on the GI tract and vagal activity may be involved. Lubiprostone may be safely used.
Prokinetic effects of large-dose lubiprostone on gastrointestinal transit in dogs and its mechanisms
Song, Jun; Yin, Jieyun; Xu, Xiaohong; Chen, Jiande
2015-01-01
Objective: To systemically explore effects of large dose of lubiprostone on gastrointestinal (GI) transit and contractions and its safety in dogs. Methods: 12 healthy dogs were studied. 6 dogs were operated to receive duodenal cannula and colon cannula and the other 6 dogs received gastric cannula. Lubiprostone was orally administrated at a dose of 24 µg or 48 µg 1 hr prior to the experiments. Gastric emptying (GE) of solids and small bowel transit were evaluated by collecting the effluents from the duodenal cannula and from the colon cannula. Gastric accommodation was measured by barostat. Gastric and intestinal contractions were by manometry. Colon transit was by X-ray pictures. Results: 1) Lubiprostone 48 µg not 24 µg accelerated GE. Atropine could block the effect; 2) Average motility index (MI) of gastric antrum in lubiprostone 48 µg session was significantly higher in both fasting state (P = 0.01) and fed state (P = 0.03). Gastric accommodation was not significantly different; 3) Lubiprostone 48 µg accelerated small bowel and colon transit. Atropine could block the effect on small bowel transit; 4) Lubiprostone 48 µg increased postprandial small bowel MI (P = 0.0008) and colon MI (P = 0.002). 5) No other adverse effects except for diarrhea were observed. Conclusion: Acute administration of lubiprostone at a dose of 48 µg accelerates GI motility and enhances GI contractions in the postprandial state. The findings suggest that lubiprostone may have an indirect prokinetic effects on the GI tract and vagal activity may be involved. Lubiprostone may be safely used. PMID:26045891
Abbasi, Hamid Reza; Bolandparvaz, Shahram; Yarmohammadi, Hooman; Geramizadeh, Bita; Tanideh, Nader; Paydar, Shahram; Hosseini, Seyed Vahid
2006-10-01
Primary repair of traumatic colonic perforation is progressively gaining acceptance as the best method of management. However, when delayed, the risk of infection-related complications may increase. Here, we present a new method of repairing colon perforation in the presence of peritonitis. Acute colon injury was simulated in 22 German shepherd dogs. The dogs were randomly divided into two groups of 11 and after 24 hours they were operated on. The perforations were repaired by subserosal suture technique. In the first group (group A), ileal patch was used. In the other group (group B), the colon was closed by debridement and anastomosis. After 6 weeks, the repairs were assessed on the basis of survival, gross and histological assessments. Nine (82%) dogs in group A and six (56%) in group B survived. Ileal patch utilization significantly decreased the mortality rate (p < 0.05). The cause of death in two group A dogs and five group B dogs was peritonitis and intra-abdominal abscess formation. None of the surviving dogs showed evidence of anastomotic leakage or breakdown. Small bowel patch used in primary repair of colon injury in the presence of peritonitis may decrease the risk of postoperative infection-related complications and the mortality rate.
Outcomes of primary repair and primary anastomosis in war-related colon injuries.
Vertrees, Amy; Wakefield, Matthew; Pickett, Chris; Greer, Lauren; Wilson, Abralena; Gillern, Sue; Nelson, Jeffery; Aydelotte, Jayson; Stojadinovic, Alexander; Shriver, Craig
2009-05-01
The role of primary repair (PR) of modern day war-related colon injuries remains controversial. Retrospective review of medical records of combat-wounded soldiers with colon injuries sustained during March 2003 to August 2006 was conducted. Injuries were analyzed according to location: right (n = 30), transverse (n = 13), and left (n = 24) sided colon injuries. Two-tailed Fisher's Exact or chi tests were used for statistical analysis. Seventy-seven soldiers returned to Walter Reed Army Medical Center with colon injuries suffered during Operations Enduring Freedom and Iraqi Freedom. Twelve patients with minor colon injuries were excluded. The remaining 65 patients (mean age, 28 +/- 7 years) sustained 67 colon injuries from secondary blast (n = 38); gunshot (n = 27); motor vehicle crash (n = 1) and crush injury (n = 1). Patients arrived at Walter Reed Army Medical Center 5 days (range, 2-16 days) after injury and damage control operations (n = 27, 42%), and were hospitalized for a median of 22 days (range, 1-306 days). Follow-up averaged 311 days (median, 198 days). PR was attempted in right (n = 18, 60%), transverse (n = 11, 85%), and left (n = 9, 38%) sided colon injuries. Delayed definitive treatment of colon injuries occurred in 42% of patients. Failure of repair occurred in 16% of patients and was more likely with concomitant pancreatic, stomach, splenic, diaphragm, and renal injuries. Overall morbidity for ostomy closure after primary ostomy formation was 30%, but increased to 75% for ostomy closure after primary anastomotic or repair failure. PR of war-related colon injuries can be performed safely in selected circumstances in the absence of concomitant organ injury. Delayed anastomosis can often be performed after damage control operations once the patient stabilizes. Ostomy closure complications are more likely after anastomotic failure.
Lewis, Michael A., Larry R. Goodman, John M. Macauley and James C. Moore. 2004. Sediment Toxicity and Community Composition of Benthos and Colonized Periphyton in the Everglades-Florida Bay Transitional Zone. Ecotoxicology. 13(3):231-244. (ERL,GB 1164).
This survey provid...
Acosta, Andrés; Camilleri, Michael; Shin, Andrea; Linker Nord, Sara; O'Neill, Jessica; Gray, Amber V; Lueke, Alan J; Donato, Leslie J; Burton, Duane D; Szarka, Lawrence A; Zinsmeister, Alan R; Golden, Pamela L; Fodor, Anthony
2016-05-26
Rifaximin relieves irritable bowel syndrome (IBS) symptoms, bloating, abdominal pain, and loose or watery stools. Our objective was to investigate digestive functions in rifaximin-treated IBS patients. In a randomized, double-blind, placebo-controlled, parallel-group study, we compared the effects of rifaximin, 550 mg t.i.d., and placebo for 14 days in nonconstipated IBS and no evidence of small intestinal bacterial overgrowth (SIBO). All subjects completed baseline and on-treatment evaluation of colonic transit by scintigraphy, mucosal permeability by lactulose-mannitol excretion, and fecal microbiome, bile acids, and short chain fatty acids measured on random stool sample. Overall comparison of primary response measures between treatment groups was assessed using intention-to-treat analysis of covariance (ANCOVA, with baseline value as covariate). There were no significant effects of treatment on bowel symptoms, small bowel or colonic permeability, or colonic transit at 24 h. Rifaximin was associated with acceleration of ascending colon emptying (14.9±2.6 h placebo; 6.9±0.9 h rifaximin; P=0.033) and overall colonic transit at 48 h (geometric center 4.0±0.3 h placebo; 4.7±0.2 h rifaximin; P=0.046); however, rifaximin did not significantly alter total fecal bile acids per g of stool or proportion of individual bile acids or acetate, propionate, or butyrate in stool. Microbiome studies showed strong associations within subjects, modest associations with time across subjects, and a small but significant association of microbial richness with treatment arm (rifaximin vs. treatment). In nonconstipated IBS without documented SIBO, rifaximin treatment is associated with acceleration of colonic transit and changes in microbial richness; the mechanism for reported symptomatic benefit requires further investigation.
Burlew, Clay Cothren; Moore, Ernest E; Cuschieri, Joseph; Jurkovich, Gregory J; Codner, Panna; Crowell, Kody; Nirula, Ram; Haan, James; Rowell, Susan E; Kato, Catherine M; MacNew, Heather; Ochsner, M Gage; Harrison, Paul B; Fusco, Cynthia; Sauaia, Angela; Kaups, Krista L
2011-02-01
Use of damage control surgery techniques has reduced mortality in critically injured patients but at the cost of the open abdomen. With the option of delayed definitive management of enteric injuries, the question of intestinal repair/anastomosis or definitive stoma creation has been posed with no clear consensus. The purpose of this study was to determine outcomes on the basis of management of enteric injuries in patients relegated to the postinjury open abdomen. Patients requiring an open abdomen after trauma from January 1, 2002 to December 31, 2007 were reviewed. Type of bowel repair was categorized as immediate repair, immediate anastomosis, delayed anastomosis, stoma and a combination. Logistic regression was used to determine independent effect of risk factors on leak development. During the 6-year study period, 204 patients suffered enteric injuries and were managed with an open abdomen. The majority was men (77%) sustaining blunt trauma (66%) with a mean age of 37.1 years±1.2 years and median Injury Severity Score of 27 (interquartile range=20-41). Injury patterns included 81 (40%) small bowel, 37 (18%) colonic, and 86 (42%) combined injuries. Enteric injuries were managed with immediate repair (58), immediate anastomosis (15), delayed anastomosis (96), stoma (10), and a combination (22); three patients died before definitive repair. Sixty-one patients suffered intra-abdominal complications: 35 (17%) abscesses, 15 (7%) leaks, and 11 (5%) enterocutaneous fistulas. The majority of patients with leaks had a delayed anastomosis; one patient had a right colon repair. Leak rate increased as one progresses toward the left colon (small bowel anastomoses, 3% leak rate; right colon, 3%; transverse colon, 20%; left colon, 45%). There were no differences in emergency department physiology, injury severity, transfusions, crystalloids, or demographic characteristics between patients with and without leak. Leak cases had higher 12-hour heart rate (148 vs. 125, p=0.02) and higher 12-hour base deficit (13.7 vs. 9.7, p=0.04), suggesting persistent shock and consequent hypoperfusion were related to leak development. There was a significant trend toward higher incidence of leak with closure day (χ for trend, p=0.01), with closure after day 5 having a four times higher likelihood of developing leak (3% vs. 12%, p=0.02). Repair or anastomosis of intestinal injuries should be considered in all patients. However, leak rate increases with fascial closure beyond day 5 and with left-sided colonic anastomoses. Investigating the physiologic basis for intestinal vulnerability of the left colon and in the open abdomen is warranted.
Rodes, Laetitia; Paul, Arghya; Coussa-Charley, Michael; Al-Salami, Hani; Tomaro-Duchesneau, Catherine; Fakhoury, Marc; Prakash, Satya
2011-12-01
Retention time, which is analogous to transit time, is an index for bacterial stability in the intestine. Its consideration is of particular importance to optimize the delivery of probiotic bacteria in order to improve treatment efficacy. This study aims to investigate the effect of retention time on Lactobacilli and Bifidobacteria stability using an established in vitro human colon model. Three retention times were used: 72, 96, and 144 h. The effect of retention time on cell viability of different bacterial populations was analyzed with bacterial plate counts and PCR. The proportions of intestinal Bifidobacteria, Lactobacilli, Enterococci, Staphylococci and Clostridia populations, analyzed by plate counts, were found to be the same as that in human colonic microbiota. Retention time in the human colon affected the stability of Lactobacilli and Bifidobacteria communities, with maximum stability observed at 144 h. Therefore, retention time is an important parameter that influences bacterial stability in the colonic microbiota. Future clinical studies on probiotic bacteria formulations should take into consideration gastrointestinal transit parameters to improve treatment efficacy.
Camilleri, Michael; Bharucha, Adil E; Ueno, Ryuji; Burton, Duane; Thomforde, George M; Baxter, Kari; McKinzie, Sanna; Zinsmeister, Alan R
2006-05-01
Chloride channels modulate gastrointestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces intestinal secretion and has been shown to relieve constipation in clinical trials; however, the effects of lubiprostone on gastric function and whole gut transit in humans are unclear. Our aim was to compare the effects of the selective ClC-2 activator lubiprostone on maximum tolerated volume (MTV) of a meal, postprandial symptoms, gastric volumes, and gastrointestinal and colonic transit in humans. We performed a randomized, parallel-group, double-blind, placebo-controlled study evaluating the effects of lubiprostone (24 microg bid) in 30 healthy volunteers. Validated methods were used: scintigraphic gastrointestinal and colonic transit, SPECT to measure gastric volumes, and the nutrient drink ("satiation") test to measure MTV and postprandial symptoms. Lubiprostone accelerated small bowel and colonic transit, increased fasting gastric volume, and retarded gastric emptying. MTV values were reduced compared with placebo; however, the MTV was within the normal range for healthy adults in 13 of 14 participants, and there was no significant change compared with baseline measurements. Lubiprostone had no significant effect on postprandial gastric volume or aggregate symptoms but did decrease fullness 30 min after the fully satiating meal. Thus the ClC-2 activator lubiprostone accelerates small intestinal and colonic transit, which confers potential in the treatment of constipation.
VRX-03011, a novel 5-HT4 agonist, enhances memory and hippocampal acetylcholine efflux.
Mohler, Eric G; Shacham, Sharon; Noiman, Silvia; Lezoualc'h, Frank; Robert, Sylvain; Gastineau, Monique; Rutkowski, Joseph; Marantz, Yael; Dumuis, Aline; Bockaert, Joel; Gold, Paul E; Ragozzino, Michael E
2007-09-01
Recent evidence suggests that 5-hydroxytryptamine (5-HT)(4) receptor activity enhances cognition and provides neuroprotection. Here we report the effects of VRX-03011, a novel partial 5-HT(4) agonist, that is both potent (K(i) approximately 30 nM) and highly selective (K(i) > 5 microM for all other 5-HT receptors tested). In separate experiments, rats received VRX-03011 (0.1-10 mg/kg i.p.) 30 min prior to spontaneous alternation testing in a no-delay or a 30-s delay condition. VRX-03011 (1, 5 and 10 mg/kg, but not 0.1 mg/kg) significantly enhanced delayed spontaneous alternation performance while none of the doses enhanced performance in the no-delay test. VRX-03011 (1 and 5 mg/kg) concomitantly enhanced hippocampal acetylcholine output and delayed spontaneous alternation scores compared to that of vehicle controls, but had no effect on hippocampal acetylcholine release under a resting condition. Moreover, suboptimal doses of VRX-03011 and the acetylcholinesterase inhibitor galanthamine combined to enhance memory. VRX-03011 also regulated amyloid precursor protein (APP) metabolism by inducing a concentration-dependent increase in the non-amyloidogenic soluble form of APP (sAPPalpha) with an EC(50) approximately 1--10 nM. VRX-03011 had no effect on contractile properties in guinea pig ileum or colon preparations with an EC(50) > 10 microM and did not alter rat intestinal transit at doses up to 10 mg/kg. These findings suggest that VRX-03011 may represent a novel treatment for Alzheimer's disease that reduces cognitive impairments and provides neuroprotection without gastrointestinal side effects.
Multicenter, randomized study to optimize bowel preparation for colon capsule endoscopy
Kastenberg, David; Jr, Wilmot C Burch; Romeo, David P; Kashyap, Pankaj K; Pound, David C; Papageorgiou, Neophytos; Sainz, Ignacio Fernández-Urien; Sokach, Carly E; Rex, Douglas K
2017-01-01
AIM To assess the cleansing efficacy and safety of a new Colon capsule endoscopy (CCE) bowel preparation regimen. METHODS This was a multicenter, prospective, randomized, controlled study comparing two CCE regimens. Subjects were asymptomatic and average risk for colorectal cancer. The second generation CCE system (PillCam® COLON 2; Medtronic, Yoqneam, Israel) was utilized. Preparation regimens differed in the 1st and 2nd boosts with the Study regimen using oral sulfate solution (89 mL) with diatrizoate meglumine and diatrizoate sodium solution (“diatrizoate solution”) (boost 1 = 60 mL, boost 2 = 30 mL) and the Control regimen oral sulfate solution (89 mL) alone. The primary outcome was overall and segmental colon cleansing. Secondary outcomes included safety, polyp detection, colonic transit, CCE completion and capsule excretion ≤ 12 h. RESULTS Both regimens had similar cleansing efficacy for the whole colon (Adequate: Study = 75.9%, Control = 77.3%; P = 0.88) and individual segments. In the Study group, CCE completion was superior (Study = 90.9%, Control = 76.9%; P = 0.048) and colonic transit was more often < 40 min (Study = 21.8%, Control = 4%; P = 0.0073). More Study regimen subjects experienced adverse events (Study = 19.4%, Control = 3.4%; P = 0.0061), and this difference did not appear related to diatrizoate solution. Adverse events were primarily gastrointestinal in nature and no serious adverse events related either to the bowel preparation regimen or the capsule were observed. There was a trend toward higher polyp detection with the Study regimen, but this did not achieve statistical significance for any size category. Mean transit time through the entire gastrointestinal tract, from ingestion to excretion, was shorter with the Study regimen while mean colonic transit times were similar for both study groups. CONCLUSION A CCE bowel preparation regimen using oral sulfate solution and diatrizoate solution as a boost agent is effective, safe, and achieved superior CCE completion. PMID:29358870
Periasamy, Srinivasan; Liu, Chung-Teng; Wu, Wang-Hung; Chien, Se-Ping; Liu, Ming-Yie
2015-01-01
Ziziphus jujuba (ZJ) fruit is rich in bioactive functional components such as polysaccharides, triterpenoid acid, flavonoids and oleamide. It has been commonly used in the treatment of various diseases including diabetes, digestive disorders, diarrhea, skin infections, liver and urinary complaints. However, dietary effects with regard to chemoprevention of colon cancer have not been studied. The present study was performed to evaluate the protective effects of dietary ZJ against colitis-associated colon carcinogenesis in azoxymethane (AOM)-dextran sodium sulphate (DSS)-treated mice. AOM was injected (10 mg/kg b.wt., i.p.) and three cycles of 2% DSS in drinking water for 7 days with 14 days of normal drinking water in-between were administered to induce colitis-associated colon cancer. ZJ fruit was supplemented into feed at levels of 5 and 10%. Dietary ZJ significantly attenuated aberrant crypt foci (ACF) formation and also decreased the progression of hyperplasia to dysplasia. In addition, it significantly reduced circulating white blood cells, lymphocytes, neutrophils, monocytes, eosinophils, basophils and platelets compared to colon cancer mice. We conclude that ZJ supplementation may delay the progression of colon cancer from hyperplasia to dysplasia and ultimately adenocarcinoma and cancer. In addition, it decreased circulating tumor-related leukocytes, main regulators of cancer inflammation. Dietary consumption of ZJ fruit attenuated the formation of ACF and delayed the progression of colon cancer.
Time-delayed transition of normal-to-abnormal glow in pin-to-water discharge
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yoon, S.-Y.; Byeon, Y.-S.; Yoo, S.
2016-08-15
Time-delayed transition of normal-to-abnormal glow was investigated in discharge between spoke-like pins and ultrapure water by applying AC-driven power at a frequency of 14.3 kHz at atmospheric pressure. The normal-to-abnormal transition can be recognized from the slope changes of current density, gas temperature, electrode temperature, and OH density. The slope changes took place in tens of minutes rather than just after discharge, in other words, the transition was delayed. The time-delay of the transition was caused by the interaction between the plasma and water. The plasma affected water properties, and then the water affected plasma properties.
Invertebrate colonization rates in the tailwater of a Kentucky flood-control reservoir
Swink, W.D.; Novotny, J.F.
1985-01-01
Invertebrate colonization on newly introduced rock substrates was examined from July through October 1982 in the tailwater of Barren River Lake, Kentucky. Chironomidae, the dominant taxon of benthic insects, reached full colonization by day 14. Colonization by Oligochaeta, the other major invertebrate taxon, was not completed by the end of the 95-day period of observation. It may have been delayed because insufficient food (periphyton and detritus) had accumulated on the clean rocks. Rapid recolonization of dewatered substrates may be especially critical for maintaining adequate fish food in tailwaters of flood-control reservoir.
Simmons, R B; Crow, S A
1995-01-01
New and used cellulosic air filters for HVAC systems including those treated with antimicrobials were suspended in vessels with a range of relative humidities (55-99%) and containing non-sterile potting soil which stimulates fungal growth. Most filters yielded fungi prior to suspension in the chambers but only two of 14 nontreated filters demonstrated fungal colonization following use in HVAC systems. Filters treated with antimicrobials, particularly a phosphated amine complex, demonstrated markedly less fungal colonization than nontreated filters. In comparison with nontreated cellulosic filters, fungal colonization of antimicrobial-treated cellulosic filters was selective and delayed.
Castillejo, Gemma; Bulló, Mònica; Anguera, Anna; Escribano, Joaquin; Salas-Salvadó, Jordi
2006-09-01
Although a diet that is rich in fiber is widely recommended for preventing and treating constipation, the efficacy of fiber supplements have not been tested sufficiently in children. Our aim with this pilot study was to evaluate if fiber supplementation is beneficial for the treatment of children with idiopathic chronic constipation. Using a parallel, randomized, double-blind, controlled trial, we conducted an interventional study to evaluate the efficacy of a supplement of cocoa husk rich in dietary fiber on intestinal transit time and other indices of constipation in children with constipation. After screening, the patients were randomly allocated to receive, for a period of 4 weeks, either a cocoa husk supplement or placebo plus standardized toilet training procedures. Before and after 4 weeks of treatment, we (1) performed anthropometry, a physical examination, and routine laboratory measurements, (2) determined total and segmental colonic transit time, (3) evaluated bowel movement habits and stool consistency using a diary, and (4) received a subjective evaluation from the parents regarding the efficacy of the treatment. The main variable for verifying the efficacy of the treatment was the total colonic transit time. Fifty-six chronically constipated children were randomly assigned into the study, but only 48 children completed it. These children, who were aged between 3 and 10 years, had a diagnosis of chronic idiopathic constipation. With respect to total, partial colon, and rectum transit time, there seemed to be a trend, although statistically nonsignificant, toward faster transit times in the cocoa husk group than in the placebo group. When we analyzed the evolution of the intestinal transit time throughout the study of children whose total basal intestinal transit time was > 50th percentile, significant differences were observed between the groups. The total transit time decreased by 45.4 +/- 38.4 hours in the cocoa husk group and by 8.7 +/- 28.9 hours in the placebo group (-38.1 hours). In the case of the right colon, changes in transit time also were significant between groups. Mean changes tended toward faster transit times in the left colon and the rectum, although the differences were not statistically significant. The children who received cocoa husk supplements tended to increase the number of bowel movements by more than that of the children of the placebo group. We also observed a reduction in the percentage of patients who reported hard stools (hard scybalous or pebble-like stools), although this reduction was significantly greater in the cocoa husk group. At the end of the intervention, 41.7% and 75.0% of the patients who received cocoa husk supplementation or placebo, respectively, reported having hard stools. Moreover, a significantly higher number of children (or their parents) reported a subjective improvement in stool consistency. No significant adverse effects were reported during the study. This study confirms the beneficial effect of a supplement of cocoa husk that is rich in dietary fiber on chronic idiopathic constipation in children. These benefits seem to be more evident in pediatric constipated patients with slow colonic transit time.
Sánchez-Martínez, Ruth; Álvarez-Fernández, Mónica; Vargas, Teodoro; Molina, Susana; García, Belén; Herranz, Jesús; Moreno-Rubio, Juan; Reglero, Guillermo; Pérez-Moreno, Mirna; Feliu, Jaime; Malumbres, Marcos; de Molina, Ana Ramírez
2015-01-01
The alterations in carbohydrate metabolism that fuel tumor growth have been extensively studied. However, other metabolic pathways involved in malignant progression, demand further understanding. Here we describe a metabolic acyl-CoA synthetase/stearoyl-CoA desaturase ACSL/SCD network causing an epithelial-mesenchymal transition (EMT) program that promotes migration and invasion of colon cancer cells. The mesenchymal phenotype produced upon overexpression of these enzymes is reverted through reactivation of AMPK signaling. Furthermore, this network expression correlates with poorer clinical outcome of stage-II colon cancer patients. Finally, combined treatment with chemical inhibitors of ACSL/SCD selectively decreases cancer cell viability without reducing normal cells viability. Thus, ACSL/SCD network stimulates colon cancer progression through conferring increased energetic capacity and invasive and migratory properties to cancer cells, and might represent a new therapeutic opportunity for colon cancer treatment. PMID:26451612
Aging transition in systems of oscillators with global distributed-delay coupling.
Rahman, B; Blyuss, K B; Kyrychko, Y N
2017-09-01
We consider a globally coupled network of active (oscillatory) and inactive (nonoscillatory) oscillators with distributed-delay coupling. Conditions for aging transition, associated with suppression of oscillations, are derived for uniform and gamma delay distributions in terms of coupling parameters and the proportion of inactive oscillators. The results suggest that for the uniform distribution increasing the width of distribution for the same mean delay allows aging transition to happen for a smaller coupling strength and a smaller proportion of inactive elements. For gamma distribution with sufficiently large mean time delay, it may be possible to achieve aging transition for an arbitrary proportion of inactive oscillators, as long as the coupling strength lies in a certain range.
Firing patterns transition and desynchronization induced by time delay in neural networks
NASA Astrophysics Data System (ADS)
Huang, Shoufang; Zhang, Jiqian; Wang, Maosheng; Hu, Chin-Kun
2018-06-01
We used the Hindmarsh-Rose (HR) model (Hindmarsh and Rose, 1984) to study the effect of time delay on the transition of firing behaviors and desynchronization in neural networks. As time delay is increased, neural networks exhibit diversity of firing behaviors, including regular spiking or bursting and firing patterns transitions (FPTs). Meanwhile, the desynchronization of firing and unstable bursting with decreasing amplitude in neural system, are also increasingly enhanced with the increase of time delay. Furthermore, we also studied the effect of coupling strength and network randomness on these phenomena. Our results imply that time delays can induce transition and desynchronization of firing behaviors in neural networks. These findings provide new insight into the role of time delay in the firing activities of neural networks, and can help to better understand the firing phenomena in complex systems of neural networks. A possible mechanism in brain that can cause the increase of time delay is discussed.
Wampach, Linda; Heintz-Buschart, Anna; Hogan, Angela; Muller, Emilie E L; Narayanasamy, Shaman; Laczny, Cedric C; Hugerth, Luisa W; Bindl, Lutz; Bottu, Jean; Andersson, Anders F; de Beaufort, Carine; Wilmes, Paul
2017-01-01
Perturbations to the colonization process of the human gastrointestinal tract have been suggested to result in adverse health effects later in life. Although much research has been performed on bacterial colonization and succession, much less is known about the other two domains of life, archaea, and eukaryotes. Here we describe colonization and succession by bacteria, archaea and microeukaryotes during the first year of life (samples collected around days 1, 3, 5, 28, 150, and 365) within the gastrointestinal tract of infants delivered either vaginally or by cesarean section and using a combination of quantitative real-time PCR as well as 16S and 18S rRNA gene amplicon sequencing. Sequences from organisms belonging to all three domains of life were detectable in all of the collected meconium samples. The microeukaryotic community composition fluctuated strongly over time and early diversification was delayed in infants receiving formula milk. Cesarean section-delivered (CSD) infants experienced a delay in colonization and succession, which was observed for all three domains of life. Shifts in prokaryotic succession in CSD infants compared to vaginally delivered (VD) infants were apparent as early as days 3 and 5, which were characterized by increased relative abundances of the genera Streptococcus and Staphylococcus , and a decrease in relative abundance for the genera Bifidobacterium and Bacteroides . Generally, a depletion in Bacteroidetes was detected as early as day 5 postpartum in CSD infants, causing a significantly increased Firmicutes/Bacteroidetes ratio between days 5 and 150 when compared to VD infants. Although the delivery mode appeared to have the strongest influence on differences between the infants, other factors such as a younger gestational age or maternal antibiotics intake likely contributed to the observed patterns as well. Our findings complement previous observations of a delay in colonization and succession of CSD infants, which affects not only bacteria but also archaea and microeukaryotes. This further highlights the need for resolving bacterial, archaeal, and microeukaryotic dynamics in future longitudinal studies of microbial colonization and succession within the neonatal gastrointestinal tract.
Wampach, Linda; Heintz-Buschart, Anna; Hogan, Angela; Muller, Emilie E. L.; Narayanasamy, Shaman; Laczny, Cedric C.; Hugerth, Luisa W.; Bindl, Lutz; Bottu, Jean; Andersson, Anders F.; de Beaufort, Carine; Wilmes, Paul
2017-01-01
Perturbations to the colonization process of the human gastrointestinal tract have been suggested to result in adverse health effects later in life. Although much research has been performed on bacterial colonization and succession, much less is known about the other two domains of life, archaea, and eukaryotes. Here we describe colonization and succession by bacteria, archaea and microeukaryotes during the first year of life (samples collected around days 1, 3, 5, 28, 150, and 365) within the gastrointestinal tract of infants delivered either vaginally or by cesarean section and using a combination of quantitative real-time PCR as well as 16S and 18S rRNA gene amplicon sequencing. Sequences from organisms belonging to all three domains of life were detectable in all of the collected meconium samples. The microeukaryotic community composition fluctuated strongly over time and early diversification was delayed in infants receiving formula milk. Cesarean section-delivered (CSD) infants experienced a delay in colonization and succession, which was observed for all three domains of life. Shifts in prokaryotic succession in CSD infants compared to vaginally delivered (VD) infants were apparent as early as days 3 and 5, which were characterized by increased relative abundances of the genera Streptococcus and Staphylococcus, and a decrease in relative abundance for the genera Bifidobacterium and Bacteroides. Generally, a depletion in Bacteroidetes was detected as early as day 5 postpartum in CSD infants, causing a significantly increased Firmicutes/Bacteroidetes ratio between days 5 and 150 when compared to VD infants. Although the delivery mode appeared to have the strongest influence on differences between the infants, other factors such as a younger gestational age or maternal antibiotics intake likely contributed to the observed patterns as well. Our findings complement previous observations of a delay in colonization and succession of CSD infants, which affects not only bacteria but also archaea and microeukaryotes. This further highlights the need for resolving bacterial, archaeal, and microeukaryotic dynamics in future longitudinal studies of microbial colonization and succession within the neonatal gastrointestinal tract. PMID:28512451
van der Plas, R N; Benninga, M; Staalman, C; Akkermans, L; Redekop, W; Taminiau, J; Buller, H
2000-01-01
BACKGROUND—Faecal impaction is frequently observed in children with chronic constipation. The term megarectum is often used to describe this finding. AIM—To evaluate rectal functioning and rectal measures in constipated children with a filled rectum, in order to define the terms faecal impaction, enlarged rectum, and megarectum. METHODS—All children underwent radiological investigation, colonic transit time study, anorectal manometry, and rectal volume and rectal wall compliance measurements. Patients with faecal impaction were compared with controls, who had an empty rectum on digital rectal examination. RESULTS—A total of 31 patients and six controls were included in the study. The mean duration of complaints was 4.2 years and all had faecal incontinence. The colonic transit times in the patients showed a distinct delay in the rectosigmoid segment. Anorectal manometry was not significantly different between patients and controls. The rectal width in patients was 0.68 and in controls 0.52 with an upper limit of 0.61. The pressure-volume curve in patients showed significant less relaxation at a distension of 50 ml. The slope of the curve (corresponding with rectal wall compliance) was comparable for patients and controls. CONCLUSIONS—We suggest that faecal impaction is a filled rectum found on digital rectal examination; an enlarged rectum is defined by a rectopelvic ratio greater than 0.61; and megarectum is defined in those with significant abnormalities found with anorectal manometry, pressure-volume curves, or rectal compliance investigation. A diminished relaxation of the rectum on rectal distension could be the first sign of megarectum in children with chronic constipation. PMID:10869000
Wehner, S; Vilz, T O; Sommer, N; Sielecki, T; Hong, G S; Lysson, M; Stoffels, B; Pantelis, D; Kalff, J C
2012-10-01
Postoperative ileus (POI) is an iatrogenic complication of abdominal surgery, mediated by a severe inflammation of the muscularis externa (ME). Previously, we demonstrated that intravenous application of the tetravalent guanylhydrazone semapimod (CNI-1493) prevents POI, but the underlying mode of action could not definitively be confirmed. Herein, we investigated the effect of a novel orally active salt of semapimod (CPSI-2364) on POI in rodents and distinguished between its inhibitory peripheral and stimulatory central nervous effects on anti-inflammatory vagus nerve signaling. Distribution of radiolabeled orally administered CPSI-2364 was analyzed by whole body autoradiography and liquid scintillation counting. POI was induced by intestinal manipulation with or without preoperative vagotomy. CPSI-2364 was administered preoperatively via gavage in a dose- and time-dependent manner. ME specimens were assessed for p38-MAP kinase activity by immunoblotting, neutrophil extravasation, and nitric oxide production. Furthermore, in vivo gastrointestinal (GIT) and colonic transit were measured. Autoradiography demonstrated a near-exclusive detection of CPSI-2364 within the gastrointestinal wall and contents. Preoperative CPSI-2364 application significantly reduced postoperative neutrophil counts, nitric oxide release, GIT deceleration, and delay of colonic transit time, while intraoperatively administered CPSI-2364 failed to improve POI. CPSI-2364 also prevents postoperative neutrophil increase and GIT deceleration in vagotomized mice. Orally administered CPSI-2364 shows a near-exclusive dispersal in the gastrointestinal tract and effectively reduces POI independently of central vagus nerve stimulation. Its efficacy after single oral dosage affirms CPSI-2364 treatment as a promising strategy for prophylaxis of POI.
Siah, Kewin T H; Wong, Reuben K; Whitehead, William E
2016-03-01
Rome III diagnostic criteria separate patients with idiopathic chronic constipation into mutually exclusive categories of constipation-predominant irritable bowel syndrome (IBS-C) or functional constipation (FC). However, several experts think that these conditions are not different disorders, but parts of a continuum. To shed light on this issue, we examined studies that compared IBS-C with FC with respect to symptoms, pathophysiologic mechanisms, and treatment response. When the Rome III requirement that patients meeting criteria for IBS cannot also be given a diagnosis of FC is suspended, most patients meet criteria for both, and, contrary to expectation, IBS-C patients have more symptoms of constipation than patients with FC. No symptoms reliably separate IBS-C from FC. Physiologic tests are not reliably associated with diagnosis, but visceral pain hypersensitivity tends to be more strongly associated with IBS-C than with FC, and delayed colonic transit tends to be more common in FC. Although some treatments are effective for both IBS-C and FC, such as prosecretory agents, other treatments are specific to IBS-C (eg, antidepressants, antispasmodics, cognitive behavior therapy) or FC (eg, prucalopride, biofeedback). Future studies should permit IBS-C and FC diagnoses to overlap. Physiologic tests comparing these disorders should include visceral pain sensitivity, colonic transit time, time to evacuate a water-filled balloon, and anal pressures or electromyographic activity from the anal canal. To date, differential responses to treatment provide the strongest evidence that IBS-C and FC may be different disorders, rather than parts of a spectrum.
Siah, Kewin T. H.; Wong, Reuben K.
2016-01-01
Rome III diagnostic criteria separate patients with idiopathic chronic constipation into mutually exclusive categories of constipation-predominant irritable bowel syndrome (IBS-C) or functional constipation (FC). However, several experts think that these conditions are not different disorders, but parts of a continuum. To shed light on this issue, we examined studies that compared IBS-C with FC with respect to symptoms, pathophysiologic mechanisms, and treatment response. When the Rome III requirement that patients meeting criteria for IBS cannot also be given a diagnosis of FC is suspended, most patients meet criteria for both, and, contrary to expectation, IBS-C patients have more symptoms of constipation than patients with FC. No symptoms reliably separate IBS-C from FC. Physiologic tests are not reliably associated with diagnosis, but visceral pain hypersensitivity tends to be more strongly associated with IBS-C than with FC, and delayed colonic transit tends to be more common in FC. Although some treatments are effective for both IBS-C and FC, such as prosecretory agents, other treatments are specific to IBS-C (eg, antidepressants, antispasmodics, cognitive behavior therapy) or FC (eg, prucalopride, biofeedback). Future studies should permit IBS-C and FC diagnoses to overlap. Physiologic tests comparing these disorders should include visceral pain sensitivity, colonic transit time, time to evacuate a water-filled balloon, and anal pressures or electromyographic activity from the anal canal. To date, differential responses to treatment provide the strongest evidence that IBS-C and FC may be different disorders, rather than parts of a spectrum. PMID:27231446
Lesions Responsible for Delayed Oral Transit Time in Post-stroke Dysphagia.
Moon, Hyun Im; Yoon, Seo Yeon; Yi, Tae Im; Jeong, Yoon Jeong; Cho, Tae Hwan
2018-06-01
Some stroke patients show oral phase dysphagia, characterized by a markedly prolonged oral transit time that hinders oral feeding. The aim of this study was to clarify the clinical characteristics and lesions responsible for delayed swallowing. We reviewed 90 patients with stroke. The oral processing time plus the postfaucial aggregation time required to swallow semisolid food was assessed. The patients were divided into two groups according to oral transit time, and we analyzed the differences in characteristics such as demographic factors, lesion factors, and cognitive function. Logistic regression analyses were performed to examine the predictors of delayed oral transit time. Lesion location and volume were measured on brain magnetic resonance images. We generated statistic maps of lesions related to delayed oral phase in swallowing using voxel-based lesion symptom mapping (VLSM). The group of patients who showed delayed oral transit time had significantly low cognitive function. Also, in a regression model, delayed oral phase was predicted with low K-MMSE (Korean version of the Mini Mental Status Exam). Using VLSM, we found the lesion location to be associated with delayed oral phase after adjusting for K-MMSE score. Although these results did not reach statistical significance, they showed the lesion pattern with predominant distribution in the left frontal lobe. Delayed oral phase in post-stroke patients was not negligible clinically. Patients' cognitive impairments affect the oral transit time. When adjusting it, we found a trend that the lesion responsible for delayed oral phase was located in the left frontal lobe, though the association did not reach significance. The delay might be related to praxis function.
Tooth, David; Garsed, Klara; Singh, Gulzar; Marciani, Luca; Lam, Ching; Fordham, Imogen; Fields, Annie; Banwait, Rawinder; Lingaya, Melanie; Layfield, Robert; Hastings, Maggie; Whorwell, Peter; Spiller, Robin
2014-05-01
Faecal serine proteases (FSPs) may play a role in irritable bowel syndrome with diarrhoea (IBS-D), but their origin is unclear. We aimed to structurally characterise them and define the impact of colonic cleansing and transit time. Faecal samples were obtained from 30 healthy volunteers (HV) and 79 patients with IBS-D participating in a trial of ondansetron versus placebo. Colonic transit was measured using radio-opaque markers. Samples were also obtained from 24 HV before and after colonic cleansing with the osmotic laxative MoviPrep. FSPs were purified from faecal extracts using benzamidine-Sepharose affinity chromatography. SDS-PAGE profiled components were identified using trypsinolysis and tandem mass spectrometry. Functional protease activity in faecal extracts was measured using a colorimetric assay based on the proteolysis of azo-casein. Protein analysis identified the most abundant FSPs as being of human origin and probably derived from pancreatic juice. Functional assays showed increased faecal protease (FP) and amylase in patients with IBS-D compared with HV. Those with higher amylase had significantly higher FP and greater anxiety. FP activity correlated negatively with whole gut transit in patients with IBS-D (Spearman r=-0.32, p=0.005) and HV (r=-0.55, p=0.014). Colon cleansing caused a significant rise in FP activity in HV from a baseline of median (IQR) 253 (140-426) to 1031 (435-2296), levels similar to those seen in patients with IBS-D. FSP activity correlated positively with days/week with urgency. The most abundant FSPs are of human origin. Rapid transit through the colon and/or decreased (possibly bacterial) proteolytic degradation increases their faecal concentration and could contribute to visceral hypersensitivity in patients with IBS-D. NCT00745004.
Wren, John T.; Blevins, Lance K.; Pang, Bing; King, Lauren B.; Perez, Antonia C.; Murrah, Kyle A.; Reimche, Jennifer L.; Alexander-Miller, Martha A.
2014-01-01
Streptococcus pneumoniae (pneumococcus) is both a widespread nasal colonizer and a leading cause of otitis media, one of the most common diseases of childhood. Pneumococcal phase variation influences both colonization and disease and thus has been linked to the bacteria's transition from colonizer to otopathogen. Further contributing to this transition, coinfection with influenza A virus has been strongly associated epidemiologically with the dissemination of pneumococci from the nasopharynx to the middle ear. Using a mouse infection model, we demonstrated that coinfection with influenza virus and pneumococci enhanced both colonization and inflammatory responses within the nasopharynx and middle ear chamber. Coinfection studies were also performed using pneumococcal populations enriched for opaque or transparent phase variants. As shown previously, opaque variants were less able to colonize the nasopharynx. In vitro, this phase also demonstrated diminished biofilm viability and epithelial adherence. However, coinfection with influenza virus ameliorated this colonization defect in vivo. Further, viral coinfection ultimately induced a similar magnitude of middle ear infection by both phase variants. These data indicate that despite inherent differences in colonization, the influenza A virus exacerbation of experimental middle ear infection is independent of the pneumococcal phase. These findings provide new insights into the synergistic link between pneumococcus and influenza virus in the context of otitis media. PMID:25156728
Koh, S D; Ward, S M; Dick, G M; Epperson, A; Bonner, H P; Sanders, K M; Horowitz, B; Kenyon, J L
1999-01-01
We used intracellular microelectrodes to record the membrane potential (Vm) of intact murine colonic smooth muscle. Electrical activity consisted of spike complexes separated by quiescent periods (Vm≈−60 mV). The spike complexes consisted of about a dozen action potentials of approximately 30 mV amplitude. Tetraethylammonium (TEA, 1–10 mM) had little effect on the quiescent periods but increased the amplitude of the action potential spikes. 4-Aminopyridine (4-AP, ⋧ 5 mM) caused continuous spiking.Voltage clamp of isolated myocytes identified delayed rectifier K+ currents that activated rapidly (time to half-maximum current, 11.5 ms at 0 mV) and inactivated in two phases (τf = 96 ms, τs = 1.5 s at 0 mV). The half-activation voltage of the permeability was −27 mV, with significant activation at −50 mV.TEA (10 mM) reduced the outward current at potentials positive to 0 mV. 4-AP (5 mM) reduced the early current but increased outward current at later times (100–500 ms) consistent with block of resting channels relieved by depolarization. 4-AP inhibited outward current at potentials negative to −20 mV, potentials where TEA had no effect.Qualitative PCR amplification of mRNA identified transcripts encoding delayed rectifier K+ channel subunits Kv1.6, Kv4.1, Kv4.2, Kv4.3 and the Kvβ1.1 subunit in murine colon myocytes. mRNA encoding Kv 1.4 was not detected.We find that TEA-sensitive delayed rectifier currents are important determinants of action potential amplitude but not rhythmicity. Delayed rectifier currents sensitive to 4-AP are important determinants of rhythmicity but not action potential amplitude. PMID:10050014
Aihara, Eitaro; Closson, Chet; Matthis, Andrea L.; Schumacher, Michael A.; Engevik, Amy C.; Zavros, Yana; Ottemann, Karen M.; Montrose, Marshall H.
2014-01-01
Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (106) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (106) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases the injured tissue towards sustained gastric damage. PMID:25033386
Aihara, Eitaro; Closson, Chet; Matthis, Andrea L; Schumacher, Michael A; Engevik, Amy C; Zavros, Yana; Ottemann, Karen M; Montrose, Marshall H
2014-07-01
Helicobacter pylori (H. pylori) is a pathogen contributing to peptic inflammation, ulceration, and cancer. A crucial step in the pathogenic sequence is when the bacterium first interacts with gastric tissue, an event that is poorly understood in vivo. We have shown that the luminal space adjacent to gastric epithelial damage is a microenvironment, and we hypothesized that this microenvironment might enhance H. pylori colonization. Inoculation with 106 H. pylori (wild-type Sydney Strain 1, SS1) significantly delayed healing of acetic-acid induced ulcers at Day 1, 7 and 30 post-inoculation, and wild-type SS1 preferentially colonized the ulcerated area compared to uninjured gastric tissue in the same animal at all time points. Gastric resident Lactobacillus spp. did not preferentially colonize ulcerated tissue. To determine whether bacterial motility and chemotaxis are important to ulcer healing and colonization, we analyzed isogenic H. pylori mutants defective in motility (ΔmotB) or chemotaxis (ΔcheY). ΔmotB (10(6)) failed to colonize ulcerated or healthy stomach tissue. ΔcheY (10(6)) colonized both tissues, but without preferential colonization of ulcerated tissue. However, ΔcheY did modestly delay ulcer healing, suggesting that chemotaxis is not required for this process. We used two-photon microscopy to induce microscopic epithelial lesions in vivo, and evaluated accumulation of fluorescently labeled H. pylori at gastric damage sites in the time frame of minutes instead of days. By 5 min after inducing damage, H. pylori SS1 preferentially accumulated at the site of damage and inhibited gastric epithelial restitution. H. pylori ΔcheY modestly accumulated at the gastric surface and inhibited restitution, but did not preferentially accumulate at the injury site. H. pylori ΔmotB neither accumulated at the surface nor inhibited restitution. We conclude that bacterial chemosensing and motility rapidly promote H. pylori colonization of injury sites, and thereby biases the injured tissue towards sustained gastric damage.
2018-02-12
Healthy Subject; Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Psychosocial Effects of Cancer and Its Treatment; Recurrent Bladder Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Gastric Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Recurrent Uterine Sarcoma; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage II Bladder Cancer; Stage II Renal Cell Cancer; Stage II Urethral Cancer; Stage IIA Cervical Cancer; Stage IIA Colon Cancer; Stage IIA Gastric Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIA Uterine Sarcoma; Stage IIB Cervical Cancer; Stage IIB Colon Cancer; Stage IIB Gastric Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIB Uterine Sarcoma; Stage IIC Colon Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Rectal Cancer; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage III Urethral Cancer; Stage IIIA Cervical Cancer; Stage IIIA Colon Cancer; Stage IIIA Gastric Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Uterine Sarcoma; Stage IIIB Cervical Cancer; Stage IIIB Colon Cancer; Stage IIIB Gastric Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Uterine Sarcoma; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC Uterine Sarcoma; Stage IV Bladder Cancer; Stage IV Gastric Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Renal Cell Cancer; Stage IV Urethral Cancer; Stage IVA Cervical Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVA Uterine Sarcoma; Stage IVB Cervical Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Stage IVB Uterine Sarcoma; Ureter Cancer; Stage IIA Lung Carcinoma; Stage IIB Lung Carcinoma; Stage IIIA Lung Carcinoma; Stage IIIB Lung Carcinoma
Stankic, Marko; Pavlovic, Svetlana; Chin, Yvette; Brogi, Edi; Padua, David; Norton, Larry; Massague, Joan; Benezra, Robert
2014-01-01
SUMMARY ID genes are required for breast cancer colonization of the lungs, but the mechanism remains poorly understood. Here, we show that Id1 expression induces a stem-like phenotype in breast cancer cells, while retaining epithelial properties, contrary to the notion that cancer stem-like properties are inextricably linked to the mesenchymal state. During metastatic colonization, Id1 induces a mesenchymal-to-epithelial transition (MET), specifically in cells whose mesenchymal state is dependent on the Id1 target protein Twist1 but not at the primary site, where this state is controlled by the zinc-finger protein Snail1. Knockdown of Id expression in metastasizing cells prevents MET and dramatically reduces lung colonization. Furthermore, Id1 is induced by TGFβ only in cells that have first undergone EMT, demonstrating that EMT is a pre-requisite for subsequent Id1-induced MET during lung colonization. Collectively, these studies underscore the importance of Id-mediated phenotypic switching during distinct stages of breast cancer metastasis. PMID:24332369
Enterococcus faecalis causing delayed spondylodiscitis in a case with retained intraspinal bullet.
Aiyer, Siddharth N; Shetty, Ajoy Prasad; Kanna, Rishi; Reddy, Srikanth; Rajasekaran, Shanmuganathan
2016-12-01
Delayed presentations have been reported following gunshot wounds (GSW) with retained intraspinal bullets due to migration of projectile or lead intoxication. We report on the rare occurrence of delayed pyogenic spondylodiscitis and neurological dysfunction following injury from low velocity GSW to the spine with a retained projectile. A 55-year-old male presented 4 months following GSW to the abdomen which resulted in colonic injury and L5 fracture. The patient was treated initially with ileo-transverse anastomosis, antibiotics, without retrieval of the bullet. He developed low back pain, claudication 4 months following GSW and investigations suggested a pyogenic spondylodiscitis at L5-S1. The patient was treated with surgical debridement of infective focus and stabilisation with definitive fusion being performed after an interval of 14 days. The biopsy of the lesion confirmed findings of spondylodiscitis and the culture isolated Enterococcus faecalis species. The patient was treated with antibiotics as per sensitivity and made an uneventful recovery over 4 weeks. The follow-up radiographs showed satisfactory healing at final follow up of 24 months. GSW with colonic perforation have higher incidence of infective complications however majority to these occur in the early postoperative period. This case report demonstrates the possibility of late onset presentation due to spinal infection occurring following colonic perforation with retained intraspinal bullet.
Egea, Laia; McAllister, Christopher S.; Lakhdari, Omar; Minev, Ivelina; Shenouda, Steve; Kagnoff, Martin F.
2012-01-01
GM-CSF is a growth factor that promotes the survival and activation of macrophages and granulocytes, and dendritic cell (DC) differentiation and survival in vitro. The mechanism by which exogenous GM-CSF ameliorates the severity of Crohn’s disease in humans and colitis in murine models has been considered mainly to reflect its activity on myeloid cells. We used GM-CSF deficient (GM-CSF−/−) mice to probe the functional role of endogenous host-produced GM-CSF in a colitis model induced after injury to the colon epithelium. Dextran sodium sulfate (DSS) at doses that resulted in little epithelial damage and mucosal ulceration in wild type (WT) mice resulted in marked colon ulceration and delayed ulcer healing in GM-CSF−/− mice. Colon crypt epithelial cell proliferation in vivo was significantly decreased in GM-CSF−/− mice at early times after DSS injury. This was paralleled by decreased expression of crypt epithelial cell genes involved in cell cycle, proliferation, and wound healing. Decreased crypt cell proliferation and delayed ulcer healing in GM-CSF−/− mice were rescued by exogenous GM-CSF, indicating the lack of a developmental abnormality in the epithelial cell proliferative response in those mice. Non-hematopoietic cells and not myeloid cells produced the GM-CSF important for colon epithelial proliferation after DSS-induced injury as revealed by bone marrow chimera and DC depletion experiments, with colon epithelial cells being the cellular source of GM-CSF. Endogenous epithelial cell produced GM-CSF has a novel non-redundant role in facilitating epithelial cell proliferation and ulcer healing in response to injury of the colon crypt epithelium. PMID:23325885
Chen, Wenbo; Lu, Xuqiang; Chen, Yuan; Li, Ming; Mo, Pingli; Tong, Zhangwei; Wang, Wei; Wan, Wei; Su, Guoqiang; Xu, Jianming; Yu, Chundong
2017-02-15
Steroid receptor coactivator 3 (SRC-3) is a transcriptional coactivator that interacts with nuclear receptors and some other transcription factors to enhance their effects on target gene transcription. We reported previously that SRC-3-deficient (SRC-3 -/- ) mice are extremely susceptible to Escherichia coli-induced septic peritonitis as a result of uncontrolled inflammation and a defect in bacterial clearance. In this study, we observed significant upregulation of SRC-3 in colonic epithelial cells in response to Citrobacter rodentium infection. Based on these findings, we hypothesized that SRC-3 is involved in host defense against attaching and effacing bacterial infection. We compared the responses of SRC-3 -/- and wild-type mice to intestinal C. rodentium infection. We found that SRC-3 -/- mice exhibited delayed clearance of C. rodentium and more severe tissue pathology after oral infection with C. rodentium compared with wild-type mice. SRC-3 -/- mice expressed normal antimicrobial peptides in the colons but exhibited delayed recruitment of neutrophils into the colonic mucosa. Accordingly, SRC-3 -/- mice showed a delayed induction of CXCL2 and CXCL5 in colonic epithelial cells, which are responsible for neutrophil recruitment. At the molecular level, we found that SRC-3 can activate the NF-κB signaling pathway to promote CXCL2 expression at the transcriptional level. Collectively, we show that SRC-3 contributes to host defense against enteric bacteria, at least in part via upregulating CXCL2 expression to recruit neutrophils. Copyright © 2017 by The American Association of Immunologists, Inc.
Manini, Mhd Louai; Camilleri, Michael; Goldberg, Michael; Sweetser, Seth; McKinzie, Sanna; Burton, Duane; Wong, Shekman; Kitt, Michael M.; Li, Yu-Ping; Zinsmeister, Alan R.
2010-01-01
Background TD-5108 is a potent, selective high intrinsic activity serotonin 5-HT4 receptor agonist. Aim To assess effects of TD-5108 on gastrointestinal transit and compare its pharmacokinetics (PK) in healthy volunteers (HV) and chronic constipation (CC) patients. Methods 60 HV were randomly assigned, double-blind to placebo, 5, 15, 30 or 50 mg TD-5108 (single and 6-day dosing). Primary endpoints were colonic transit (geometric center at 24 hours, GC24) and ascending colon emptying (ACE) T1/2 after first dose. Secondary endpoints included gastric emptying (GE) T1/2 and colonic filling at 6 h (CF6). Results Single dose TD-5108 significantly accelerated GC24, ACE T1/2, and CF6; 30 and 50°mg TD-5108 accelerated all 3 endpoints. With multiple doses, TD-5108 30 mg accelerated GC24, and overall accelerated GE T1/2 at 15–50 mg. PK studies showed dose proportionality in health, and no significant differences between health and chronic constipation with a 15 mg oral dose of TD-5108. Stimulation of bowel function after15 mg TD-5108 were similar in CC and controls. There were no serious adverse events; notable adverse were the predictable GI effects such as diarrhea or altered bowel movements. Conclusions TD-5108 significantly accelerated intestinal and colonic transit after single dosing and accelerated gastric emptying after multiple dosing. Further studies of its potential as a gastrointestinal and colonic prokinetic are warranted. PMID:19691492
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bhat, Ajaz A.; Ahmad, Rizwan; Uppada, SrijayaPrakash B.
Epithelial-mesenchymal transition (EMT) is an important mechanism in cancer progression and malignancy including colorectal cancer (CRC). Importantly, inflammatory mediators are critical constituents of the local tumor environment and an intimate link between CRC progression and inflammation is now validated. We and others have reported key role of the deregulated claudin-1 expression in colon carcinogenesis including colitis-associated colon cancer (CAC). However, the causal association between claudin-1 expression and inflammation-induced colon cancer progression remains unclear. Here we demonstrate, TNF-α, a pro-inflammatory cytokine, regulates claudin-1 to modulate epithelial to mesenchymal transition (EMT) and migration in colon adenocarcinoma cells. Importantly, colon cancer cells culturedmore » in the presence of TNF-α (10 ng/ml), demonstrated a sharp decrease in E-cadherin expression and an increase in vimentin expression (versus control cells). Interestingly, TNF-α treatment also upregulated (and delocalized) claudin-1 expression in a time-dependent manner accompanied by increase in proliferation and wound healing. Furthermore, similar to our previous observation that claudin-1 overexpression in CRC cells induces ERK1/2 and Src- activation, signaling associated with colon cancer cell survival and transformation, TNF-α-treatment induced upregulation of phospho-ERK1/2 and -Src expression. The shRNA-mediated inhibition of claudin-1 expression largely abrogated the TNF-α-induced changes in EMT, proliferation, migration, p-Erk and p-Src expression. Taken together, our data demonstrate TNF-α mediated regulation of claudin-1 and tumorigenic abilities of colon cancer cells and highlights a key role of deregulated claudin-1 expression in inflammation-induced colorectal cancer growth and progression, through the regulation of the ERK and Src-signaling.« less
Fukuda, Hiroyuki; Chen, Cindy; Mantyh, Christopher; Ludwig, Kirk; Pappas, Theodore N; Takahashi, Toku
2006-04-01
Post-operative ileus (POI) is a transient bowel dysmotility after operation. We have previously shown that laparotomy alone significantly delayed gastrointestinal (GI) transit, compared to anesthesia alone. The GI transit was further delayed after laparotomy plus intestinal manipulation. Dai-Kenchu-to (DKT), an herbal medicine, has been used for treating adhesive bowel obstruction in Japan. We studied whether DKT improves delayed GI transit after the operation, with or without morphine administration in rats. Under isoflurane anesthesia, POI was induced by laparotomy with intestinal manipulation. Immediately after the operation, the rats received 51Cr by gavage. Three hours after the operation, the rats were sacrificed and GI transit was estimated by calculating the geometric center (GC). DKT (120, 360, and 1,200 mg/kg) were administered by gavage after the operation, with or without morphine administration (1 mg/kg s.c.). A muscarinic receptor antagonist (atropine; 50 mug/kg), a 5HT3 receptor antagonist (ondansetron; 1 mg/kg) and a 5HT4 receptor antagonist (GR113,808; 3 mg/kg) were administered before the operation. Truncal vagotomy was performed preceding the operation. Laparotomy with intestinal manipulation produced a significant delay in GI transit (GC = 2.93 +/- 0.16), compared to that of anesthesia alone (9.51 +/- 0.45). DKT at the dose of 360 mg/kg (GC = 3.77 +/- 0.10, P < 0.01) and 1,200 mg/kg (GC = 3.77 +/- 0.20, P < 0.01) significantly accelerated delayed GI transit induced by operation. Ondansetron, GR113,808, atropine, and truncal vagotomy abolished the stimulatory effect of DKT (360 mg/kg). When morphine was administered, GI transit was further reduced (GC = 1.97 +/- 0.10). DKT at the dose of 360 mg/kg (GC = 2.81 +/- 0.22, P < 0.05) and 1,200 mg/kg (GC = 2.87 +/- 0.23, P < 0.05) significantly improved delayed GI transit in morphine treated rats. DKT accelerates delayed GI transit induced by intestinal manipulation with and without concomitant morphine administration. DKT treatment may be useful for the patients with POI.
Lara, René H; García-Meza, J Viridiana; Cruz, Roel; Valdez-Pérez, Donato; González, Ignacio
2012-08-01
Massive pyrite (FeS₂) electrodes were potentiostatically modified by means of variable oxidation pulse to induce formation of diverse surface sulfur species (S(n)²⁻, S⁰). The evolution of reactivity of the resulting surfaces considers transition from passive (e.g., Fe(1-x )S₂) to active sulfur species (e.g., Fe(1-x )S(2-y ), S⁰). Selected modified pyrite surfaces were incubated with cells of sulfur-oxidizing Acidithiobacillus thiooxidans for 24 h in a specific culture medium (pH 2). Abiotic control experiments were also performed to compare chemical and biological oxidation. After incubation, the attached cells density and their exopolysaccharides were analyzed by confocal laser scanning microscopy (CLMS) and atomic force microscopy (AFM) on bio-oxidized surfaces; additionally, S(n)²⁻/S⁰ speciation was carried out on bio-oxidized and abiotic pyrite surfaces using Raman spectroscopy. Our results indicate an important correlation between the evolution of S(n)²⁻/S⁰ surface species ratio and biofilm formation. Hence, pyrite surfaces with mainly passive-sulfur species were less colonized by A. thiooxidans as compared to surfaces with active sulfur species. These results provide knowledge that may contribute to establishing interfacial conditions that enhance or delay metal sulfide (MS) dissolution, as a function of the biofilm formed by sulfur-oxidizing bacteria.
Wren, John T; Blevins, Lance K; Pang, Bing; King, Lauren B; Perez, Antonia C; Murrah, Kyle A; Reimche, Jennifer L; Alexander-Miller, Martha A; Swords, W Edward
2014-11-01
Streptococcus pneumoniae (pneumococcus) is both a widespread nasal colonizer and a leading cause of otitis media, one of the most common diseases of childhood. Pneumococcal phase variation influences both colonization and disease and thus has been linked to the bacteria's transition from colonizer to otopathogen. Further contributing to this transition, coinfection with influenza A virus has been strongly associated epidemiologically with the dissemination of pneumococci from the nasopharynx to the middle ear. Using a mouse infection model, we demonstrated that coinfection with influenza virus and pneumococci enhanced both colonization and inflammatory responses within the nasopharynx and middle ear chamber. Coinfection studies were also performed using pneumococcal populations enriched for opaque or transparent phase variants. As shown previously, opaque variants were less able to colonize the nasopharynx. In vitro, this phase also demonstrated diminished biofilm viability and epithelial adherence. However, coinfection with influenza virus ameliorated this colonization defect in vivo. Further, viral coinfection ultimately induced a similar magnitude of middle ear infection by both phase variants. These data indicate that despite inherent differences in colonization, the influenza A virus exacerbation of experimental middle ear infection is independent of the pneumococcal phase. These findings provide new insights into the synergistic link between pneumococcus and influenza virus in the context of otitis media. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Shukla, Nandani; Awasthi, R P; Rawat, Laxmi; Kumar, J
2012-05-01
Rice is one of the most important food crops drastically affected by drought in lowland rice ecosystems. In the present study, the impact of drought tolerant isolates of endophytic fungus Trichoderma harzianum on rice response to drought was investigated. Out of 43 Trichoderma isolates studied, only five isolates viz., Th 56, Th 69, Th 75, Th 82 and Th 89 were selected to be drought tolerant as these were able to colonize well on cow dung at low moisture content of 10-20 percent, though two isolates, Th 56 and Th 75, grew even at 5 percent moisture content. Trichoderma-colonized rice seedlings were slower to wilt in response to drought. Colonization delayed drought induced changes like stomatal conductance, net photosynthesis and leaf greenness. Drought conditions varying from 3 to 9 days of withholding water led to an increase in the concentration of many stress induced metabolites in rice leaves and decrease of MSI, while Trichoderma colonization caused a decrease in proline, MDA and H₂O₂ contents, and increase in phenolics concentration and MSI. Among test isolates, Th 56 induced maximum drought tolerance as treated plants recorded only 20-40 percent wilting even at 9 DDS. With or without exposure to drought, colonization by Trichoderma promoted seedling growth, with Th 56 giving the most consistent effect. The primary direct effect of Trichoderma colonization was promotion of root growth, regardless of water status, which caused delay in the drought responses of rice plants. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Louie, Jacob; Shalaby, Amer; Habib, Khandker Nurul
2017-01-01
Most investigations of incident-related delay duration in the transportation context are restricted to highway traffic, with little attention given to delays due to transit service disruptions. Studies of transit-based delay duration are also considerably less comprehensive than their highway counterparts with respect to examining the effects of non-causal variables on the delay duration. However, delays due to incidents in public transit service can have serious consequences on the overall urban transportation system due to the pivotal and vital role of public transit. The ability to predict the durations of various types of transit system incidents is indispensable for better management and mitigation of service disruptions. This paper presents a detailed investigation on incident delay durations in Toronto's subway system over the year 2013, focusing on the effects of the incidents' location and time, the train-type involved, and the non-adherence to proper recovery procedures. Accelerated Failure Time (AFT) hazard models are estimated to investigate the relationship between these factors and the resulting delay duration. The empirical investigation reveals that incident types that impact both safety and operations simultaneously generally have longer expected delays than incident types that impact either safety or operations alone. Incidents at interchange stations are cleared faster than incidents at non-interchange stations. Incidents during peak periods have nearly the same delay durations as off-peak incidents. The estimated models are believed to be useful tools in predicting the relative magnitude of incident delay duration for better management of subway operations. Copyright © 2016 Elsevier Ltd. All rights reserved.
Delayed diaphragmatic herniation masquerading as a complicated parapneumonic effusion.
Tsang, J; Ryan, F
1999-01-01
Injury to the diaphragm following blunt or penetrating thoracoabdominal trauma is not uncommon. Recognition of this important complication of trauma continues to be a challenge because of the lack of specific clinical and plain radiographic features, the frequent presence of other serious injuries and the potential for delayed presentation. Delayed diaphragmatic herniation often presents with catastrophic bowel obstruction or strangulation. Early recognition of diaphragmatic injury is required to avoid this potentially lethal complication. The case of a 35-year-old man with a history of a knife wound to the left flank 15 years previously, who presented with unexplained acute hypoxemic respiratory failure and a unilateral exudative pleural effusion that was refractory to tube thoracostomy drainage, is reported. After admission to hospital, he developed gross dilation of his colon; emergency laparotomy revealed an incarcerated colonic herniation into the left hemithorax. Interesting clinical features of this patient's case included the patient's hobby of weightlifting, a persistently deviated mediastinum despite drainage of the pleural effusion and deceptive pleural fluid biochemical indices.
Turk, Harmony F.; Monk, Jennifer M.; Fan, Yang-Yi; Callaway, Evelyn S.; Weeks, Brad
2013-01-01
Epidermal growth factor receptor (EGFR)-mediated signaling is required for optimal intestinal wound healing. Since n-3 polyunsaturated fatty acids (PUFA), specifically docosahexaenoic acid (DHA), alter EGFR signaling and suppress downstream activation of key signaling pathways, we hypothesized that DHA would be detrimental to the process of intestinal wound healing. Using a mouse immortalized colonocyte model, DHA uniquely reduced EGFR ligand-induced receptor activation, whereas DHA and its metabolic precursor eicosapentaenoic acid (EPA) reduced wound-induced EGFR transactivation compared with control (no fatty acid or linoleic acid). Under wounding conditions, the suppression of EGFR activation was associated with a reduction in downstream activation of cytoskeletal remodeling proteins (PLCγ1, Rac1, and Cdc42). Subsequently, DHA and EPA reduced cell migration in response to wounding. Mice were fed a corn oil-, DHA-, or EPA-enriched diet prior to intestinal wounding (2.5% dextran sodium sulfate for 5 days followed by termination after 0, 3, or 6 days of recovery). Mortality was increased in EPA-fed mice and colonic histological injury scores were increased in EPA- and DHA-fed mice compared with corn oil-fed (control) mice. Although kinetics of colonic EGFR activation and downstream signaling (PLCγ1, Rac1, and Cdc42) were delayed by both n-3 PUFA, colonic repair was increased in EPA- relative to DHA-fed mice. These results indicate that, during the early response to intestinal wounding, DHA and EPA uniquely delay the activation of key wound-healing processes in the colon. This effect is mediated, at least in part, via suppression of EGFR-mediated signaling and downstream cytoskeletal remodeling. PMID:23426968
Nuclear Scintigraphy in Practice: Gastrointestinal Motility.
Solnes, Lilja B; Sheikhbahaei, Sara; Ziessman, Harvey A
2018-05-29
The purpose of this article is to describe the clinical utility of state-of-theart gastrointestinal transit scintigraphy, including the standardized esophageal transit, solid and liquid gastric emptying, small-bowel transit, colon transit, and whole-gut transit scintigraphy, with an emphasis on procedure performance. Radionuclide gastrointestinal motility studies are noninvasive, quantitative, and physiologic diagnostic tools for evaluating patients with gastrointestinal complaints.
Enterococcus faecalis causing delayed spondylodiscitis in a case with retained intraspinal bullet
Aiyer, Siddharth N.; Kanna, Rishi; Reddy, Srikanth; Rajasekaran, Shanmuganathan
2016-01-01
Delayed presentations have been reported following gunshot wounds (GSW) with retained intraspinal bullets due to migration of projectile or lead intoxication. We report on the rare occurrence of delayed pyogenic spondylodiscitis and neurological dysfunction following injury from low velocity GSW to the spine with a retained projectile. A 55-year-old male presented 4 months following GSW to the abdomen which resulted in colonic injury and L5 fracture. The patient was treated initially with ileo-transverse anastomosis, antibiotics, without retrieval of the bullet. He developed low back pain, claudication 4 months following GSW and investigations suggested a pyogenic spondylodiscitis at L5–S1. The patient was treated with surgical debridement of infective focus and stabilisation with definitive fusion being performed after an interval of 14 days. The biopsy of the lesion confirmed findings of spondylodiscitis and the culture isolated Enterococcus faecalis species. The patient was treated with antibiotics as per sensitivity and made an uneventful recovery over 4 weeks. The follow-up radiographs showed satisfactory healing at final follow up of 24 months. GSW with colonic perforation have higher incidence of infective complications however majority to these occur in the early postoperative period. This case report demonstrates the possibility of late onset presentation due to spinal infection occurring following colonic perforation with retained intraspinal bullet. PMID:28097252
Satoh, Kazuko; Kase, Yoshio; Yuzurihara, Mitsutoshi; Mizoguchi, Kazushige; Kurauchi, Kouji; Ishige, Atsushi
2003-05-01
This study was conducted to evaluate the effect of Dai-kenchu-to on chlorpromazine-induced hypoperistalsis in mice. Oral administration of Dai-kenchu-to (30-300 mg/kg) dose-dependently improved small intestinal and distal colonic propulsion decreased by chlorpromazine (3 mg/kg, p.o.). Although the improvement of small intestinal propulsion due to Dai-kenchu-to was partially inhibited by atropine (1 mg/kg, s.c.), this action was completely inhibited by the concomitant administration of lorglumide (10 mg/kg, i.p.), a CCKA receptor antagonist. The distal colonic propulsion-improving effect of Dai-kenchu-to was abolished by atropine (1 mg/kg, s.c.). When the effects of the respective components of Dai-kenchu-to were evaluated, oral administration of Zanthoxylum Fruit improved both delayed small intestinal and distal colonic propulsion caused by chlorpromazine. On the other hand, Malt Sugar was effective against only delayed small intestinal propulsion. The action of Zanthoxylum Fruit was completely inhibited by atropine (1 mg/kg, s.c.), and the effect of Malt Sugar was inhibited by lorglumide (10 mg/kg, i.p.). These results demonstrated that Dai-kenchu-to improves chlorpromazine-induced hypoperistalsis via cholinergic systems and that Zanthoxylum Fruit is the main contributor to this action of Dai-kenchu-to. In addition, endogenous CCK due to Malt Sugar may also contribute to this effect of Dai-kenchu-to.
Stathopoulos, Lefteris; King, Sebastian K; Southwell, Bridget R; Hutson, John M
2016-08-01
Long-term problems with faecal incontinence occur in up to 50 % of patients after pull-through for Hirschsprung disease (HSCR). The cause often remains unknown, leading to empirical treatments. Using nuclear transit study, we found some patients surprisingly had rapid proximal colonic transit, suspicious of occult diarrhoea. We aimed to assess whether these patients had unrecognized adverse reactions to food. Patients (n = 10, all males, 9.6 year; 4.25-15.5 years) with persistent faecal incontinence following pull-through for HSCR referred to the senior author and after exclusion of anatomical defects, underwent nuclear transit studies. Most (8) subsequently underwent breath hydrogen tests for sugar malabsorption and were tested for adverse reactions to food. Exclusion diets for protein allergens, lactose or fructose were then trialed. Of the 10 patients with rapid intestinal transit proven on nuclear transit study, breath hydrogen tests for fructose and/or lactose malabsorption were done in 8, and were positive in 7/8 patients. Exclusion diets contributed to either resolution or improvement in faecal incontinence in 9/10 patients. Rapid transit in the proximal, ganglionated colon may be present in children with faecal incontinence following pull-through for HSCR, possibly secondary to adverse reactions to food. This study suggests that children with post-operative soiling may benefit from a transit study and hydrogen breath tests to diagnose adverse reactions to food caused by sugar malabsorption.
Colon transit scintiraphy in health and constipation using oral iodine-131-cellulose
DOE Office of Scientific and Technical Information (OSTI.GOV)
McLean, R.G.; Smart, R.C.; Gaston-Parry, D.
1990-06-01
The purpose of the study was to assess if a new scintigraphic method for noninvasive assessment of colonic transit could differentiate between subjects with normal bowel transit and those with constipation. Eleven normal subjects and 29 constipated patients were given 4 MBq iodine-131-cellulose ({sup 131}I-cellulose) orally and sequential abdominal scans were performed at 6, 24, 48, 72, and 96 hr from which total and segmental percent retentions were calculated. There were clear differences between the normal subjects and the constipated patients for the total percent retention at all time intervals, on a segmental basis in the right colon at 24more » hr, and in all segments at 48 and 72 hr. Three-day urinary excretion of radioiodine was minimal; 2.4% +/- 1.2% (mean +/- s.d.) in constipated patients and 3.1% +/- 0.8% in normals, with approximately 75% occurring in the first day. The use of oral radiotracers in the investigation of constipation appears promising.« less
Weigt, S. Samuel; Elashoff, Robert M.; Huang, Cathy; Ardehali, Abbas; Gregson, Aric L.; Kubak, Bernard; Fishbein, Michael C.; Saggar, Rajeev; Keane, Michael P.; Saggar, Rajan; Lynch, Joseph P.; Zisman, David A.; Ross, David J.; Belperio, John A.
2014-01-01
Multiple infections have been linked with the development of bronchiolitis obliterans syndrome (BOS) post-lung transplantation. Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We hypothesized that Aspergillus colonization may promote the development of BOS and may decrease survival post-lung transplantation. We reviewed all lung transplant recipients transplanted in our center between 1/2000 and 6/2006. Bronchoscopy was performed according to a surveillance protocol and when clinically indicated. Aspergillus colonization was defined as a positive culture from bronchoalveolar lavage or two sputum cultures positive for the same Aspergillus species, in the absence of invasive pulmonary Aspergillosis. We found that Aspergillus colonization was strongly associated with BOS and BOS related mortality in Cox regression analyses. Aspergillus colonization typically preceded the development of BOS by a median of 261 days (95% CI 87 to 520). Furthermore, in a multivariate Cox regression model, Aspergillus colonization was a distinct risk factor for BOS, independent of acute rejection. These data suggest a potential causative role for Aspergillus colonization in the development of BOS post-lung transplantation and raise the possibility that strategies aimed to prevent Aspergillus colonization may help delay or reduce the incidence of BOS. PMID:19459819
Slow transit constipation: a review of a colonic functional disorder.
Frattini, Jared C; Nogueras, Juan J
2008-05-01
Constipation is a common gastrointestinal complaint that can cause significant physical and psychosocial problems. It has been categorized as slow transit constipation, normal transit constipation, and obstructed defecation. Both the definition and pathophysiology of constipation are unclear, but attempts to describe each of the three types have been made. Slow transit constipation, a functional colonic disorder represents approximately 15 to 30% of constipated patients. The theorized etiologies are disorders of the autonomic and enteric nervous system and/or a dysfunctional neuroendocrine system. Slow transit constipation can be diagnosed with a complete history, physical exam, and a battery of specific diagnostic studies. Once the diagnosis is affirmed and medical management has failed, there are several treatment options. Biofeedback, sacral nerve stimulation, segmental colectomy, and subtotal colectomy with various anastomoses have all been used. Of those treatment options, a subtotal colectomy with ileorectal anastomosis is the most efficacious with the data to support its use.
Oxytocin decreases colonic motility of cold water stressed rats via oxytocin receptors.
Yang, Xiao; Xi, Tao-Fang; Li, Yu-Xian; Wang, Hai-Hong; Qin, Ying; Zhang, Jie-Ping; Cai, Wen-Ting; Huang, Meng-Ting; Shen, Ji-Qiao; Fan, Xi-Min; Shi, Xuan-Zheng; Xie, Dong-Ping
2014-08-21
To investigate whether cold water intake into the stomach affects colonic motility and the involvement of the oxytocin-oxytocin receptor pathway in rats. Female Sprague Dawley rats were used and some of them were ovariectomized. The rats were subjected to gastric instillation with cold (0-4 °C, cold group) or room temperature (20-25 °C, control group) saline for 14 consecutive days. Colon transit was determined with a bead inserted into the colon. Colonic longitudinal muscle strips were prepared to investigate the response to oxytocin in vitro. Plasma concentration of oxytocin was detected by ELISA. Oxytocin receptor expression was investigated by Western blot analysis. Immunohistochemistry was used to locate oxytocin receptors. Colon transit was slower in the cold group than in the control group (P < 0.05). Colonic smooth muscle contractile response to oxytocin decreased, and the inhibitory effect of oxytocin on muscle contractility was enhanced by cold water intake (0.69 ± 0.08 vs 0.88 ± 0.16, P < 0.05). Atosiban and tetrodotoxin inhibited the effect of oxytocin on colonic motility. Oxytocin receptors were located in the myenteric plexus, and their expression was up-regulated in the cold group (P < 0.05). Cold water intake increased blood concentration of oxytocin, but this effect was attenuated in ovariectomized rats (286.99 ± 83.72 pg/mL vs 100.56 ± 92.71 pg/mL, P < 0.05). However, in ovariectomized rats, estradiol treatment increased blood oxytocin, and the response of colonic muscle strips to oxytocin was attenuated. Cold water intake inhibits colonic motility partially through oxytocin-oxytocin receptor signaling in the myenteric nervous system pathway, which is estrogen dependent.
[Creation and Evaluation of Educational Programs for Additional Delayed Scan of FDG-PET/CT].
Wada, Ryota; Kamiya, Takashi; Fujino, Kouichi; Ueda, Junpei; Isohashi, Kayako; Tatsumi, Mitsuaki; Hatazawa, Jun
Generally, FDG-PET/CT image is acquired at the 60th minute after tracer administration. Depending on the clinical case, additional delayed scans may be useful. However, it is difficult to judge whether additional delayed scan is useful or not. The purposes of this study were creation and evaluation of educational programs to help radiological technologists to decide the usefulness of additional delayed scan of FDG-PET/CT. Educational programs consisted of the instructional materials and the judgment test of clinical cases. The instructional materials provided the valuable findings for differentiation between uptake in the wall of the colon and colon content, distinction between uptake in the lymph node and urinary tract, and evaluation of malignancy. The judgment test of clinical cases consisted of 10 cases selected by a nuclear medicine physician (for 5 of that cases additional delayed scan was decided to be useful). Five experienced technologists and five inexperienced technologists scored the volubility of additional delayed scan pre- and post-training using the instructional materials (the full marks of score is 5). After the educational programs using the instructional materials, the score was improved with the significant difference in both experienced (pre: 3.6±1.4, post: 4.0±1.2) and inexperienced (pre: 2.8±1.5, post: 3.7±1.5) groups (p<0.05). According to the educational programs, technologist might be able to decide whether the additional delayed scan is useful or not. The successful results of this study may improve the interpretation or reduce the total exposure dose of the PET/CT scan.
Zhou, Jieqiong; Tang, Xiaowei; Wang, Jing; Chen, Zhenyu; Wang, Xinying; Jiang, Bo
2017-08-01
Bowel preparation regimens for colon capsule endoscopy are not yet standardized since they are not well optimized. The aim of the present study was to evaluate the feasibility of a novel low-volume and sodium phosphate-free bowel preparation regimen for colon capsule endoscopy. A total of 31 patients were prospectively enrolled. In the novel regimen, on the day prior to examination, a low-fiber diet was permitted, 5 mg mosapride citrate was administered twice (1 h prior to lunch and supper) and 1 l polyethylene glycol was administered in the evening. On the day of the examination, an additional 1 l polyethylene glycol, 5 mg mosapride citrate and 200 mg simethicone were administered before capsule ingestion. Polyethylene glycol booster (0.5 l) was administered twice, at 1 and 4 h following capsule ingestion. Colon cleansing levels, ileocecal valve transit time and completion rate were evaluated. A total of 29 patients were included in the final analysis, 90% of whom achieved adequate preparation of the overall colon. Ileocecal valve transit time was 2.35±0.82 h and completion rate was 79.3%. The results revealed that the novel low-volume and sodium phosphate-free bowel preparation regimen for colon capsule endoscopy was feasible, with adequate colon cleansing and completion rates, and has the potential to be used as an alternative regimen.
Expression and Significance of Neuroligins in Myenteric Cells of Cajal in Hirschsprung's Disease
Wang, Jian; Mou, Yaru; Zhang, Qiangye; Zhang, Fan; Yang, Hongchao; Zhang, Wentong; Li, Aiwu
2013-01-01
Purpose The aim of this study was to investigate the expression and significance of neuroligins in myenteric cells of Cajal (ICC-MY) in Hirschsprung’s disease (HSCR). Methods Longitudinal muscle with adherent myenteric plexus (LMMP) from surgical excision waste colon of HSCR children were prepared by peeling off the mucous layer, sub-mucosal layer and circular muscle. Neuroligins, c-Kit (c-Kit-immunoreactivity representing ICC) and their relationship were assessed by double labeling immunofluorescence staining. ICC-MY were dissociated and cultured from LMMP by enzymolysis method, and were purified and analyzed using a combination of magnetic-activated cell sorting (MACS) and flow cytometry (FCM). Western-blot analysis was applied to compare and evaluate the expression levels of neuroligins in ICC-MY which were dissociated from different segments of HSCR (ganglionic colonic segment, transitional colonic segment and aganglionic colonic segment). Results Neuroligins and c-Kit were expressed on the same cells (ICC-MY); ICC-MY were dissociated, cultured and purified. For HSCR, neuroligins were expressed significantly in ICC-MY from ganglionic colonic segments, moderately in those from transitional colonic segments and down-regulated significantly in those from aganglionic colonic segments. Conclusions Neuroligins were expressed in ICC-MY of human beings, and the expression varies from different segments of HSCR. This abnormal expression might play an important role in the pathogenesis of this disease through affecting the synaptic function of ICC-MY. PMID:23840625
Luo, Jia-Lie; Qin, Hong-Yan; Wong, Chun-Kit; Tsang, Suk-Ying; Huang, Yu; Bian, Zhao-Xiang
2011-05-01
Irritable bowel syndrome (IBS), characterized mainly by abdominal pain, is a functional bowel disorder. The present study aimed to examine changes in the excitability and the activity of the voltage-gated K(+) channel in dorsal root ganglia (DRG) neurons innervating the colon of rats subjected to neonatal maternal separation (NMS). Colonic DRG neurons from NMS rats as identified by FAST DiI™ labeling showed an increased cell size compared with those from nonhandled (NH) rats. Whole cell current-clamp recordings showed that colonic DRG neurons from NMS rats displayed: 1) depolarized resting membrane potential; 2) increased input resistance; 3) a dramatic reduction in rheobase; and 4) a significant increase in the number of action potentials evoked at twice rheobase. Whole cell voltage-clamp recordings revealed that neurons from both groups exhibited transient A-type (I(A)) and delayed rectifier (I(K)) K(+) currents. Compared with NH rat neurons, the averaged density of I(K) was significantly reduced in NMS rat neurons. Furthermore, the Kv1.2 expression was significantly decreased in NMS rat colonic DRG neurons. These results suggest that NMS increases the excitability of colonic DRG neurons mainly by suppressing the I(K) current, which is likely accounted for by the downregulation of the Kv1.2 expression and somal hypertrophy. This study demonstrates the alteration of delayed rectifier K current and Kv1.2 expression in DRG neurons from IBS model rats, representing a molecular mechanism underlying visceral pain and sensitization in IBS, suggesting the potential of Kv1.2 as a therapeutic target for the treatment of IBS. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.
Prolonged intestinal transit and diarrhea in patients with an activating GUCY2C mutation
Brønstad, Ingeborg; Gilja, Odd Helge; R. Tronstad, Rune; Sangnes, Dag Andre; Nortvedt, Ragnar; Hausken, Trygve; Dimcevski, Georg; Fiskerstrand, Torunn; Nylund, Kim
2017-01-01
Introduction Increased intestinal hydration by activation of the epithelial enzyme linked receptor guanylate cyclase C (GC-C) is a pharmacological principle for treating constipation. Activating mutations in the GUCY2C gene encoding GC-C cause Familial GUCY2C diarrhea syndrome (FGDS) which has been diagnosed with severe dysmotility. Aim To investigate gut motility and hormones before and after a meal in FGDS patients and compare with healthy controls (HC). Subjects and methods Bristol stool chart and stool frequency was assessed. Before and after a meal occlusive and non-occlusive contractions were obtained using ultrasound. A wireless motility capsule (WMC) recorded gut transit time, pH, contractions and pressure. Plasma levels of selected gut hormones were measured at different time points. Results The FGDS patients had 4 (range 1–10) loose stools/day and prolonged total gut transit time compared to HC, 55.5 h vs 28.5 h, respectively,with significantly increased colon transit time. In FGDS patients, pH in duodenum, small bowel and colon was increased and the number of contractions and the intraluminal pressure were significantly decreased, measured by WMC. Ultrasound showed in small bowel increased number of non-occlusive contractions in the FGDS patients. Serotonin (5-HT) plasma levels in the HC peaked 30 min after the meal, while the FGDS patients had no response. Conclusion Despite having diarrhea, the FGDS patients have prolonged transit time through the gut compared to HC, particularly in colon. The reduced number of intestinal contractions and lack of 5-HT release after a meal in FGDS patients surprisingly resemble colonic motility disturbances seen in patients with constipation. PMID:28957388
Nikolov, Svetoslav; Santos, Guido; Wolkenhauer, Olaf; Vera, Julio
2018-02-01
Mathematical modeling of cell differentiated in colonic crypts can contribute to a better understanding of basic mechanisms underlying colonic tissue organization, but also its deregulation during carcinogenesis and tumor progression. Here, we combined bifurcation analysis to assess the effect that time delay has in the complex interplay of stem cells and semi-differentiated cells at the niche of colonic crypts, and systematic model perturbation and simulation to find model-based phenotypes linked to cancer progression. The models suggest that stem cell and semi-differentiated cell population dynamics in colonic crypts can display chaotic behavior. In addition, we found that clinical profiling of colorectal cancer correlates with the in silico phenotypes proposed by the mathematical model. Further, potential therapeutic targets for chemotherapy resistant phenotypes are proposed, which in any case will require experimental validation.
Daikenchuto stimulates colonic motility after laparoscopic-assisted colectomy.
Yaegashi, Mizunori; Otsuka, Koki; Itabashi, Tetsuya; Kimura, Toshimoto; Kato, Kuniyuki; Fujii, Hitoshi; Koeda, Keisuke; Sasaki, Akira; Wakabayashi, Go
2014-01-01
Paralytic ileus after laparoscopic-assisted surgery often occurs. We investigated whether daikenchuto (DKT), a traditional Japanese herbal medicine, improves intestinal motility in patients undergoing laparoscopic-assisted colectomy for colon cancer. Fifty-four patients who underwent colectomy at Iwate Medical University Hospital between October 2010 and March 2012 were randomized to either the DKT group (7.5 g/day, p.o.) or the control group (lactobacillus preparation, 3g/day, p.o.). Primary endpoints included time to first flatus, bowel movement, and tolerance of diet after extubation. Secondary endpoints were WBC count, C-reactive protein (CRP) level, length of hospital stay, and postoperative ileus. Colonic transit time was measured using radiopaque markers and abdominal radiographs. Fifty-one patients (DKT, 26 vs. control, 25) were included in the per-protocol analysis. The DKT group had significantly faster time until first flatus (67.5 +/- 13.6h vs. 77.9 +/- 11.8h, P < 0.01) and bowel movement (82.9 +/- 17.8h vs. 99.5 +/- 18.9h, P < 0.01) and colonic transit time (91.9 +/- 19.8h vs. 115.2 +/- 12.8 h, P < 0.05). There were no significant intergroup differences in secondary endpoints and adverse events. DKT accelerates colonic motility in patients undergoing laparoscopic-assisted colectomy for colon cancer.
Qian, Yu
2014-01-01
The synchronization transitions in Newman-Watts small-world neuronal networks (SWNNs) induced by time delay τ and long-range connection (LRC) probability P have been investigated by synchronization parameter and space-time plots. Four distinct parameter regions, that is, asynchronous region, transition region, synchronous region, and oscillatory region have been discovered at certain LRC probability P = 1.0 as time delay is increased. Interestingly, desynchronization is observed in oscillatory region. More importantly, we consider the spatiotemporal patterns obtained in delayed Newman-Watts SWNNs are the competition results between long-range drivings (LRDs) and neighboring interactions. In addition, for moderate time delay, the synchronization of neuronal network can be enhanced remarkably by increasing LRC probability. Furthermore, lag synchronization has been found between weak synchronization and complete synchronization as LRC probability P is a little less than 1.0. Finally, the two necessary conditions, moderate time delay and large numbers of LRCs, are exposed explicitly for synchronization in delayed Newman-Watts SWNNs.
Qian, Yu
2014-01-01
The synchronization transitions in Newman-Watts small-world neuronal networks (SWNNs) induced by time delay and long-range connection (LRC) probability have been investigated by synchronization parameter and space-time plots. Four distinct parameter regions, that is, asynchronous region, transition region, synchronous region, and oscillatory region have been discovered at certain LRC probability as time delay is increased. Interestingly, desynchronization is observed in oscillatory region. More importantly, we consider the spatiotemporal patterns obtained in delayed Newman-Watts SWNNs are the competition results between long-range drivings (LRDs) and neighboring interactions. In addition, for moderate time delay, the synchronization of neuronal network can be enhanced remarkably by increasing LRC probability. Furthermore, lag synchronization has been found between weak synchronization and complete synchronization as LRC probability is a little less than 1.0. Finally, the two necessary conditions, moderate time delay and large numbers of LRCs, are exposed explicitly for synchronization in delayed Newman-Watts SWNNs. PMID:24810595
Purely temporal figure-ground segregation.
Kandil, F I; Fahle, M
2001-05-01
Visual figure-ground segregation is achieved by exploiting differences in features such as luminance, colour, motion or presentation time between a figure and its surround. Here we determine the shortest delay times required for figure-ground segregation based on purely temporal features. Previous studies usually employed stimulus onset asynchronies between figure- and ground-containing possible artefacts based on apparent motion cues or on luminance differences. Our stimuli systematically avoid these artefacts by constantly showing 20 x 20 'colons' that flip by 90 degrees around their midpoints at constant time intervals. Colons constituting the background flip in-phase whereas those constituting the target flip with a phase delay. We tested the impact of frequency modulation and phase reduction on target detection. Younger subjects performed well above chance even at temporal delays as short as 13 ms, whilst older subjects required up to three times longer delays in some conditions. Figure-ground segregation can rely on purely temporal delays down to around 10 ms even in the absence of luminance and motion artefacts, indicating a temporal precision of cortical information processing almost an order of magnitude lower than the one required for some models of feature binding in the visual cortex [e.g. Singer, W. (1999), Curr. Opin. Neurobiol., 9, 189-194]. Hence, in our experiment, observers are unable to use temporal stimulus features with the precision required for these models.
Acute physiological stress and mortality following fire in a long-unburned longleaf pine ecosystem
J.J. O’Brien; J.K. Hiers; R.J. Mitchell; J.M. Varner; K. Mordecai
2010-01-01
One important legacy of fire exclusion in ecosystems dependent upon frequent fire is the development of organic soil horizons (forest floor) that can be colonized by fine roots. When fire is re-introduced, the forest floor is often consumed by fire and heavy overstory mortality, often delayed by months, results. We hypothesized that the delayed post-fire tree mortality...
Yu, Haitao; Wang, Jiang; Du, Jiwei; Deng, Bin; Wei, Xile
2015-02-01
Effects of time delay on the local and global synchronization in small-world neuronal networks with chemical synapses are investigated in this paper. Numerical results show that, for both excitatory and inhibitory coupling types, the information transmission delay can always induce synchronization transitions of spiking neurons in small-world networks. In particular, regions of in-phase and out-of-phase synchronization of connected neurons emerge intermittently as the synaptic delay increases. For excitatory coupling, all transitions to spiking synchronization occur approximately at integer multiples of the firing period of individual neurons; while for inhibitory coupling, these transitions appear at the odd multiples of the half of the firing period of neurons. More importantly, the local synchronization transition is more profound than the global synchronization transition, depending on the type of coupling synapse. For excitatory synapses, the local in-phase synchronization observed for some values of the delay also occur at a global scale; while for inhibitory ones, this synchronization, observed at the local scale, disappears at a global scale. Furthermore, the small-world structure can also affect the phase synchronization of neuronal networks. It is demonstrated that increasing the rewiring probability can always improve the global synchronization of neuronal activity, but has little effect on the local synchronization of neighboring neurons.
The development of colon innervation in trisomy 16 mice and Hirschsprungs disease
Li, Ji Cheng; Mi, Kai Hong; Zhou, Ji Lin; Busch, LC; Kuhnel, W
2001-01-01
AIM: To study the colon innervation of trisomy 16 mouse, an animal model for Down’s syndrome, and the expression of protein gene product 9.5 (PGP 9.5) in the stenosed segment of colon in Hirschsprungs disease (HD). METHODS: Trisomy 16 mouse breeding; cytogenetic analysis of trisomy 16 mice; and PGP 9.5 immunohistochemistry of colons of trisomy 16 mice and HD were carried out. RESULTS: Compared with their normal littermates, the nervous system of colon in trisomy 16 mice was abnormally developed. There existed developmental delay of muscular plexuses of colon, no submucosal plexus was found in the colon, and there was 5 mm aganglionic bowel aparting from the anus in trisomy 16 mice. The mesentery nerve fibers were as well developed as shown in their normal littermates. Abundant proliferation of PGP 9.5 positive nerve fibers was evealed in the stenosed segment of HD colon. CONCLUSION: Trisomy 16 mice could serve as an animal model for Hirschsprung’s disease for aganglionic bowel in the distal part of colon. Abundant proliferation of PGP 9.5 positive fibers resulted from extrinsic nerve compensation, since no ganglionic cells were observed in the stenosed segment of the colon in HD. HD has a genetic tendency. PMID:11819726
Hirschsprung's disease in twin to twin transfusion syndrome: a case report.
Park, Hye Won; Cho, Min Jeng; Kim, Wook Youn; Kwak, Byung Ok; Kim, Min Hee
2014-12-14
Twin to twin transfusion syndrome (TTTS) is caused by aberrant vascular connections between infant twins and results in high morbidity and mortality in the perinatal period. In donor infants with TTTS and symptoms of intestinal obstruction, small-bowel lesions have been reported in most cases. We report on a 33(+6) gestational wk donor infant with TTTS who had intermittent obstructive episodes, including delayed meconium passage and colonic dilatation on abdominal X-ray. The diagnosis of Hirschsprung's disease was based on a lateral pelvic film with a reversed rectosigmoid ratio. A subsequent barium colon study and rectal suction biopsy indicated a short segment aganglionosis of the colon.
Dynamics of scroll waves with time-delay propagation in excitable media
NASA Astrophysics Data System (ADS)
Chen, Jiang-Xing; Xiao, Jie; Qiao, Li-Yan; Xu, Jiang-Rong
2018-06-01
Information transmission delay can be widely observed in various systems. Here, we study the dynamics of scroll waves with time-delay propagation among slices in excitable media. Weak time delay induces scroll waves to meander. Through increasing the time delay, we find a series of dynamical transitions. Firstly, the straight filament of a scroll wave becomes twisted. Then, the scroll wave breaks and forms interesting patterns. With long time delay, loosed scroll waves are maintained while their period are greatly decreased. Also, cylinder waves appears. The influences of diffusively coupling strength on the time-delay-induced scroll waves are studied. It is found that the critical time delay characterizing those transitions decreases as the coupling strength is increased. A phase diagram in the diffusive coupling-time delay plane is presented.
Long-term results of subtotal colectomy with cecorectal anastomosis for isolated colonic inertia
Iannelli, Antonio; Piche, Thierry; Dainese, Raffaella; Fabiani, Pascal; Tran, Albert; Mouiel, Jean; Gugenheim, Jean
2007-01-01
AIM: To evaluate the results of sub total colectomy with cecorectal anastomosis (STC-CRA) for isolated colonic inertia (CI). METHODS: Fourteen patients (mean age 57.5 ± 16.5 year) underwent surgery for isolated CI between January 1986 and December 2002. The mean frequency of bowel motions with the aid of laxatives was 1.2 ± 0.6 per week. All subjects underwent colonoscopy, anorectal manometry, cinedefaecography and colonic transit time (CTT). CI was defined as diffuse markers delay on CTT without evidence of pelvic floor dysfunction. All patients underwent STC-CRA. Long-term follow-up was obtained prospectively by clinical visits between October 2005 and February 2006 at a mean of 10.5 ± 3.6 years (range 5-16 years) during which we considered the number of stool emissions, the presence of abdominal pain or digitations, the use of pain killers, laxatives and/or fibers. Patients were also asked if they were satisfied with the surgery. RESULTS: There was no postoperative mortality. Postoperative complications occurred in 21.4% (3/14). At the end of follow-up, bowel frequency was significantly (P < 0.05) increased to a mean of 4.8 ± 7.5 per day (range 1-30). One patient reported disabling diarrhea. Two patients used laxatives less than three times per month without complaining of what they called constipation. Overall, 78.5% of patients would have chosen surgery again if necessary. CONCLUSION: STC-CRA is feasible and safe in patients with CI achieving 79% of success at a mean follow-up of 10.5 years. A prospective controlled evaluation is warranted to verify the advantages of this surgical approach in patients with CI. PMID:17552007
Placidi, E; Marciani, L; Hoad, C L; Napolitano, A; Garsed, K C; Pritchard, S E; Cox, E F; Costigan, C; Spiller, R C; Gowland, P A
2012-07-01
Loperamide (LOP) is an anti-diarrhoeal agent which is thought to act largely by slowing transit with an uncertain effect on the fluid content of the small and large bowel in humans. Adding simethicone (SIM) to LOP improves its efficacy, but the mechanism of interaction is unclear. Novel MRI techniques to assess small bowel water content (SBWC) have shown that mannitol solutions markedly increase SBWC and can be used as a model of diarrhoea. We aimed to use quantitative MRI techniques to compare the actions in the gut of LOP and LOP + SIM in a model of secretory diarrhoea using mannitol. A total of 18 healthy volunteers ingested capsules containing placebo (PLA) or 12 mg LOP or 12 mg LOP + 125 mg SIM. After 100 min they were given a drink containing 5% mannitol in 350 mL of water. They underwent baseline fasting and postprandial serial MRI scans at 45 min intervals for 4.5 h after ingesting the drink. A range of MRI sequences was acquired to image the gut. LOP and LOP + SIM significantly accelerated gastric emptying (P < 0.03) and reduced SBWC during the late phase (135-270 min after mannitol ingestion), P < 0.009, while delaying arrival of fluid in the ascending colon (AC). The relaxation time T2 of the contents of the AC was reduced by both drugs (P < 0.0001). LOP and LOP + SIM accelerate gastric emptying, but reduce small bowel water content which may contribute to the delay in oral-caecal transit and overall anti-diarrhoeal effect. © 2012 Blackwell Publishing Ltd.
NASA Astrophysics Data System (ADS)
Gong, Yubing; Xie, Huijuan
2017-09-01
Using spike-timing-dependent plasticity (STDP), we study the effect of channel noise on temporal coherence and synchronization of adaptive scale-free Hodgkin-Huxley neuronal networks with time delay. It is found that the spiking regularity and spatial synchronization of the neurons intermittently increase and decrease as channel noise intensity is varied, exhibiting transitions of temporal coherence and synchronization. Moreover, this phenomenon depends on time delay, STDP, and network average degree. As time delay increases, the phenomenon is weakened, however, there are optimal STDP and network average degree by which the phenomenon becomes strongest. These results show that channel noise can intermittently enhance the temporal coherence and synchronization of the delayed adaptive neuronal networks. These findings provide a new insight into channel noise for the information processing and transmission in neural systems.
Edwards, Ruth; Harding, Keith G
2004-04-01
Wound healing is a complex process with many potential factors that can delay healing. There is increasing interest in the effects of bacteria on the processes of wound healing. All chronic wounds are colonized by bacteria, with low levels of bacteria being beneficial to the wound healing process. Wound infection is detrimental to wound healing, but the diagnosis and management of wound infection is controversial, and varies between clinicians. There is increasing recognition of the concept of critical colonization or local infection, when wound healing may be delayed in the absence of the typical clinical features of infection. The progression from wound colonization to infection depends not only on the bacterial count or the species present, but also on the host immune response, the number of different species present, the virulence of the organisms and synergistic interactions between the different species. There is increasing evidence that bacteria within chronic wounds live within biofilm communities, in which the bacteria are protected from host defences and develop resistance to antibiotic treatment. An appreciation of the factors affecting the progression from colonization to infection can help clinicians with the interpretation of clinical findings and microbiological investigations in patients with chronic wounds. An understanding of the physiology and interactions within multi-species biofilms may aid the development of more effective methods of treating infected and poorly healing wounds. The emergence of consensus guidelines has helped to optimize clinical management.
USDA-ARS?s Scientific Manuscript database
In adults with irritable bowel syndrome (IBS), bacterial gas production (colonic fermentation) is related to both symptom generation and intestinal transit. Whether gas production affects symptom generation, psychosocial distress, or intestinal transit in childhood IBS is unknown. Children (ages 7-1...
Novel mesalamine-loaded beads in tablets for delayed release of drug to the colon.
Nguyen, Chien; Christensen, J Mark; Ayres, James W
2012-01-01
Novel 'beads-in-a-tablet' formulations (total weight ∼740-780 mg) have been prepared that meet USP 31 requirements for Delayed Release of mesalamine. Several methods are presented that overcome breakage of beads during tablet compaction were explored. Bead formulations comprise a combination of extrusion and spheronization to produce a relatively high drug load (80%), followed by coating (25%) with a colonic-targeted drug release polymer (polymethacrylates, Eudragit(®) S100), overcoated (3%) with hydroxypropyl methylcellulose (Opadry(®)) to improve bead binding and compactability, and using 20% coat of lactose/sodium starch glycolate (Explotab(®)) as binder/disintegrant/cushioning agent, thus allowing a sufficiently thick coating to be uniform and without being broken during tablet compaction. Then, the aforementioned beads were compressed into tablets at 1500 pounds of pressure containing 400 mg of mesalamine, and finally coating the compressed tablets with Surelease(®) (ethylcellulose):Opadry(®) = 1:0.5 ranging from 1.5-2.5% weight gain; the resulting tablets met USP 31 dissolution requirements for delayed release tablets.
NASA Astrophysics Data System (ADS)
Banerjee, Tanmoy; Biswas, Debabrata
2013-12-01
We explore and experimentally demonstrate the phenomena of amplitude death (AD) and the corresponding transitions through synchronized states that lead to AD in coupled intrinsic time-delayed hyperchaotic oscillators interacting through mean-field diffusion. We identify a novel synchronization transition scenario leading to AD, namely transitions among AD, generalized anticipatory synchronization (GAS), complete synchronization (CS), and generalized lag synchronization (GLS). This transition is mediated by variation of the difference of intrinsic time-delays associated with the individual systems and has no analogue in non-delayed systems or coupled oscillators with coupling time-delay. We further show that, for equal intrinsic time-delays, increasing coupling strength results in a transition from the unsynchronized state to AD state via in-phase (complete) synchronized states. Using Krasovskii-Lyapunov theory, we derive the stability conditions that predict the parametric region of occurrence of GAS, GLS, and CS; also, using a linear stability analysis, we derive the condition of occurrence of AD. We use the error function of proper synchronization manifold and a modified form of the similarity function to provide the quantitative support to GLS and GAS. We demonstrate all the scenarios in an electronic circuit experiment; the experimental time-series, phase-plane plots, and generalized autocorrelation function computed from the experimental time series data are used to confirm the occurrence of all the phenomena in the coupled oscillators.
Tebbe, J J; Mronga, S; Tebbe, C G; Ortmann, E; Arnold, R; Schäfer, M K-H
2005-09-01
Peptides participating in the hypothalamic control of feeding behaviour are also involved in the central autonomic control of gastrointestinal functions, such as secretion and motility. An anatomical interaction and functional relationship in the central nervous system between the feeding-related peptides neuropeptide Y and ghrelin is well documented. Furthermore, it has been shown that feeding-related peptides can influence digestive function via central corticotrophin-releasing factor (CRF) pathways. In the present study, we investigated the role of ghrelin in the central autonomic control of colonic motility. Furthermore, we addressed the hypothesis that ghrelin is involved in the hypothalamic control of colonic motor function, utilizing central neuropeptide Y receptors and hypothalamic CRF pathways. Ghrelin (0.03, 0.06 and 0.12 nmol) bilaterally microinjected into the paraventricular nucleus (PVN) induced a significant stimulation of colonic propulsion. In particular, the colonic transit time decreased from 312+/-7 min to 198+/-12 min. Microinjection of the neuropeptide Y1 receptor antagonist, BIBP-3226 (200 pmol), or the nonselective CRF receptor antagonist, astressin (30 pmol), into the PVN abolished the stimulatory effect of ghrelin injected into the PVN on colonic transit time, whereas pretreatment with the selective CRF2 receptor, antisauvagine-30 (28 pmol), failed to affect the effect of PVN-ghrelin injection on colonic propulsion. These results suggest that ghrelin can act as central modulator of gastrointestinal motor functions at the level of the PVN via neuropeptide Y1- and CRF1 receptor-dependent mechanisms.
NASA Astrophysics Data System (ADS)
Xie, Huijuan; Gong, Yubing; Wang, Baoying
In this paper, we numerically study the effect of channel noise on synchronization transitions induced by time delay in adaptive scale-free Hodgkin-Huxley neuronal networks with spike-timing-dependent plasticity (STDP). It is found that synchronization transitions by time delay vary as channel noise intensity is changed and become most pronounced when channel noise intensity is optimal. This phenomenon depends on STDP and network average degree, and it can be either enhanced or suppressed as network average degree increases depending on channel noise intensity. These results show that there are optimal channel noise and network average degree that can enhance the synchronization transitions by time delay in the adaptive neuronal networks. These findings could be helpful for better understanding of the regulation effect of channel noise on synchronization of neuronal networks. They could find potential implications for information transmission in neural systems.
Zhi, M; Zhou, Z; Chen, H; Xiong, F; Huang, J; He, H; Zhang, M; Su, M; Gao, X; Hu, P
2017-06-01
As a traditional method for the assessment of colon dynamics, radio-opaque markers (ROMs) are limited in clinical use because of their ionizing radiation. We compared the accuracy and applicability of gadolinium-based capsules with ROMs in the measurement of colon dynamics in healthy controls and slow transit constipation (STC) patients. Seven patients with STC and nine healthy controls under a normal diet orally consumed ROMs and gadolinium-based capsules simultaneously. All subjects underwent X-ray and magnetic resonance imaging (MRI). Healthy control images were acquired at 12, 24, and 48 h, and STC patient images were acquired at 24, 48, and 72 h. The scores based on the position of the labeling capsules and ROMs in the colon and the colon transit times (CTTs) in the two groups were compared. The CTTs obtained via the ROMs were 34.7±17.4 and 67.3±6.5 h in the healthy controls and STC patients, respectively (P<.05). The CTTs obtained via MRI were 30.9±15.9 and 74.1±7.2 h in the healthy controls and STC patients, respectively (P<.05). The CTTs of the STC patients were significantly longer than the healthy controls. The correlation (r s ) between the scores based on the position of the labeling capsule and ROMs in the healthy group and the STC patients was .880 (P<.05) and .889 (P<.05), respectively. As a MRI contrast label, gadolinium-based capsules exhibit results comparable to ROMs in colon motility measurements. © 2017 John Wiley & Sons Ltd.
Templeton, Alan R; Brazeal, Hilary; Neuwald, Jennifer L
2011-09-01
Habitat fragmentation often arises from human-induced alterations to the matrix that reduce or eliminate dispersal between habitat patches. Elimination of dispersal increases local extinction and decreases recolonization. These phenomena were observed in the eastern collared lizard (Crotaphytus collaris collaris), which lives in the mid-continental highland region of the Ozarks (Missouri, USA) on glades: habitats of exposed bedrock that form desert-like habitats imbedded in a woodland matrix. With the onset of woodland fire suppression, glade habitats degenerated and the woodland matrix was altered to create a strong barrier to dispersal. By 1980, lizard populations in the Ozarks were rapidly going extinct. In response to this decline, some glades were restored by clearing and burning. Starting in 1984, collared lizard populations were translocated onto these restored habitats. The translocated populations persisted but did not colonize nearby glades or disperse among one another. In 1994 prescribed woodland fires were initiated, which unleashed much dispersal and colonizing behavior. Dispersal was highly nonrandom by both intrinsic variables (age, gender) and extrinsic variables (overall demography, glade population sizes, glade areas, landscape features), resulting in different classes of lizards being dominant in creating demographic cohesiveness among glades, colonizing new glades on a mountain, and colonizing new mountain systems. A dramatic transition was documented from isolated fragments, to a nonequilibrium colonizing metapopulation, and finally to a stable metapopulation. This transition is characterized by the convergence of rates of extinction and recolonization and a major alteration of dispersal probabilities and pattern in going from the nonequilibrium to stable metapopulation states.
Dispersal time for ancient human migrations: Americas and Europe colonization
NASA Astrophysics Data System (ADS)
Flores, J. C.
2007-07-01
I apply the recently proposed intermittence strategy to investigate the ancient human migrations in the world. That is, the Americas colonization (Bering-bridge and Pacific-coast theories) and Neanderthal replacement in Europe around 45000 years before the present. Using a mathematical equation related to diffusion and ballistic motion, I calculate the colonization time in all these cases in good agreement with archeological data (including Neolithic transition in Europe). Moreover, to support these calculations, I obtain analytically the effective speed of colonization in Europe veff=0.62 [km/yr] and related to the Aurignacian culture propagation.
Ord, Terry J; Cooke, Georgina M
2016-08-01
We know little about on how frequently transitions into new habitats occur, especially the colonization of novel environments that are the most likely to instigate adaptive evolution. One of the most extreme ecological transitions has been the shift in habitat associated with the move from water to land by amphibious fish. We provide the first phylogenetic investigation of these transitions for living fish. Thirty-three families have species reported to be amphibious and these are likely independent evolutionary origins of fish emerging onto land. Phylogenetic reconstructions of closely related taxa within one of these families, the Blenniidae, inferred as many as seven convergences on a highly amphibious lifestyle. Taken together, there appear to be few constraints on fish emerging onto land given amphibious behavior has evolved repeatedly many times across ecologically diverse families. The colonization of novel habitats by other taxa resulting in less dramatic changes in environment should be equally, if not, more frequent in nature, providing an important prerequisite for subsequent adaptive differentiation. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.
Sia, Tiong C; Whiting, Malcolm; Kyloh, Melinda; Nicholas, Sarah J; Oliver, John; Brookes, Simon J; Dinning, Phil G; Wattchow, David A; Spencer, Nick J
2013-01-01
Recent studies have shown that endogenous serotonin is not required for colonic peristalsis in vitro, nor gastrointestinal (GI) transit in vivo. However, antagonists of 5-Hydroxytryptamine (5-HT) receptors can inhibit peristalsis and GI-transit in mammals, including humans. This raises the question of how these antagonists inhibit GI-motility and transit, if depletion of endogenous 5-HT does not cause any significant inhibitory changes to either GI-motility or transit? We investigated the mechanism by which 5-HT3 and 5-HT4 antagonists inhibit distension-evoked peristaltic contractions in guinea-pig distal colon. In control animals, repetitive peristaltic contractions of the circular muscle were evoked in response to fixed fecal pellet distension. Distension-evoked peristaltic contractions were unaffected in animals with mucosa and submucosal plexus removed, that were also treated with reserpine (to deplete neuronal 5-HT). In control animals, peristaltic contractions were blocked temporarily by ondansetron (1-10 μM) and SDZ-205-557 (1-10 μM) in many animals. Interestingly, after this temporary blockade, and whilst in the continued presence of these antagonists, peristaltic contractions recovered, with characteristics no different from controls. Surprisingly, similar effects were seen in mucosa-free preparations, which had no detectable 5-HT, as detected by mass spectrometry. In summary, distension-evoked peristaltic reflex contractions of the circular muscle layer of the guinea-pig colon can be inhibited temporarily, or permanently, in the same preparation by selective 5-HT3 and 5-HT4 antagonists, depending on the concentration of the antagonists applied. These effects also occur in preparations that lack any detectable 5-HT. We suggest caution should be exercised when interpreting the effects of 5-HT3 and 5-HT4 antagonists; and the role of endogenous 5-HT, in the generation of distension-evoked colonic peristalsis.
Yoshimoto, Sazu; Babygirija, Reji; Dobner, Anthony; Ludwig, Kirk; Takahashi, Toku
2012-05-01
Disorders of colonic motility may contribute to symptoms in patients with irritable bowel syndrome (IBS), and stress is widely believed to play a major role in developing IBS. Stress increases corticotropin releasing factor (CRF) of the hypothalamus, resulting in acceleration of colonic transit in rodents. In contrast, hypothalamic oxytocin (OXT) has an anti-stress effect via inhibiting CRF expression and hypothalamic-pituitary-adrenal axis activity. Although transcutaneous electrical nerve stimulation (TENS) and acupuncture have been shown to have anti-stress effects, the mechanism of the beneficial effects remains unknown. We tested the hypothesis that TENS upregulates hypothalamic OXT expression resulting in reduced CRF expression and restoration of colonic dysmotility in response to chronic stress. Male SD rats received different types of stressors for seven consecutive days (chronic heterotypic stress). TENS was applied to the bilateral hind limbs every other day before stress loading. Another group of rats did not receive TENS treatment. TENS significantly attenuated accelerated colonic transit induced by chronic heterotypic stress, which was antagonized by a central injection of an OXT antagonist. Immunohistochemical study showed that TENS increased OXT expression and decreased CRF expression at the paraventricular nucleus (PVN) following chronic heterotypic stress. It is suggested that TENS upregulates hypothalamic OXT expression which acts as an anti-stressor agent and mediates restored colonic dysmotility following chronic stress. TENS may be useful to treat gastrointestinal symptoms associated with stress.
Recovery Temperature, Transition, and Heat Transfer Measurements at Mach 5
NASA Technical Reports Server (NTRS)
Brinich, Paul F.
1961-01-01
Schlieren, recovery temperature, and heat-transfer measurements were made on a hollow cylinder and a cone with axes alined parallel to the stream. Both the cone and cylinder were equipped with various bluntnesses, and the tests covered a Reynolds number range up to 20 x 10(exp 6) at a free-stream Mach number of 4.95 and wall to free-stream temperature ratios from 1.8 to 5.2 (adiabatic). A substantial transition delay due to bluntness was found for both the cylinder and the cone. For the present tests (Mach 4.95), transition was delayed by a factor of 3 on the cylinder and about 2 on the cone, these delays being somewhat larger than those observed in earlier tests at Mach 3.1. Heat-transfer tests on the cylinder showed only slight effects of wall temperature level on transition location; this is to be contrasted to the large transition delays observed on conical-type bodies at low surface temperatures at Mach 3.1. The schlieren and the peak-recovery-temperature methods of detecting transition were compared with the heat-transfer results. The comparison showed that the first two methods identified a transition point which occurred just beyond the end of the laminar run as seen in the heat-transfer data.
Delay of Transition Using Forced Damping
NASA Technical Reports Server (NTRS)
Exton, Reginald J.
2014-01-01
Several experiments which have reported a delay of transition are analyzed in terms of the frequencies of the induced disturbances generated by different flow control elements. Two of the experiments employed passive stabilizers in the boundary layer, one leading-edge bluntness, and one employed an active spark discharge in the boundary layer. It is found that the frequencies generated by the various elements lie in the damping region of the associated stability curve. It is concluded that the creation of strong disturbances in the damping region stabilizes the boundary-layer and delays the transition from laminar to turbulent flow.
Zhang, Wen-Qiang; Yan, Guo-Zheng; Yu, Lian-Zhi; Yang, Xin-Qing
2006-01-01
AIM: To study the prolonged colonic motility under normal conditions with a novel capsule-style micro-system and to assess its clinical significance. METHODS: A single use telemetry capsule (10 mm in diameter, 20 mm in length) embedded with a pressure sensor was ingested by the subjects. The sensor is capable of transmitting colonic pressure wirelessly for more than 130 h. The time of capsule entering the segmental colon was detected by ultrasound. The ultrasonic electrodes were mounted on the surface of the ileocecum and navel and at the junction of the left and rectosigmoid colon of the subjects in sequence, which were identified by abdominal X-rays with radiopaque markers. To verify the accuracy and reliability of ultrasonic detection of telemetry capsules at key points of colon, the segmental colonic transit time was simultaneously recorded by using radiopaque markers. RESULTS: The signal lamp showed that all recorders could receive the radio signal transmitted by the telemetry capsule. The X-rays showed that all telemetry capsules were detected successfully when they were passing through the key points of colon. There was a significant correlation between the transit results obtained by ultrasonic detection or by radiopaque markers. Colorectal recording was obtained from 20 healthy subjects during 613 h (411 h during waking, 202 h during sleep). Compared to waking, the number of pressure contractions and the area under pressure contractions were significantly (P < 0.05) decreased during sleep (21 ± 5 h-1 vs 15 ± 4 h-1, 463 ± 54 mmHg·s/min vs 342 ± 45 mmHg·s/min). The colonic motility exhibited significant regional variations both in the circadian behavior and in response to waking and meal. CONCLUSION: The capsule-style micro-system is reliable and noninvasive, and may represent a useful tool for the study of physiology and pathology of colonic motor disorders. PMID:17171801
van Bree, Sjoerd H W; Bemelman, Willem A; Hollmann, Markus W; Zwinderman, Aeilko H; Matteoli, Gianluca; El Temna, Shaima; The, Frans O; Vlug, Malaika S; Bennink, Roelof J; Boeckxstaens, Guy E E
2014-04-01
To identify clinical hallmarks associated with recovery of gastrointestinal transit. Impaired gastrointestinal transit or postoperative ileus largely determines clinical recovery after abdominal surgery. However, validated clinical hallmarks of gastrointestinal recovery to evaluate new treatments and readiness for discharge from the hospital are lacking. Gastric emptying and colonic transit were scintigraphically assessed from postoperative day 1 to 3 in 84 patients requiring elective colonic surgery and were compared with clinical parameters. The clinical hallmark that best reflected recovery of gastrointestinal transit was validated using data from a multicenter trial of 320 segmental colectomy patients. Seven of 84 patients developed a major complication with paralytic ileus characterized by total inhibition of gastrointestinal motility and were excluded from further analysis. In the remaining patients, recovery of colonic transit (defined as geometric center of radioactivity ≥2 on day 3), but not gastric emptying, was significantly correlated with clinical recovery (ρ = -0.59, P < 0.001). Conversely, the combined outcome measure of tolerance of solid food and having had defecation (SF + D) (area under the curve = 0.9, SE = 0.04, 95% CI = 0.79-0.95, P < 0.001), but not time to first flatus, best indicated recovery of gastrointestinal transit with a positive predictive value of 93% (95% CI = 78-99). Also in the main clinical trial, multiple regression analysis revealed that SF + D best predicted the duration of hospital stay. Our data indicate that the time to SF + D best reflects recovery of gastrointestinal transit and therefore should be considered as primary outcome measure in future clinical trials on postoperative ileus.(Netherlands National Trial Register, number NTR1884 and NTR222).
Changes in colonic motility induced by sennosides in dogs: evidence of a prostaglandin mediation.
Staumont, G; Fioramonti, J; Frexinos, J; Bueno, L
1988-01-01
The effects of sennosides on colonic motility were investigated in eight conscious dogs chronically fitted with two strain gauge transducers in the proximal colon, an intracolonic silicone catheter and a polyethylene catheter implanted in a branch of the right colonic artery. Oral sennosides (30 mg/kg) inhibited colonic motility for 12 to 18 h after a three to six hours delay, and associated with giant contractions and diarrhoea. The minimal oral dose of sennosides to produce such changes varied from 5 to 15 mg/kg. Intracolonic sennosides at the minimal effective dose and at 30 mg/kg reproduced the effects of oral sennosides, but with a shorter latency (0.5-1.5 h). Intracolonic PGE2 (100 micrograms/kg) in viscous gel medium or intra-arterial PGE2 (10 micrograms/h) inhibited colonic motility and induced giant contractions often associated with defecation. The colonic motor changes induced by intracolonic sennosides at the minimal effective dose, but not those induced by intracolonic PGE2, were blocked by intra-arterial indomethacin (10 micrograms/h) or piroxicam (5 micrograms/h). These results suggest that colonic motor actions of sennosides are mediated through a local prostaglandins synthesis, as they were blocked by cyclooxygenase inhibitor and reproduced by PGE2. PMID:3197991
Edwards, Joan E; Kingston-Smith, Alison H; Jimenez, Hugo R; Huws, Sharon A; Skøt, Kirsten P; Griffith, Gareth W; McEwan, Neil R; Theodorou, Michael K
2008-12-01
Anaerobic fungi (Neocallimastigales) are active degraders of fibrous plant material in the rumen. However, only limited information is available relating to how quickly they colonize ingested feed particles. The aim of this study was to determine the dynamics of initial colonization of forage by anaerobic fungi in the rumen and the impact of different postsampling wash procedures used to remove loosely associated microorganisms. Neocallimastigales-specific molecular techniques were optimized to ensure maximal coverage before application to assess the population size (quantitative PCR) and composition (automated ribosomal intergenic spacer analysis) of the colonizing anaerobic fungi. Colonization of perennial ryegrass (PRG) was evident within 5 min, with no consistent effect of time or wash procedure on fungal population composition. Wash procedure had no effect on population size unlike time, which had a significant effect. Colonizing fungal population size continued to increase over the incubation period after an initial lag of c. 4 min. This dynamic differs from that reported previously for rumen bacteria, where substantial colonization of PRG occurred within 5 min. The observed delay in colonization of plant material by anaerobic fungi is suggested to be primarily mediated by the time taken for fungal zoospores to locate, attach and encyst on plant material.
Barlow, Amanda J.; Dixon, Jill; Dixon, Michael J.; Trainor, Paul A.
2012-01-01
The enteric nervous system (ENS) comprises a complex neuronal network that regulates peristalsis of the gut wall and secretions into the lumen. The ENS is formed from a multipotent progenitor cell population called the neural crest, which is derived from the neuroepithelium. Neural crest cells (NCCs) migrate over incredible distances to colonize the entire length of the gut and during their migration they must survive, proliferate and ultimately differentiate. The absence of an ENS from variable lengths of the colon results in Hirschsprung's disease (HSCR) or colonic aganglionosis. Mutations in about 12 different genes have been identified in HSCR patients but the complex pattern of inheritance and variable penetrance suggests that additional genes or modifiers must be involved in the etiology and pathogenesis of this disease. We discovered that Tcof1 haploinsufficiency in mice models many of the early features of HSCR. Neuroepithelial apoptosis diminished the size of the neural stem cell pool resulting in reduced NCC numbers and their delayed migration along the gut from E10.5 to E14.5. Surprisingly however, we observe continued and complete colonization of the entire colon throughout E14.5–E18.5, a period in which the gut is considered to be non- or less-permissive to NCC. Thus, we reveal for the first time that reduced NCC progenitor numbers and delayed migration do not unequivocally equate with a predisposition for the pathogenesis of HSCR. In fact, these deficiencies can be overcome by balancing NCC intrinsic processes of proliferation and differentiation with extrinsic influences of the gut microenvironment. PMID:22228097
Barlow, Amanda J; Dixon, Jill; Dixon, Michael J; Trainor, Paul A
2012-04-15
The enteric nervous system (ENS) comprises a complex neuronal network that regulates peristalsis of the gut wall and secretions into the lumen. The ENS is formed from a multipotent progenitor cell population called the neural crest, which is derived from the neuroepithelium. Neural crest cells (NCCs) migrate over incredible distances to colonize the entire length of the gut and during their migration they must survive, proliferate and ultimately differentiate. The absence of an ENS from variable lengths of the colon results in Hirschsprung's disease (HSCR) or colonic aganglionosis. Mutations in about 12 different genes have been identified in HSCR patients but the complex pattern of inheritance and variable penetrance suggests that additional genes or modifiers must be involved in the etiology and pathogenesis of this disease. We discovered that Tcof1 haploinsufficiency in mice models many of the early features of HSCR. Neuroepithelial apoptosis diminished the size of the neural stem cell pool resulting in reduced NCC numbers and their delayed migration along the gut from E10.5 to E14.5. Surprisingly however, we observe continued and complete colonization of the entire colon throughout E14.5-E18.5, a period in which the gut is considered to be non- or less-permissive to NCC. Thus, we reveal for the first time that reduced NCC progenitor numbers and delayed migration do not unequivocally equate with a predisposition for the pathogenesis of HSCR. In fact, these deficiencies can be overcome by balancing NCC intrinsic processes of proliferation and differentiation with extrinsic influences of the gut microenvironment.
Bendas, Ehab R; Christensen, J Mark; Ayres, James W
2010-04-01
The basic objective of this study was to develop a novel technique that aids in compaction of coated pellets into tablets and obtain a release pattern from compressed pellets resembling the same pattern before compression. Multi-unit dosage forms of mesalamine targeted to the colon were formulated by extrusion-spheronization, and then coated with Eudragit S (30%). These pellets were filled into gelatin capsules or further formulated and compressed into tablets. Tablets for colonic delivery of mesalamine were prepared by mixing the coated beads with cushioning agents like stearic acid and Explotab, or by applying an additional coat of gelatin (4% weight gain) onto the Eudragit S coated pellets, and then compressing into tablets (tableted reservoir-type pellets). Then additional coating of the tablets prepared by the coating technique was applied utilizing Eudragit L 100-55 (5% weight gain). This technique provides additive protection for the coated beads to withstand the compression force during tableting. Excellent in vitro dissolution results were obtained, which were comparable to the results of the release of mesalamine from uncompressed beads filled in capsules. Mesalamine release from the capsules was 0.3% after 2 hours in gastric pH, 0.37% was released after an additional 1 hour in pH 6, and 89% was released after 1.5 hours in colonic pH 7.2. Various formulation and process parameters have to be optimized in order to obtain tableted reservoir-type pellets having the same release properties as the uncompressed pellets. The coating technique delays the release of mesalamine until the beads reach the terminal ileum and colon. Once released in the colon, mesalamine is minimally absorbed and can act locally to treat ulcerative colitis.
O'Malley, Dervla; Julio-Pieper, Marcela; Gibney, Sinead M; Dinan, Timothy G; Cryan, John F
2010-03-01
Stress and anxiety are important causal and exacerbating factors in functional gastro-intestinal (GI) disorders such as irritable bowel syndrome. Stress affects GI motility, faecal transit and visceral pain sensitivity. Additionally, permeability and function of the gut epithelium, which acts as a barrier between the external environment and the body's internal milieu is altered by stress. However, the effects of an enhanced stress response on colonic morphology require further investigation. We have used two animal models of stress and anxiety, the maternally separated (MS) and Wistar Kyoto (WKY) rats to examine colonic morphology. These rats exhibit increased anxiety behaviours, visceral hypersensitivity and increased stress-induced defecation in the open field arena. At a morphological level, increased mucus secretion and an associated elevation in the number of mucosal goblet cells was observed in the high anxiety rats. Additionally, the mucosal layer was flattened in MS and WKY rats, a finding indicative of mild mucosal damage. Furthermore, the muscular layer of the distal colon in these animals was thickened, an observation that may have implications for faecal transit and visceral pain perception. This study provides evidence of altered colonic function and morphology in two animal models with a heightened response to stress.
Algal ancestor of land plants was preadapted for symbiosis.
Delaux, Pierre-Marc; Radhakrishnan, Guru V; Jayaraman, Dhileepkumar; Cheema, Jitender; Malbreil, Mathilde; Volkening, Jeremy D; Sekimoto, Hiroyuki; Nishiyama, Tomoaki; Melkonian, Michael; Pokorny, Lisa; Rothfels, Carl J; Sederoff, Heike Winter; Stevenson, Dennis W; Surek, Barbara; Zhang, Yong; Sussman, Michael R; Dunand, Christophe; Morris, Richard J; Roux, Christophe; Wong, Gane Ka-Shu; Oldroyd, Giles E D; Ané, Jean-Michel
2015-10-27
Colonization of land by plants was a major transition on Earth, but the developmental and genetic innovations required for this transition remain unknown. Physiological studies and the fossil record strongly suggest that the ability of the first land plants to form symbiotic associations with beneficial fungi was one of these critical innovations. In angiosperms, genes required for the perception and transduction of diffusible fungal signals for root colonization and for nutrient exchange have been characterized. However, the origin of these genes and their potential correlation with land colonization remain elusive. A comprehensive phylogenetic analysis of 259 transcriptomes and 10 green algal and basal land plant genomes, coupled with the characterization of the evolutionary path leading to the appearance of a key regulator, a calcium- and calmodulin-dependent protein kinase, showed that the symbiotic signaling pathway predated the first land plants. In contrast, downstream genes required for root colonization and their specific expression pattern probably appeared subsequent to the colonization of land. We conclude that the most recent common ancestor of extant land plants and green algae was preadapted for symbiotic associations. Subsequent improvement of this precursor stage in early land plants through rounds of gene duplication led to the acquisition of additional pathways and the ability to form a fully functional arbuscular mycorrhizal symbiosis.
NASA Astrophysics Data System (ADS)
Harrer, Christian; Kirchhoff, Sonja; Keil, Andreas; Kirchhoff, Chlodwig; Mussack, Thomas; Lienemann, Andreas; Reiser, Maximilian; Navab, Nassir
2008-03-01
Functional gastrointestinal disorders result in a significant number of consultations in primary care facilities. Chronic constipation and diarrhea are regarded as two of the most common diseases affecting between 2% and 27% of the population in western countries 1-3. Defecatory disorders are most commonly due to dysfunction of the pelvic floor or the anal sphincter. Although an exact differentiation of these pathologies is essential for adequate therapy, diagnosis is still only based on a clinical evaluation1. Regarding quantification of constipation only the ingestion of radio-opaque markers or radioactive isotopes and the consecutive assessment of colonic transit time using X-ray or scintigraphy, respectively, has been feasible in clinical settings 4-8. However, these approaches have several drawbacks such as involving rather inconvenient, time consuming examinations and exposing the patient to ionizing radiation. Therefore, conventional assessment of colonic transit time has not been widely used. Most recently a new technique for the assessment of colonic transit time using MRI and MR-contrast media filled capsules has been introduced 9. However, due to numerous examination dates per patient and corresponding datasets with many images, the evaluation of the image data is relatively time-consuming. The aim of our study was to develop a computer tool to facilitate the detection of the capsules in MRI datasets and thus to shorten the evaluation time. We present a semi-automatic tool which provides an intensity, size 10, and shape-based 11,12 detection of ingested Gd-DTPA-saline filled capsules. After an automatic pre-classification, radiologists may easily correct the results using the application-specific user interface, therefore decreasing the evaluation time significantly.
Han, Eon Chul; Oh, Heung-Kwon; Ha, Heon-Kyun; Choe, Eun Kyung; Moon, Sang Hui; Ryoo, Seung-Bum; Park, Kyu Joo
2012-01-01
AIM: To determine long-term outcomes of surgical treatments for patients with constipation and features of colonic pseudo-obstruction. METHODS: Consecutive 42 patients who underwent surgery for chronic constipation within the last 13 years were prospectively collected. We identified a subgroup with colonic pseudo-obstruction (CPO) features, with dilatation of the colon proximal to the narrowed transitional zone, in contrast to typical slow-transit constipation (STC), without any dilated colonic segments. The outcomes of surgical treatments for chronic constipation with features of CPO were analyzed and compared with outcomes for STC. RESULTS: Of the 42 patients who underwent surgery for constipation, 33 patients had CPO with dilatation of the colon proximal to the narrowed transitional zone. There were 16 males and 17 females with a mean age of 51.2 ± 16.1 years. All had symptoms of chronic intestinal obstruction, including abdominal distension, pain, nausea, or vomiting, and the mean duration of symptoms was 67 mo (range: 6-252 mo). Preoperative defecation frequency was 1.5 ± 0.6 times/wk (range: 1-2 times/wk). Thirty-two patients underwent total colectomy, and one patient underwent diverting transverse colostomy. There was no surgery-related mortality. Postoperative histologic examination showed hypoganglionosis or agangliosis in 23 patients and hypoganglionosis combined with visceral neuropathy or myopathy in 10 patients. In contrast, histology of STC group revealed intestinal neuronal dysplasia type B (n = 6) and visceral myopathy (n = 3). Early postoperative complications developed in six patients with CPO; wound infection (n = 3), paralytic ileus (n = 2), and intraabdominal abscess (n = 1). Defecation frequencies 3 mo after surgery improved to 4.2 ± 3.2 times/d (range: 1-15 times/d). Long-term follow-up (median: 39.7 mo) was available in 32 patients; all patients had improvements in constipation symptoms, but two patients needed intermittent medication for management of diarrhea. All 32 patients had distinct improvements in constipation symptoms (with a mean bowel frequency of 3.3 ± 1.3 times/d), social activities, and body mass index (20.5 kg/m2 to 22.1 kg/m2) and were satisfied with the results of their surgical treatment. In comparison with nine patients who underwent colectomy for STC without colon dilatation, those in the CPO group had a lower incidence of small bowel obstructions (0% vs 55.6%, P < 0.01) and less difficulty with long-distance travel (6.7% vs 66.7%, P = 0.007) on long-term follow-up. CONCLUSION: Chronic constipation patients with features of CPO caused by narrowed transitional zone in the left colon had favorable outcomes after total colectomy. PMID:22969211
The kinetics and acoustics of fingering and note transitions on the flute.
Almeida, André; Chow, Renee; Smith, John; Wolfe, Joe
2009-09-01
Motion of the keys was measured in a transverse flute while beginner, amateur, and professional flutists played a range of exercises. The time taken for a key to open or close was typically 10 ms when pushed by a finger or 16 ms when moved by a spring. Because the opening and closing of keys will never be exactly simultaneous, transitions between notes that involve the movement of multiple fingers can occur via several possible pathways with different intermediate fingerings. A transition is classified as "safe" if it is possible to be slurred from the initial to final note with little perceptible change in pitch or volume. Some transitions are "unsafe" and possibly involve a transient change in pitch or a decrease in volume. Players, on average, used safe transitions more frequently than unsafe transitions. Delays between the motion of the fingers were typically tens of milliseconds, with longer delays as more fingers become involved. Professionals exhibited smaller average delays between the motion of their fingers than did amateurs.
Gong, Yubing; Wang, Baoying; Xie, Huijuan
2016-12-01
In this paper, we numerically study the effect of spike-timing-dependent plasticity (STDP) on synchronization transitions induced by autaptic activity in adaptive Newman-Watts Hodgkin-Huxley neuron networks. It is found that synchronization transitions induced by autaptic delay vary with the adjusting rate A p of STDP and become strongest at a certain A p value, and the A p value increases when network randomness or network size increases. It is also found that the synchronization transitions induced by autaptic delay become strongest at a certain network randomness and network size, and the values increase and related synchronization transitions are enhanced when A p increases. These results show that there is optimal STDP that can enhance the synchronization transitions induced by autaptic delay in the adaptive neuronal networks. These findings provide a new insight into the roles of STDP and autapses for the information transmission in neural systems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Evidence of a Critical Phase Transition in Purely Temporal Dynamics with Long-Delayed Feedback
NASA Astrophysics Data System (ADS)
Faggian, Marco; Ginelli, Francesco; Marino, Francesco; Giacomelli, Giovanni
2018-04-01
Experimental evidence of an absorbing phase transition, so far associated with spatiotemporal dynamics, is provided in a purely temporal optical system. A bistable semiconductor laser, with long-delayed optoelectronic feedback and multiplicative noise, shows the peculiar features of a critical phenomenon belonging to the directed percolation universality class. The numerical study of a simple, effective model provides accurate estimates of the transition critical exponents, in agreement with both theory and our experiment. This result pushes forward a hard equivalence of nontrivial stochastic, long-delayed systems with spatiotemporal ones and opens a new avenue for studying out-of-equilibrium universality classes in purely temporal dynamics.
Does the transition into daylight saving time really cause partial sleep deprivation?
Toth Quintilham, Manoel Carlos; Adamowicz, Taísa; Pereira, Erico Felden; Pedrazzoli, Mario; Louzada, Fernando Mazzilli
2014-01-01
To identify possible changes in the sleep patterns according to chronotype in undergraduate students during the daylight saving time (DST) transition. A total of 378 students answered the Morningness-Eveningness Questionnaire (MEQ) to determine their chronotype and kept a diary about sleep-wake schedules 1 week before and after the DST transition. Oral mucosal cell samples were collected for genetic analysis. After the DST transition, intermediate types (I-types) delayed bedtime and increased their time in bed and all groups delayed their wake-up time. All groups presented a shorter phase angle between sunset and the bedtime after the DST transition. On the other hand, only E-types showed a tendency to reduce the phase angle between sunrise and wake-up time, while I-types and M-types kept the same phase angles between sunrise and wake-up time after the DST transition. The polymorphisms in the human genes CLOCK and PER3 were not associated with individual differences in sleep patterns, nor were they associated with an adjustment to the DST transition. Under the new set of social times determined by DST, the adjustment was only partial. I-types delayed bedtime and all groups delayed their wake-up times after the beginning of DST. Consequently, the time in bed after the DST transition was not reduced; Morning (M-types) and Evening-types (E-types) kept the same time in bed and I-types showed an increase on it.
Delayed Ionization in Transition Metal Carbon Clusters
NASA Astrophysics Data System (ADS)
Kooi, S. E.; Castleman, A. W., Jr.
1997-03-01
Mass spectrometric studies of several single and binary transition metal carbon cluster systems, produced in a laser vaporization source, reveal several species that undergo delayed ionization. Pulsed extraction and blocking electric fields, in a time-of-flight mass spectrometer, allow the study of delayed ionization over a time window after excitation with a pulsed laser. In systems where metallocarbohedrenes (Met-Cars) are produced, the Met-Cars are the dominate delayed species. Delayed ionization of binary metal Met-Cars Ti_xM_yC_12 (M=Zr,Nb,Y; x+y=8) is dependent on the ratio of the two metals. Delayed behavior is investigated over a range of photoionization wavelengths and fluences. In order to determine the degree to which the delayed ionization is thermionic in character, the experimental data have been compared to Klots's model for thermionic emission from small particles.
Stress increases descending inhibition in mouse and human colon.
Reed, D E; Zhang, Y; Beyak, M J; Lourenssen, S; Blennerhassett, M G; Paterson, W G; Vanner, S J
2016-04-01
A relationship between stress and the symptoms of irritable bowel syndrome (IBS) has been well established but the cellular mechanisms are poorly understood. Therefore, we investigated effects of stress and stress hormones on colonic descending inhibition and transit in mouse models and human tissues. Stress was applied using water avoidance stress (WAS) in the animal model or mimicked using stress hormones, adrenaline (5 nM), and corticosterone (1 μM). Intracellular recordings were obtained from colonic circular smooth muscle cells in isolated smooth muscle/myenteric plexus preparations and the inhibitory junction potential (IJP) was elicited by nerve stimulation or balloon distension oral to the site of recording. Water avoidance stress increased the number of fecal pellets compared to control (p < 0.05). WAS also caused a significant increase in IJP amplitude following balloon distension. Stress hormones also increased the IJP amplitude following nerve stimulation and balloon distension (p < 0.05) in control mice but had no effect in colons from stressed mice. No differences were observed with application of ATP between stress and control tissues, suggesting the actions of stress hormones were presynaptic. Stress hormones had a large effect in the nerve stimulated IJP in human colon (increased >50%). Immunohistochemical studies identified alpha and beta adrenergic receptor immunoreactivity on myenteric neurons in human colon. These studies suggest that WAS and stress hormones can signal via myenteric neurons to increase inhibitory neuromuscular transmission. This could lead to greater descending relaxation, decreased transit time, and subsequent diarrhea. © 2016 John Wiley & Sons Ltd.
Mechanism of aqueous fructus aurantii immaturus extracts in neuroplexus of cathartic colons
Wang, Shi-Yi; Liu, Yan-Ping; Fan, Yi-Hong; Zhang, Lu; Cai, Li-Jun; Lv, Bin
2015-01-01
AIM: To examine the effect of aqueous fructus aurantii immaturus (FAI) extracts on the intestinal plexus of cathartic colons. METHODS: Cathartic colons were induced in rats with dahuang, a laxative used in traditional Chinese medicine. Once the model was established (after approximately 12 wk), rats were administered mosapride (1.54 mg/kg) or various doses of aqueous FAI extracts (1-4 g/kg) for 14 d. Transit function was assessed using an ink propulsion test. Rats were then sacrificed, and the ultramicrostructure of colonic tissue was examined using transmission electron microscopy. The expression of the 5-hydroxytryptamine receptor 4 (5-HTR4) and neurofilament-H was assessed in colon tissues using real-time PCR, Western blot, and immunohistochemistry. RESULTS: Mosapride and high dose (4 g/kg) of aqueous FAI extracts significantly improved the bowel movement in cathartic colons compared to untreated model colons as measured by the intestinal transit rate (70.06 ± 7.25 and 72.02 ± 8.74, respectively, vs 64.12 ± 5.19; P < 0.05 for both). Compared to controls, the ultramicrostructure of cathartic colons showed signs of neural degeneration. Treatment with mosapride and aqueous FAI extracts resulted in recovery of ultrastructural pathology. Treatment with mosapride alone upregulated the gene and protein expression of 5-HTR4 compared to untreated controls (P < 0.05 for both). Treatment with aqueous FAI extracts (≥ 2 g/kg) increased 5-HTR4 mRNA levels (P < 0.05), but no change in protein level was observed by Western blot or immunohistochemistry. The mRNA and protein levels of neurofilament-H were significantly increased with mosapride and ≥ 2 g/kg aqueous FAI extracts compared to controls (P < 0.05 for all). CONCLUSION: Aqueous FAI extracts and mosapride strengthen bowel movement in cathartic colons via increasing the expression of 5-HTR4 and neurofilament-H. PMID:26309361
Ma, Yiming; Fuchs, Adrian V; Boase, Nathan R B; Rolfe, Barbara E; Coombes, Allan G A; Thurecht, Kristofer J
2015-08-01
Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.
Guo, Li-ke; Zhang, Chao-xian; Guo, Xiao-feng
2011-11-01
Functional constipation is one of the most common gastrointestinal diseases. Currently, there is no effective Western medical therapy for functional constipation and it significantly impacts the quality of life of the patients. Integrated traditional Chinese and Western medicine therapies were reported to have better therapeutic effects than routine Western medicine therapies. To explore the efficacy of acupuncture combined with Chinese herbal medicine Plantain and Senna Granule in the treatment of functional constipation. A total of 390 patients with confirmed functional constipation enrolled from the Department of Gastroenterology, the First Affiliated Hospital of Xinxiang Medical College in China from February 2008 to January 2010 were randomly divided into three groups, with 130 cases in each group. Acupuncture group was treated with puncture of point Tianshu (ST25), Shangjuxu (ST37), Zusanli (ST36), Dachangyu (BL25) and Zhigou (SJ6) twice daily for four weeks, while Plantain and Senna Granule group was treated with 5 g of Plantain and Senna Granule once daily, and the combination group was given above-mentioned acupuncture and Plantain and Senna Granule. The defecation cycle, stool property, constipation symptom, accompanying symptoms, gastrointestinal transit time, including total gastrointestinal transit time, mouth-intestine transit time, colonic transit time, right colonic transit time, left colonic transit time and rectosigmoid colonic transit time, and adverse reactions of the three groups were evaluated before treatment, at the end of treatment and 64 weeks after treatment, respectively. Compared with before treatment, the scores of defecation cycle, stool property, constipation symptoms and accompanying symptoms, and gastrointestinal transit time all decreased significantly at the end of treatment in each group (P<0.01), and the combination group showed better results than the other groups (P<0.05). Compared with the end of treatment, the above-mentioned indexes recurred insignificantly in the combination group and acupuncture group after 64 weeks of follow-up (P>0.05), but all recurred significantly in the Plantain and Senna Granule group (P>0.05). Both short- and long-term total response rates of the combination group showed significant differences compared with those of the other two groups (P<0.05 or P<0.01). No serious adverse reactions occurred in all the three groups. Acupuncture plus Plantain and Senna Granule can significantly decrease gastrointestinal transit time and defecation cycle in patients with functional constipation; it can also change stool property and alleviate constipation symptom and accompanying symptoms, with good security and tolerance.
Primary Adenocarcinoma of Intestinal Type Arising From a Vaginal Mass: A Case Report.
Morrell, Lindsay H; Matthews, Kirk J; Chafe, Weldon E
2015-07-01
A patient with a history of a severe vaginal laceration during vaginal birth, unknown degree, presented with recurrent vaginal discharge and was found to have a vaginal mass. Pathologic analysis showed squamous mucosa transitioning into colonic type of mucosa with adenocarcinoma developed from colonic type of mucosa, reminiscent of anorectal junction.
Time delay induced different synchronization patterns in repulsively coupled chaotic oscillators
NASA Astrophysics Data System (ADS)
Yao, Chenggui; Yi, Ming; Shuai, Jianwei
2013-09-01
Time delayed coupling plays a crucial role in determining the system's dynamics. We here report that the time delay induces transition from the asynchronous state to the complete synchronization (CS) state in the repulsively coupled chaotic oscillators. In particular, by changing the coupling strength or time delay, various types of synchronous patterns, including CS, antiphase CS, antiphase synchronization (ANS), and phase synchronization, can be generated. In the transition regions between different synchronous patterns, bistable synchronous oscillators can be observed. Furthermore, we show that the time-delay-induced phase flip bifurcation is of key importance for the emergence of CS. All these findings may light on our understanding of neuronal synchronization and information processing in the brain.
Growth dominates choice in network percolation
NASA Astrophysics Data System (ADS)
Vijayaraghavan, Vikram S.; Noël, Pierre-André; Waagen, Alex; D'Souza, Raissa M.
2013-09-01
The onset of large-scale connectivity in a network (i.e., percolation) often has a major impact on the function of the system. Traditionally, graph percolation is analyzed by adding edges to a fixed set of initially isolated nodes. Several years ago, it was shown that adding nodes as well as edges to the graph can yield an infinite order transition, which is much smoother than the traditional second-order transition. More recently, it was shown that adding edges via a competitive process to a fixed set of initially isolated nodes can lead to a delayed, extremely abrupt percolation transition with a significant jump in large but finite systems. Here we analyze a process that combines both node arrival and edge competition. If started from a small collection of seed nodes, we show that the impact of node arrival dominates: although we can significantly delay percolation, the transition is of infinite order. Thus, node arrival can mitigate the trade-off between delay and abruptness that is characteristic of explosive percolation transitions. This realization may inspire new design rules where network growth can temper the effects of delay, creating opportunities for network intervention and control.
Recording In Vivo Human Colonic Motility: What Have We Learnt Over the Past 100 Years?
Dinning, Phil G
To understand the abnormalities that underpin functional gut disorders we must first gain insight into the normal patterns of gut motility. While detailed information continually builds on the motor patterns (and mechanisms that control them) of the human esophagus and anorectum, our knowledge of normal and abnormal motility in the more inaccessible regions of the gut remains poor. This particularly true of the human colon. Investigation of in vivo colonic motor patterns is achieved through measures of transit (radiology, scintigraphy and, more recently, "smart pills") or by direct real-time recording of colonic contractility (intraluminal manometry). This short review will provide an overview of findings from the past and present and attempt to piece together the complex nature of colonic motor patterns. In doing so it will build a profile of human colonic motility and determine the likely mechanisms that control this motility.
Lactose intolerance: a non-allergic disorder often managed by allergologists.
Perino, A; Cabras, S; Obinu, D; Cavalli Sforza, L
2009-02-01
Lactose malabsorption is a very common condition characterized by intestinal lactase deficiency. Primary lactose malabsorption is an inherited deficit present in the majority of the world's population, while secondary bypolactasia can be the consequence of an intestinal disease. The presence of malabsorbed lactose in the colonic lumen may cause gastrointestinal symptoms. This condition is known as lactose intolerance. Lactase non-persistence is the ancestral state, whilst two single nucleotide polymorphisms in the lactase gene have been associated with lactase persistence. These are C/T 13910 and G/A 22018 substitutions. Lactase persistence, this Mendelian dominant trait, only became advantageous after the invention of agriculture, when milk from domesticated animals became available for adults to drink. Lactase persistence is then strongly correlated with the diary history of the population. Diagnosis is assessed clinically by elimination of dietary lactose or, better, by non-invasive tests including hydrogen breath test and genetic test. In patients with lactase non-persistence, treatment should be considered exclusively if intolerance symptoms are present. In the absence of guidelines, the common therapeutic approach tends to exclude milk and dairy products from the diet. However, this strategy may have serious nutritional disadvantages. Several studies have been carried out to find alternative approaches, such as exogenous beta-galactosidase, yogurt and probiotics for their bacterial lactase activity, strategies that can prolong contact time between enzyme and substrate delaying gastrointestinal transit time, and chronic lactose ingestion to enhance colonic adaptation.
Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats.
Soret, Rodolphe; Chevalier, Julien; De Coppet, Pierre; Poupeau, Guillaume; Derkinderen, Pascal; Segain, Jean Pierre; Neunlist, Michel
2010-05-01
Little is known about the environmental and nutritional regulation of the enteric nervous system (ENS), which controls gastrointestinal motility. Short-chain fatty acids (SCFAs) such as butyrate regulate colonic mucosa homeostasis and can modulate neuronal excitability. We investigated their effects on the ENS and colonic motility. Effects of butyrate on the ENS were studied in colons of rats given a resistant starch diet (RSD) or intracecal perfusion of SCFAs. Effects of butyrate were also studied in primary cultures of ENS. The neurochemical phenotype of the ENS was analyzed with antibodies against Hu, choline acetyltransferase (ChAT), and neuronal nitric oxide synthase (nNOS) and by quantitative polymerase chain reaction. Signaling pathways involved were analyzed by pharmacologic and molecular biology methods. Colonic motility was assessed in vivo and ex vivo. In vivo and in vitro, RSD and butyrate significantly increased the proportion of ChAT- but not nNOS-immunoreactive myenteric neurons. Acetate and propionate did not reproduce the effects of butyrate. Enteric neurons expressed monocarboxylate transporter 2 (MCT2). Small interfering RNAs silenced MCT2 and prevented the increase in the proportion of ChAT- immunoreactive neurons induced by butyrate. Butyrate and trichostatin A increased histone H3 acetylation in enteric neurons. Effects of butyrate were prevented by inhibitors of the Src signaling pathway. RSD increased colonic transit, and butyrate increased the cholinergic-mediated colonic circular muscle contractile response ex vivo. Butyrate or histone deacetylase inhibitors might be used, along with nutritional approaches, to treat various gastrointestinal motility disorders associated with inhibition of colonic transit. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Janakiram, Naveena B.; Mohammed, Altaf; Bryant, Taylor; Zhang, Yuting; Brewer, Misty; Duff, Ashley; Biddick, Laura; Singh, Anil; Lightfoot, Stan; Steele, Vernon E; Rao, Chinthalapally V.
2016-01-01
Colorectal cancer (CRC) is the second highest cause of cancer-related deaths. A successful strategy to improve chemopreventive efficacies is by down-regulating tumor polyamines and enhancing NK cell activities. Colonic carcinogenesis was induced by azoxymethane (AOM) in male F344 rats. Eight weeks after AOM treatment, animals were fed diets containing Rosuvastatin and difluromethylornithine (DFMO) individually and in combination for 40 weeks. Both agents showed significant suppression of adenocarcinoma multiplicity and incidence with no toxicity compared to untreated rats. Low-dose Rosuvastatin plus DFMO suppressed colon adenocarcinoma multiplicity by 76% compared to low-dose Rosuvastatin (29%) and DFMO (46%), suggesting additive efficacy. Furthermore, low-dose combination caused a delay in colonic adenocarcinoma progression. DFMO, Rosuvastatin and/or combinations significantly decreased polyamine content and increased intra-tumoral NK cells expressing perforin plus IFN-γ compared to untreated colon tumors. Further ex-vivo analysis of splenic NK cells exposed to DFMO, Rosuvastatin or combination resulted in an increase of NKs with perforin expression. This is the first report on Rosuvastatin alone or combination strategy using clinically relevant statin plus DFMO doses which shows a significant suppression of colon adenocarcinomas, and their potential in increasing functional NK cells. This strategy has potential for further testing in high risk individuals for colon cancer. PMID:27841323
Sundram, Vasudha; Ganju, Aditya; Hughes, Joshua E.; Khan, Sheema; Chauhan, Subhash C.; Jaggi, Meena
2014-01-01
Over 80% of colon cancer development and progression is a result of the dysregulation of β-catenin signaling pathway. Herein, for the first time, we demonstrate that a serine-threonine kinase, Protein Kinase D1 (PKD1), modulates the functions of β-catenin to suppress colon cancer growth. Analysis of normal and colon cancer tissues reveals downregulation of PKD1 expression in advanced stages of colon cancer and its co-localization with β-catenin in the colon crypts. This PKD1 downregulation corresponds with the aberrant expression and nuclear localization of β-catenin. In-vitro investigation of the PKD1-β-catenin interaction in colon cancer cells reveal that PKD1 overexpression suppresses cell proliferation and clonogenic potential and enhances cell-cell aggregation. We demonstrate that PKD1 directly interacts with β-catenin and attenuates β-catenin transcriptional activity by decreasing nuclear β-catenin levels. Additionally, we show that inhibition of nuclear β-catenin transcriptional activity is predominantly influenced by nucleus targeted PKD1. This subcellular modulation of β-catenin results in enhanced membrane localization of β-catenin and thereby increases cell-cell adhesion. Studies in a xenograft mouse model indicate that PKD1 overexpression delayed tumor appearance, enhanced necrosis and lowered tumor hypoxia. Overall, our results demonstrate a putative tumor-suppressor function of PKD1 in colon tumorigenesis via modulation of β-catenin functions in cells. PMID:25149539
O'Dea, C J; Brookes, J H; Wattchow, D A
2010-06-01
Disorders of colonic motility, such as severe constipation and pseudo-obstruction, remain difficult to treat. The pathophysiology of these conditions is not completely understood, but previous studies suggest a deficiency of cholinergic innervation and an imbalance in autonomic regulation of colonic motor function as contributing factors. Therefore, increasing the availability of acetylcholine in the bowel wall with a cholinesterase inhibitor, such as pyridostigmine, may improve symptoms. We studied thirteen patients with severe constipation (slow transit type) or recurrent pseudo-obstruction. The six patients with slow transit constipation had mechanical obstruction and pelvic floor dysfunction excluded, and normal calibre colon and slow transit confirmed. These patients were offered pyridostigmine in an attempt to avoid surgery. The seven patients with pseudo-obstruction had dilated bowel on imaging, and mechanical obstruction was excluded. These patients received pyridostigmine when symptoms recurred, despite previous treatments. Pyridostigmine was initiated at 10 mg b.i.d. and increased if required. One of the six patients with slow transit constipation reported improvement of symptoms and had concurrently weaned anti-psychotic medications. Pyridostigmine was ceased in the remaining five patients due to lack of efficacy and/or side effects. Four patients proceeded to surgery for refractory symptoms. All seven patients with pseudo-obstruction had some improvement of symptoms with few side effects. Of these, two later had surgery for recurrent symptoms. In patients with slow transit constipation, treatment with pyridostigmine does not improve symptoms. However, it does improve symptoms in patients with recurrent pseudo-obstruction with few side effects, offering an extra treatment option for these patients.
Breakdown and invertebrate colonization of dead wood in wetland, upland, and river habitats
A Braccia; D Batzer
2010-01-01
Breakdown of woody debris in river and upland habitats as well as the interactions between wood and invertebrates have been well described. Studies of wood in wetlands are rare, and far less is known about breakdown and invertebrate use of wood in these transitional habitats. This study experimentally assessed breakdown and invertebrate colonization of wood in a...
Wigner time-delay distribution in chaotic cavities and freezing transition.
Texier, Christophe; Majumdar, Satya N
2013-06-21
Using the joint distribution for proper time delays of a chaotic cavity derived by Brouwer, Frahm, and Beenakker [Phys. Rev. Lett. 78, 4737 (1997)], we obtain, in the limit of the large number of channels N, the large deviation function for the distribution of the Wigner time delay (the sum of proper times) by a Coulomb gas method. We show that the existence of a power law tail originates from narrow resonance contributions, related to a (second order) freezing transition in the Coulomb gas.
Sajad, Amirsaman; Sadeh, Morteza; Yan, Xiaogang; Wang, Hongying; Crawford, John Douglas
2016-01-01
The frontal eye fields (FEFs) participate in both working memory and sensorimotor transformations for saccades, but their role in integrating these functions through time remains unclear. Here, we tracked FEF spatial codes through time using a novel analytic method applied to the classic memory-delay saccade task. Three-dimensional recordings of head-unrestrained gaze shifts were made in two monkeys trained to make gaze shifts toward briefly flashed targets after a variable delay (450-1500 ms). A preliminary analysis of visual and motor response fields in 74 FEF neurons eliminated most potential models for spatial coding at the neuron population level, as in our previous study (Sajad et al., 2015). We then focused on the spatiotemporal transition from an eye-centered target code (T; preferred in the visual response) to an eye-centered intended gaze position code (G; preferred in the movement response) during the memory delay interval. We treated neural population codes as a continuous spatiotemporal variable by dividing the space spanning T and G into intermediate T-G models and dividing the task into discrete steps through time. We found that FEF delay activity, especially in visuomovement cells, progressively transitions from T through intermediate T-G codes that approach, but do not reach, G. This was followed by a final discrete transition from these intermediate T-G delay codes to a "pure" G code in movement cells without delay activity. These results demonstrate that FEF activity undergoes a series of sensory-memory-motor transformations, including a dynamically evolving spatial memory signal and an imperfect memory-to-motor transformation.
Time synchronization via the transit satellite at Mizusawa
NASA Technical Reports Server (NTRS)
Hara, J.; Sato, K. H.
1978-01-01
Time signals emitted from Transit satellites and received by the NAVICODE type receiver at Mizusawa, Japan are presented. The International Latitude Observatory of Mizusawa and the U. S. Naval Observatory were compared using the time signals. Propagation delays, a receiver delay, effects of relative motion of satellites, and effects of the ionosphere are discussed.
NASA Astrophysics Data System (ADS)
Liu, Chen; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xile; Tsang, Kaiming; Chan, Wailok
2013-09-01
The combined effects of the information transmission delay and the ratio of the electrical and chemical synapses on the synchronization transitions in the hybrid modular neuronal network are investigated in this paper. Numerical results show that the synchronization of neuron activities can be either promoted or destroyed as the information transmission delay increases, irrespective of the probability of electrical synapses in the hybrid-synaptic network. Interestingly, when the number of the electrical synapses exceeds a certain level, further increasing its proportion can obviously enhance the spatiotemporal synchronization transitions. Moreover, the coupling strength has a significant effect on the synchronization transition. The dominated type of the synapse always has a more profound effect on the emergency of the synchronous behaviors. Furthermore, the results of the modular neuronal network structures demonstrate that excessive partitioning of the modular network may result in the dramatic detriment of neuronal synchronization. Considering that information transmission delays are inevitable in intra- and inter-neuronal networks communication, the obtained results may have important implications for the exploration of the synchronization mechanism underlying several neural system diseases such as Parkinson's Disease.
Kaur, Rupinderjeet; Gulati, Monica; Singh, Sachin Kumar
2017-02-01
The present study explains the effect of concomitant administration of synbiotics with the polysaccharide based colon targeted delivery system. As the gut microflora get deranged on administration of mesalamine, drug release from such delivery systems is expected to be jeopardised because the release trigger is dependent solely on the colonic microbiota. To overcome this limitation, mesalamine was formulated as microspheres with guar gum and xanthan gum (prebiotics). These were combined with probiotics containing Lactobacillus acidophilus, L. rhamnosus, Bifidobacterium longumand Saccharomyces boulardi. Dissolution studies of the prepared formulation conducted in simulated colonic fluid clearly demonstrated its superiority over the marketed, delayed release dosage forms of mesalamine. The therapeutic benefit of the concomitant administration of synbiotic with mesalamine was evidenced by the comparative evaluation of faecal contents, weight gain trend and histopathological studies conducted in rats. The results suggest that co-administration of synbiotics with mesalamine can be used as a convenient methodology to achieve efficient and cost-effective targeting of the drug to colon. Copyright © 2016 Elsevier B.V. All rights reserved.
Experiments and modelling of rate-dependent transition delay in a stochastic subcritical bifurcation
NASA Astrophysics Data System (ADS)
Bonciolini, Giacomo; Ebi, Dominik; Boujo, Edouard; Noiray, Nicolas
2018-03-01
Complex systems exhibiting critical transitions when one of their governing parameters varies are ubiquitous in nature and in engineering applications. Despite a vast literature focusing on this topic, there are few studies dealing with the effect of the rate of change of the bifurcation parameter on the tipping points. In this work, we consider a subcritical stochastic Hopf bifurcation under two scenarios: the bifurcation parameter is first changed in a quasi-steady manner and then, with a finite ramping rate. In the latter case, a rate-dependent bifurcation delay is observed and exemplified experimentally using a thermoacoustic instability in a combustion chamber. This delay increases with the rate of change. This leads to a state transition of larger amplitude compared with the one that would be experienced by the system with a quasi-steady change of the parameter. We also bring experimental evidence of a dynamic hysteresis caused by the bifurcation delay when the parameter is ramped back. A surrogate model is derived in order to predict the statistic of these delays and to scrutinize the underlying stochastic dynamics. Our study highlights the dramatic influence of a finite rate of change of bifurcation parameters upon tipping points, and it pinpoints the crucial need of considering this effect when investigating critical transitions.
Experiments and modelling of rate-dependent transition delay in a stochastic subcritical bifurcation
Noiray, Nicolas
2018-01-01
Complex systems exhibiting critical transitions when one of their governing parameters varies are ubiquitous in nature and in engineering applications. Despite a vast literature focusing on this topic, there are few studies dealing with the effect of the rate of change of the bifurcation parameter on the tipping points. In this work, we consider a subcritical stochastic Hopf bifurcation under two scenarios: the bifurcation parameter is first changed in a quasi-steady manner and then, with a finite ramping rate. In the latter case, a rate-dependent bifurcation delay is observed and exemplified experimentally using a thermoacoustic instability in a combustion chamber. This delay increases with the rate of change. This leads to a state transition of larger amplitude compared with the one that would be experienced by the system with a quasi-steady change of the parameter. We also bring experimental evidence of a dynamic hysteresis caused by the bifurcation delay when the parameter is ramped back. A surrogate model is derived in order to predict the statistic of these delays and to scrutinize the underlying stochastic dynamics. Our study highlights the dramatic influence of a finite rate of change of bifurcation parameters upon tipping points, and it pinpoints the crucial need of considering this effect when investigating critical transitions. PMID:29657803
Coherent Pattern Prediction in Swarms of Delay-Coupled Agents
NASA Astrophysics Data System (ADS)
Mier-Y-Teran-Romero, Luis; Forgoston, Eric; Scwartz, Ira
2013-03-01
We consider a general swarm model of self-propelling particles interacting through a pairwise potential in the presence of a fixed communication time delay. Previous work has shown that swarms with communication time delays and noise may display pattern transitions that depend on the size of the coupling amplitude. We extend these results by completely unfolding the bifurcation structure of the mean field approximation. Our analysis reveals a direct correspondence between the different dynamical behaviors found in different regions of the coupling-time delay plane with the different classes of simulated coherent swarm patterns. We derive the spatio-temporal scales of the swarm structures, and also demonstrate how the complicated interplay of coupling strength, time delay, noise intensity, and choice of initial conditions can affect the swarm. In addition, when adding noise to the system, we find that for sufficiently large values of the coupling strength and/or the time delay, there is a noise intensity threshold that forces a transition of the swarm from a misaligned state into an aligned state. We show that this alignment transition exhibits hysteresis when the noise intensity is taken to be time dependent. Office of Naval Research, NIH (LMR and IBS) and NRL (EF)
Ordoñez, Carlos A; Pino, Luis F; Badiel, Marisol; Sánchez, Alvaro I; Loaiza, Jhon; Ballestas, Leonardo; Puyana, Juan Carlos
2011-01-01
Background Recent studies report the safety and feasibility of performing delayed anastomosis (DA) in patients undergoing damage control laparotomy (DCL) for destructive colon injuries (DCI). Despite accumulating experience in both civilian and military trauma, questions regarding how to best identify high risk patients and minimize the number of anastomosis-associated complications remain. Our current practice is to perform a definitive closure of the colon during DCL, unless there is persistent acidosis, bowel wall edema, or evidence of intra-abdominal abscess. In this study, we evaluated the safety of this approach by comparing outcomes of patients with DCI who underwent definitive closure of the colon during DCL versus patients managed with colostomy with or without DCL. Methods We performed a retrospective chart review of patients with penetrating DCI during 2003–2009. Severity of injury, surgical management, and clinical outcome were assessed. Results Sixty patients with severe gunshot wounds (GSW) and 3 patients with stab wounds were included in the analysis. DCL was required in 30 patients, all with GSW. Three patients died within the first 48 hours, 3 underwent colostomy, and 24 were managed with DA. Thirty-three patients were managed with standard laparotomy: 26 patients with primary anastomosis, and 7 with colostomy. Overall mortality rate was 9.5%. Three late deaths occurred in the DCL group, and only one death was associated with an anastomotic leak. Conclusions Performing a DA in DCI during DCL is a reliable and feasible approach as long as severe acidosis, bowel wall edema, and/or persistent intra-abdominal infections are not present. PMID:22182861
Ordoñez, Carlos A; Pino, Luis F; Badiel, Marisol; Sánchez, Alvaro I; Loaiza, Jhon; Ballestas, Leonardo; Puyana, Juan Carlos
2011-12-01
Recent studies report the safety and feasibility of performing delayed anastomosis (DA) in patients undergoing damage control laparotomy (DCL) for destructive colon injuries (DCIs). Despite accumulating experience in both civilian and military trauma, questions regarding how to best identify high-risk patients and minimize the number of anastomosis-associated complications remain. Our current practice is to perform a definitive closure of the colon during DCL, unless there is persistent acidosis, bowel wall edema, or evidence of intra-abdominal abscess. In this study, we evaluated the safety of this approach by comparing outcomes of patients with DCI who underwent definitive closure of the colon during DCL versus patients managed with colostomy with or without DCL. We performed a retrospective chart review of patients with penetrating DCI during 2003 to 2009. Severity of injury, surgical management, and clinical outcome were assessed. Sixty patients with severe gunshot wounds and three patients with stab wounds were included in the analysis. DCL was required in 30 patients, all with gunshot wounds. Three patients died within the first 48 hours, three underwent colostomy, and 24 were managed with DA. Thirty-three patients were managed with standard laparotomy: 26 patients with primary anastomosis and 7 with colostomy. Overall mortality rate was 9.5%. Three late deaths occurred in the DCL group, and only one death was associated with an anastomotic leak. Performing a DA in DCI during DCL is a reliable and feasible approach as long as severe acidosis, bowel wall edema, and/or persistent intra-abdominal infections are not present.
Impaction of swallowed dentures in the sigmoid colon requiring sigmoid colectomy.
Flanagan, Michael; Clancy, Cillian; O Riordain, Micheal G
2018-05-07
Foreign body (FB) ingestion results in perforation in 1% of cases and is associated with significant morbidity and rarely mortality. Clinical presentation is variable and can present a diagnostic challenge. We report our experience and management of a patient with a delayed presentation of a sigmoid colon foreign body as a result of ingestion of a dental plate. A 67 year old female attended the colorectal outpatient clinic following an incidental finding of a sigmoid mass on computed tomography (CT) abdomen. Further investigation identified a dental plate impacted in a thickened sigmoid colon. On further questioning the patient recalled losing her dentures three years previously. At surgery the dental plate had partially eroded through the sigmoid colon into the pelvic side wall. A sigmoid colectomy and hand sewn end-to-end colo-colic anastomosis was performed. Localised perforation following ingestion of a foreign body may result in significant morbidity. Extra luminal migration and local inflammatory response resulted in the formation of a walled off collection. Delayed complications of perforation include abscess and fistula formation. Clinicians need to exhibit a high index of suspicion when treating edentulous patients and alcohol and drug abusers who present with an acute abdomen or a sub-acute presentation with associated atypical imaging and endoscopic findings. The decision regarding intervention and management strategy in cases of perforation by foreign body depends on chronicity of the case, extent of localised or diffuse peritonitis, and size of the lesion or area of bowel involved. Copyright © 2018. Published by Elsevier Ltd.
Prognostic and predictive potential molecular biomarkers in colon cancer.
Nastase, A; Pâslaru, L; Niculescu, A M; Ionescu, M; Dumitraşcu, T; Herlea, V; Dima, S; Gheorghe, C; Lazar, V; Popescu, I
2011-01-01
An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.
Neurogenic and myogenic motor patterns of rabbit proximal, mid, and distal colon.
Dinning, P G; Costa, M; Brookes, S J; Spencer, N J
2012-07-01
The rabbit colon consists of four distinct regions. The motility of each region is controlled by myogenic and neurogenic mechanisms. Associating these mechanisms with specific motor patterns throughout all regions of the colon has not previously been achieved. Three sections of the colon (the proximal, mid, and distal colon) were removed from euthanized rabbits. The proximal colon consists of a triply teniated region and a single tenia region. Spatio-temporal maps were constructed from video recordings of colonic wall diameter, with associated intraluminal pressure recorded from the aboral end. Hexamethonium (100 μM) and tetrodotoxin (TTX; 0.6 μM) were used to inhibit neural activity. Four distinct patterns of motility were detected: 1 myogenic and 3 neurogenic. The myogenic activity consisted of circular muscle (CM) contractions (ripples) that occurred throughout the colon and propagated in both antegrade (anal) and retrograde (oral) directions. The neural activity of the proximal colon consisted of slowly (0.1 mm/s) propagating colonic migrating motor complexes, which were abolished by hexamethonium. These complexes were observed in the region of the proximal colon with a single band of tenia. In the distal colon, tetrodotoxin-sensitive, thus neurally mediated, but hexamethonium-resistant, peristaltic (anal) and antiperistaltic (oral) contractions were identified. The distinct patterns of neurogenic and myogenic motor activity recorded from isolated rabbit colon are specific to each anatomically distinct region. The regional specificity motor pattern is likely to facilitate orderly transit of colonic content from semi-liquid to solid composition of feces.
Williams, Michael D; Watts, Dorraine; Fakhry, Samir
2003-11-01
Blunt injury to the colon is rare. Few studies of adequate size and design exist to allow clinically useful conclusions. The Eastern Association for the Surgery of Trauma Multi-institutional Hollow Viscus Injury (HVI) Study presents a unique opportunity to definitively study these injuries. Patients with blunt HVI were identified from the registries of 95 trauma centers over 2 years (1998-1999). Patients with colon injuries (cases) were compared with blunt trauma patient undergoing a negative laparotomy (controls). Data were abstracted by chart review. Of the 227,972 patients represented, 2,632 (1.0%) had an HVI and 798 had a colonic/rectal injury (0.3%). Of patients diagnosed with HVI, 30.2% had a colon injury. No physical findings or imaging modalities were able to discriminate colonic injury. Logistic regression modeling yielded no clinically useful combination of findings that would reliably predict colonic injury. In patients undergoing laparotomy, presence of colon injury was associated with a higher risk of some complications but not mortality. Colon injury was associated with increased hospital (17.4 vs. 13.1, p < 0.001) and intensive care unit (9.7 vs. 6.9, p = 0.003) length of stay. Almost all colon patients (92.0%) underwent laparotomy within 24 hours of injury. Colonic injury after blunt trauma is rare and difficult to diagnose. No diagnostic test or combination of findings reliably excluded blunt colonic injury. Despite the inadequacy of current diagnostic tests, almost all patients with colonic injury were taken to the operating room within 24 hours. Even with relatively prompt surgery, patients with colon injury were at significantly higher risk for serious complications and increased length of stay. In contrast to small bowel perforation, delay in operative intervention appears to be less common but is still associated with serious morbidity.
Rapid genetic restoration of a keystone species exhibiting delayed demographic response
USDA-ARS?s Scientific Manuscript database
Genetic founder effects are often expected when animals colonize restored habitat in fragmented landscapes, but empirical data on genetic responses to restoration are limited. We examined the genetic response of banner-tailed kangaroo rats (Dipodomys spectabilis) to landscape-scale grassland restor...
Ding, Chao; Fan, Wenting; Gu, Lili; Tian, Hongliang; Ge, Xiaolong; Gong, Jianfeng; Nie, Yongzhan; Li, Ning
2018-05-01
Gut microbiota may contribute to regulate colonic motility, which is involved in the etiology of constipation. Fecal microbiota transplantation (FMT) has been demonstrated to restore intestinal homeostasis. The aim of this study was to evaluate the clinical outcomes and prognostic factors of FMT for the treatment of slow transit constipation (STC). Fifty-two patients with STC received standardized FMT and were followed up for 6 months. Bowel habit, colonic transit time, constipation-related symptoms (PAC-SYM score), quality of life (PAC-QOL score), treatment satisfaction scores and adverse events were monitored. The primary efficacy endpoint was the proportion of patients having on average three or more complete spontaneous bowel movements (CSBMs) per week. The primary efficacy endpoint was achieved in 50.0%, 38.5% and 32.7% of patients over week intervals 3-4, 9-12 and 21-24, respectively ( P < 0.01 for all comparisons). Significant improvements were also observed in other bowel movement assessments, colonic transit time, constipation-related symptoms and quality of life; but all improvements diminished at weeks 12 and 24. Incompleteness of evacuation served as the only factor associated with efficacy. No serious treatment-related adverse events were observed. This study suggested FMT was effective and safe for STC, while a late loss of efficacy was also observed. A lower degree of sensation of incompleteness predicted a better outcome.
Increased colonic bile acid exposure: a relevant factor for symptoms and treatment in IBS.
Bajor, Antal; Törnblom, Hans; Rudling, Mats; Ung, Kjell-Arne; Simrén, Magnus
2015-01-01
Bile acids may play a role in the pathogenesis of IBS. We investigated the potential effects of bile acids entering the colon and its role in the symptom pattern in IBS. We measured 75Se-labelled homocholic acid-taurine (75SeHCAT) retention, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor (FGF) 19 in patients with IBS (n=141) and control subjects (75SeHCAT n=29; C4 and FGF19 n=435). In patients with IBS stool frequency and form, as well as GI symptom severity were registered, and in a proportion of patients colonic transit time and rectal sensitivity were measured (n=66). An 8-week open-label treatment with colestipol was offered to patients with 75SeHCAT <20%, and the effect of treatment was evaluated with IBS severity scoring system and adequate relief of IBS symptoms. Compared with controls, patients with IBS had lower 75SeHCAT values (p=0.005), higher C4c levels (C4 corrected for cholesterol) (p<0.001), but similar FGF19 levels. Abnormal 75SeHCAT retention (<10%) was seen in 18% of patients, whereas 23% had elevated C4c levels. Patients with IBS with 75SeHCAT retention <10% had more frequent stools, accelerated colonic transit time, rectal hyposensitivity, a higher body mass index, higher C4c and lower FGF19 levels. Colestipol treatment improved IBS symptoms (IBS severity scoring system 220±109 vs. 277±106; p<0.01), and 15/27 patients fulfilled criteria for treatment response (adequate relief ≥50% of weeks 5-8). Increased colonic bile acid exposure influences bowel habit and colonic transit time in patients with IBS. A high response rate to open label treatment with colestipol supports this, but placebo-controlled studies are warranted. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Pelvic floor dyssynergia: efficacy of biofeedback training.
Gadel Hak, Nabil; El-Hemaly, Mohamed; Hamdy, Emad; El-Raouf, Ahmed Abd; Atef, Ehab; Salah, Tarek; El-Hanafy, Ehab; Sultan, Ahmad; Haleem, Magdy; Hamed, Hala
2011-03-01
Paradoxical contraction of the pelvic floor during attempts to defaecate is described as pelvic floor dyssynergia (anismus). It is a behavioural disorder (no associated morphological or neurological abnormalities); consequently, biofeedback training has been recommended as a behavioural therapy for such a disorder. The aim of the present study was to evaluate long-term satisfaction of patients diagnosed with pelvic floor dyssynergia after biofeedback. Sixty patients (35 females and 25 males) with a mean age of 30±12years and a 4year duration of constipation were included. Forty-five patients had normal colonic transit and 15 patients had slow colonic transit. History, physical examination and barium enema were done to exclude constipation secondary to organic causes. Colonic and pelvic floor functions (colon-transit time, anorectal manometry, EMG and defaecography) were performed before and after biofeedback treatments. Patients were treated on a weekly basis with an average of (6±2) sessions. At the end of sessions, 55 out of 60 patients (91.6%) reported a subjectively overall improvement. Symptoms of dyschezia were reported less frequently after biofeedback. Age and gender were not predictive factors of outcome. No symptoms at initial assessment were predictive for patient's satisfaction but the only factor of predictive value was the diagnosis of anismus and the motivated patient who wanted to continue the sessions. Biofeedback remains a morbidity free, low-cost and effective outpatient therapy for well-motivated patients complaining of functional constipation and diagnosed as pelvic floor dyssynergia. Copyright © 2011 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.
Pectin-based oral drug delivery to the colon.
Sande, Sverre Arne
2005-05-01
This review presents an overview of studies concerning oral formulations intended for site-specific drug delivery to the colon with pectin as the main excipient. The biological aspects covered include gastrointestinal transit and the enzymatic degradation of pectin. Scintigraphic methods demonstrating the functionality of pectin formulations are discussed. The main focus is on the various formulations reported, including matrix tablets, multiparticulate formulations as pellets and hydrogel beads, and pectin-based coatings. Also included is an evaluation of common excipients employed to improve colon specificity by crosslinking or increasing the hydrophobicity. Finally, properties of the pectin molecules that are important for successful formulations are examined. The conclusion is that the studies found in the literature provide an excellent platform for the development of pectin-based colon delivery systems.
Operative colonoscopic endoscopy.
Van Gossum, A; Bourgeois, F; Gay, F; Lievens, P; Adler, M; Cremer, M
1992-01-01
There are several conditions where operative colonoscopy is useful. Acute colonic pseudo-obstruction or Ogilvie's syndrome is characterized by a acute distension of the colon. Although medical management may be sufficient in many cases, endoscopic decompression must be performed when colonic distension is greater than 12 cm. Insertion of decompression tube to avoid rapid recurrence seems to be adequate. In case of massive lower intestinal hemorrhage, colonoscopy seems to be more accurate than mesenteric angiography. Such endoscopic examination requires an experienced endoscopist. Colonoscopic polypectomy has become the standard method for removal of colonic polyps. Factors influencing the rate of complications have been studied. While the number of complications was very low, we have observed that all the major hemorrhages were immediate when the blended current was used, but delayed when the pure coagulation current was applied. Endoscopic laser photocavitation is a valuable palliative method treating rectal adenocarcinoma in well selected patients. Indeed, if the patients survive sufficiently long after initial therapy, it becomes increasingly difficult to achieve persistent palliation with laser therapy.
Sajad, Amirsaman; Sadeh, Morteza; Yan, Xiaogang; Wang, Hongying
2016-01-01
Abstract The frontal eye fields (FEFs) participate in both working memory and sensorimotor transformations for saccades, but their role in integrating these functions through time remains unclear. Here, we tracked FEF spatial codes through time using a novel analytic method applied to the classic memory-delay saccade task. Three-dimensional recordings of head-unrestrained gaze shifts were made in two monkeys trained to make gaze shifts toward briefly flashed targets after a variable delay (450-1500 ms). A preliminary analysis of visual and motor response fields in 74 FEF neurons eliminated most potential models for spatial coding at the neuron population level, as in our previous study (Sajad et al., 2015). We then focused on the spatiotemporal transition from an eye-centered target code (T; preferred in the visual response) to an eye-centered intended gaze position code (G; preferred in the movement response) during the memory delay interval. We treated neural population codes as a continuous spatiotemporal variable by dividing the space spanning T and G into intermediate T–G models and dividing the task into discrete steps through time. We found that FEF delay activity, especially in visuomovement cells, progressively transitions from T through intermediate T–G codes that approach, but do not reach, G. This was followed by a final discrete transition from these intermediate T–G delay codes to a “pure” G code in movement cells without delay activity. These results demonstrate that FEF activity undergoes a series of sensory–memory–motor transformations, including a dynamically evolving spatial memory signal and an imperfect memory-to-motor transformation. PMID:27092335
Switching Characteristics of Ferroelectric Transistor Inverters
NASA Technical Reports Server (NTRS)
Laws, Crystal; Mitchell, Coey; MacLeod, Todd C.; Ho, Fat D.
2010-01-01
This paper presents the switching characteristics of an inverter circuit using a ferroelectric field effect transistor, FeFET. The propagation delay time characteristics, phl and plh are presented along with the output voltage rise and fall times, rise and fall. The propagation delay is the time-delay between the V50% transitions of the input and output voltages. The rise and fall times are the times required for the output voltages to transition between the voltage levels V10% and V90%. Comparisons are made between the MOSFET inverter and the ferroelectric transistor inverter.
New Technologies in Using Recombinant Attenuated Salmonella Vaccine Vectors
Curtiss, Roy; Xin, Wei; Li, Yuhua; Kong, Wei; Wanda, Soo-Young; Gunn, Bronwyn; Wang, Shifeng
2014-01-01
Recombinant attenuated Salmonella vaccines (RASVs) have been constructed to deliver antigens from other pathogens to induce immunity to those pathogens in vaccinated hosts. The attenuation means should ensure that the vaccine survives following vaccination to colonize lymphoid tissues without causing disease symptoms. This necessitates that attenuation and synthesis of recombinant gene encoded protective antigens do not diminish the ability of orally administered vaccines to survive stresses encountered in the gastrointestinal tract. We have eliminated these problems by using RASVs with regulated delayed expression of attenuation and regulated delayed synthesis of recombinant antigens. These changes result in RASVs that colonize effector lymphoid tissues efficiently to serve as “factories” to synthesize protective antigens that induce higher protective immune responses than achieved when using previously constructed RASVs. We have devised a biological containment system with regulated delayed lysis to preclude RASV persistence in vivo and survival if excreted. Attributes were added to reduce the mild diarrhea sometimes experienced with oral live RASVs and to ensure complete safety in newborns. These collective technologies have been used to develop a novel, low-cost, RASV-synthesizing, multiple-protective Streptococcus pneumoniae antigens that will be safe for newborns/infants and will induce protective immunity to diverse S. pneumoniae serotypes after oral immunization. PMID:20370633
Seatbelt sign in a case of blunt abdominal trauma; what lies beneath it?
Vailas, Michail G; Moris, Demetrios; Orfanos, Stamatios; Vergadis, Chrysovalantis; Papalampros, Alexandros
2015-10-30
The reported incidence of hollow viscus injuries (HVI) in blunt trauma patients is approximately 1%. The most common site of injury to the intestine in blunt abdominal trauma (BAT) is the small bowel followed by colon, with mesenteric injuries occurring three times more commonly than bowel injuries. Isolated colon injury is a rarely encountered condition. Clinical assessment alone in patients with suspected intestinal or mesenteric injury after blunt trauma is associated with unacceptable diagnostic delays. This is a case of a 31-year-old man, admitted to the emergency department after being the restrained driver, involved in a car accident. After initial resuscitation, focused assessment with sonography for trauma examination (FAST) was performed revealing a subhepatic mass, suspicious for intraperitoneal hematoma. A computed tomography scan (CT) that followed showed a hematoma of the mesocolon of the ascending colon with active extravasation of intravenous contrast material. An exploratory laparotomy was performed, hemoperitomeum was evacuated, and a subserosal hematoma of the cecum and ascending colon with areas of totally disrupted serosal wall was found. Hematoma of the adjacent mesocolon expanding to the root of mesenteric vessels was also noted. A right hemicolectomy along with primary ileocolonic anastomosis was performed. Patient's recovery progressed uneventfully. Identifying an isolated traumatic injury to the bowel or mesentery after BAT can be a clinical challenge because of its subtle and nonspecific clinical findings; meeting that challenge may eventually lead to a delay in diagnosis and treatment with subsequent increase in associated morbidity and mortality. Isolated colon injury is a rare finding after blunt trauma and usually accompanied by other intra-abdominal organ injuries. Abdominal 'seatbelt' sign, ecchymosis of the abdominal wall, increasing abdominal pain and distension are all associated with HVI. However, the accuracy of these findings remains low. Diagnostic peritoneal lavage, ultrasound, CT and diagnostic laparoscopy are used to evaluate BAT. Although CT has become the main diagnostic tool for this type of injuries, there are few pathognomonic signs of colon injury on CT. Given the potential for devastating outcomes, prompt diagnosis and treatment is necessary and high clinical suspicion is required.
Shao, Lili; Melero, Jose; Zhang, Nu; Arulanandam, Bernard; Baseman, Joel; Liu, Quanzhong; Zhong, Guangming
2017-01-01
Chlamydia has been detected in the gastrointestinal tracts of both animals and humans. However, the mechanism by which Chlamydia colonizes the gut remains unclear. Chlamydia muridarum is known to spread from the genital to the gastrointestinal tracts hematogenously. The C. muridarum plasmid is a key pathogenic determinant in the mouse upper genital tract although plasmid-deficient C. muridarum is still able to colonize the upper genital tract. We now report that plasmid-deficient C. muridarum exhibits significantly delayed/reduced spreading from the mouse genital to the gastrointestinal tracts. C. muridarum with or without plasmid maintained similar levels in the mouse circulatory system following intravenous inoculation but the hematogenous plasmid-deficient C. muridarum was significantly less efficient in colonizing the gastrointestinal tract. Consistently, plasmid-deficient C. muridarum failed to restore normal colonization in the gastrointestinal tract even after intragastric inoculation at a high dose. Thus, we have demonstrated a plasmid-dependent colonization of C. muridarum in the gastrointestinal tract, supporting the concept that C. muridarum may have acquired the plasmid for adaptation to the mouse gastrointestinal tract during oral-fecal transmission. Since the plasmid is more important for C. muridarum to colonize the gastrointestinal tract than to infect the genital tract, the current study has laid a foundation for further defining the host pathways targeted by the plasmid-encoded or -regulated chlamydial effectors.
Shao, Lili; Melero, Jose; Zhang, Nu; Arulanandam, Bernard; Baseman, Joel; Liu, Quanzhong
2017-01-01
Chlamydia has been detected in the gastrointestinal tracts of both animals and humans. However, the mechanism by which Chlamydia colonizes the gut remains unclear. Chlamydia muridarum is known to spread from the genital to the gastrointestinal tracts hematogenously. The C. muridarum plasmid is a key pathogenic determinant in the mouse upper genital tract although plasmid-deficient C. muridarum is still able to colonize the upper genital tract. We now report that plasmid-deficient C. muridarum exhibits significantly delayed/reduced spreading from the mouse genital to the gastrointestinal tracts. C. muridarum with or without plasmid maintained similar levels in the mouse circulatory system following intravenous inoculation but the hematogenous plasmid-deficient C. muridarum was significantly less efficient in colonizing the gastrointestinal tract. Consistently, plasmid-deficient C. muridarum failed to restore normal colonization in the gastrointestinal tract even after intragastric inoculation at a high dose. Thus, we have demonstrated a plasmid-dependent colonization of C. muridarum in the gastrointestinal tract, supporting the concept that C. muridarum may have acquired the plasmid for adaptation to the mouse gastrointestinal tract during oral-fecal transmission. Since the plasmid is more important for C. muridarum to colonize the gastrointestinal tract than to infect the genital tract, the current study has laid a foundation for further defining the host pathways targeted by the plasmid-encoded or -regulated chlamydial effectors. PMID:28542376
Rawat, David J; Haddad, Munther; Geoghegan, Niamh; Clarke, Simon; Fell, John M
2004-07-01
The antegrade colonic enema is accepted as effective for management of intractable constipation in children when conventional bowel management has failed. This study describes experience with a new, minimally invasive technique, the distal antegrade colonic enema, which involves percutaneous endoscopic colostomy of the left colon. Fifteen children with refractory constipation and soiling who had radiographic evidence of megarectum and/or distal colonic delay were selected for the procedure. The junction of the descending and the sigmoid colon was identified colonoscopically, and the percutaneous endoscopic colostomy tube, through which antegrade distal colonic enema are administered, was inserted. Fourteen children underwent distal percutaneous endoscopic colostomy insertion. The median time required for the procedure was 30 minutes (20-50 minutes). Excluding one child (technical difficulties with percutaneous endoscopic colostomy placement), median post-procedural hospital stay was 4 days (2-27 days). Thirteen children were no longer soiling, and improvement in quality of life was reported at 2 months' follow-up. At 6 months' follow-up, 90% of children were clean during intervals between enemas. All children evaluated at 12 months' follow-up remained clean. Median duration of follow-up was 12.5 months (2-51 months). The distal percutaneous endoscopic colostomy is a simple alternative to established methods for delivery of antegrade enemas. It is less invasive and on reversal leaves only minor scarring.
Pykälä, Juha
2017-06-01
Assisted colonization of vascular plants is considered by many ecologists an important tool to preserve biodiversity threatened by climate change. I argue that assisted colonization may have negative consequences in arctic-alpine and boreal regions. The observed slow movement of plants toward the north has been an argument for assisted colonization. However, these range shifts may be slow because for many plants microclimatic warming (ignored by advocates of assisted colonization) has been smaller than macroclimatic warming. Arctic-alpine and boreal plants may have limited possibilities to disperse farther north or to higher elevations. I suggest that arctic-alpine species are more likely to be driven to extinction because of competitive exclusion by southern species than by increasing temperatures. If so, the future existence of arctic-alpine and boreal flora may depend on delaying or preventing the migration of plants toward the north to allow northern species to evolve to survive in a warmer climate. In the arctic-alpine region, preventing the dispersal of trees and shrubs may be the most important method to mitigate the negative effects of climate change. The purported conservation benefits of assisted colonization should not be used to promote the migration of invasive species by forestry. © 2016 Society for Conservation Biology.
Mass transit : many management successes at WMATA, but capital planning could be enhanced
DOT National Transportation Integrated Search
2001-07-01
In recent years, the Washington Metropolitan Area Transit Authority's (WMATA) public transit system has experienced problems related to the safety and reliability of its transit services, including equipment breakdowns, delays in scheduled service, u...
Santos, Alessandra Marques Dos; Coelho, Joao Paulo Ferreira; Juanes, Camila de Carvalho; Azevedo, Rafael Barbosa de; Diniz, Clara Araujo; Jamacaru, Francisco Vagnaldo Fechine; Dornelas, Conceição Aparecida
2017-04-01
To evaluated the effects of L-lysine on the intestinal and urothelial epithelia in cystoplasty in rats. Twenty-eight 9-week-old rats were assigned to 4 groups: Group A (n=8) cystoplasty followed by administration of L-lysine (150 mg/kg body weight by gavage) for 30 weeks; Group B (n=8) cystoplasty + water for 30 weeks; Group C (n=6) L-lysine for 30 weeks; Group D (n=6) water for 30 weeks. On histopathology with hematoxylin and eosin, mild to moderate hyperplasia transitional was observed in at the site of anastomosis in all animals submitted to cystoplasty (Groups A and B), but "transitional metaplasia" of the intestinal glandular epithelium was more accentuated in Group A (p=0.045). No inflammatory cells, dysplasia or abnormalities were observed. Staining with Alcian blue revealed a substantial reduction of goblet cells and mucins in the colon segment (Groups A and B). The administration of L-lysine to rats accelerated the development of transitional metaplasia in the epithelium of the colon segment in cystoplasty.
Suresh, R; Senthilkumar, D V; Lakshmanan, M; Kurths, J
2012-07-01
We report the nature of transitions from the nonsynchronous to a complete synchronization (CS) state in arrays of time-delay systems, where the systems are coupled with instantaneous diffusive coupling. We demonstrate that the transition to CS occurs distinctly for different coupling configurations. In particular, for unidirectional coupling, locally (microscopically) synchronization transition occurs in a very narrow range of coupling strength but for a global one (macroscopically) it occurs sequentially in a broad range of coupling strength preceded by an intermittent synchronization. On the other hand, in the case of mutual coupling, a very large value of coupling strength is required for local synchronization and, consequently, all the local subsystems synchronize immediately for the same value of the coupling strength and, hence, globally, synchronization also occurs in a narrow range of the coupling strength. In the transition regime, we observe a type of synchronization transition where long intervals of high-quality synchronization which are interrupted at irregular times by intermittent chaotic bursts simultaneously in all the systems and which we designate as global intermittent synchronization. We also relate our synchronization transition results to the above specific types using unstable periodic orbit theory. The above studies are carried out in a well-known piecewise linear time-delay system.
The pathophysiology of chronic constipation
Andrews, Christopher N; Storr, Martin
2011-01-01
Constipation is broadly defined as an unsatisfactory defecation characterized by infrequent stools, difficult stool passage or both. The common approach to the pathophysiology of constipation groups the disorder into primary and secondary causes. Primary causes are intrinsic problems of colonic or anorectal function, whereas secondary causes are related to organic disease, systemic disease or medications. The normal process of colonic transit and defecation is discussed, and the etiology of constipation is reviewed. PMID:22114753
Mosińska, P; Jacenik, D; Sałaga, M; Wasilewski, A; Cygankiewicz, A; Sibaev, A; Mokrowiecka, A; Małecka-Panas, E; Pintelon, I; Storr, M; Timmermans, J P; Krajewska, W M; Fichna, J
2018-05-01
The role of fatty acid binding protein 4 (FABP4) in lower gastrointestinal (GI) motility is unknown. We aimed to verify the effect of inhibition of FABP4 on GI transit in vivo, and to determine the expression of FABP4 in mouse and human tissues. Fatty acid binding protein 4 inhibitor, BMS309403, was administered acutely or chronically for 6 and 13 consecutive days and its effect on GI transit was assessed in physiological conditions and in loperamide-induced constipation. Intracellular recordings were made to examine the effects of BMS309403 on colonic excitatory and inhibitory junction potentials. Abdominal pain was evaluated using behavioral pain response. Localization and expression of selected adipokines were determined in the mouse colon and serum using immunohistochemistry and Enzyme-Linked ImmunoSorbent Assay respectively. mRNA expression of FABP4 and selected adipokines in colonic and serum samples from irritable bowel syndrome (IBS) patients and control group were assessed. Acute injection of BMS309403 significantly increased GI motility and reversed inhibitory effect of loperamide. BMS309403 did not change colonic membrane potentials. Chronic treatment with BMS309403 increased the number of pain-induced behaviors. In the mouse serum, level of resistin was significantly decreased after acute administration; no changes in adiponectin level were detected. In the human serum, level of adiponectin and resistin, but not of FABP4, were significantly elevated in patients with constipation-IBS (IBS-C). FABP4 mRNA expression was significantly downregulated in the human colon in IBS-C. Fatty acid binding protein 4 may be involved in IBS pathogenesis and become a novel target in the treatment of constipation-related diseases. © 2017 John Wiley & Sons Ltd.
NASA Astrophysics Data System (ADS)
Yao, Deyin; Lu, Renquan; Xu, Yong; Ren, Hongru
2017-10-01
In this paper, the sliding mode control problem of Markov jump systems (MJSs) with unmeasured state, partly unknown transition rates and random sensor delays is probed. In the practical engineering control, the exact information of transition rates is hard to obtain and the measurement channel is supposed to subject to random sensor delay. Design a Luenberger observer to estimate the unmeasured system state, and an integral sliding mode surface is constructed to ensure the exponential stability of MJSs. A sliding mode controller based on estimator is proposed to drive the system state onto the sliding mode surface and render the sliding mode dynamics exponentially mean-square stable with H∞ performance index. Finally, simulation results are provided to illustrate the effectiveness of the proposed results.
Regulation of body temperature in the blue-tongued lizard.
Hammel, H T; Caldwell, F T; Abrams, R M
1967-06-02
Lizards (Tiliqua scincoides) regulated their internal body temperature by moving back and forth between 15 degrees and 45 degrees C environments to maintain colonic and brain temperatures between 30 degrees and 37 degrees C. A pair of thermodes were implanted across the preoptic region of the brain stem, and a reentrant tube for a thermocouple was implanted in the brain stem. Heating the brain stem to 41 degrees C activated the exit response from the hot environment at a colonic temperature 1 degrees to 2 degrees C lower than normal, whereas cooling the brain stem to 25 degrees C delayed the exit from the hot environment until the colonic temperature was 1 degrees to 2 degrees C higher than normal. The behavioral thermoregulatory responses of this ectotherm appear to be activated by a combination of hypothalamic and other body temperatures.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, S.; Kazim, D.; Kraveka, J.
Normal human fibroblast cells have not been reported to escape crisis--that is they die after about 24 doublings in culture. The authors have been studying the growth properties of skin fibroblast cells from persons in families with familial adenopolyposis of the colon (FAP). An individual hemizygous at the FAP locus will develop hyperplasia of the colonic epithelium followed by colonic polyps, both at an early age. Polyps themselves still retain a single functional FAP allele. A mutation or deletion in this allele in a polyp is hypothesized to lead to further loss of growth control; thus, a tumor is formed.more » They found that the in vitro life-span of skin fibroblast cells from FAP individuals and from some asymptomatic children were markedly extended when compared with normal individuals.« less
Nuclear Chk1 prevents premature mitotic entry.
Matsuyama, Makoto; Goto, Hidemasa; Kasahara, Kousuke; Kawakami, Yoshitaka; Nakanishi, Makoto; Kiyono, Tohru; Goshima, Naoki; Inagaki, Masaki
2011-07-01
Chk1 inhibits the premature activation of the cyclin-B1-Cdk1. However, it remains controversial whether Chk1 inhibits Cdk1 in the centrosome or in the nucleus before the G2-M transition. In this study, we examined the specificity of the mouse monoclonal anti-Chk1 antibody DCS-310, with which the centrosome was stained. Conditional Chk1 knockout in mouse embryonic fibroblasts reduced nuclear but not centrosomal staining with DCS-310. In Chk1(+/myc) human colon adenocarcinoma (DLD-1) cells, Chk1 was detected in the nucleus but not in the centrosome using an anti-Myc antibody. Through the combination of protein array and RNAi technologies, we identified Ccdc-151 as a protein that crossreacted with DCS-310 on the centrosome. Mitotic entry was delayed by expression of the Chk1 mutant that localized in the nucleus, although forced immobilization of Chk1 to the centrosome had little impact on the timing of mitotic entry. These results suggest that nuclear but not centrosomal Chk1 contributes to correct timing of mitotic entry.
Effects of dark chocolate on azoxymethane-induced colonic aberrant crypt foci.
Hong, Mee Young; Nulton, Emily; Shelechi, Mahshid; Hernández, Lisa M; Nemoseck, Tricia
2013-01-01
Epidemiologic evidence supports that diets rich in polyphenols promote health and may delay the onset of colon cancer. Cocoa and chocolate products have some of the highest polyphenolic concentrations compared to other polyphenolic food sources. This study tested the hypothesis that a diet including dark chocolate can protect against colon cancer by inhibiting aberrant crypt foci (ACF) formation, downregulating gene expression of inflammatory mediators, and favorably altering cell kinetics. We also investigated whether bloomed dark chocolate retains the antioxidant capacity and protects against colon cancer. Forty-eight rats received either a diet containing control (no chocolate), regular dark chocolate, or bloomed dark chocolate and were injected subcutaneously with saline or azoxymethane. Relative to control, both regular and bloomed dark chocolate diets lowered the total number of ACF (P = 0.022). Chocolate diet-fed animals downregulated transcription levels of COX-2 (P = 0.035) and RelA (P = 0.045). Both chocolate diets lowered the proliferation index (P = 0.001). These results suggest that a diet including dark chocolate can reduce cell proliferation and some gene expression involving inflammation, which may explain the lower number of early preneoplastic lesions. These results provide new insight on polyphenol-rich chocolate foods and colon cancer prevention.
Sun, Dongdong; Shen, Weixing; Zhang, Feng; Fan, Huisen; Xu, Changliang; Li, Liu; Tan, Jiani; Miao, Yunjie; Zhang, Haibin; Yang, Ye; Cheng, Haibo
2018-05-01
Colon cancer is the third most frequently diagnosed malignancy and has high morbidity worldwide. Epithelial-mesenchymal transition (EMT) has been increasingly implicated in colon cancer progression and metastasis. The present study was aimed to evaluate the potential antitumor activity of α-hederin, a monodesmosidic triterpenoid saponin isolated from Hedera helix, in human SW620 colon cancer cells stimulated with interleukin 6 (IL-6) for mimicking the tumor inflammatory microenvironment in vivo. Cell viability assay showed that IL-6 at 6.25 ng/ml significantly enhanced viability of SW620 cells, and thus this concentration was used to stimulate SW620 cells throughout this study. We observed that α-hederin concentration-dependently inhibited cell viability, migration and invasion in IL-6-treated SW620 cells. Moreover, α-hederin significantly restored IL-6-induced decrease in E-cadherin expression and abolished IL-6-induced increase in N-cadherin, vimentin, fibronectin, twist and snail at both mRNA and protein levels in SW620 cells. These data suggested that α-hederin suppressed IL-6-indcued EMT in colon cancer cells. Further molecular examinations showed that α-hederin inhibited phosphorylation of Janus Kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3(STAT3), and halted the nuclear translocation of phosphorylated STAT3 in IL-6-treated SW620 cells. In addition, JAK2/STAT3 signaling inhibitor AG490 not only produced similar inhibitory effects on EMT markers as α-hederin, but also synergistically enhanced α-hederin's inhibitory effects on EMT markers in IL-6-treated SW620 cells. Altogether, we demonstrated that α-hederin suppressed IL-6-induced EMT associated with disruption of JAK2/STAT3 signaling in colon cancer cells. Our data strongly suggested α-hederin as a promising candidate for intervention of colon cancer and metastasis. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
Relativity time-delay experiments utilizing 'Mariner' spacecraft
NASA Technical Reports Server (NTRS)
Esposito, P. B.; Anderson, J. D.
1974-01-01
Relativity predicts that the transit time of a signal propagated from the earth to a spacecraft and retransmitted back to earth ought to exhibit an additional, variable time delay. The present work describes some of the analytical techniques employed in experiments using Mariner spacecraft designed to test the accuracy of this prediction. Two types of data are analyzed in these relativity experiments; these include phase-coherent, two-way Doppler shift and round-trip, transit-time measurements. Results of Mariner 6 and 7 relativistic time-delay experiments are in agreement with Einstein's theory of general relativity with an uncertainty of 3%.
NASA Astrophysics Data System (ADS)
Geng, Xi; Shi, Zhiwei; Cheng, Keming; Dong, Hao; Zhao, Qun; Chen, Sinuo
2018-03-01
Plasma-based flow control is one of the most promising techniques for aerodynamic problems, such as delaying the boundary layer transition. The boundary layer’s characteristics induced by AC-DBD plasma actuators and applied by the actuators to delay the boundary layer transition on airfoil at Ma = 0.3 were experimentally investigated. The PIV measurement was used to study the boundary layer’s characteristics induced by the plasma actuators. The measurement plane, which was parallel to the surface of the actuators and 1 mm above the surface, was involved in the test, including the perpendicular plane. The instantaneous results showed that the induced flow field consisted of many small size unsteady vortices which were eliminated by the time average. The subsequent oil-film interferometry skin friction measurement was conducted on a NASA SC(2)-0712 airfoil at Ma = 0.3. The coefficient of skin friction demonstrates that the plasma actuators successfully delay the boundary layer transition and the efficiency is better at higher driven voltage.
Data eye monitor method and apparatus
Gara, Alan G [Mount Kisco, NY; Marcella, James A [Rochester, MN; Ohmacht, Martin [Yorktown Heights, NY
2012-01-31
An apparatus and method for providing a data eye monitor. The data eye monitor apparatus utilizes an inverter/latch string circuit and a set of latches to save the data eye for providing an infinite persistent data eye. In operation, incoming read data signals are adjusted in the first stage individually and latched to provide the read data to the requesting unit. The data is also simultaneously fed into a balanced XOR tree to combine the transitions of all incoming read data signals into a single signal. This signal is passed along a delay chain and tapped at constant intervals. The tap points are fed into latches, capturing the transitions at a delay element interval resolution. Using XORs, differences between adjacent taps and therefore transitions are detected. The eye is defined by segments that show no transitions over a series of samples. The eye size and position can be used to readjust the delay of incoming signals and/or to control environment parameters like voltage, clock speed and temperature.
Zielińska, Marta; Jarmuż, Agata; Wasilewski, Andrzej; Cami-Kobeci, Gerta; Husbands, Stephen; Fichna, Jakub
2017-04-01
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a functional disorder of the gastrointestinal (GI) tract. The major IBS-D symptoms include diarrhea, abdominal pain and discomfort. High density of opioid receptors (ORs) in the GI tract and their participation in the maintenance of GI homeostasis make ORs ligands an attractive option for developing new anti-IBS-D treatments. The aim of this study was to characterize the effect of methyl-orvinol on the GI motility and secretion and in mouse models mimicking symptoms of IBS-D. In vitro, the effects of methyl-orvinol on electrical field stimulated smooth muscle contractility and epithelial ion transport were characterized in the mouse colon. In vivo, the following tests were used to determine methyl-orvinol effect on mouse GI motility: colonic bead expulsion, whole GI transit and fecal pellet output. An antinociceptive action of methyl-orvinol was assessed in the mouse model of visceral pain induced by mustard oil. Methyl-orvinol (10 -10 to 10 -6 M) inhibited colonic smooth muscle contractions in a concentration-dependent manner. This effect was reversed by naloxone (non-selective opioid antagonist) and β-funaltrexamine (selective MOP antagonist). Experiments with a selective KOP receptor agonist, U50488 revealed that methyl-orvinol is a KOP receptor antagonist in the GI tract. Methyl-orvinol enhanced epithelial ion transport. In vivo, methyl-orvinol inhibited colonic bead expulsion and prolonged GI transit. Methyl-orvinol improved hypermotility and reduced abdominal pain in the mouse models mimicking IBS-D symptoms. Methyl-orvinol could become a promising drug candidate in chronic therapy of functional GI diseases such as IBS-D. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
Vlad, Marcel Ovidiu; Ross, John
2002-12-01
We introduce a general method for the systematic derivation of nonlinear reaction-diffusion equations with distributed delays. We study the interactions among different types of moving individuals (atoms, molecules, quasiparticles, biological organisms, etc). The motion of each species is described by the continuous time random walk theory, analyzed in the literature for transport problems, whereas the interactions among the species are described by a set of transformation rates, which are nonlinear functions of the local concentrations of the different types of individuals. We use the time interval between two jumps (the transition time) as an additional state variable and obtain a set of evolution equations, which are local in time. In order to make a connection with the transport models used in the literature, we make transformations which eliminate the transition time and derive a set of nonlocal equations which are nonlinear generalizations of the so-called generalized master equations. The method leads under different specified conditions to various types of nonlocal transport equations including a nonlinear generalization of fractional diffusion equations, hyperbolic reaction-diffusion equations, and delay-differential reaction-diffusion equations. Thus in the analysis of a given problem we can fit to the data the type of reaction-diffusion equation and the corresponding physical and kinetic parameters. The method is illustrated, as a test case, by the study of the neolithic transition. We introduce a set of assumptions which makes it possible to describe the transition from hunting and gathering to agriculture economics by a differential delay reaction-diffusion equation for the population density. We derive a delay evolution equation for the rate of advance of agriculture, which illustrates an application of our analysis.
Gregory, Katherine E.; LaPlante, Rose D.; Shan, Gururaj; Kumar, Deepak Vijaya; Gregas, Matt
2015-01-01
Background Intestinal colonization during infancy is important to short and long term health outcomes. Bacteroides, an early member of the intestinal microbiome, are necessary for breaking down complex molecules within the intestine and function to assist the body’s immune system in fighting against potentially harmful pathogens. Little is known about the colonization pattern of Bacteroides in preterm infants during the early neonatal period. Purpose This study measured Bacteroides colonization during the early neonatal period in a population of preterm infants based on clinical factors including mode of birth, antibiotics, and nutrition. Methods Bacterial DNA was isolated from 144 fecal samples from 29 preterm infants and analyzed using quantitative real time polymerase chain reaction (PCR). Analyses included liner mixed models to determine which clinical factors affect Bacteroides colonization of the infant gut. Results We found that infants born via vaginal canal had a higher rate of increase in Bacteroides than infants born via Cesarean section (p<.001). We did not find significant associations between antibiotic administration and differences in nutritional exposures with Bacteroides colonization. Implications for Practice These findings highlight the significant influence of mode of birth on Bacteroides colonization. While mode of birth is not always modifiable, these study findings may help develop interventions for preterm infants born via Cesarean section aimed at overcoming delayed Bacteroides colonization. Implications for Research Greater study of the intestinal microbiome and the clinical factors relevant to the preterm infant is needed so that interventions may be developed and tested, resulting in optimal microbial and immune health. PMID:26551793
Effects of female steroid hormones on A-type K+ currents in murine colon.
Beckett, Elizabeth A H; McCloskey, Conor; O'Kane, Neil; Sanders, Kenton M; Koh, Sang Don
2006-06-01
Idiopathic constipation is higher in women of reproductive age than postmenopausal women or men, suggesting that female steroid hormones influence gastrointestinal motility. How female hormones affect motility is unclear. Colonic motility is regulated by ion channels in colonic myocytes. Voltage-dependent K(+) channels serve to set the excitability of colonic muscles. We investigated regulation of Kv 4.3 channel expression in response to acute or chronic changes in female hormones. Patch clamp experiments and quantitative PCR were used to compare outward currents and transcript expression in colonic myocytes from male, non-pregnant, pregnant and ovariectomized mice. Groups of ovariectomized mice received injections of oestrogen or progesterone to investigate the effects of hormone replacement. The capacitance of colonic myocytes from non-pregnant females was larger than in males. Net outward current density in male and ovariectomized mice was higher than in non-pregnant females and oestrogen-treated ovariectomized mice. Current densities in late pregnancy were lower than in female controls. Progesterone had no effect on outward currents. A-type currents were decreased in non-pregnant females compared with ovariectomized mice, and were further decreased by pregnancy or oestrogen replacement. Kv 4.3 transcripts did not differ significantly between groups; however, expression of the potassium channel interacting protein KChIP1 was elevated in ovariectomized mice compared with female controls and oestrogen-treated ovariectomized mice. Delayed rectifier currents were not affected by oestrogen. In the mouse colon, oestrogen suppresses A-type currents, which are important for regulating excitability. These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause.
Colonic transit times and behaviour profiles in children with defecation disorders
Benninga, M; Voskuijl, W; Akkerhuis, G; Taminiau, J; Buller, H
2004-01-01
Aims: To evaluate children referred for defecation disorders using the child behavioural checklist (CBCL). Methods: A total of 215 patients were divided into three groups: 135 (5–14 years of age) with paediatric constipation (PC), 56 (5–17 years) with functional non-retentive faecal soiling (FNRFS), and 24 (5–16 years) with recurrent abdominal pain (RAP). Behavioural scores were correlated with colonic transit time (CTT) and anorectal function parameters (manometry and EMG). Results: No significant differences in the mean CBCL scores were found among the three patient groups. However, children with PC and FNRFS had significantly more behavioural problems than the Dutch normative sample, while children with RAP had scores within the normal range. No significant differences were found between CTT in the patient groups, with respect to the CBCL. Similarly, no significant difference existed between children able or unable to relax their pelvic floor muscles during defecation attempts and their behaviour profiles. Conclusion: There seems to be no relation between colonic/anorectal function and specific behavioural profiles. On the other hand, children with defecation disorders show more behavioural problems than do controls. PMID:14709493
Ransjö, U.
1979-01-01
Previous investigations have shown that cross-contamination in a burn unit is mainly clothes-borne. New barrier garments have been designed and tried experimentally. The aim of the present study was to investigate the effects of different clothing routines on cross-contamination. In a long-term study, the rates and routes of colonizations with Staphylococcus aureus, Streptococcus groups A, B, C, F, and G and Pseudomonas aeruginosa were examined. The exogenous colonization rates were, with S. aureus 77%, with Streptococcus species 52% and with Ps. aeruginosa 32%. The colonization rate with Ps. aeruginosa was higher in patients with larger burns. Patients dispersed Streptococcus and Ps. aeruginosa as well as S. aureus into the air of their rooms in considerable amounts, but dispersers were not more important as sources of cross-colonization than non-dispersers. In comparison of clothing routines, there was no difference in overall colonization rates. The newly designed barrier garment that was made from apparently particle-tight material did not reduce the transfer of bacteria from patient to patient. A less rigid routine than that previously used did not increase the risk of cross-contamination. A thorough change of barrier dress after close contact nursing delayed the first exogenous S. aureus colonization from day 6 to day 14 after admission. This routine might be recommended for clinical use. Otherwise, methods must be developed for adequate selection of materials intended for barrier garments. Images Plate 1 PMID:109498
Bielecki, K; Grotowski, M; Kalczak, M
1995-01-01
The purpose of this study was to evaluate the healing of an experimental left-sided colonic anastomosis in rats protected by an end diverting proimal colostomy. The anastomoses were studied by radiological and biochemical examination and breaking strength was estimated. The results were compared with a non-operated group and with a group of rats having a non-defunctional anastomosis constructed in the same manner. In animals with an end diverting colostomy, anastomotic protein levels and enzymic activity were lower than in those with a colostomy, and the development of anastomotic strength was delayed compared with those not defunctioned.
The role of a low Earth orbiter in intercontinental time synchronization via GPS satellites
NASA Technical Reports Server (NTRS)
Wu, S. C.; Ondrasik, V. J.
1985-01-01
Time synchronization between two sites using differential GPS has been investigated by a number of researchers. When the two sites are widely separated, the common view period of any GPS satellite becomes shorter; low elevation observations are inevitable. This increase the corrupting effects of the atmospheric delay and, at the same time, narrows the window for such time synchronization. This difficulty can be alleviated by synchronization. This difficulty can be alleviated by using a transit site located midway between the two main sites. The main sites can now look at different GPS satellites which are also in view at the transit site. However, a ground transit site may not always be conveniently available, especially across the Pacific Ocean; also, the inclusion of a ground transit site introduce additional errors due to its location error and local atmospheric delay. An alternative is to use a low Earth orbiter (LEO) as the transit site. A LEO is superior to a ground transit site in three ways: (1) It covers a large part of the Earth in a short period of time and, hence, a single LEO provides worldwide transit services; (2) it is above the troposphere and thus its inclusion does not introduce additional tropospheric delay error; and (3) it provides strong dynamics needed to improve GPS satellite positions which are of importance to ultraprecise time synchronization.
NASA Astrophysics Data System (ADS)
Hou, Lin; Shi, Yuyang; Jiang, Guixiang; Liu, Wei; Han, Huili; Feng, Qianhua; Ren, Junxiao; Yuan, Yujie; Wang, Yongchao; Shi, Jinjin; Zhang, Zhenzhong
2016-08-01
A safe and efficient nanocomposite hydrogel for colon cancer drug delivery was synthesized using pH-sensitive and biocompatible graphene oxide (GO) containing azoaromatic crosslinks as well as poly (vinyl alcohol) (PVA) (GO-N=N-GO/PVA composite hydrogels). Curcumin (CUR), an anti-cancer drug, was encapsulated successfully into the hydrogel through a freezing and thawing process. Fourier transform infrared spectroscopy, scanning electron microscopy and Raman spectroscopy were performed to confirm the formation and morphological properties of the nanocomposite hydrogel. The hydrogels exhibited good swelling properties in a pH-sensitive manner. Drug release studies under conditions mimicking stomach to colon transit have shown that the drug was protected from being released completely into the physiological environment of the stomach and small intestine. In vivo imaging analysis, pharmacokinetics and a distribution of the gastrointestinal tract experiment were systematically studied and evaluated as colon-specific drug delivery systems. All the results demonstrated that GO-N=N-GO/PVA composite hydrogels could protect CUR well while passing through the stomach and small intestine to the proximal colon, and enhance the colon-targeting ability and residence time in the colon site. Therefore, CUR loaded GO-N=N-GO/PVA composite hydrogels might potentially provide a theoretical basis for the treatment of colon cancer with high efficiency and low toxicity.
Colon targeted curcumin delivery using guar gum.
Elias, Edwin J; Anil, Singhal; Ahmad, Showkat; Daud, Anwar
2010-06-01
Curcumin is used in the treatment of colon cancer, but its very poor absorption in the upper part of the GIT is a major concern. As a site for drug delivery, the colon offers a near neutral pH, reduced digestive enzymatic activity, a long transit time and an increased responsiveness to absorption enhancers. The aim of the present study was to identify a suitable polymer (guar gum) based matrix tablet for curcumin with sufficient mechanical strength and promising in vitro mouth-to-colon release profile. Three formulations of curcumin were prepared using varying concentrations of guar gum containing 50 mg curcumin by the wet granulation method. Tablets were subjected to evaluation by studying parameter like hardness, friability, drug content uniformity, and in-vitro drug release. In vitro drug release was evaluated using simulated stomach, intestinal and colonic fluids. The susceptibility of guar gum to colonic bacteria was also assessed by a drug release study with rat caecal contents. The 40% guar gum containing formulation (F-1) showed better drug release (91.1%) after 24 hours in the presence of rat caecal contents in comparison with the 50% guar gum containing formulation (F-2) (82.1%). Curcumin could, thus, be positively delivered to the colon for effective colon cancer treatment using guar gum.
A ten-year study of penetrating injuries of the colon.
Adesanya, Adedoyin A; Ekanem, Ekanem E
2004-12-01
Colon injury has been associated with a high risk of septic complications and mortality. We prospectively studied the pattern, management, outcome, and prognostic factors in patients who sustained penetrating colon injuries. Sixty patients who presented to our hospital with penetrating colon injuries over a ten-year period (1992 to 2001) were studied. Colon wounds were caused by gunshots in 55 (91.7 percent) patients and knife stabs in 5 (8.3 percent). There was a delay of more than 12 hours before laparotomy in 30 (50 percent) patients. Moderate or major fecal contamination of the peritoneal cavity occurred in 58 (96.7 percent) patients. The average penetrating abdominal trauma index score was 25.9 and 20 (33.3 percent) patients sustained Flint Grade 3 colon injury. Associated intra-abdominal injuries occurred in the small bowel (73.3 percent), liver (25 percent), stomach (23.3 percent), and mesentery (16.7 percent). Right colon wounds (35) were managed by primary repair in 24 (68.6 percent) patients and proximal diverting colostomy in 11 (31.4 percent), whereas left colon wounds (25) were managed by diverting colostomy in 22 (88.0 percent) patients and primary repair in 3 (12.0 percent) patients. Common complications included wound infection (56.7 percent), septicemia (31.7 percent), and enterocutaneous fistula (16.7 percent). The overall mortality rate was 33.3 percent and colon injury-related mortality was 21.7 percent. Presence of destructive colon injury was associated with a greater than fourfold increased incidence of death. Other significant risk factors included shock on admission, major fecal contamination, duration of operation more than four hours, penetrating abdominal trauma index score >25, and more than two postoperative complications. There was no difference in outcome between patients who had primary repair and those undergoing diverting colostomy. Colostomy closure-related morbidity was 21 percent and mortality was 5.3 percent. A more liberal use of primary repair is required in our patients with penetrating injuries of the colon.
Gastric emptying and orocaecal transit time of meals containing lactulose or inulin in men.
Clegg, Miriam; Shafat, Amir
2010-08-01
The H(2) breath test is ideal for orocaecal transit time (OCTT) measurement, as it is non-invasive and inexpensive. Indigestible substrates added to a test meal are metabolised by the colonic bacteria, resulting in the production of H(2) which is detected in end-exhalation breath. However, the substrates themselves can alter the transit times in the gastrointestinal tract. The aim of the present study is to compare OCTT and gastric emptying (GE) when lactulose in liquid (L-L), solid lactulose (L-S) and solid inulin (IN-S) are added to a test meal, and subsequently, to examine if inulin alters GE. Firstly, ten male volunteers were tested on three occasions. Volunteers ate a pancake breakfast containing 100 mg of (13)C-octanoic acid and either 12 g of L-L, 12 g of L-S or 12 g of IN-S in a randomised order. Secondly, seven male volunteers were tested twice with meals containing either 12 g of IN-S or no substrate (NO-S). L-L induced the shortest OCTT (85.3 (sd 42.8) min) compared with L-S (162.4 (sd 62.6) min) and inulin (292.4 (sd 66.7) min; P = 0.007). GE half-time and lag phase (L-L: 61 (sd 9); L-S: 57 (sd 10); IN-S: 52 (sd 10) min; P = 0.005) were also affected, with L-L being the slowest. Thirdly, inulin reduced GE lag and latency phases (P < 0.05) compared with NO-S. Lactulose accelerates OCTT but delays GE compared with inulin. Inulin accelerates the onset of stomach emptying, but it has no effect on GE half-time. For these reasons, inulin is the preferred substrate for the H(2) breath test.
Hao, Guang-Wei; Chen, Yu-Sheng; He, De-Ming; Wang, Hai-Yu; Wu, Guo-Hao; Zhang, Bo
2015-01-01
Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, which may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat. Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The three diets were compared for tumor growth and survival time (interval between tumor cell injection and attainment of target tumor volume). The tumor growth in the MKD and LKD groups was significantly delayed compared to that in the SD group. Application of an unrestricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and the impact on other tumor-relevant parameters such as invasion and metastasis.
Neves, Robério C. S.; Colares, Felipe; Torres, Jorge B.; Santos, Roberta L.; Bastos, Cristina S.
2014-01-01
Because boll weevil, Anthonomus grandis Boh. develops partially protected inside cotton fruiting structures, once they become established in a field, they are difficult to control, even with nearly continuous insecticide spray. During two cotton-growing seasons in the Semiárido region of Pernambuco State, Brazil, we tested the use of kaolin sprays to disrupt plant colonization through visual cue interference, combined with removal of fallen fruiting bodies to restrain boll weevil population growth after colonization. Kaolin spray under non-choice trials resulted in 2.2×, 4.4×, and 8.6× fewer weevils, oviposition and feeding punctures on kaolin-treated plants, respectively, despite demonstrating no statistical differences for colonization and population growth. Early season sprays in 2010 occurred during a period of rainfall, and hence, under our fixed spraying schedule no significant differences in boll weevil colonization were detected. In 2011, when kaolin sprays were not washed out by rain, delayed boll weevil colonization and reduction on attacked fruiting bodies were observed in eight out of 12 evaluations, and kaolin-treated plots had 2.7× fewer damaged fruiting bodies compared to untreated plots. Adoption of simple measures such as removal of fallen fruiting bodies and prompt reapplication of kaolin sprays after rainfall show promise in reducing boll weevil infestation. PMID:26462942
Neves, Robério C S; Colares, Felipe; Torres, Jorge B; Santos, Roberta L; Bastos, Cristina S
2014-10-31
Because boll weevil, Anthonomus grandis Boh. develops partially protected inside cotton fruiting structures, once they become established in a field, they are difficult to control, even with nearly continuous insecticide spray. During two cotton-growing seasons in the Semiárido region of Pernambuco State, Brazil, we tested the use of kaolin sprays to disrupt plant colonization through visual cue interference, combined with removal of fallen fruiting bodies to restrain boll weevil population growth after colonization. Kaolin spray under non-choice trials resulted in 2.2×, 4.4×, and 8.6× fewer weevils, oviposition and feeding punctures on kaolin-treated plants, respectively, despite demonstrating no statistical differences for colonization and population growth. Early season sprays in 2010 occurred during a period of rainfall, and hence, under our fixed spraying schedule no significant differences in boll weevil colonization were detected. In 2011, when kaolin sprays were not washed out by rain, delayed boll weevil colonization and reduction on attacked fruiting bodies were observed in eight out of 12 evaluations, and kaolin-treated plots had 2.7× fewer damaged fruiting bodies compared to untreated plots. Adoption of simple measures such as removal of fallen fruiting bodies and prompt reapplication of kaolin sprays after rainfall show promise in reducing boll weevil infestation.
Historical Amnesia? The Politics of Textbooks in Post-Apartheid South Africa.
ERIC Educational Resources Information Center
Polakow-Suransky, Sasha S.
The issue of history, specifically history textbooks, has been at the center of South Africa's educational reform debates for years. One of the consequences of South Africa's delayed curricular reform is the continued use of apartheid-era history textbooks, which, among other things, deny European colonization and conquest and claim that whites…
End-colostomy diverticulitis with parastomal phlegmon: A case report.
Muradbegovic, Mirza; St-Amour, Pénélope; Martin, David; Petermann, David; Benabidallah, Samir; Di Mare, Luca
2017-10-01
Acute colonic diverticulitis is a well-known surgical emergency, which occurs in about 10 percent of patients known for diverticulosis. The case of a 77-year-old woman is reported, with past history of abdominoperineal resection with end-colostomy for low rectal adenocarcinoma, and who developed an acute colonic diverticulitis in a subcutaneous portion of colostomy with parastomal phlegmon. Initial computed tomography imaging demonstrated a significant submucosal parietal edema with local fat tissues infiltration in regard of 3 diverticula. A two-step treatment was decided: first a nonoperative treatment was initiated with 2 weeks antibiotics administration, followed by, 6 weeks after, a segmental resection of the terminal portion of the colon with redo of a new colostomy by direct open approach. Patient was discharged on the second postoperative day without complications. Follow-up at 2 weeks revealed centimetric dehiscence of the stoma, which was managed conservatively until sixth postoperative week by stomatherapists. Treatment of acute diverticulitis with parastomal phlegmon in a patient with end-colostomy could primary be nonoperative. Delayed surgical treatment with segmental colonic resection was proposed to avoid recurrence and potential associated complications.
Accounting for Socioeconomic Differences in Delaying the Transition to College
ERIC Educational Resources Information Center
Goldrick-Rab, Sara; Han, Seong Won
2011-01-01
Despite popular conceptions of the "gap year" as a time of personal enrichment, the incidence of delay between high school and college is greatest among students from socioeconomically disadvantaged families, suggesting other motivations. This article examines two explanations for socioeconomic inequalities in rates of delay: disparities in high…
Bowel urgency in patients with irritable bowel syndrome.
Basilisco, Guido; De Marco, Elisabetta; Tomba, Carolina; Cesana, Bruno Mario
2007-01-01
Bowel urgency is the most bothersome symptom in irritable bowel syndrome patients with diarrhea, but its pathophysiology is poorly understood. Our aim was to assess the relationships among reporting the symptom, the reservoir functions of the colon and rectum, and the patients' psychologic profile. The study involved 28 consecutive patients with irritable bowel syndrome and 17 healthy subjects. The presence or absence of bowel urgency was verified by means of a questionnaire during the 3 days required for the ingestion of radio-opaque markers. On the fourth day, an abdominal x-ray was taken to assess colonic transit time, and rectal sensory and motor responses were measured during rectal distention. The subjects' psychologic profiles were assessed using a psychologic symptoms checklist. Forty-six percent of the patients reported urgency associated with at least 1 defecation. The multivariate logistic regression analysis showed that colonic transit was the only variable independently associated with reported bowel urgency, but the threshold for the sensation of urgency was not removed from the model since its borderline significance level. Rectal compliance was closely associated with the threshold for the sensation of urgency during rectal distention but was not an independent factor for reporting the sensation. The patients with and without urgency showed altered psychologic profiles. The symptom of urgency is associated with objective alterations in the colonic and rectal reservoir of patients with irritable bowel syndrome.
Togashi, Kazutomo; Fujita, Tomoki; Utano, Kenichi; Waga, Eriko; Katsuki, Shinichi; Isohata, Noriyuki; Endo, Shungo; Lefor, Alan K.
2015-01-01
Background and study aims: Sodium phosphate is a key component of bowel preparation regimen for colon capsule endoscopy (CCE), but may cause serious complications. The aim of this study is to evaluate the use of Gastrografin, substituted for sodium phosphate, in CCE bowel preparation. Patients and methods: In total, 29 patients (median age 64 years; 23 females) underwent CCE, covered by the national health insurance system of Japan. All had a history of laparotomy and/or previously incomplete colonoscopy. On the day before examination, patients ingested 1 L of polyethylene glycol + ascorbic acid with 0.5 L of water in the evening, and again the same laxative on the morning of examination. After capsule ingestion, 50 mL of Gastrografin diluted with 0.9 L of magnesium citrate was administered, and then repeated after 1 hour. Results: The capsule excretion rate was 97 % (28/29). The median colon transit time was 2 hours 45 minutes and rapid transit (< 40 minutes) through the colon occurred in one patient (3.4 %). Bowel cleansing level was adequate in 90 % of patients. The polyp (≥ 6 mm) detection rate was 52 %. Diluted Gastrografin was well tolerated by patients. No adverse events occurred. Conclusion: Gastrografin can be an alternative to sodium phosphate in CCE bowel preparation regimen. PMID:26716132
Discriminating movements of liquid and gas in the rabbit colon with impedance manometry.
Mohd Rosli, R; Leibbrandt, R E; Wiklendt, L; Costa, M; Wattchow, D A; Spencer, N J; Brookes, S J; Omari, T I; Dinning, P G
2018-05-01
High-resolution impedance manometry is a technique that is well established in esophageal motility studies for relating motor patterns to bolus flow. The use of this technique in the colon has not been established. In isolated segments of rabbit proximal colon, we recorded motor patterns and the movement of liquid or gas boluses with a high-resolution impedance manometry catheter. These detected movements were compared to video recorded changes in gut diameter. Using the characteristic shapes of the admittance (inverse of impedance) and pressure signals associated with gas or liquid flow we developed a computational algorithm for the automated detection of these events. Propagating contractions detected by video were also recorded by manometry and impedance. Neither pressure nor admittance signals alone could distinguish between liquid and gas transit, however the precise relationship between admittance and pressure signals during bolus flow could. Training our computational algorithm upon these characteristic shapes yielded a detection accuracy of 87.7% when compared to gas or liquid bolus events detected by manual analysis. Characterizing the relationship between both admittance and pressure recorded with high-resolution impedance manometry can not only help in detecting luminal transit in real time, but also distinguishes between liquid and gaseous content. This technique holds promise for determining the propulsive nature of human colonic motor patterns. © 2017 John Wiley & Sons Ltd.
McCann, Conor J.; Cooper, Julie E.; Natarajan, Dipa; Jevans, Benjamin; Burnett, Laura E.; Burns, Alan J.; Thapar, Nikhil
2017-01-01
Enteric nervous system neuropathy causes a wide range of severe gut motility disorders. Cell replacement of lost neurons using enteric neural stem cells (ENSC) is a possible therapy for these life-limiting disorders. Here we show rescue of gut motility after ENSC transplantation in a mouse model of human enteric neuropathy, the neuronal nitric oxide synthase (nNOS−/−) deficient mouse model, which displays slow transit in the colon. We further show that transplantation of ENSC into the colon rescues impaired colonic motility with formation of extensive networks of transplanted cells, including the development of nNOS+ neurons and subsequent restoration of nitrergic responses. Moreover, post-transplantation non-cell-autonomous mechanisms restore the numbers of interstitial cells of Cajal that are reduced in the nNOS−/− colon. These results provide the first direct evidence that ENSC transplantation can modulate the enteric neuromuscular syncytium to restore function, at the organ level, in a dysmotile gastrointestinal disease model. PMID:28671186
Staphylococcus aureus Regulatory RNAs as Potential Biomarkers for Bloodstream Infections
Bordeau, Valérie; Cady, Anne; Revest, Matthieu; Rostan, Octavie; Sassi, Mohamed; Tattevin, Pierre; Donnio, Pierre-Yves
2016-01-01
Staphylococcus aureus is a commensal bacterium and pathogen. Identifying biomarkers for the transition from colonization to disease caused by this organism would be useful. Several S. aureus small RNAs (sRNAs) regulate virulence. We investigated presence and expression of 8 sRNAs in 83 S. aureus strains from 42 patients with sepsis or septic shock and 41 asymptomatic colonized carriers. Small pathogenicity island sRNAs sprB and sprC were clade specific. Six sRNAs had variable expression not correlated with clinical status. Expression of RNAIII was lower in strains from septic shock patients than in strains from colonized patients. When RNAIII was associated with expression of sprD, colonizing strains could be discriminated from strains in patients with bloodstream infections, including patients with sepsis and septic shock. Isolates associated with colonization might have sRNAs with target expression different from those of disease isolates. Monitoring expression of RNAIII and sprD could help determine severity of bloodstream infections. PMID:27224202
Staphylococcus aureus Regulatory RNAs as Potential Biomarkers for Bloodstream Infections.
Bordeau, Valérie; Cady, Anne; Revest, Matthieu; Rostan, Octavie; Sassi, Mohamed; Tattevin, Pierre; Donnio, Pierre-Yves; Felden, Brice
2016-09-01
Staphylococcus aureus is a commensal bacterium and pathogen. Identifying biomarkers for the transition from colonization to disease caused by this organism would be useful. Several S. aureus small RNAs (sRNAs) regulate virulence. We investigated presence and expression of 8 sRNAs in 83 S. aureus strains from 42 patients with sepsis or septic shock and 41 asymptomatic colonized carriers. Small pathogenicity island sRNAs sprB and sprC were clade specific. Six sRNAs had variable expression not correlated with clinical status. Expression of RNAIII was lower in strains from septic shock patients than in strains from colonized patients. When RNAIII was associated with expression of sprD, colonizing strains could be discriminated from strains in patients with bloodstream infections, including patients with sepsis and septic shock. Isolates associated with colonization might have sRNAs with target expression different from those of disease isolates. Monitoring expression of RNAIII and sprD could help determine severity of bloodstream infections.
Family Background and Early Life Course Transitions in Kinshasa.
ERIC Educational Resources Information Center
Tambashe, B. Oleko; Shapiro, David
1996-01-01
Examines the impact of a woman's family background on transitions to sexual activity, marriage, and motherhood. Documents how parental education, parental survival status, and other factors are important in the transition to adult roles. Findings suggest that increases in educational levels should contribute to delays in these transitions and…
Green, Michael J; Leyland, Alastair H; Sweeting, Helen; Benzeval, Michaela
2017-08-01
Transitions into work and family roles have become increasingly delayed as participation in tertiary education widens. Such transitions may have adverse or beneficial effects on health behaviours such as smoking and drinking (alcohol). Role socialisation effects may reduce smoking or drinking, but clustering of transitions may lead to role overload, weakening or reversing any role socialisation effects. Effects of transitions were examined in three UK cohorts: the 1958 National Child Development Study, the 1970 British Birth Cohort Study, and the West of Scotland: Twenty-07 Youth Cohort (from around Glasgow, growing up in the same time period as the 1970 cohort). Latent class analysis was employed to identify heterogeneous patterns of transition timing for leaving education, entering employment, starting cohabitation, having a first child, and leaving the parental home. Propensity weighting was then used to estimate causal effects of transition patterns (relative to tertiary education) on smoking and heavy drinking in early adulthood (ages 22-26), adjusting for background confounders (gender, parental socioeconomic position, family structure, parental and adolescent health behaviours, adolescent distress and school performance). Three groups made early (age 16) transitions from education to employment and then either delayed other transitions, made other transitions quickly, or staggered transitions with cohabitation beginning around ages 19-21; a fourth group transitioned from education to employment around ages 17-18. Compared to those in tertiary education with similar background characteristics, those in these groups generally had higher levels of smoking, especially where transitions were more clustered, but less heavy drinking (except those who delayed other transitions after moving into employment). Results partially supported role socialisation effects for drinking, and role overload effects for smoking. Wider participation in tertiary education could have helped reduce smoking levels in these cohorts, but might also have increased risk for heavy drinking. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
A Critique of the DoD Materiel Distribution Study,
1979-03-01
are generated on order cycle times by their components: communication times, depot order processing times, depot capacity delay times, and transit...exceeded, the order was placed in one of three priority queues. The order processing time was determined by priority group by depot. A 20-point probability...time was defined to be the sum of communication, depot order processing , depot capacity delay, and transit times. As has been argued, the first three of
Vandeputte, Doris; Falony, Gwen; Vieira-Silva, Sara; Tito, Raul Y; Joossens, Marie; Raes, Jeroen
2016-01-01
The assessment of potentially confounding factors affecting colon microbiota composition is essential to the identification of robust microbiome based disease markers. Here, we investigate the link between gut microbiota variation and stool consistency using Bristol Stool Scale classification, which reflects faecal water content and activity, and is considered a proxy for intestinal colon transit time. Through 16S rDNA Illumina profiling of faecal samples of 53 healthy women, we evaluated associations between microbiome richness, Bacteroidetes:Firmicutes ratio, enterotypes, and genus abundance with self-reported, Bristol Stool Scale-based stool consistency. Each sample's microbiota growth potential was calculated to test whether transit time acts as a selective force on gut bacterial growth rates. Stool consistency strongly correlates with all known major microbiome markers. It is negatively correlated with species richness, positively associated to the Bacteroidetes:Firmicutes ratio, and linked to Akkermansia and Methanobrevibacter abundance. Enterotypes are distinctly distributed over the BSS-scores. Based on the correlations between microbiota growth potential and stool consistency scores within both enterotypes, we hypothesise that accelerated transit contributes to colon ecosystem differentiation. While shorter transit times can be linked to increased abundance of fast growing species in Ruminococcaceae-Bacteroides samples, hinting to a washout avoidance strategy of faster replication, this trend is absent in Prevotella-enterotyped individuals. Within this enterotype adherence to host tissue therefore appears to be a more likely bacterial strategy to cope with washout. The strength of the associations between stool consistency and species richness, enterotypes and community composition emphasises the crucial importance of stool consistency assessment in gut metagenome-wide association studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Kim, Su Young; Woo, Hyun Sun; Kim, Kyoung Oh; Choi, Sung Han; Kwon, Kwang An; Chung, Jun-Won; Kim, Yoon Jae; Kim, Jung Ho; Kim, Su Ji; Park, Dong Kyun
2017-12-01
DA-9701, a newly developed prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, has been shown to effectively treat functional dyspepsia. Recently, it has also been suspected to improve gastrointestinal motor function. The aims of this study were to assess the effect of DA-9701 on colonic transit time (CTT) and symptoms of functional constipation. Thirty-three patients with functional constipation based on the Rome III criteria were prospectively enrolled. The patients received 30-mg DA-9701 three times a day for 24 days. CTT was estimated initially and at the end of treatment. Symptoms such as spontaneous bowel movements, straining, stool form, feeling of incomplete emptying and anorectal blockage, abdominal discomfort and pain, overall defecation satisfaction, and incidence of adverse events were also analyzed. Twenty-seven patients completed the study. DA-9701 was associated with a significantly reduced CTT from 34.9 ± 17.6 to 23.7 ± 19.1 h (P = 0.001). Segmental CTT also significantly decreased after treatment (right CTT: from 16.8 [0.0-28.8] to 6.0 [0.0-25.2] hours, P < 0.001; rectosigmoid transit time: from 13.2 [0.0-38.4] to 6.0 [0.0-33.6] hours, P = 0.021). In addition, all constipation-related subjective symptoms, including spontaneous bowel movement frequency, significantly improved compared with those before treatment. Serious adverse events did not occur. DA-9701 accelerates colonic transit and safely improves symptoms in patients with functional constipation. Therefore, we suggest that this novel agent could help to treat patients with this condition. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
Li, Lai-Fu; Lu, Yan-Yu; Xiong, Wei; Liu, Juan-Ying; Chen, Qiang
2008-10-24
The central or systemic administration of 3-carboxy-4-octyl-2-methylenebutyrolactone (C75), a synthetic inhibitor of fatty acid synthase (FAS), causes anorexia and profound weight loss in rodents. The amount of food intake and gastrointestinal mobility are closely related. In this study, an attempt has been made to investigate the effects and mechanisms of C75 on gastric emptying and gastrointestinal transit after intracerebroventricular (i.c.v.) injection in mice. Our data showed that C75 (1, 5, 10 microg/mouse) dose-dependently delayed gastric emptying and gastrointestinal transit in fasted mice. 10 microg C75 delayed gastric emptying by about 21.4% and reduced gastrointestinal transit by about 31.0% compared with vehicle control group. Administration (i.c.v.) of 5-(tetradecyloxy)-2-furoic acid (TOFA, an acetyl-CoA carboxylase (ACC) inhibitor) or ghrelin attenuated the delayed gastrointestinal mobility effect induced by 10 microg C75. Taken together, C75 is able to decrease gastrointestinal mobility and it seems possible that malonyl-CoA and ghrelin might play an intermediary role in these processes.
Clostridium perfringens epsilon toxin inhibits the gastrointestinal transit in mice.
Losada-Eaton, D M; Fernandez-Miyakawa, M E
2010-12-01
Epsilon toxin produced by Clostridium perfringens type B and D is a potent toxin that is responsible for a highly fatal enterotoxemia in sheep and goats. In vitro, epsilon toxin produces contraction of the rat ileum as the result of an indirect action, presumably mediated through the autonomic nervous system. To examine the impact of epsilon toxin in the intestinal transit, gastric emptying (GE) and gastrointestinal transit (GIT) were evaluated after intravenous and oral administration of epsilon toxin in mice. Orally administered epsilon toxin produced a delay on the GIT. Inhibition of the small intestinal transit was observed as early as 1 h after the toxin was administered orally but the effects were not observed after 1 week. Epsilon toxin also produced an inhibition in GE and a delay on the GIT when relatively high toxin concentrations were given intravenously. These results indicate that epsilon toxin administered orally or intravenously to mice transitorily inhibits the GIT. The delay in the GIT induced by epsilon toxin could be relevant in the pathogenesis of C. perfringens type B and D enterotoxemia. Copyright © 2010 Elsevier Ltd. All rights reserved.
Valuing real estate externality-based option in development of transit system projects.
DOT National Transportation Integrated Search
2010-03-01
Capital-intensive transit projects rely on strong public support and availability of funds. While the general : public has become a strong advocate for transit systems, budget shortfalls and financial constraints are still : resulting in delays in pr...
Caufield, Page W.; Dasanayake, Ananda P.; Li, Yihong; Pan, Yaping; Hsu, Jay; Hardin, J. Michael
2000-01-01
The heterogeneous group of oral bacteria within the sanguinis (sanguis) streptococci comprise members of the indigenous biota of the human oral cavity. While the association of Streptococcus sanguinis with bacterial endocarditis is well described in the literature, S. sanguinis is thought to play a benign, if not a beneficial, role in the oral cavity. Little is known, however, about the natural history of S. sanguinis and its specific relationship with other oral bacteria. As part of a longitudinal study concerning the transmission and acquisition of oral bacteria within mother-infant pairs, we examined the initial acquisition of S. sanguinis and described its colonization relative to tooth emergence and its proportions in plaque and saliva as a function of other biological events, including subsequent colonization with mutans streptococci. A second cohort of infants was recruited to define the taxonomic affiliation of S. sanguinis. We found that the colonization of the S. sanguinis occurs during a discrete “window of infectivity” at a median age of 9 months in the infants. Its colonization is tooth dependent and correlated to the time of tooth emergence; its proportions in saliva increase as new teeth emerge. In addition, early colonization of S. sanguinis and its elevated levels in the oral cavity were correlated to a significant delay in the colonization of mutans streptococci. Underpinning this apparent antagonism between S. sanguinis and mutans streptococci is the observation that after mutans streptococci colonize the infant, the levels of S. sanguinis decrease. Children who do not harbor detectable levels of mutans streptococci have significantly higher levels of S. sanguinis in their saliva than do children colonized with mutans streptococci. Collectively, these findings suggest that the colonization of S. sanguinis may influence the subsequent colonization of mutans streptococci, and this in turn may suggest several ecological approaches toward controlling dental caries. PMID:10858217
Caufield, P W; Dasanayake, A P; Li, Y; Pan, Y; Hsu, J; Hardin, J M
2000-07-01
The heterogeneous group of oral bacteria within the sanguinis (sanguis) streptococci comprise members of the indigenous biota of the human oral cavity. While the association of Streptococcus sanguinis with bacterial endocarditis is well described in the literature, S. sanguinis is thought to play a benign, if not a beneficial, role in the oral cavity. Little is known, however, about the natural history of S. sanguinis and its specific relationship with other oral bacteria. As part of a longitudinal study concerning the transmission and acquisition of oral bacteria within mother-infant pairs, we examined the initial acquisition of S. sanguinis and described its colonization relative to tooth emergence and its proportions in plaque and saliva as a function of other biological events, including subsequent colonization with mutans streptococci. A second cohort of infants was recruited to define the taxonomic affiliation of S. sanguinis. We found that the colonization of the S. sanguinis occurs during a discrete "window of infectivity" at a median age of 9 months in the infants. Its colonization is tooth dependent and correlated to the time of tooth emergence; its proportions in saliva increase as new teeth emerge. In addition, early colonization of S. sanguinis and its elevated levels in the oral cavity were correlated to a significant delay in the colonization of mutans streptococci. Underpinning this apparent antagonism between S. sanguinis and mutans streptococci is the observation that after mutans streptococci colonize the infant, the levels of S. sanguinis decrease. Children who do not harbor detectable levels of mutans streptococci have significantly higher levels of S. sanguinis in their saliva than do children colonized with mutans streptococci. Collectively, these findings suggest that the colonization of S. sanguinis may influence the subsequent colonization of mutans streptococci, and this in turn may suggest several ecological approaches toward controlling dental caries.
Carbon economy of sour orange in response to different Glomus spp.
Graham, J. H.; Drouillard, D. L.; Hodge, N. C.
1996-01-01
Vesicular-arbuscular mycorrhizal (M) fungal colonization, growth, and nonstructural carbohydrate status of sour orange (Citrus aurantium L.) seedlings were compared at low- and high-phosphorus (P) supply following inoculation with four Glomus isolates: G. intraradices (Gi, FL208), G. etunicatum (Ge, UT316), G. claroideum (Gc, SC186), and Glomus sp. (G329, FL906). Nonmycorrhizal (NM) seedlings served as controls. At low-P supply, increases in incidence of M colonization, vesicles and accumulation of fungal fatty acid 16:1omega(5)C in roots were most rapid for G329-inoculated seedlings, followed closely by Gi- and Gc-inoculated seedlings. Glomus etunicatum was a less aggressive colonizer and produced lower rates of fungal fatty acid accumulation in seedling roots than the other Glomus species. Nonmycorrhizal and Ge-inoculated seedlings had lower P status and growth rates than seedlings inoculated with Gi or G329. Glomus claroideum increased seedling P status, but growth rate was lower than for seedlings colonized by Gi or G329, suggesting higher belowground costs for Gc colonization. In P-sufficient roots colonized by Gi, Gc, or G329, starch and ketone sugar concentrations were lower than in P-deficient NM and Ge-inoculated plants. Under conditions of high-P supply where mycorrhizae provided no P benefit to the seedlings, colonization by Gc, Gi, and G329 was delayed and reduced compared to that at low-P supply; however, the relative colonization rates among Glomus spp. were similar. Colonization by Ge was not detected in roots until 64 days after inoculation. Compared to NM seedlings, growth rates of mycorrhizal seedlings were reduced by the three aggressive fungi but not by the less aggressive Ge. After 64 days, starch and ketone sugar concentrations were lower in fibrous roots colonized by Gc, Gi, and G329 than in NM roots, indicating greater utilization of nonstructural carbohydrates in roots colonized by the aggressive fungi. After 49 days, colonization by the aggressive fungi increased root biomass allocation which may have contributed to the lower growth rate of mycorrhizal seedlings compared to NM seedlings. Thus, Glomus spp. that were aggressive colonizers of roots at low-P supply were also aggressive colonizers at high-P supply, resulting in greater belowground C costs and growth depression compared with the less aggressive colonizer, Ge.
NASA Astrophysics Data System (ADS)
Premraj, D.; Suresh, K.; Palanivel, J.; Thamilmaran, K.
2017-09-01
A periodically forced series LCR circuit with Chua's diode as a nonlinear element exhibits slow passage through Hopf bifurcation. This slow passage leads to a delay in the Hopf bifurcation. The delay in this bifurcation is a unique quantity and it can be predicted using various numerical analysis. We find that when an additional periodic force is added to the system, the delay in bifurcation becomes chaotic which leads to an unpredictability in bifurcation delay. Further, we study the bifurcation of the periodic delay to chaotic delay in the slow passage effect through strange nonchaotic delay. We also report the occurrence of strange nonchaotic dynamics while varying the parameter of the additional force included in the system. We observe that the system exhibits a hitherto unknown dynamical transition to a strange nonchaotic attractor. With the help of Lyapunov exponent, we explain the new transition to strange nonchaotic attractor and its mechanism is studied by making use of rational approximation theory. The birth of SNA has also been confirmed numerically, using Poincaré maps, phase sensitivity exponent, the distribution of finite-time Lyapunov exponents and singular continuous spectrum analysis.
Bistability and State Transition of a Delay Differential Equation Model of Neutrophil Dynamics
NASA Astrophysics Data System (ADS)
Ma, Suqi; Zhu, Kaiyi; Lei, Jinzhi
This paper studies the existence of bistable states and control strategies to induce state transitions of a delay differential equation model of neutrophil dynamics. We seek the conditions that a stable steady state and an oscillatory state coexist in the neutrophil dynamical system. Physiologically, stable steady state represents the healthy state, while oscillatory state is usually associated with diseases such as cyclical neutropenia. We study the control strategies to induce the transitions from the disease state to the healthy state by introducing temporal perturbations to system parameters. This study is valuable in designing clinical protocols for the treatment of cyclical neutropenia.
Amarillo-Suárez, A; Repizo, A; Robles, J; Diaz, J; Bustamante, S
2017-08-01
The colonization of an exotic species by native herbivores is more likely to occur if that herbivore is a generalist. There is little information on the life-history mechanisms used by native generalist insects to colonize exotic hosts and how these mechanisms are affected by host properties. We examined the ability of the generalist seed beetle Stator limbatus Horn to colonize an exotic species. We compared its host preference, acceptability, performance, and egg size when ovipositing and developing on two native (Pithecellobium dulce (Roxb.) Benth and Senegalia riparia (Kunth)) and one exotic legume species (Leucaena leucocephala (Lam.)). We also analyzed the seed chemistry. We found that females recognize the exotic species as an unfavorable host for larval development and that they delayed oviposition and laid fewer and larger eggs on the exotic species than on the native species. Survivorship on the exotic host was 0%. Additionally, seeds of the native species contain five chemical compounds that are absent in the exotic species, and the exotic species contains three sterols, which are absent in the native legumes. Genetically based differences between beetles adapted to different hosts, plastic responses toward new hosts, and chemical differences among seeds are important in host colonization and recognition of the exotic host. In conclusion, the generalist nature of S. limbatus does not influence its ability to colonize L. leucocephala. Explanations for the colonization of exotic hosts by generalist native species and for the success of invasive species must be complemented with studies measuring local adaptation and plasticity.
Coca-colonization and hybridization of diets among the Tz'utujil Maya.
Nagata, Jason M; Barg, Frances K; Valeggia, Claudia R; Bream, Kent D W
2011-01-01
Biomedical health professionals express increasing concern that rising consumption of soft drinks and processed foods in Mayan and Latin American eating patterns may lead to detrimental nutritional and health consequences. Scholars debate whether the pervading presence of Coca-Cola and Pepsi in developing countries represents "Coca-Colonization," synonymous with cultural imperialism, or cultural hybridization. Using mixed qualitative and quantitative research methods, including participant observation and semi-structured interviews, this study explores the development of Coca-Colonization and cultural hybridization among the Tz'utujil Maya of Santiago Atitlán, Guatemala. By specifically examining biomedical perspectives, cycles of conquest, the political economy, religion, celebrations, and the physical environment through the lens of soft drinks, this study finds that Coca-Colonization and cultural hybridization are complementary rather than mutually exclusive processes that contribute to dietary transitions, economic development, and differential health beliefs related to soft drink consumption.
Transit and lifespan in neutrophil production: implications for drug intervention.
Câmara De Souza, Daniel; Craig, Morgan; Cassidy, Tyler; Li, Jun; Nekka, Fahima; Bélair, Jacques; Humphries, Antony R
2018-02-01
A comparison of the transit compartment ordinary differential equation modelling approach to distributed and discrete delay differential equation models is studied by focusing on Quartino's extension to the Friberg transit compartment model of myelosuppression, widely relied upon in the pharmaceutical sciences to predict the neutrophil response after chemotherapy, and on a QSP delay differential equation model of granulopoiesis. An extension to the Quartino model is provided by considering a general number of transit compartments and introducing an extra parameter that allows for the decoupling of the maturation time from the production rate of cells. An overview of the well established linear chain technique, used to reformulate transit compartment models with constant transit rates as distributed delay differential equations (DDEs), is then given. A state-dependent time rescaling of the Quartino model is performed to apply the linear chain technique and rewrite the Quartino model as a distributed DDE, yielding a discrete DDE model in a certain parameter limit. Next, stability and bifurcation analyses are undertaken in an effort to situate such studies in a mathematical pharmacology context. We show that both the original Friberg and the Quartino extension models incorrectly define the mean maturation time, essentially treating the proliferative pool as an additional maturation compartment. This misspecification can have far reaching consequences on the development of future models of myelosuppression in PK/PD.
Digestive sensitivity varies according to size of dogs: a review.
Weber, M P; Biourge, V C; Nguyen, P G
2017-02-01
Field observations on food tolerance have repeatedly shown that when fed an identical diet, large breed (>25 kg) dogs present softer and moister faeces than small breed ones (<15 kg). The purpose of this review is to highlight the findings of four PhD theses, carried out between 1998 and 2013, whose objectives were to investigate the anatomical and physiological peculiarities that would explain, at least in part, this observation, as well as their nutritional implication. This work showed that large breed dogs, in contrast with smaller breeds, present a highly developed caecum and colon, which could explain the relatively longer colonic transit time. A prolonged colonic transit time could explain higher colonic fermentative activity, as supported by higher faecal concentrations of fermentative by-products. This effect would be reinforced by increased intestinal permeability and reduced sodium net-absorption. Taken together, these elements could be a possible cause of higher digestive sensitivity in large breed dogs. When prescribing a diet to a small or large breed dog, several aspects of the formulation must be taken into account. For a large breed dog, the general goal is to limit any ingredient that could increase the level of fermentable undigested residues and, in fine, exacerbate colonic fermentation. Highly digestible sources of proteins and starches are therefore strongly recommended to maintain an optimal digestive tolerance. Fermentable fibre sources (i.e. beet pulp and FOS) must also be used in limited quantity in their diet. Conversely, the incorporation of non-fermentable fibre (i.e. cellulose) appears useful to increase their stool quality. For a small breed dog, the general objective is to minimize any ingredient that could excessively limit colonic fermentation and induce in fine constipation. Purified starches and cellulose are therefore not really suitable for them. In contrast, cereals flours as well as non-fermentable fibre provided by cereals are recommended. © 2016 Royal Canin SAS. Journal of Animal Physiology and Animal Nutrition published by Blackwell Verlag GmbH.
[Iatrogen perforation of the rectum after colon radiography].
Eggum, R; Kressner, U; Haffner, J
1998-05-10
Perforation of the rectum following barium enema is relatively rare, occurring in 1 of 3,000 procedures. Colorectal perforation is a serious condition and early diagnosis is of paramount importance in order to avoid any delay in treating the patient. Direct suture of the perforation, lavage, presacral drainage and stomia are the preferred methods of primary surgical treatment.
Disturbed gastric emptying in the short bowel syndrome. Evidence for a 'colonic brake'.
Nightingale, J M; Kamm, M A; van der Sijp, J R; Morris, G P; Walker, E R; Mather, S J; Britton, K E; Lennard-Jones, J E
1993-01-01
Gastric emptying of liquid (orange juice containing technetium-99m (99mTc) labelled antimony sulphide colloid) and solid (570 kcal pancake containing 0.5 mm resin microspheres labelled with Indium-111 (111-In)) was measured in seven patients with jejunum and no colon (jejunal lengths 30-160 cm), six patients with jejunum in continuity with the colon (jejunal length 25-75 cm), and in 12 normal subjects. In patients with no colon early emptying of liquid was rapid (median 25% emptying: 7 v 25 min, no colon v normal, p < 0.05); early gastric emptying of solid was rapid in two (each with less than 100 cm jejunum) and normal in the other five. Gastric emptying of liquid and solid for patients with jejunum in continuity with the colon was normal for the first three hours. There was increased liquid and solid retained in the stomach at six hours in both groups of patients (p < 0.01). Small bowel transit time was faster than in normal subjects for liquid in both groups of patients (p < 0.05) and for solid in those with no colon (p < 0.05). Rapid gastric emptying of liquid may contribute to the large stomal output in patients with a high jejunostomy. Preservation of the colon after a major small intestinal resection exerts a braking effect on the rate of early gastric emptying of liquid. PMID:8406148
Ocaña, Oscar H; Córcoles, Rebeca; Fabra, Angels; Moreno-Bueno, Gema; Acloque, Hervé; Vega, Sonia; Barrallo-Gimeno, Alejandro; Cano, Amparo; Nieto, M Angela
2012-12-11
The epithelial-mesenchymal transition (EMT) is required in the embryo for the formation of tissues for which cells originate far from their final destination. Carcinoma cells hijack this program for tumor dissemination. The relevance of the EMT in cancer is still debated because it is unclear how these migratory cells colonize distant tissues to form macrometastases. We show that the homeobox factor Prrx1 is an EMT inducer conferring migratory and invasive properties. The loss of Prrx1 is required for cancer cells to metastasize in vivo, which revert to the epithelial phenotype concomitant with the acquisition of stem cell properties. Thus, unlike the classical EMT transcription factors, Prrx1 uncouples EMT and stemness, and is a biomarker associated with patient survival and lack of metastasis. Copyright © 2012 Elsevier Inc. All rights reserved.
David, Muriel; Naudin, Cécile; Letourneur, Martine; Polrot, Mélanie; Renoir, Jack-Michel; Lazar, Vladimir; Dessen, Philippe; Roche, Serge; Bertoglio, Jacques; Pierre, Josiane
2014-07-01
Suppressor of cytokine signaling (SOCS) 1 is an inducible negative regulator of cytokine signaling but its role in human cancer is not completely established. Here we report that, while SOCS1 is expressed in normal colonic epithelium and colon adenocarcinomas, its level decreases during progression of colon adenocarcinomas, the lowest level being found in the most aggressive stage and least differentiated carcinomas. Forced expression of SOCS1 in metastatic colorectal SW620 cells reverses many characteristics of Epithelial-Mesenchymal Transition (EMT), as highlighted by the disappearance of the transcription factor ZEB1 and the mesenchymal form of p120ctn and the re-expression of E-cadherin. Furthermore, miRNA profiling indicated that SOCS1 also up-regulates the expression of the mir-200 family of miRNAs, which can promote the mesenchymal-epithelial transition and reduce tumor cell migration. Accordingly, overexpression of SOCS1 induced cell morphology changes and dramatically reduced tumor cell invasion in vitro. When injected in nude mice, SOCS1-expressing SW620 cells induced metastases in a smaller number of animals than parental SW620 cells, and did not generate any adrenal gland or bone metastasis. Overall, our results suggest that SOCS1 controls metastatic progression of colorectal tumors by preventing the mesenchymal-epithelial transition (MET), including E-cadherin expression. This pathway may be associated with survival to colorectal cancer by reducing the capacity of generating metastases. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
van der Lugt, Benthe; Rusli, Fenni; Lute, Carolien; Lamprakis, Andreas; Salazar, Ethel; Boekschoten, Mark V; Hooiveld, Guido J; Müller, Michael; Vervoort, Jacques; Kersten, Sander; Belzer, Clara; Kok, Dieuwertje E G; Steegenga, Wilma T
2018-05-16
The aging process is associated with diminished colonic health. In this study, we applied an integrative approach to reveal potential interactions between determinants of colonic health in aging C57BL/6J mice. Analysis of gut microbiota composition revealed an enrichment of various potential pathobionts, including Desulfovibrio spp . , and a decline of the health-promoting Akkermansia spp . and Lactobacillus spp. during aging. Intraluminal concentrations of various metabolites varied between ages and we found evidence for an increased gut permeability at higher age. Colonic gene expression analysis suggested that during the early phase of aging (between 6 and 12 months), expression of genes involved in epithelial-to-mesenchymal transition and (re)organization of the extracellular matrix were increased. Differential expression of these genes was strongly correlated with Bifidobacterium spp. During the later phase of aging (between 12 and 28 months), gene expression profiles pointed towards a diminished antimicrobial defense and were correlated with an uncultured Gastranaerophilales spp. This study demonstrates that aging is associated with pronounced changes in gut microbiota composition and colonic gene expression. Furthermore, the strong correlations between specific bacterial genera and host gene expression may imply that orchestrated interactions take place in the vicinity of the colonic wall and potentially mediate colonic health during aging.
Mordecai, Erin A.; Jaramillo, Alejandra G.; Ashford, Jacob E.; Hechinger, Ryan F.; Lafferty, Kevin D.
2016-01-01
Competition – colonization tradeoffs occur in many systems, and theory predicts that they can strongly promote species coexistence. However, there is little empirical evidence that observed competition – colonization tradeoffs are strong enough to maintain diversity in natural systems. This is due in part to a mismatch between theoretical assumptions and biological reality in some systems. We tested whether a competition – colonization tradeoff explains how a diverse trematode guild coexists in California horn snail populations, a system that meets the requisite criteria for the tradeoff to promote coexistence. A field experiment showed that subordinate trematode species tended to have higher colonization rates than dominant species. This tradeoff promoted coexistence in parameterized models but did not fully explain trematode diversity and abundance, suggesting a role of additional diversity maintenance mechanisms. Spatial heterogeneity is an alternative way to promote coexistence if it isolates competing species. We used scale transition theory to expand the competition – colonization tradeoff model to include spatial variation. The parameterized model showed that spatial variation in trematode prevalence did not isolate most species sufficiently to explain the overall high diversity, but could benefit some rare species. Together, the results suggest that several mechanisms combine to maintain diversity, even when a competition – colonization tradeoff occurs.
Yin, Yue; Zhong, Lei; Wang, Jian-Wei; Zhao, Xue-Ying; Zhao, Wen-Jing; Kuang, Hai-Xue
2015-01-01
AIM: To investigate whether the Chinese medicine Tong Xie Yao Fang (TXYF) improves dysfunction in an irritable bowel syndrome (IBS) rat model. METHODS: Thirty baby rats for IBS modeling were separated from mother rats (1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine (5-HT) and substance P (SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity. RESULTS: Defecation frequency was 1.8 ± 1.03 in normal rats and 4.5 ± 1.58 in IBS model rats (P < 0.001). However, the defecation frequency was significantly decreased (3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time (in seconds) of colon transit function was significantly increased (256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. CONCLUSION: TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS. PMID:25914462
Yin, Yue; Zhong, Lei; Wang, Jian-Wei; Zhao, Xue-Ying; Zhao, Wen-Jing; Kuang, Hai-Xue
2015-04-21
To investigate whether the Chinese medicine Tong Xie Yao Fang (TXYF) improves dysfunction in an irritable bowel syndrome (IBS) rat model. Thirty baby rats for IBS modeling were separated from mother rats (1 h per day) from days 8 to 21, and the rectum was expanded by angioplasty from days 8 to 12. Ten normal rats were used as normal controls. We examined the effects of TXYF on defection frequency, colonic transit function and smooth muscle contraction, and the expression of 5-hydroxytryptamine (5-HT) and substance P (SP) in colonic and hypothalamus tissues by Western blot and RT-PCT techniques in both normal rats and IBS model rats with characterized visceral hypersensitivity. Defecation frequency was 1.8 ± 1.03 in normal rats and 4.5 ± 1.58 in IBS model rats (P < 0.001). However, the defecation frequency was significantly decreased (3.0 ± 1.25 vs 4.5 ± 1.58, P < 0.05), while the time (in seconds) of colon transit function was significantly increased (256.88 ± 20.32 vs 93.36 ± 17.28, P < 0.001) in IBS + TXYF group rats than in IBS group rats. Increased colonic smooth muscle tension and contract frequency in IBS model rats were significantly decreased by administration of TXYF. Exogenous agonist stimulants increased spontaneous activity and elicited contractions of colon smooth muscle in IBS model rats, and all of these actions were significantly reduced by TXYF involving 5-HT and SP down-regulation. TXYF can modulate the activity of the enteric nervous system and alter 5-HT and SP activities, which may contribute to the symptoms of IBS.
Falke, Jeffrey A; Bailey, Larissa L; Fausch, Kurt D; Bestgen, Kevin R
2012-04-01
Despite the importance of habitat in determining species distribution and persistence, habitat dynamics are rarely modeled in studies of metapopulations. We used an integrated habitat-occupancy model to simultaneously quantify habitat change, site fidelity, and local colonization and extinction rates for larvae of a suite of Great Plains stream fishes in the Arikaree River, eastern Colorado, USA, across three years. Sites were located along a gradient of flow intermittency and groundwater connectivity. Hydrology varied across years: the first and third being relatively wet and the second dry. Despite hydrologic variation, our results indicated that site suitability was random from one year to the next. Occupancy probabilities were also independent of previous habitat and occupancy state for most species, indicating little site fidelity. Climate and groundwater connectivity were important drivers of local extinction and colonization, but the importance of groundwater differed between periods. Across species, site extinction probabilities were highest during the transition from wet to dry conditions (range: 0.52-0.98), and the effect of groundwater was apparent with higher extinction probabilities for sites not fed by groundwater. Colonization probabilities during this period were relatively low for both previously dry sites (range: 0.02-0.38) and previously wet sites (range: 0.02-0.43). In contrast, no sites dried or remained dry during the transition from dry to wet conditions, yielding lower but still substantial extinction probabilities (range: 0.16-0.63) and higher colonization probabilities (range: 0.06-0.86), with little difference among sites with and without groundwater. This approach of jointly modeling both habitat change and species occupancy will likely be useful to incorporate effects of dynamic habitat on metapopulation processes and to better inform appropriate conservation actions.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gandara, Ricardo M.C.; Mahida, Yashwant R., E-mail: yash.mahida@nottingham.ac.uk; Potten, Christopher S.
2012-03-01
Purpose: The intestinal epithelium has a high rate of cell turnover, which is regulated by stem cells located near the base of crypts. We aimed to investigate stem cell-dependent characteristics of cell proliferation, apoptosis, and crypt size in terminal ileum and different regions of the colon. Methods and Materials: Mice were studied under steady-state conditions and after radiation-induced stem cell apoptosis. Percentage of proliferating or apoptotic cells at a particular cell position (cp) along the crypt axis was expressed as labeling or apoptotic index. Results: Under steady-state conditions: crypt size was smallest in the ascending colon. In contrast to othermore » regions of the colon, the distribution profile of proliferating cells in ascending colon showed some similarity to that in the terminal ileum. Postirradiation: apoptotic cells were prominent at the bottom of the crypt of mid- and descending colon but in the ascending colon, they were seen with similar frequency from cp 1 to 4. During regeneration, a constant proliferative capacity was seen above Paneth cells in the terminal ileum. In the ascending (but not mid- or descending) colon, the profile of proliferating cells over the first 4 days after irradiation showed a similarity to that in the terminal ileum. Conclusions: Profiles of proliferating epithelial cells (under steady-state conditions and postirradiation) and apoptotic cells (postirradiation) suggest similarities in the location of stem cells in the ascending colon and terminal ileum.« less
Wang, Chang-lin; Diao, Yu-xiang; Xiang, Qiong; Ren, Yu-kun; Gu, Ning
2014-09-05
Diabetes affects the entire gastrointestinal tract from the esophagus to the anus. In the present study, the charcoal meal test was undertaken to evaluate and compare the effects of intracerebroventricular (i.c.v.) administration of endomorphins (EMs) on gastrointestinal transit in non-diabetic and diabetic mice. Significantly delayed gastrointestinal transit was found in both 4 and 8 weeks alloxan-induced diabetes compared to non-diabetes. Moreover, i.c.v. EM-1 and EM-2 dose-dependently delayed gastrointestinal transit in non-diabetes and diabetes. The EM-1-induced inhibitory effects of gastrointestinal transit in 4 weeks diabetes were qualitatively similar to those of non-diabetes. However, at higher doses, the EM-1-induced effects in 8 weeks diabetes were largely enhanced. Different to EM-1, the EM-2-induced inhibition of gastrointestinal transit in diabetic mice was significantly attenuated compared to non-diabetic mice. Moreover, these effects were further decreased in 8 weeks diabetes. The delayed gastrointestinal transit effects caused by EM-1 may be primarily mediated by μ2-opioid receptor in both non-diabetes and 4 weeks diabetes. Interestingly, in 8 weeks diabetes, these effects were mediated by μ2- and δ-receptors. However, the inhibitory effects of EM-2 were mediated by μ1-opioid receptor, which exerted a reduced function in diabetes. Also, poor blood glucose control might result in the attenuated effects of EM-2. Our present results demonstrated that diabetes attenuates the inhibitory effects of EM-2, but not EM-1 on gastrointestinal transit in mice. The different effects of EM-1 and EM-2 on gastrointestinal transit in diabetes may be due to changes of opioid receptor subtypes and their functional responses. Copyright © 2014 Elsevier B.V. All rights reserved.
Time delay between cardiac and brain activity during sleep transitions
NASA Astrophysics Data System (ADS)
Long, Xi; Arends, Johan B.; Aarts, Ronald M.; Haakma, Reinder; Fonseca, Pedro; Rolink, Jérôme
2015-04-01
Human sleep consists of wake, rapid-eye-movement (REM) sleep, and non-REM (NREM) sleep that includes light and deep sleep stages. This work investigated the time delay between changes of cardiac and brain activity for sleep transitions. Here, the brain activity was quantified by electroencephalographic (EEG) mean frequency and the cardiac parameters included heart rate, standard deviation of heartbeat intervals, and their low- and high-frequency spectral powers. Using a cross-correlation analysis, we found that the cardiac variations during wake-sleep and NREM sleep transitions preceded the EEG changes by 1-3 min but this was not the case for REM sleep transitions. These important findings can be further used to predict the onset and ending of some sleep stages in an early manner.
Assessment of nevirapine bioavailability from targeted sites in the human gastrointestinal tract.
Macha, Sreeraj; Yong, Chan-Loi; MacGregor, Thomas R; Castles, Mark; Quinson, Anne-Marie; Rouyrre, Nicolas; Wilding, Ian
2009-12-01
This study investigated absorption of nevirapine (NVP) from targeted sites of the gastrointestinal tract using remotely activated capsules and gamma scintigraphy. A total of 24 participants were randomized to receive 50 mg NVP orally as a suspension or via remotely activated capsules for release into the ascending colon. The 24 participants were then rerandomized into parallel groups of n = 8 for drug release into the ileum, jejunum, or descending colon. The mean gastric emptying time of capsules ranged from 0.88 to 3.35 hours. The small intestinal and colon transit time ranged from 4.08 to 7.76 hours and 17.6 to 21.2 hours, respectively, and capsule recovery time ranged from 27.6 to 34.4 hours. The relative bioavailability ratio of NVP in the jejunum was 1.06 (90% confidence interval [CI]: 1.00-1.12) compared to suspension. In the ileum, ascending colon, and descending colon, bioavailability decreased to 0.89 (0.80-0.99), 0.82 (0.71-0.95), and 0.58 (0.22-1.53), respectively. The absorption rate decreased by approximately 10-fold from the jejunum (3.83 h(-1)) to the descending colon (0.338 h(-1)), and t(max) increased from 2.42 hours (jejunum) to 16.3 hours (descending colon). Overall, NVP is absorbed from all 4 sites of the gastrointestinal tract, and the rate of absorption decreased from the jejunum to the descending colon. Relative bioavailability of NVP was in the order of jejunum > ileum > ascending colon > descending colon.
Al-Qasem, Abeer; Al-Howail, Huda A; Al-Swailem, Mashael; Al-Mazrou, Amer; Al-Otaibi, Basem; Al-Jammaz, Ibrahim; Al-Khalaf, Huda H; Aboussekhra, Abdelilah
2016-03-01
Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality worldwide. Although response rates and overall survival have been improved in recent years, resistance to multiple drug combinations is inevitable. Therefore, the development of more efficient drugs, with fewer side effects is urgently needed. To this end, we have investigated in the present report the effect of PAC, a novel cucumin analogue, on CRC cells both in vitro and in vivo. We have shown that PAC induces apoptosis, mainly via the internal mitochondrial route, and inhibits cell proliferation through delaying the cell cycle at G2/M phase. Interestingly, the pro-apoptotic effect was mediated through STAT3-dependent down-regulation of cyclin D1 and its downstream target survivin. Indeed, change in the expression level of cyclin D1 modulated the expression of survivin and the response of CRC cells to PAC. Furthermore, using the ChIP assay, we have shown PAC-dependent reduction in the binding of STAT3 to the cyclin D1 promoter in vivo. Additionally, PAC suppressed the epithelial-to-mesenchymal process through down-regulating the mesenchymal markers (N-cadherin, vimentin and Twist1) and inhibiting the invasion/migration abilities of the CRC cells via repressing the pro-migration/invasion protein kinases AKT and ERK1/2. In addition, PAC inhibited tumor growth and repressed the JAK2/STAT3, AKT/mTOR and MEK/ERK pathways as well as their common downstream effectors cyclin D1 and survivin in humanized CRC xenografts. Collectively, these results indicate that PAC has potent anti-CRC effects, and therefore could constitute an effective alternative chemotherapeutic agent, which may consolidate the adjuvant treatment of colon cancer. © 2015 Wiley Periodicals, Inc.
Koziolek, Mirko; Grimm, Michael; Becker, Dieter; Iordanov, Ventzeslav; Zou, Hans; Shimizu, Jeff; Wanke, Christoph; Garbacz, Grzegorz; Weitschies, Werner
2015-09-01
Gastrointestinal (GI) pH and temperature profiles under fasted-state conditions were investigated in two studies with each 10 healthy human subjects using the IntelliCap(®) system. This telemetric drug delivery device enabled the determination of gastric emptying time, small bowel transit time, and colon arrival time by significant pH and temperature changes. The study results revealed high variability of GI pH and transit times. The gastric transit of IntelliCap(®) was characterized by high fluctuations of the pH with mean values ranging from pH 1.7 to pH 4.7. Gastric emptying was observed after 7-202 min (median: 30 min). During small bowel transit, which had a duration of 67-532 min (median: 247 min), pH values increased slightly from pH 5.9-6.3 in proximal parts to pH 7.4-7.8 in distal parts. Colonic pH conditions were characterized by values fluctuating mainly between pH 5 and pH 8. The pH profiles and transit times described in this work are highly relevant for the comprehension of drug delivery of solid oral dosage forms comprising ionizable drugs and excipients with pH-dependent solubility. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
Lindfors, Perjohan; Törnblom, Hans; Sadik, Riadh; Björnsson, Einar S; Abrahamsson, Hasse; Simrén, Magnus
2012-12-01
Gut-directed hypnotherapy is an effective treatment in irritable bowel syndrome (IBS) but little is known about the mechanisms of action. In this study we aimed to investigate the effects on gastrointestinal motility when treating IBS with gut-directed hypnotherapy. We randomized 90 patients with IBS, refractory to standard management to receive gut-directed hypnotherapy 1 h/week for 12 weeks or supportive treatment for the same time period. Eighty-one subjects (40 hypnotherapy, 41 controls) could be evaluated by one or more of the following investigations, both before and after the intervention: gastric emptying time, small bowel transit time, colonic transit time, and antroduodenojejunal manometry. No significant differences in gastric emptying time, small bowel transit time, or colonic transit time was found when comparing the baseline and post-intervention measurements in the hypnotherapy group or in the control group. The same was true concerning the results of the antroduodenojejunal manometry. However, there was a numerical trend toward a higher number of migrating motor complexes at manometry and an accelerated gastric emptying time after hypnotherapy that did not reach statistical significance. In this study, we were not able to find evidence for long-standing effects on gastrointestinal motility as a mediator of the effects on IBS when treating the condition with gut-directed hypnotherapy. Further research to understand the mechanism of action is needed.
Ma, Yan-Hui; Cheng, Wei-Zhi; Gong, Fang; Ma, An-Lun; Yu, Qi-Wen; Zhang, Ji-Ying; Hu, Chao-Ying; Chen, Xue-Hua; Zhang, Dong-Qing
2008-01-01
AIM: To investigate the potential role of Active Chinese mistletoe lectin-55 (ACML-55) in tumor immune surveillance. METHODS: In this study, an experimental model was established by hypodermic inoculating the colon cancer cell line CT26 (5 × 105 cells) into BALB/c mice. The experimental treatment was orally administered with ACML-55 or PBS, followed by the inoculation of colon cancer cell line CT26. Intracellular cytokine staining was used to detect IFN-γ production by tumor antigen specific CD8+ T cells. FACS analysis was employed to profile composition and activation of CD4+, CD8+, γδ T and NK cells. RESULTS: Our results showed, compared to PBS treated mice, ACML-55 treatment significantly delayed colon cancer development in colon cancer -bearing Balb/c mice in vivo. Treatment with ACML-55 enhanced both Ag specific activation and proliferation of CD4+ and CD8+ T cells, and increased the number of tumor Ag specific CD8+ T cells. It was more important to increase the frequency of tumor Ag specific IFN-γ producing-CD8+ T cells. Interestingly, ACML-55 treatment also showed increased cell number of NK, and γδT cells, indicating the role of ACML-55 in activation of innate lymphocytes. CONCLUSION: Our results demonstrate that ACML-55 therapy can enhance function in immune surveillance in colon cancer-bearing mice through regulating both innate and adaptive immune responses. PMID:18785279
Nandi, Bisweswar; Shapiro, Mia; Samur, Mehmet K.; Pai, Christine; Frank, Natasha Y.; Yoon, Charles; Prabhala, Rao H.; Munshi, Nikhil C.; Gold, Jason S.
2016-01-01
ABSTRACT Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been implicated in promoting colon cancer; however, the mechanisms behind this effect are poorly understood. We have previously demonstrated that deficiency of CCR6 is associated with decreased tumor macrophage accumulation in a model of sporadic intestinal tumorigenesis. In this study, we aimed to determine the role of stromal CCR6 expression in a murine syngeneic transplantable colon cancer model. We show that deficiency of host CCR6 is associated with decreased growth of syngeneic CCR6-expressing colon cancers. Colon cancers adoptively transplanted into CCR6-deficient mice have decreased tumor-associated macrophages without alterations in the number of monocytes in blood or bone marrow. CCL20, the unique ligand for CCR6, promotes migration of monocytes in vitro and promotes accumulation of macrophages in vivo. Depletion of tumor-associated macrophages decreases the growth of tumors in the transplantable tumor model. Macrophages infiltrating the colon cancers in this model secrete the inflammatory mediators CCL2, IL-1α, IL-6 and TNFα. Ccl2, Il1α and Il6 are consequently downregulated in tumors from CCR6-deficient mice. CCL2, IL-1α and IL-6 also promote proliferation of colon cancer cells, linking the decreased macrophage migration into tumors mediated by CCL20–CCR6 interactions to the delay in tumor growth in CCR6-deficient hosts. The relevance of these findings in human colon cancer is demonstrated through correlation of CCR6 expression with that of the macrophage marker CD163 as well as that of CCL2, IL1α and TNFα. Our findings support the exploration of targeting the CCL20–CCR6 pathway for the treatment of colon cancer. PMID:27622061
Panos, Marios Z; Koumi, Andriani
2014-05-01
The 40W-0.8 l/min setting is widely recommended for argon plasma coagulation (APC) in the right colon. Until March 2012, we used the 60W-1.2 l/min setting for all sites of the colon. By auditing our experience, we assessed the safety-risk profile of the 60W-1.2 l/min setting in the right and left colon. All cases treated with APC by a single endoscopist, using the 60W-1.2 l/min setting for all sites of the colon between October 2001 and December 2007 were identified retrospectively and site, type, number of lesions, and complications were recorded. Between January 2008 and March 2012, information was recorded prospectively. In the retrospective audit, 290 lesions (101 cecum/ascending, 120 sigmoid/descending, 69 transverse) were treated in 241 patient endoscopies. There were no perforations. In the prospective audit, 156 lesions (83 cecum/ascending, 47 sigmoid/descending, 26 transverse) were treated in 132 patient endoscopies. There was 1/83 (1.2%) perforation in the cecum/ascending colon and none in the transverse or sigmoid/descending (n.s.). Combined, the results yield a cecal/ascending perforation rate of 1/153 (0.6%) patient endoscopies, 1/184 (0.5%) lesions treated and overall perforation rate for all sites of the colon of 1/373 (0.3%) patient endoscopies and 1/446 (0.2%) lesions. Post-polypectomy syndrome and delayed bleeding each occurred in 3/373 (0.8%) patient endoscopies and 3/446 (0.7%) lesions. There were no deaths. In the cecum and ascending colon, the APC perforation rate at the 60W-1.2 l/min setting was no higher than in the left colon and is similar to that reported in previously published series. Therefore, it appears safe, provided the precautions we describe are strictly followed.
de Gracia Roldán, Javier; Olveira, Casilda; Vendrell, Montserrat; Martínez-García, Miguel Ángel; de la Rosa, David; Máiz, Luis; Ancochea, Julio; Vázquez, Liliana; Borderías, Luis; Polverino, Eva; Martínez-Moragón, Eva; Rajas, Olga; Soriano, Joan B
2017-01-01
Diagnostic delay is common in most respiratory diseases, particularly in bronchiectasis. However, sex bias in diagnostic delay has not been studied to date. Objective: Assessment of diagnostic delay in bronchiectasis by sex. Methods: The Spanish Historical Registry of Bronchiectasis recruited adults diagnosed with bronchiectasis from 2002 to 2011 in 36 centres in Spain. From a total of 2113 patients registered we studied 2099, of whom 1125 (53.6%) were women. Results: No differences were found for sex or age (61.0 ± 20.6, p = 0.88) or for localization of bronchiectasis (p = 0.31). Bronchiectasis of unknown aetiology and secondary to asthma, childhood infections and tuberculosis was more common in women (all ps < 0.05). More men than women were chronic obstructive pulmonary disease-related bronchiectasis and colonized by Haemophilus influenzae (p < 0.001 for both). Onset of symptoms was earlier in women. The diagnostic delay for women with bronchiectasis was 2.1 years more than for men (p = 0.001). Discussion: We recorded a substantial delay in the diagnosis of bronchiectasis. This delay was significantly longer in women than in men (>2 years). Independent factors associated with this sex bias were age at onset of symptoms, smoking history, daily expectoration and reduced lung function. PMID:28393532
Long-Distance Rescue and Slow Extinction Dynamics Govern Multiscale Metapopulations.
Huth, Géraldine; Haegeman, Bart; Pitard, Estelle; Munoz, François
2015-10-01
Rare long-distance dispersal is known to be critical for species dynamics, but how the interplay between short- and long-distance colonization influences regional persistence in a fragmented habitat remains poorly understood. We propose a metapopulation model that combines local colonization within habitat islands and long-distance colonization between islands. We study how regional occupancy dynamics are affected by the multiscale colonization process. We find that the island size distribution (ISD) is a key driver of the long-term occupancy dynamics. When the ISD is heterogeneous-that is, when the size of islands is variable-we show that extinction dynamics become very slow. We demonstrate that this behavior is unrelated to the well-known extinction debt near the critical extinction threshold. Hence, this finding questions the equivalence between extinction debt and critical transitions in the context of metapopulation collapse. Furthermore, we show that long-distance colonization can rescue small islands from extinction and sustain a steady regional occupancy. These results provide novel theoretical and practical insights into extinction dynamics and persistence in fragmented habitats and are thus relevant for the design of conservation strategies.
End-colostomy diverticulitis with parastomal phlegmon
Muradbegovic, Mirza; St-Amour, Pénélope; Martin, David; Petermann, David; Benabidallah, Samir; Di Mare, Luca
2017-01-01
Abstract Rationale: Acute colonic diverticulitis is a well-known surgical emergency, which occurs in about 10 percent of patients known for diverticulosis. Patient concerns: The case of a 77-year-old woman is reported, with past history of abdominoperineal resection with end-colostomy for low rectal adenocarcinoma, and who developed an acute colonic diverticulitis in a subcutaneous portion of colostomy with parastomal phlegmon. Diagnoses: Initial computed tomography imaging demonstrated a significant submucosal parietal edema with local fat tissues infiltration in regard of 3 diverticula. Interventions: A two-step treatment was decided: first a nonoperative treatment was initiated with 2 weeks antibiotics administration, followed by, 6 weeks after, a segmental resection of the terminal portion of the colon with redo of a new colostomy by direct open approach. Outcomes: Patient was discharged on the second postoperative day without complications. Follow-up at 2 weeks revealed centimetric dehiscence of the stoma, which was managed conservatively until sixth postoperative week by stomatherapists. Lessons subsections: Treatment of acute diverticulitis with parastomal phlegmon in a patient with end-colostomy could primary be nonoperative. Delayed surgical treatment with segmental colonic resection was proposed to avoid recurrence and potential associated complications. PMID:29069019
Fiber and colorectal diseases: Separating fact from fiction
Tan, Kok-Yang; Seow-Choen, Francis
2007-01-01
Whilst fruits and vegetables are an essential part of our dietary intake, the role of fiber in the prevention of colorectal diseases remains controversial. The main feature of a high-fiber diet is its poor digestibility. Soluble fiber like pectins, guar and ispaghula produce viscous solutions in the gastrointestinal tract delaying small bowel absorption and transit. Insoluble fiber, on the other hand, pass largely unaltered through the gut. The more fiber is ingested, the more stools will have to be passed. Fermentation in the intestines results in build up of large amounts of gases in the colon. This article reviews the physiology of ingestion of fiber and defecation. It also looks into the impact of dietary fiber on various colorectal diseases. A strong case cannot be made for a protective effect of dietary fiber against colorectal polyp or cancer. Neither has fiber been found to be useful in chronic constipation and irritable bowel syndrome. It is also not useful in the treatment of perianal conditions. The fiber deficit - diverticulosis theory should also be challenged. The authors urge clinicians to keep an open mind about fiber. One must be aware of the truths and myths about fiber before recommending it. PMID:17696243
Wu, Florence TH; Lee, Christina R; Bogdanovic, Elena; Prodeus, Aaron; Gariépy, Jean; Kerbel, Robert S
2015-01-01
Angiopoietin-1 (Ang1) activation of Tie2 receptors on endothelial cells (ECs) reduces adhesion by tumor cells (TCs) and limits junctional permeability to TC diapedesis. We hypothesized that systemic therapy with Vasculotide (VT)—a purported Ang1 mimetic, Tie2 agonist—can reduce the extravasation of potentially metastatic circulating TCs by similarly stabilizing the host vasculature. In vitro, VT and Ang1 treatments impeded endothelial hypermeability and the transendothelial migration of MDA-MB-231•LM2-4 (breast), HT29 (colon), or SN12 (renal) cancer cells to varying degrees. In mice, VT treatment inhibited the transit of TCs through the pulmonary endothelium, but not the hepatic or lymphatic endothelium. In the in vivo LM2-4 model, VT monotherapy had no effect on primary tumors, but significantly delayed distant metastatic dissemination to the lungs. In the post-surgical adjuvant treatment setting, VT therapeutically complemented sunitinib therapy, an anti-angiogenic tyrosine kinase inhibitor which limited the local growth of residual disease. Unexpectedly, detailed investigations into the putative mechanism of action of VT revealed no evidence of Tie2 agonism or Tie2 binding; alternative mechanisms have yet to be determined. PMID:25851538
Fiber and colorectal diseases: separating fact from fiction.
Tan, Kok-Yang; Seow-Choen, Francis
2007-08-21
Whilst fruits and vegetables are an essential part of our dietary intake, the role of fiber in the prevention of colorectal diseases remains controversial. The main feature of a high-fiber diet is its poor digestibility. Soluble fiber like pectins, guar and ispaghula produce viscous solutions in the gastrointestinal tract delaying small bowel absorption and transit. Insoluble fiber, on the other hand, pass largely unaltered through the gut. The more fiber is ingested, the more stools will have to be passed. Fermentation in the intestines results in build up of large amounts of gases in the colon. This article reviews the physiology of ingestion of fiber and defecation. It also looks into the impact of dietary fiber on various colorectal diseases. A strong case cannot be made for a protective effect of dietary fiber against colorectal polyp or cancer. Neither has fiber been found to be useful in chronic constipation and irritable bowel syndrome. It is also not useful in the treatment of perianal conditions. The fiber deficit - diverticulosis theory should also be challenged. The authors urge clinicians to keep an open mind about fiber. One must be aware of the truths and myths about fiber before recommending it.
Murugan, Sengottuvelan; Dave, Yatee; Rakhit, Ankush; Sarkar, Dipak K
2017-01-01
In recent years, experimental studies demonstrated negative impacts of impaired body stress response on colonic pathologies. In this study, we tested if reducing body stress response by the use of β-endorphin (BEP) neuronal transplants in the hypothalamus suppresses pre-neoplastic and neoplastic lesions. Colon cancer was induced by injecting 1,2-dimethylhydrazine (DMH) for sixteen weeks in Sprague Dawley rats with BEP neuron transplants or control neuron transplants, and their colonic histopathologies, colon tissue levels of pro-inflammatory cytokines and epithelial-mesenchymal transition (EMT) proteins and splenic levels of cytotoxic proteins were measured. Our results revealed that DMH induced tumors in colon at 100% incidence in control rats but failed to induce colonic tumors in 70% of animal with BEP neuronal transplants. The mean volume of tumor at the colon was smaller in BEP neurons transplanted rats than those in controls. Histopathologies of colon tissues revealed that BEP neurons transplanted animals had lesser tissue lesions such as aberrant crypt foci (ACF) and adenocarcinoma development in the colon than those in control groups. Immunohistochemical and western blot analyses identified reduced expression of Ki-67, TNF-α and NF-κB nuclear translocation in colonic tissues of BEP neurons transplanted rats than those in controls. BEP neurons transplanted rats also showed reduced expressions of transcription factors linked to EMT like Snail, Twist, and N-cadherin, but increased the levels of an epithelial cell marker E-cadherin in colon tissue. Furthermore, splenic NK cells cytolytic proteins such as perforin, granzyme B and IFN-γ levels in BEP neurons transplanted rats were higher than those in control rats. These data suggest that BEP neuron transplants suppress the growth and progression of colonic tumors possibly by decreasing inflammatory mileu and EMT via activation of innate immune responses.
Unger, Sabine; Büche, Claudia; Boso, Susana; Kassemeyer, Hanns-Heinz
2007-07-01
ABSTRACT The course of colonization of leaf mesophyll by the causal agent of grapevine downy mildew, Plasmopara viticola, in a susceptible and a resistant grapevine genotype was examined in order to characterize the development of the pathogen in compatible and incompatible host-pathogen interactions. Within a few hours after inoculation, the pathogen was established in the susceptible Vitis vinifera cv. Müller-Thurgau and formed primary hyphae with a first haustorium. No further development occurred in the following 10 to 18 h. The next step, in which the hyphae grew and branched to colonize the intercellular space of the host tissue, was observed 1.5 days after inoculation. After 3 days, the intercostal fields were entirely filled with mycelium and sporulation was abundant under favorable environmental conditions. The first infection steps were essentially the same in the resistant V. rupestris. However, the invasive growth of P. viticola was delayed, and further development ceased before the intercostal fields were filled with mycelium.
Yetışır, Fahri; Şarer, Akgün Ebru; Acar, H Zafer
2015-01-01
Management of necrotizing fasciitis and severe faecal peritonitis following ostomy in elderly patient with comorbid disease is challenging. We would like to report management of frozen Open Abdomen (OA) with colonic fistula following ostomy necrosis and detachment in an elderly patient with comorbid disease and malignancy. 78-year-old woman with high stage rectum carcinoma was admitted to emergency department and underwent operation for severe peritonitis and sigmoid colonic perforation. Loop sigmoidostomy was performed. At postoperative 15th day, she was transferred to our clinic with necrotizing fasciitis and severe faecal peritonitis due to ostomy necrosis and detachment. Enteric effluent was removed from the OA wound by using the Flexi-Seal Fecal Management System (FMS) (ConvaTec) and pesser tube in deeply located colonic fistula in conjunction with Negative Pressure Therapy (NPT). Maturation of ostomy was facilitated by using second NPT on ostomy side. After source control, delayed abdominal closure was achieved by skin flap approximation.
Illuminati, Giulio; Ricco, Jean-Baptiste; Schneider, Fabrice; Caliò, Francesco G; Ceccanei, Gianluca; Pacilè, Maria A; Pizzardi, Giulia; Palumbo, Piergaspare; Vietri, Francesco
2014-07-01
The purpose of this study was to evaluate the strategy for treatment of patients presenting with asymptomatic diverticular disease of the large bowel associated with an asymptomatic aortoiliac aneurysmal (AAA) disease. Sixty-nine patients were included in this retrospective study. The patients were divided into 5 groups according to the type and sequence of the surgical treatment: 32 patients (47%) underwent colectomy followed by a staged open AAA repair (group A); 10 patients (14%) were treated with open AAA repair followed by a staged colectomy (group B); 13 patients (18%) received endovascular aneurysm repair (EVAR) followed by a staged bowel resection (group C); 8 patients (12%) had a bowel resection followed by staged EVAR (group D); and 6 patients (9%) underwent simultaneous open AAA repair and bowel resection (group E). Primary end points were mortality and complications after any of the procedures. Secondary end point was the time interval between the staged procedures. The cumulative death rate for delayed treatment of AAA was 6.5% and 0% for delayed treatment of diverticular disease [P=0.22]. The mean time interval between the staged procedures was 11 days for EVAR/colon resection (group C and group D) and 73 days for open AAA repair/colon resection (group A and group B; P<0.01). EVAR allows a significant reduction in the time required between AAA repair and colon resection, but no definite rule can be established regarding the sequence of staged procedures. Combined procedures should be reserved for selected cases. Copyright © 2014 Elsevier Inc. All rights reserved.
Transitional and Steady-State Choice Behavior under an Adjusting-Delay Schedule
ERIC Educational Resources Information Center
Torres, L. Valencia; Araujo, S. da Costa; Sanchez, C. M. Olarte; Body, S.; Bradshaw, C. M.; Szabadi, E.
2011-01-01
Twelve rats made repeated choices on an adjusting-delay schedule between a smaller reinforcer (A) that was delivered immediately after a response and a larger reinforcer (B) that was delivered after a delay which increased or decreased by 20% depending on the subject's choices in successive blocks of trials. In two phases of the experiment (100…
An Experimental Investigation of Hypergolic Ignition Delay of Hydrogen Peroxide with Fuel Mixtures
NASA Technical Reports Server (NTRS)
Blevins, John A.; Gostowski, Rudy; Chianese, Silvio
2003-01-01
An experimental evaluation of decomposition and ignition delay of hydrogen peroxide at concentrations of 80% to 98% with combinations of hydrocarbon fuels, tertiary amines and transition metal chelates will be presented in the proposed paper. The results will be compared to hydrazine ignition delays with hydrogen peroxide and nitric acid mixtures using the same test apparatus.
NASA Astrophysics Data System (ADS)
Song, Juan; Tao, Wenjun; Song, Hui; Gong, Min; Ma, Guohong; Dai, Ye; Zhao, Quanzhong; Qiu, Jianrong
2016-04-01
In this paper, a time-delay-adjustable double-pulse train with 800-nm wavelength, 200-fs pulse duration and a repetition rate of 1 kHz, produced by a collinear two-beam optical system like a Mach-Zehnder interferometer, was employed for irradiation of 6H-SiC crystal. The dependence of the induced structures on time delay of double-pulse train for parallel-polarization configuration was studied. The results show that as the time delay of collinear parallel-polarization dual-pulse train increased, the induced near-subwavelength ripples (NSWRs) turn from irregular rippled pattern to regularly periodic pattern and have their grooves much deepened. The characteristics timescale for this transition is about 6.24 ps. Besides, the areas of NSWR were found to decay exponentially for time delay from 0 to 1.24 ps and then slowly increase for time delay from 1.24 to 14.24 ps. Analysis shows that multiphoton ionization effect, grating-assisted surface plasmon coupling effect, and timely intervene of second pulse in a certain physical stage experienced by 6H-SiC excited upon first pulse irradiation may contribute to the transition of morphology details.
Nath, Bipul; Nath, Lila Kanta
2013-01-01
The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon-targeted drug delivery system (MCDDS) which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microflora degradation property of gum was investigated in rat caecal medium. Drug release study in simulated colonic fluid revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics. In vivo study in rabbits shows delayed T max, prolonged absorption time, decreased C max, and absorption rate constant (Ka), indicating a reduced systemic toxicity of the drug as compared to other dosage forms. PMID:26555985
Zhao, Di; Cai, Chenwen; Zheng, Qing; Jin, Shuang; Song, Dongjuan; Shen, Jun; Ran, Zhihua
2017-01-29
The interplay between luminal microbes and innate immunity during colonic epithelial repair has been well noted. At the same time, antibiotic has widely been used during flare-ups of ulcerative colitis. The possible effects of luminal microbiota disruption caused by antibiotics usage on epithelial repairing have been scarcely discussed. Innate lymphoid cells (ILCs) embedded in the lamina propria can be modulated by gut microbes, resulting in altered colonic IL-22/pSTAT3 levels, which is considered a prominent molecular axis in tissue repairing after epithelium damage. This study aimed to investigate whether antibiotics could interfere with ILCs-dependent tissue repair. Dextran sodium sulfate (DSS)-induced colitis was established in mice pre-treated with reagent of different antibiotic spectrum. Both morphological and molecular markers of tissue repair after DSS cessation were detected. ILCs population and function status were also recorded. Further attention was paid to the response of dendritic cells after antibiotics treatment, which were claimed to regulate colonic ILC3s in an IL-23 dependent way. Using of vancomycin resulted in delayed tissue repairing after experimental colitis. Both colonic IL-22/pSTAT3 axis and ILC3 population were found decreased in this situation. Vancomycin treatment diminished the upstream IL-23 and producer dendritic cell population. The reduced dendritic cell number may due to inadequate chemokines and colony-stimulating factors supply. Presence of vancomycin-sensitive microbiota is required for the maturation of ILC3-activating dendritic cells hence maintain the sufficient IL-22/pSTAT3 level in the colon during tissue healing. Manipulation of colonic microbiota may help achieve colonic mucosal healing post inflammation and injury. Copyright © 2016. Published by Elsevier Inc.
Stanton, Thad B; Humphrey, Samuel B
2011-10-01
Megasphaera elsdenii is a lactate-fermenting, obligately anaerobic bacterium commonly present in the gastrointestinal tracts of mammals, including humans. Swine M. elsdenii strains were previously shown to have high levels of tetracycline resistance (MIC=64 to >256 μg/ml) and to carry mosaic (recombinant) tetracycline resistance genes. Baby pigs inherit intestinal microbiota from the mother sow. In these investigations we addressed two questions. When do M. elsdenii strains from the sow colonize baby pigs? Can five antibiotic-sensitive M. elsdenii strains administered intragastrically to newborn pigs affect natural colonization of the piglets by antibiotic-resistant (AR) M. elsdenii strains from the mother? M. elsdenii natural colonization of newborn pigs was undetectable (<10(4) CFU/g [wet weight] of feces) prior to weaning (20 days after birth). After weaning, all pigs became colonized (4 × 10(5) to 2 × 10(8) CFU/g feces). In a separate study, 61% (76/125) of M. elsdenii isolates from a gravid sow never exposed to antibiotics were resistant to chlortetracycline, ampicillin, or tylosin. The inoculation of the sow's offspring with mixtures of M. elsdenii antibiotic-sensitive strains prevented colonization of the offspring by maternal AR strains until at least 11 days postweaning. At 25 and 53 days postweaning, however, AR strains predominated. Antibiotic susceptibility phenotypes and single nucleotide polymorphism (SNP)-based identities of M. elsdenii isolated from sow and offspring were unexpectedly diverse. These results suggest that dosing newborn piglets with M. elsdenii antibiotic-sensitive strains delays but does not prevent colonization by maternal resistant strains. M. elsdenii subspecies diversity offers an explanation for the persistence of resistant strains in the absence of antibiotic selection.
Human evolution, life history theory, and the end of biological reproduction.
Last, Cadell
2014-01-01
Throughout primate history there have been three major life history transitions towards increasingly delayed sexual maturation and biological reproduction, as well as towards extended life expectancy. Monkeys reproduce later and live longer than do prosimians, apes reproduce later and live longer than do monkeys, and humans reproduce later and live longer than do apes. These life history transitions are connected to increased encephalization. During the last life history transition from apes to humans, increased encephalization co-evolved with increased dependence on cultural knowledge for energy acquisition. This led to a dramatic pressure for more energy investment in growth over current biological reproduction. Since the industrial revolution socioeconomic development has led to even more energy being devoted to growth over current biological reproduction. I propose that this is the beginning of an ongoing fourth major primate life history transition towards completely delayed biological reproduction and an extension of the evolved human life expectancy. I argue that the only fundamental difference between this primate life history transition and previous life history transitions is that this transition is being driven solely by cultural evolution, which may suggest some deeper evolutionary transition away from biological evolution is already in the process of occurring.
Gendered transitions to adulthood by college field of study in the United States.
Han, Siqi; Tumin, Dmitry; Qian, Zhenchao
2016-01-01
Field of study may influence the timing of transitions to the labor market, marriage, and parenthood among college graduates. Research to date has yet to study how field of study is associated with the interweaving of these transitions in the USA. The current study examines gendered influences of college field of study on transitions to a series of adult roles, including full-time work, marriage, and parenthood. We use Cox proportional hazards models and multinomial logistic regression to examine gendered associations between field of study and the three transitions among college graduates of the NLSY97 (National Longitudinal Survey of Youth) cohort. Men majoring in STEM achieve early transitions to full-time work, marriage, and parenthood; women majoring in STEM show no significant advantage in finding full-time work and delayed marriage and childbearing; women in business have earlier transitions to full-time work and marriage than women in other fields, demonstrating an advantage similar to that of men in STEM. The contrast between men and women in STEM shows that transition to adulthood remains gendered; the contrast between women in STEM and women in business illustrates that a prestigious career may not necessarily delay family formation.
Sweetser, Seth; Busciglio, Irene A; Camilleri, Michael; Bharucha, Adil E; Szarka, Lawrence A; Papathanasopoulos, Athanasios; Burton, Duane D; Eckert, Deborah J; Zinsmeister, Alan R
2009-02-01
Lubiprostone, a bicyclic fatty acid chloride channel activator, is efficacious in treatment of chronic constipation and constipation-predominant irritable bowel syndrome. The study aim was to compare effects of lubiprostone and placebo on colonic sensory and motor functions in humans. In double-blind, randomized fashion, 60 healthy adults received three oral doses of placebo or 24 microg lubiprostone per day in a parallel-group, placebo-controlled trial. A barostat-manometry tube was placed in the left colon by flexible sigmoidoscopy and fluoroscopy. We measured treatment effects on colonic sensation and motility with validated methods, with the following end points: colonic compliance, fasting and postprandial tone and motility indexes, pain thresholds, and sensory ratings to distensions. Among participants receiving lubiprostone or placebo, 26 of 30 and 28 of 30, respectively, completed the study. There were no overall effects of lubiprostone on compliance, fasting tone, motility indexes, or sensation. However, there was a treatment-by-sex interaction effect for compliance (P = 0.02), with lubiprostone inducing decreased fasting compliance in women (P = 0.06) and an overall decreased colonic tone contraction after a standard meal relative to fasting tone (P = 0.014), with greater effect in women (P < 0.01). Numerical differences of first sensation and pain thresholds (P = 0.11 in women) in the two groups were not significant. We concluded that oral lubiprostone 24 microg does not increase colonic motor function. The findings of decreased colonic compliance and decreased postprandial colonic tone in women suggest that motor effects are unlikely to cause accelerated colonic transit with lubiprostone, although they may facilitate laxation. Effects of lubiprostone on sensitivity deserve further study.
Sweetser, Seth; Busciglio, Irene A.; Camilleri, Michael; Bharucha, Adil E.; Szarka, Lawrence A.; Papathanasopoulos, Athanasios; Burton, Duane D.; Eckert, Deborah J.; Zinsmeister, Alan R.
2009-01-01
Lubiprostone, a bicyclic fatty acid chloride channel activator, is efficacious in treatment of chronic constipation and constipation-predominant irritable bowel syndrome. The study aim was to compare effects of lubiprostone and placebo on colonic sensory and motor functions in humans. In double-blind, randomized fashion, 60 healthy adults received three oral doses of placebo or 24 μg lubiprostone per day in a parallel-group, placebo-controlled trial. A barostat-manometry tube was placed in the left colon by flexible sigmoidoscopy and fluoroscopy. We measured treatment effects on colonic sensation and motility with validated methods, with the following end points: colonic compliance, fasting and postprandial tone and motility indexes, pain thresholds, and sensory ratings to distensions. Among participants receiving lubiprostone or placebo, 26 of 30 and 28 of 30, respectively, completed the study. There were no overall effects of lubiprostone on compliance, fasting tone, motility indexes, or sensation. However, there was a treatment-by-sex interaction effect for compliance (P = 0.02), with lubiprostone inducing decreased fasting compliance in women (P = 0.06) and an overall decreased colonic tone contraction after a standard meal relative to fasting tone (P = 0.014), with greater effect in women (P < 0.01). Numerical differences of first sensation and pain thresholds (P = 0.11 in women) in the two groups were not significant. We concluded that oral lubiprostone 24 μg does not increase colonic motor function. The findings of decreased colonic compliance and decreased postprandial colonic tone in women suggest that motor effects are unlikely to cause accelerated colonic transit with lubiprostone, although they may facilitate laxation. Effects of lubiprostone on sensitivity deserve further study. PMID:19033530
Fairbrother, S E; Smith, J E; Borman, R A; Cox, H M
2011-08-01
Prostaglandin E(2) (PGE(2) ) is an inflammatory mediator implicated in several gastrointestinal pathologies that affect normal intestinal transit. The aim was to establish the contribution of the four EP receptor types (EP(1-4) ), in human colon, that mediate PGE(2) -induced longitudinal smooth muscle contraction. Changes in isometric muscle tension of human colon, mouse colon and mouse ileum were measured in organ baths in response to receptor-specific agonists and antagonists. In addition, lidocaine was used to block neurogenic activity to investigate whether EP receptors were pre- or post-junctional. PGE(2) contracted longitudinal muscle from human and mouse colon and mouse ileum. These contractions were inhibited by the EP(1) receptor antagonist, EP(1) A in human colon, whereas a combination of EP(1) A and the EP(3) antagonist, L798106 inhibited agonist responses in both mouse preparations. The EP(3) agonist, sulprostone also increased muscle tension in both mouse tissues, and these responses were inhibited by lidocaine in the colon but not in the ileum. Although PGE(2) consistently contracted all three muscle preparations, butaprost decreased tension by activating smooth muscle EP(2) receptors in both colonic tissues. Alternatively, in mouse ileum, butaprost responses were lidocaine-sensitive, suggesting that it was activating prejunctional EP(2) receptors on inhibitory motor neurons. Conversely, EP(4) receptors were not functional in all the intestinal muscle preparations tested. PGE(2) -induced contraction of longitudinal smooth muscle is mediated by EP(1) receptors in human colon and by a combination of EP(1) and EP(3) receptors in mouse intestine, whereas EP(2) receptors modulate relaxation in all three preparations. © 2011 Blackwell Publishing Ltd.
Valverde-Barrantes, Oscar J.; Horning, Amber L.; Smemo, Kurt A.; ...
2016-02-10
In this study, there is little quantitative information about the relationship between root traits and the extent of arbuscular mycorrhizal fungi (AMF) colonization. We expected that ancestral species with thick roots will maximize AMF habitat by maintaining similar root traits across root orders (i.e., high root trait integration), whereas more derived species are expected to display a sharp transition from acquisition to structural roots. Moreover, we hypothesized that interspecific morphological differences rather than soil conditions will be the main driver of AMF colonization We analyzed 14 root morphological and chemical traits and AMF colonization rates for the first three rootmore » orders of 34 temperate tree species grown in two common gardens. We also collected associated soil to measure the effect of soil conditions on AMF colonization Results Thick-root magnoliids showed less variation in root traits along root orders than more-derived angiosperm groups. Variation in stele:root diameter ratio was the best indicator of AMF colonization within and across root orders. Root functional traits rather than soil conditions largely explained the variation in AMF colonization among species. In conclusion, not only the traits of first order but the entire structuring of the root system varied among plant lineages, suggesting alternative evolutionary strategies of resource acquisition. Understanding evolutionary pathways in below ground organs could open new avenues to understand tree species influence on soil carbon and nutrient cycling.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Valverde-Barrantes, Oscar J.; Horning, Amber L.; Smemo, Kurt A.
In this study, there is little quantitative information about the relationship between root traits and the extent of arbuscular mycorrhizal fungi (AMF) colonization. We expected that ancestral species with thick roots will maximize AMF habitat by maintaining similar root traits across root orders (i.e., high root trait integration), whereas more derived species are expected to display a sharp transition from acquisition to structural roots. Moreover, we hypothesized that interspecific morphological differences rather than soil conditions will be the main driver of AMF colonization We analyzed 14 root morphological and chemical traits and AMF colonization rates for the first three rootmore » orders of 34 temperate tree species grown in two common gardens. We also collected associated soil to measure the effect of soil conditions on AMF colonization Results Thick-root magnoliids showed less variation in root traits along root orders than more-derived angiosperm groups. Variation in stele:root diameter ratio was the best indicator of AMF colonization within and across root orders. Root functional traits rather than soil conditions largely explained the variation in AMF colonization among species. In conclusion, not only the traits of first order but the entire structuring of the root system varied among plant lineages, suggesting alternative evolutionary strategies of resource acquisition. Understanding evolutionary pathways in below ground organs could open new avenues to understand tree species influence on soil carbon and nutrient cycling.« less
Barbour, Michele E; Maddocks, Sarah E; Grady, Helena J; Roper, James A; Bass, Mark D; Collins, Andrew M; Dommett, Rachel M; Saunders, Margaret
2016-08-01
In this study, chlorhexidine hexametaphosphate (CHX-HMP) is investigated as a persistent antimicrobial coating for wound care materials. CHX-HMP was used as a wound care material coating and compared with chlorhexidine digluconate materials with respect to antimicrobial efficacy, toxicity and wound closure. Antimicrobial efficacy at day 1, 3 and 7 was observed with experimental and commercial materials. CHX-HMP coated materials had less toxic effect on human placental cells than commercial chlorhexidine dressings. CHX-HMP in pluronic gel did not delay healing but reduced wound colonization by E. faecalis. CHX-HMP could become a useful component of wound care materials with sustained antimicrobial efficacy, lower toxicity than chlorhexidine digluconate materials, and reduction in wound colonization without affecting closure.
King, Sebastian K; Catto-Smith, Anthony G; Stanton, Michael P; Sutcliffe, Jonathan R; Simpson, Dianne; Cook, Ian; Dinning, Phil; Hutson, John M; Southwell, Bridget R
2008-08-01
The physiological basis of slow transit constipation (STC) in children remains poorly understood. We wished to examine pan-colonic motility in a group of children with severe chronic constipation refractory to conservative therapy. We performed 24 h pan-colonic manometry in 18 children (13 boys, 11.6 +/- 0.9 yr, range 6.6-18.7 yr) with scintigraphically proven STC. A water-perfused, balloon tipped, 8-channel, silicone catheter with a 7.5 cm intersidehole distance was introduced through a previously formed appendicostomy. Comparison data were obtained from nasocolonic motility studies in 16 healthy young adult controls and per-appendicostomy motility studies in eight constipated children with anorectal retention and/or normal transit on scintigraphy (non-STC). Antegrade propagating sequences (PS) were significantly less frequent (P < 0.01) in subjects with STC (29 +/- 4 per 24 h) compared to adult (53 +/- 4 per 24 h) and non-STC (70 +/- 14 per 24 h) subjects. High amplitude propagating sequences (HAPS) were of a normal frequency in STC subjects. Retrograde propagating sequences were significantly more frequent (P < 0.05) in non-STC subjects compared to STC and adult subjects. High amplitude retrograde propagating sequences were only identified in the STC and non-STC pediatric groups. The normal increase in motility index associated with waking and ingestion of a meal was absent in STC subjects. Prolonged pancolonic manometry in children with STC showed significant impairment in antegrade propagating motor activity and failure to respond to normal physiological stimuli. Despite this, HAPS occurred with normal frequency. These findings suggest significant clinical differences between STC in children and adults.
Rhee, P L; Choi, M S; Kim, Y H; Son, H J; Kim, J J; Koh, K C; Paik, S W; Rhee, J C; Choi, K W
2000-10-01
Biofeedback is an effective therapy for a majority of patients with anismus. However, a significant proportion of patients still failed to respond to biofeedback, and little has been known about the factors that predict response to biofeedback. We evaluated the factors associated with poor response to biofeedback. Biofeedback therapy was offered to 45 patients with anismus with decreased bowel frequency (less than three times per week) and normal colonic transit time. Any differences in demographics, symptoms, and parameters of anorectal physiologic tests were sought between responders (in whom bowel frequency increased up to three times or more per week after biofeedback) and nonresponders (in whom bowel frequency remained less than three times per week). Thirty-one patients (68.9 percent) responded to biofeedback and 14 patients (31.1 percent) did not. Anal canal length was longer in nonresponders than in responders (4.53 +/- 0.5 vs. 4.08 +/- 0.56 cm; P = 0.02), and rectal maximum tolerable volume was larger in nonresponders than in responders. (361 +/- 87 vs. 302 +/- 69 ml; P = 0.02). Anal canal length and rectal maximum tolerable volume showed significant differences between responders and nonresponders on multivariate analysis (P = 0.027 and P = 0.034, respectively). This study showed that a long anal canal and increased rectal maximum tolerable volume are associated with poor short-term response to biofeedback for patients with anismus with decreased bowel frequency and normal colonic transit time.
The role of mast cell stabilization in treatment of postoperative ileus: a pilot study.
The, Frans O; Buist, Marrije R; Lei, Aaltje; Bennink, Roelof J; Hofland, Jan; van den Wijngaard, René M; de Jonge, Wouter J; Boeckxstaens, Guy E
2009-09-01
Although postoperative ileus (POI) is considered multifactorial, intestinal inflammation resulting from manipulation-induced mast cell activation is recognized as an important pathophysiological mechanism. Therefore, mast cell stabilization may represent a new therapeutic approach to shortening POI. The aim of this paper was to study the effect of ketotifen, a mast cell stabilizer, on postoperative gastrointestinal transit in patients who underwent abdominal surgery. In this pilot study, 60 patients undergoing major abdominal surgery for gynecological malignancy with standardized anesthesia were randomized to treatment with ketotifen (4 or 12 mg) or placebo. Patients were treated for 6 days, starting 3 days before surgery. Gastric emptying of liquids, selected as a primary outcome parameter, was measured 24 h after surgery using scintigraphy. Secondary end points were (scintigraphically assessed) colonic transit, represented as geometrical center of activity (segment 1(cecum) to 7(stool)) and clinical parameters. Gastric retention 1 h after liquid intake was significantly reduced by 12 mg (median 3% (1-7), P=0.01), but not by 4 mg ketotifen (18% (3-45), P=0.6) compared with placebo (16% (5-75)). Twenty-four hour colonic transit in placebo was 0.8 (0.0-1.1) vs. 1.2 (0.2-1.4) colon segments in the 12 mg ketotifen group (P=0.07). Abdominal cramps were significantly relieved in patients treated with 12 mg ketotifen, whereas other clinical parameters were not affected. Ketotifen significantly improves gastric emptying after abdominal surgery and warrants further exploration of mast cell stabilizers as putative therapy for POI.
Müller, Mattea; Canfora, Emanuel E.; Blaak, Ellen E.
2018-01-01
Gastrointestinal transit time may be an important determinant of glucose homeostasis and metabolic health through effects on nutrient absorption and microbial composition, among other mechanisms. Modulation of gastrointestinal transit may be one of the mechanisms underlying the beneficial health effects of dietary fibers. These effects include improved glucose homeostasis and a reduced risk of developing metabolic diseases such as obesity and type 2 diabetes mellitus. In this review, we first discuss the regulation of gastric emptying rate, small intestinal transit and colonic transit as well as their relation to glucose homeostasis and metabolic health. Subsequently, we briefly address the reported health effects of different dietary fibers and discuss to what extent the fiber-induced health benefits may be mediated through modulation of gastrointestinal transit. PMID:29495569
NASA Astrophysics Data System (ADS)
Joslin, R. D.
1991-04-01
The use of passive devices to obtain drag and noise reduction or transition delays in boundary layers is highly desirable. One such device that shows promise for hydrodynamic applications is the compliant coating. The present study extends the mechanical model to allow for three-dimensional waves. This study also looks at the effect of compliant walls on three-dimensional secondary instabilities. For the primary and secondary instability analysis, spectral and shooting approximations are used to obtain solutions of the governing equations and boundary conditions. The spectral approximation consists of local and global methods of solution while the shooting approach is local. The global method is used to determine the discrete spectrum of eigenvalue without any initial guess. The local method requires a sufficiently accurate initial guess to converge to the eigenvalue. Eigenvectors may be obtained with either local approach. For the initial stage of this analysis, two and three dimensional primary instabilities propagate over compliant coatings. Results over the compliant walls are compared with the rigid wall case. Three-dimensional instabilities are found to dominate transition over the compliant walls considered. However, transition delays are still obtained and compared with transition delay predictions for rigid walls. The angles of wave propagation are plotted with Reynolds number and frequency. Low frequency waves are found to be highly three-dimensional.
Belanche, Alejandro; Newbold, Charles J.; Lin, Wanchang; Rees Stevens, Pauline; Kingston-Smith, Alison H.
2017-01-01
Increasing the efficiency of utilization of fresh and preserved forage is a key target for ruminant science. Vitamin E is often used as additive to improve product quality but its impact of the rumen function is unknown. This study investigated the successional microbial colonization of ryegrass (GRA) vs. ryegrass hay (HAY) in presence of zero or 50 IU/d supplementary vitamin E, using a rumen simulation technique. A holistic approach was used to link the dynamics of feed degradation with the structure of the liquid-associated (LAB) and solid-associated bacteria (SAB). Results showed that forage colonization by SAB was a tri-phasic process highly affected by the forage conservation method: Early colonization (0–2 h after feeding) by rumen microbes was 2× faster for GRA than HAY diets and dominated by Lactobacillus and Prevotella which promoted increased levels of lactate (+56%) and ammonia (+18%). HAY diets had lower DM degradation (-72%) during this interval being Streptococcus particularly abundant. During secondary colonization (4–8 h) the SAB community increased in size and decreased in diversity as the secondary colonizers took over (Pseudobutyrivibrio) promoting the biggest differences in the metabolomics profile between diets. Secondary colonization was 3× slower for HAY vs. GRA diets, but this delay was compensated by a greater bacterial diversity (+197 OTUs) and network complexity resulting in similar feed degradations. Tertiary colonization (>8 h) consisted of a slowdown in the colonization process and simplification of the bacterial network. This slowdown was less evident for HAY diets which had higher levels of tertiary colonizers (Butyrivibrio and Ruminococcus) and may explain the higher DM degradation (+52%) during this interval. The LAB community was particularly active during the early fermentation of GRA and during the late fermentation for HAY diets indicating that the availability of nutrients in the liquid phase reflects the dynamics of feed degradation. Vitamin E supplementation had minor effects but promoted a simplification of the LAB community and a slight acceleration in the SAB colonization sequence which could explain the higher DM degradation during the secondary colonization. Our findings suggest that when possible, grass should be fed instead of hay, in order to accelerate feed utilization by rumen microbes. PMID:28824585
Effects of methanolic extract from leaves of Rubus imperialis in DSS-induced colitis in mice.
da Silva, Luisa Mota; Somensi, Lincon Bordignon; Boeing, Thaise; Barp, Cristiane; Cechinel-Filho, Valdir; Niero, Rivaldo; de Andrade, Sérgio Faloni
2016-12-01
This study investigated the effects of Rubus imperialis, a berry known as "amora-branca", in colitis dextran sulfate sodium (DSS)-induced in mice. Animals were treated orally with vehicle (water), 5-aminosalicylic acid (100 mg/kg) or methanolic extract from leaves of R. imperialis (MERI, 100 mg/kg), once a day during seven days. The disease activity index (DAI) was observed daily. Colons were collected for histological, histochemical and biochemical analysis. The administration of MERI exacerbated colitis, as indicated by DAI heightened weight loss and increased histological colonic injury. MERI also decreased the colon mucin levels and increased colonic TNF content. The colonic levels of reduced glutathione and the superoxide dismutase activity in colitic group treated with MERI were decreased. Despite the worsening of colitis, MERI not altered the intestinal transit, body weight, colon length or organs weight in normal mice. Tormentic acid (TA) and 2β,3β,19α-trihydroxyursolic acid (THA), compounds isolated from MERI, reduced the L929 cells viability. Thus, MERI may have aggravated the DSS-induced colitis through intense intestinal mucus barrier impairment, which would lead to inflammatory responses, TA and THA contribute to the intestinal damage verified suggesting caution about the use of R. imperialis preparations, particularly in inflammatory bowel diseases.
Methane-related metabolisms of deep-sea sediments captured with a colonization experiment.
NASA Astrophysics Data System (ADS)
Carr, S. A.; Wheat, C. G.; Orcutt, B.; Kopf, A.; Saffer, D. M.; Toczko, S.
2016-12-01
NanTroSEIZE is a multi-expedition project of the International Ocean Discovery Program (IODP) designed to investigate the Nankai Trough subduction zone. In 2016, a long-term borehole instrument package known as the "GeniusPlug" was collected from Hole C0010A after a six-year deployment within the sediment of a major fault zone, at a depth of 400 mbsf. This GeniusPlug included a set of osmotically-driven pumps, which continuously pumped in situ deep seated, formation water through a microbiological colonization experiment (flow-through osmo colonization system (FLOCS)). This FLOCS experiment contained cassettes of olivine, barite, and sediment collected from nearby Hole C0004D, to serve as colonization substrates. While similar FLOCS have been deployed within boreholes in the igneous oceanic crust, this FLOCS experiment represents the first to be deployed within a sedimentary environment, and thus represents the first opportunity to observe how pore water communities colonize sediment and rock substrates. Initial geochemistry results suggest that conditions within the FLOCS experiment were similar to a methane-sulfate transition zone, and initial enrichment cultures inoculated with the FLOCS substrates demonstrate methane production. Here, we will present integrated results of culturing experiments and culture-independent genomic investigations as a means to elucidate the methane-related metabolisms of these colonizing communities.
Growth control in colon epithelial cells: gadolinium enhances calcium-mediated growth regulation.
Attili, Durga; Jenkins, Brian; Aslam, Muhammad Nadeem; Dame, Michael K; Varani, James
2012-12-01
Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1-5 μM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet.
Left-colon antegrade continence enema (LACE) procedure for fecal incontinence.
Churchill, Bernard M; De Ugarte, Daniel A; Atkinson, James B
2003-12-01
Antegrade continence enemas (ACE) are an efficacious therapeutic option for patients with fecal incontinence. The authors review their institution's experience with a variation of the Monti-Malone ACE procedure using the left colon as a source of an intestinal conduit and enema reservoir. From 2000 to 2002, 18 patients with fecal incontinence or intractable constipation underwent left-colon ACE (LACE) procedure. Concomitant Mitrofanoff appendicovesicostomy was performed in 15 patients and bladder augmentation in 9. The majority of patients had neural tube defects. A segment of left colon was tubularized, tunneled into the muscular wall of the distal colon, and exteriorized through the left upper quadrant or midabdomen. Stomal catherization and enema installation were started one month postoperatively. Fifteen patients (83%) achieved fecal continence, 2 remain incontinent of stool, and 1 experienced stomal closure (mean follow-up was 24 +/- 9 months). Two patients had stomal stenosis that required revision. The mean enema volume in patient's achieving continence was 360 +/- 216 mL, and the mean transit time was 18 +/- 12 minutes. LACE is an efficacious procedure for fecal incontinence that can be performed safely at the time of major urologic reconstruction. Administration of enemas into the left colon has several physiologic advantages that result in predictable bowel evacuation.
Transition Delay in Hypersonic Boundary Layers via Optimal Perturbations
NASA Technical Reports Server (NTRS)
Paredes, Pedro; Choudhari, Meelan M.; Li, Fei
2016-01-01
The effect of nonlinear optimal streaks on disturbance growth in a Mach 6 axisymmetric flow over a 7deg half-angle cone is investigated in an e ort to expand the range of available techniques for transition control. Plane-marching parabolized stability equations are used to characterize the boundary layer instability in the presence of azimuthally periodic streaks. The streaks are observed to stabilize nominally planar Mack mode instabilities, although oblique Mack mode disturbances are destabilized. Experimentally measured transition onset in the absence of any streaks correlates with an amplification factor of N = 6 for the planar Mack modes. For high enough streak amplitudes, the transition threshold of N = 6 is not reached by the Mack mode instabilities within the length of the cone, but subharmonic first mode instabilities, which are destabilized by the presence of the streaks, reach N = 6 near the end of the cone. These results suggest a passive flow control strategy of using micro vortex generators to induce streaks that would delay transition in hypersonic boundary layers.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Burmer, G.C.; Rabinovitch, P.S.; Loeb, L.A.
1991-06-01
Sporadic colon carcinomas, carcinomas arising in chronic ulcerative colitis, and pancreatic adenocarcinomas have been analyzed for the presence of c-Ki-ras mutations by a combination of histological enrichment, cell sorting, polymerase chain reaction, and direct sequencing. Although 60% (37/61) of sporadic colon carcinomas contained mutations in codon 12, only 1 of 17 specimens of dysplasia or carcinoma from ulcerative colitis patients contained c-Ki-ras mutations, despite a high frequency of aneuploid tumors. In contrast, a higher percentage (16/20 = 80%) of pancreatic adenocarcinomas contained mutations in c-Ki-ras 2, despite a lower frequency of DNA aneuploidy in these neoplasms. Moreover, the spectrum ofmore » mutations differed between sporadic colon carcinoma, where the predominant mutation was a G to A transition, and pancreatic carcinomas, which predominantly contained G to C or T transversions. These results suggest that the etiology of ras mutations is different in these three human neoplasms.« less
[Dietary prevention and treatment of diverticular disease of the colon].
Milewska, Magdalena; Sińska, Beata; Kluciński, Andrzej
2015-04-01
Diverticular disease is more often categorized as a civilization disease that affects both women and men, especially at an old age. The pathophysiology remains complex and arises from the interaction between dietary fiber intake, bowel motility and mucosal changes in the colon. Obesity, smoking, low physical activity, low-fiber diet (poor in vegetables, fruit, whole grain products, seeds and nuts) are among factors that increase the risk for developing diverticular disease. Additionally, the colonic outpouchings may be influenced by involutional changes of the gastrointestinal tract. Therefore, the fiber rich diet (25-40 g/day) plays an important role in prevention, as well as nonpharmacological treatment of uncomplicated diverticular disease. The successful goal of the therapy can be achieved by well-balanced diet or fiber supplements intake. Research indicate the effectiveness of probiotics in dietary management during the remission process. Moreover, drinking of appropriate water amount and excluding from the diet products decreasing colonic transit time - should be also applied. © 2015 MEDPRESS.
The time-delay signature of quark-gluon plasma formation in relativistic nuclear collisions
NASA Astrophysics Data System (ADS)
Rischke, Dirk H.; Gyulassy, Miklos
1996-02-01
The hydrodynamic expansion of quark-gluon plasmas with spherical and longitudinally boost-invariant geometries is studied as a function of the initial energy density. The sensitivity of the collective flow pattern to uncertainties in the nuclear matter equation of state is explored. We concentrate on the effect of a possible finite width, ΔT ˜ 0.1 Tc, of the transition region between quark-gluon plasma and hadronic phase. Although slow deflagration solutions that act to stall the expansion do not exist for ΔT > 0.08 Tc, we find, nevertheless, that the equation of state remains sufficiently soft in the transition region to delay the propagation of ordinary rarefaction waves for a considerable time. We compute the dependence of the pion-interferometry correlation function on ΔT, since this is the most promising observable for time-delayed expansion. The signature of time delay, proposed by Pratt and Bertsch, is an enhancement of the ratio of the inverse width of the pion correlation function in out-direction to that in side-direction. One of our main results is that this generic signature of quark-gluon plasma formation is rather robust to the uncertainties in the width of the transition region. Furthermore, for longitudinal boost-invariant geometries, the signal is likely to be maximized around RHIC energies
NASA Astrophysics Data System (ADS)
Kim, Hyun-Tak; Chae, Byung-Gyu; Kim, Bong-Jun; Lee, Yong-Wook; Yun, Sun-Jin; Kang, Kwang-Yong
2006-03-01
An abrupt first-order metal-insulator transition (MIT) is observed during the application of a switching pulse voltage to VO2-based two-terminal devices. When the abrupt MIT occurs, the structural phase transition (SPT) is investigated by a micro- Raman spectroscopy and a micro-XRD. The result shows that the MIT is not accompanied with the structural phase transition (SPT); the abrupt MIT is prior to the SPT. Moreover, any switching pulse over a threshold voltage of 7.1 V for the MIT enabled the device material to transform efficiently from an insulator to a metal. The measured delay time from the source switching pulse to an induced MIT pulse is an order of 20 nsec which is much less than a delay time of about one msec deduced by thermal model. This indicates that the first-order MIT does not occur due to thermal. We think this MIT is the Mott transition. (Reference: New J. Phys. 6 (1994) 52 (www.njp.org), Appl. Phys. Lett. 86 (2005) 242101, Physica B 369 (2005. December) xxxx)
Gao, Lijun; Jiang, Xiaoxiao; Wang, Dandan
2016-03-01
This paper investigates the problem of robust finite time H∞ sliding mode control for a class of Markovian switching systems. The system is subjected to the mode-dependent time-varying delay, partly unknown transition rate and unmeasurable state. The main difficulty is that, a sliding mode surface cannot be designed based on the unknown transition rate and unmeasurable state directly. To overcome this obstacle, the set of modes is firstly divided into two subsets standing for known transition rate subset and unknown one, based on which a state observer is established. A component robust finite-time sliding mode controller is also designed to cope with the effect of partially unknown transition rate. It is illustrated that the reachability, finite-time stability, finite-time boundedness, finite-time H∞ state feedback stabilization of sliding mode dynamics can be ensured despite the unknown transition rate. Finally, the simulation results verify the effectiveness of robust finite time control problem. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.
The best of both worlds? A review of delayed selfing in flowering plants.
Goodwillie, Carol; Weber, Jennifer J
2018-04-01
In a seminal body of theory, Lloyd showed that the fitness consequences of selfing will depend on its timing in anthesis. Selfing that occurs after opportunities for outcrossing or pollen dispersal can provide reproductive assurance when pollinators are limited and is expected to incur little cost, even when inbreeding depression is high. As a result, delayed selfing is often interpreted as a "best-of-both-worlds" mating system that combines the advantages of selfing and outcrossing. We surveyed 65 empirical studies of delayed selfing, recording floral mechanisms and examining information on inbreeding depression, autofertility, and other parameters to test the support for delayed selfing as a best-of-both-worlds strategy. Phylogenetic distribution of the diverse floral mechanisms suggests that some basic floral structures may predispose plant taxa to evolve delayed selfing. Delayed selfing appears to serve as a best-of-both-worlds strategy in some but not all species. While the capacity for autonomous selfing is often high, it is lower, in some cases, than in related species with earlier modes of selfing. In other delayed-selfers, low inbreeding depression and reduced investment in corollas and pollen suggest limited benefits from outcrossing. Despite a growing literature on the subject, experimental evidence for delayed selfing is limited and major gaps in knowledge remain, particularly with respect to the stability of delayed selfing and the conditions that may favor transitions between delayed and earlier selfing. Finally, we suggest a potential role of delayed selfing in facilitating transitions from self-incompatibility to selfing. © 2018 The Authors. American Journal of Botany is published by Wiley Periodicals, Inc. on behalf of the Botanical Society of America.
Transition Control with Dielectric Barrier Discharge Plasmas
2010-10-01
AFRL-AFOSR-UK-TR-2011-0007 Transition Control with Dielectric Barrier Discharge Plasmas Cameron Tropea Technische...Discharge Plasmas 5a. CONTRACT NUMBER FA8655-08-1-3032 5b. GRANT NUMBER Grant 08-3032 5c. PROGRAM ELEMENT NUMBER 61102F 6. AUTHOR(S...is to control natural boundary-layer transition through the use of plasma actuators. Transition delay or even suppression has its merits not only in
Knoblochová, Tereza; Kohout, Petr; Püschel, David; Doubková, Pavla; Frouz, Jan; Cajthaml, Tomáš; Kukla, Jaroslav; Vosátka, Miroslav; Rydlová, Jana
2017-11-01
The arbuscular mycorrhizal (AM) grass Calamagrostis epigejos and predominantly ectomycorrhizal (EcM) tree Salix caprea co-occur at post-mining sites spontaneously colonized by vegetation. During succession, AM herbaceous vegetation is replaced by predominantly EcM woody species. To better understand the interaction of AM and EcM plants during vegetation transition, we studied the reciprocal effects of these species' coexistence on their root-associated fungi (RAF). We collected root and soil samples from three different microenvironments: stand of C. epigejos, under S. caprea canopy, and contact zone where roots of the two species interacted. RAF communities and mycorrhizal colonization were determined in sampled roots, and the soil was tested for EcM and AM inoculation potentials. Although the microenvironment significantly affected composition of the RAF communities in both plant species, the effect was greater in the case of C. epigejos RAF communities than in that of S. caprea RAF communities. The presence of S. caprea also significantly decreased AM fungal abundance in soil as well as AM colonization and richness of AM fungi in C. epigejos roots. Changes observed in the abundance and community composition of AM fungi might constitute an important factor in transition from AM-dominated to EcM-dominated vegetation during succession.
Zelmer, Andrea; Bowen, Mark; Jokilammi, Anne; Finne, Jukka; Luzio, J Paul; Taylor, Peter W
2008-08-01
Escherichia coli K1 isolates synthesize a polysialic acid (polySia) capsule, are components of the adult gastrointestinal microbiota and may cause lethal bacteraemia and meningitis if acquired maternally by newborn infants. We used a neonatal rat pup K1 infection model to establish that prompt administration of a selective capsule depolymerase reverses the bacteraemic state and prevents death of almost all pups. In untreated animals, bacteria colonize the gastrointestinal tract and gain entry to the blood compartment, where they express the non-O-acetylated form of polySia. The bacteria invade the major organs of the host; histological and histochemical analysis of brain sections revealed that at least some bacteria enter the central nervous system through the blood-cerebrospinal fluid barrier at the choroid plexus prior to colonization of the meninges. Once in this location, they cease expression of polySia. The unexpected abrogation of polySia, a factor associated with the pathogenesis of meningitis and essential for transit through the blood, suggests that the neuropathogen dispenses with its protective capsule once it has colonized protected niches. Thus, systemic infections due to encapsulated pathogens may be resolved by capsule depolymerization only if the enzyme modifies the bacteria whilst they are in the blood compartment.
Pei, Yanlong; Parreira, Valeria R.; Roland, Kenneth L.; Curtiss, Roy; Prescott, John F.
2014-01-01
Salmonella hold considerable promise as vaccine delivery vectors for heterologous antigens in chickens. Such vaccines have the potential additional benefit of also controlling Salmonella infection in immunized birds. As a way of selecting attenuated strains with optimal immunogenic potential as antigen delivery vectors, this study screened 20 novel Salmonella Typhimurium vaccine strains, differing in mutations associated with delayed antigen synthesis and delayed attenuation, for their efficacy in controlling colonization by virulent Salmonella Typhimurium, as well as for their persistence in the intestine and the spleen. Marked differences were observed between strains in these characteristics, which provide the basis for selection for further study as vaccine vectors. PMID:24396177
Pei, Yanlong; Parreira, Valeria R; Roland, Kenneth L; Curtiss, Roy; Prescott, John F
2014-01-01
Salmonella hold considerable promise as vaccine delivery vectors for heterologous antigens in chickens. Such vaccines have the potential additional benefit of also controlling Salmonella infection in immunized birds. As a way of selecting attenuated strains with optimal immunogenic potential as antigen delivery vectors, this study screened 20 novel Salmonella Typhimurium vaccine strains, differing in mutations associated with delayed antigen synthesis and delayed attenuation, for their efficacy in controlling colonization by virulent Salmonella Typhimurium, as well as for their persistence in the intestine and the spleen. Marked differences were observed between strains in these characteristics, which provide the basis for selection for further study as vaccine vectors.
Mutual reinforcement of pathophysiological host-microbe interactions in intestinal stasis models
DOE Office of Scientific and Technical Information (OSTI.GOV)
Touw, Ketrija; Ringus, Daina L.; Hubert, Nathaniel
Chronic diseases arise when there is mutual reinforcement of pathophysiological processes that cause an aberrant steady state. Such a sequence of events may underlie chronic constipation, which has been associated with dysbiosis of the gut. In this study we hypothesized that assemblage of microbial communities, directed by slow gastrointestinal transit, affects host function in a way that reinforces constipation and further maintains selection on microbial communities. In our study, we used two models – an opioid-induced consti- pation model in mice, and a humanized mouse model where germ-free mice were colonized with stool from a patient with constipation-predominant irritable bowelmore » syndrome (IBS-C) in humans. We examined the impact of pharmacologically (loperamide)-induced constipation (PIC) and IBS-C on the structural and functional profile of the gut microbiota. Germ-free (GF) mice were colonized with microbiota from PIC donor mice and IBS-C patients to determine how the microbiota affects the host. PIC and IBS-C promoted changes in the gut microbiota, characterized by increased relative abundance of Bacteroides ovatus and Parabacteroides distasonis in both models. PIC mice exhibited decreased luminal concentrations of butyrate in the cecum and altered metabolic profiles of the gut microbiota. Colonization of GF mice with PIC-associated mice cecal or human IBS-C fecal microbiota significantly increased GI transit time when compared to control microbiota recipients. IBS-C-associated gut microbiota also impacted colonic contractile properties. Lastly, our findings support the concept that constipation is characterized by dis- ease-associated steady states caused by reinforcement of pathophysiological factors in host-microbe interactions.« less
Mutual reinforcement of pathophysiological host-microbe interactions in intestinal stasis models
Touw, Ketrija; Ringus, Daina L.; Hubert, Nathaniel; ...
2017-03-20
Chronic diseases arise when there is mutual reinforcement of pathophysiological processes that cause an aberrant steady state. Such a sequence of events may underlie chronic constipation, which has been associated with dysbiosis of the gut. In this study we hypothesized that assemblage of microbial communities, directed by slow gastrointestinal transit, affects host function in a way that reinforces constipation and further maintains selection on microbial communities. In our study, we used two models – an opioid-induced consti- pation model in mice, and a humanized mouse model where germ-free mice were colonized with stool from a patient with constipation-predominant irritable bowelmore » syndrome (IBS-C) in humans. We examined the impact of pharmacologically (loperamide)-induced constipation (PIC) and IBS-C on the structural and functional profile of the gut microbiota. Germ-free (GF) mice were colonized with microbiota from PIC donor mice and IBS-C patients to determine how the microbiota affects the host. PIC and IBS-C promoted changes in the gut microbiota, characterized by increased relative abundance of Bacteroides ovatus and Parabacteroides distasonis in both models. PIC mice exhibited decreased luminal concentrations of butyrate in the cecum and altered metabolic profiles of the gut microbiota. Colonization of GF mice with PIC-associated mice cecal or human IBS-C fecal microbiota significantly increased GI transit time when compared to control microbiota recipients. IBS-C-associated gut microbiota also impacted colonic contractile properties. Lastly, our findings support the concept that constipation is characterized by dis- ease-associated steady states caused by reinforcement of pathophysiological factors in host-microbe interactions.« less
Cappello, Carmelina; Tremolaterra, Fabrizio; Pascariello, Annalisa; Ciacci, Carolina; Iovino, Paola
2013-03-01
The aim of this study is to test in a double-blinded, randomised placebo-controlled study the effects of a commercially available multi-strain symbiotic mixture on symptoms, colonic transit and quality of life in irritable bowel syndrome (IBS) patients who meet Rome III criteria. There is only one other double-blinded RCT on a single-strain symbiotic mixture in IBS. This is a double-blinded, randomised placebo-controlled study of a symbiotic mixture (Probinul, 5 g bid) over 4 weeks after 2 weeks of run-in. The primary endpoints were global satisfactory relief of abdominal flatulence and bloating. Responders were patients who reported at least 50 % of the weeks of treatment with global satisfactory relief. The secondary endpoints were change in abdominal bloating, flatulence, pain and urgency by a 100-mm visual analog scale, stool frequency and bowel functions on validated adjectival scales (Bristol Scale and sense of incomplete evacuation). Pre- and post-treatment colonic transit time (Metcalf) and quality of life (SF-36) were assessed. Sixty-four IBS patients (symbiotic n = 32, 64 % females, mean age 38.7 ± 12.6 years) were studied. This symbiotic mixture reduced flatulence over a 4-week period of treatment (repeated-measures analysis of covariance, p < 0.05). Proportions of responders were not significantly different between groups. At the end of the treatment, a longer rectosigmoid transit time and a significant improvement in most SF-36 scores were observed in the symbiotic group. This symbiotic mixture has shown a beneficial effect in decreasing the severity of flatulence in IBS patients, a lack of adverse events and a good side-effect profile; however, it failed to achieve an improvement in global satisfactory relief of abdominal flatulence and bloating. Further studies are warranted.
Yu, Xiaochun; Cui, Changxiang; Yang, Zhaokun; Shi, Hong; Jing, Xianghong; Zhu, Bing
2016-01-01
Acupuncture at homotopic acupoints or heterotopic acupoints is known to either inhibit or facilitate gastrointestinal motility, depending on the acupoint location. However, little effort has been made to investigate the roles of specific receptors (such as adrenergic and muscarinic acetylcholine receptors) in mediating the effects of acupuncture at heterotopic and homotopic acupoints. Different adrenergic receptor subtypes or cholinergic receptor subtypes are predominantly expressed in various sections of the gut, resulting in variations between the effects of acupuncture at heterotopic or homotopic acupoints on gastrointestinal motility. Here, we investigated the role of β1/β2 receptors and M2/M3 receptors in gastrointestinal motility regulated by acupuncture at ST37, a heterotopic acupoint, and ST25, a homotopic acupoint, by simultaneously recording intraluminal pressures in the distal colon and stomach or jejunum and examining fecal phenol red excretion in β1/2 receptor-knockout mice and M2/3 receptor-knockout mice. We found that knockout of the M2/3 receptor significantly inhibited ST37 acupuncture-induced enhancement of gastric motility, jejunal motility, and colonic motility. Additionally, knocking out of the β1/2 receptor significantly diminished the ST25 acupuncture-induced inhibition of gastric motility and jejunal motility without significantly altering the enhancement of colonic motility induced by acupuncture at ST25. Acupuncture at ST37 significantly accelerated gastrointestinal transition in β1/2 receptor-knockout mice and their wild-type littermates. However, this acceleration of gastrointestinal transition was markedly diminished in M2/3 receptor-knockout mice relative to their wild-type littermates. Acupuncture at ST25 significantly increased gastrointestinal transition in β1/2 receptor-knockout mice and significantly decreased gastrointestinal transition in M2/3 receptor-knockout mice without altering gastrointestinal transition in wild-type littermates of either. Our study revealed that M2/3 receptors are required for the gastrointestinal motility associated with whole gastrointestinal transition enhanced by acupuncture at heterotopic acupoints, whereas β1/2 receptors are required for the same gastrointestinal motility processes inhibited by acupuncture at homotopic acupoints. Therefore, our findings reveal important biological mechanisms underlying acupuncture treatment of disorders involving gastrointestinal motility dysfunction. PMID:27978539
Asp, Michelle L; Tian, Min; Kliewer, Kara L; Belury, Martha A
2011-12-01
Cachexia is characterized by severe weight loss, including adipose and muscle wasting, and occurs in a large percentage of cancer patients. Insulin resistance contributes to dysregulated metabolism in cachexia and occurs prior to weight loss in mice with colon-26 tumor-induced cachexia. Therefore, we hypothesized that the insulin sensitizer, rosiglitazone, would attenuate the loss of adipose and muscle to result in improved outcomes for mice with late-stage cachexia. Male CD2F1 mice were inoculated with colon-26 adenocarcinoma cells or vehicle. Treatments included vehicle, rosiglitazone (10 mg/kg body weight/day) or rosiglitazone plus pair-feeding to food intake of vehicle-treated mice with tumors. Rosiglitazone delayed weight loss onset by 2 d over the 16 d duration of this aggressive tumor model. This finding was associated, in part, with increased food intake. In addition, adipose mass, adipocyte cross-sectional area and inflammation were improved with rosiglitazone. However, at the time of necropsy 16 d after tumor inoculation rosiglitazone had no effect on retention of muscle mass, strength or proteolysis in late-stage cachexia. We did not measure stamina or endurance in this study. In early-stage cachexia, rosiglitazone normalized PDK4 and PPAR-delta mRNA in quadriceps muscle and rescued the decrease in insulin-stimulated glucose disappearance in mice with tumors. Rosiglitazone may delay weight loss onset by decreasing tumor-induced markers of metabolic change in early-stage cachexia. These changes predict for modest improvement in adipose, but no improvement in muscle strength in late-stage cachexia.
Asp, Michelle L.; Tian, Min; Kliewer, Kara L.
2011-01-01
Cachexia is characterized by severe weight loss, including adipose and muscle wasting, and occurs in a large percentage of cancer patients. Insulin resistance contributes to dysregulated metabolism in cachexia and occurs prior to weight loss in mice with colon-26 tumor-induced cachexia. Therefore, we hypothesized that the insulin sensitizer, rosiglitazone, would attenuate the loss of adipose and muscle to result in improved outcomes for mice with late-stage cachexia. Male CD2F1 mice were inoculated with colon-26 adenocarcinoma cells or vehicle. Treatments included vehicle, rosiglitazone (10 mg/kg body weight/day) or rosiglitazone plus pair-feeding to food intake of vehicle-treated mice with tumors. Rosiglitazone delayed weight loss onset by 2 d over the 16 d duration of this aggressive tumor model. This finding was associated, in part, with increased food intake. In addition, adipose mass, adipocyte cross-sectional area and inflammation were improved with rosiglitazone. However, at the time of necropsy 16 d after tumor inoculation rosiglitazone had no effect on retention of muscle mass, strength or proteolysis in late-stage cachexia. We did not measure stamina or endurance in this study. In early-stage cachexia, rosiglitazone normalized PDK4 and PPAR-delta mRNA in quadriceps muscle and rescued the decrease in insulin-stimulated glucose disappearance in mice with tumors. Rosiglitazone may delay weight loss onset by decreasing tumor-induced markers of metabolic change in early-stage cachexia. These changes predict for modest improvement in adipose, but no improvement in muscle strength in late-stage cachexia. PMID:22104958
Anismus: a marker of multi-site functional disorders?
Bouchoucha, Michel; Devroede, Ghislain; Arsac, Michel
2004-07-01
This study was undertaken to assess the clinical significance of anismus in patients who complain of constipation. Thirty control subjects and 93 consecutive patients complaining of functional constipation took part in the study. Colonic transit time study and anorectal manometry were performed. Questions about depression and urinary and sexual diseases were added to a questionnaire based on the Rome II criteria, and visual analog scales about four items (constipation, diarrhoea, abdominal bloating and abdominal pain). Constipated patients have lower threshold sensation volume, lower constant sensation volume, and lower maximum tolerable volume than controls. Thirty-seven patients (40%) were found to have anismus, based on anorectal manometry. No significant difference was found between constipated patients with anismus and constipated patients without anismus, using anorectal manometry. Constipated patients had longer colorectal transit time than controls, but neither total nor segmental colonic transit time was correlated with the presence or absence of anismus. In patients with anismus, a higher frequency of oesophageal symptoms, dysmotility-like dyspepsia, aerophagia, functional bowel disorders, functional abdominal pain, soiling, and dyschezia was found. In addition, a higher frequency of urinary complaints, sexual complaints, and depression was found. Anismus was associated with increased awareness of constipation, abdominal bloating, and abdominal pain, but not with diarrhoea.
Attosecond delay in the molecular photoionization of asymmetric molecules.
Chacón, Alexis; Ruiz, Camilo
2018-02-19
We report theoretical calculations of the delay in photoemission from CO with particular emphasis on the role of the ultrafast electronic bound dynamics. We study the delays in photoionization in the HOMO and HOMO-1 orbitals of the CO molecule by looking into the stereo Wigner time delay technique. That compares the delay in photoemission from electrons emitted to the left and right to extract structural and dynamical information of the ionization process. For this we apply two techniques: The attosecond streak camera and the time of flight technique. Although they should provide the same results we have found large discrepancies of up to 36 in the case of HOMO, while for the HOMO-1 we obtain the same results with the two techniques. We have found that the large time delays observed in the HOMO orbital with the streaking technique are a consequence of the resonant transition triggered by the streaking field. This resonant transition produces a bound electron wavepacket that modifies the measurements of delay in photoionization. As a result of this observation, our technique allows us to reconstruct the bound wavepacket dynamics induced by the streaking field. By measuring the expected value of the electron momentum along the polarization direction after the streaking field has finished, we can recover the relative phase between the complex amplitudes of the HOMO and LUMO orbitals. These theoretical calculations pave the way for the measurement of ultrafast bound-bound electron transitionsand its crucial role for the delay in photoemission observation.
Non-Gaussian noise-weakened stability in a foraging colony system with time delay
NASA Astrophysics Data System (ADS)
Dong, Xiaohui; Zeng, Chunhua; Yang, Fengzao; Guan, Lin; Xie, Qingshuang; Duan, Weilong
2018-02-01
In this paper, the dynamical properties in a foraging colony system with time delay and non-Gaussian noise were investigated. Using delay Fokker-Planck approach, the stationary probability distribution (SPD), the associated relaxation time (ART) and normalization correlation function (NCF) are obtained, respectively. The results show that: (i) the time delay and non-Gaussian noise can induce transition from a single peak to double peaks in the SPD, i.e., a type of bistability occurring in a foraging colony system where time delay and non-Gaussian noise not only cause transitions between stable states, but also construct the states themselves. Numerical simulations are presented and are in good agreement with the approximate theoretical results; (ii) there exists a maximum in the ART as a function of the noise intensity, this maximum for ART is identified as the characteristic of the non-Gaussian noise-weakened stability of the foraging colonies in the steady state; (iii) the ART as a function of the noise correlation time exhibits a maximum and a minimum, where the minimum for ART is identified as the signature of the non-Gaussian noise-enhanced stability of the foraging colonies; and (iv) the time delay can enhance the stability of the foraging colonies in the steady state, while the departure from Gaussian noise can weaken it, namely, the time delay and departure from Gaussian noise play opposite roles in ART or NCF.
Kim, Eun-Kyung; Cho, Jae Hee; Kim, EuiJoo; Kim, Yoon Jae
2017-01-01
The regulation of reactive oxygen species (ROS) exists as a therapeutic target for cancer treatments. Previous studies have shown that ursodeoxycholic acid (UDCA) suppresses the proliferation of colon cancer cells. The aim of this study was to evaluate the effect of UDCA upon the proliferation of colon cancer cells as a direct result of the regulation of ROS. Colon cancer cell lines (HT29 and HCT116) were treated with UDCA. The total number of cells and the number of dead cells were determined using cell counters. A fluorescein isothiocyanate-bromodeoxyuridine flow kit was used to analyze cell cycle variations. Upon exposure to UDCA, the protein levels of p27, p21, CDK2, CDK4 and CDK6 were determined using western blotting, and qRT-PCR was used to determine levels of mRNA. We preformed dichlorofluorescindiacetate (DCF-DA) staining to detect alteration of intracellular ROS using fluorescence activated cell sorting (FACS). Colon cancer stem-like cell lines were generated by tumorsphere culture and treated with UDCA for seven days. The total number of tumorspheres was determined using microscopy. We found that UDCA reduced the total number of colon cancer cells, but did not increase the number of dead cells. UDCA inhibited the G1/S and G2/M transition phases in colon cancer cells. UDCA induced expression of cell cycle inhibitors such as p27 and p21. However, it was determined that UDCA suppressed levels of CDK2, CDK4, and CDK6. UDCA regulated intracellular ROS generation in colon cancer cells, and induced activation of Erk1/2. Finally, UDCA inhibited formation of colon cancer stem-like cells. Our results indicate that UDCA suppresses proliferation through regulation of oxidative stress in colon cancer cells, as well as colon cancer stem-like cells.
Kim, EuiJoo
2017-01-01
Introduction The regulation of reactive oxygen species (ROS) exists as a therapeutic target for cancer treatments. Previous studies have shown that ursodeoxycholic acid (UDCA) suppresses the proliferation of colon cancer cells. The aim of this study was to evaluate the effect of UDCA upon the proliferation of colon cancer cells as a direct result of the regulation of ROS. Method Colon cancer cell lines (HT29 and HCT116) were treated with UDCA. The total number of cells and the number of dead cells were determined using cell counters. A fluorescein isothiocyanate-bromodeoxyuridine flow kit was used to analyze cell cycle variations. Upon exposure to UDCA, the protein levels of p27, p21, CDK2, CDK4 and CDK6 were determined using western blotting, and qRT-PCR was used to determine levels of mRNA. We preformed dichlorofluorescindiacetate (DCF-DA) staining to detect alteration of intracellular ROS using fluorescence activated cell sorting (FACS). Colon cancer stem-like cell lines were generated by tumorsphere culture and treated with UDCA for seven days. The total number of tumorspheres was determined using microscopy. Results We found that UDCA reduced the total number of colon cancer cells, but did not increase the number of dead cells. UDCA inhibited the G1/S and G2/M transition phases in colon cancer cells. UDCA induced expression of cell cycle inhibitors such as p27 and p21. However, it was determined that UDCA suppressed levels of CDK2, CDK4, and CDK6. UDCA regulated intracellular ROS generation in colon cancer cells, and induced activation of Erk1/2. Finally, UDCA inhibited formation of colon cancer stem-like cells. Conclusion Our results indicate that UDCA suppresses proliferation through regulation of oxidative stress in colon cancer cells, as well as colon cancer stem-like cells. PMID:28708871
Mărginean, Cristina Oana; Mărginean, Maria Oana; Simu, Iunius; Horvath, Adrienne; Meliţ, Lorena Elena
2016-10-01
Adenomas of the colon are usually benign tumors which carry a tendency for malignancy. These tumors can be villous, tubular, tubulovillous, or sessile serrated. Those with adenomatous structure can develop malignant characteristics in 1.5% to 9.4% of cases. We present a case report of a 16-year-old female adolescent with an adenoma of the descending colon. History revealed prolonged diarrheic syndrome for the past 6 months, repeated headache, and a weight loss of ∼5 kg in the past month. One week before the admission, the patient presented an episode of inferior digestive hemorrhage. On admission laboratory tests revealed iron deficiency anemia, and a mildly increased erythrocyte sedimentation rate. The abdominal ultrasound revealed an inhomogeneous mass of the descending colon and 2 hyperechoic lesions in the liver. The colonoscopy showed a tumor of the descending colon, a tubular adenoma according to the pathological examination. Additionally, we noted an atypical presentation of the tumor and the signs of mild dysplasia identified at the pathological examination. Weight loss, bowel transit alterations, loss of appetite, and inferior hemorrhage in an adolescent can be symptoms of a benign or malignant tumor of the colon.
NASA Astrophysics Data System (ADS)
Wang, Kang-Kang; Zong, De-Cai; Wang, Ya-Jun; Li, Sheng-Hong
2016-05-01
In this paper, the transition between the stable state of a big density and the extinction state and stochastic resonance (SR) for a time-delayed metapopulation system disturbed by colored cross-correlated noises are investigated. By applying the fast descent method, the small time-delay approximation and McNamara and Wiesenfeld's SR theory, we investigate the impacts of time-delay, the multiplicative, additive noises and colored cross-correlated noise on the SNR and the shift between the two states of the system. Numerical results show that the multiplicative, additive noises and time-delay can all speed up the transition from the stable state to the extinction state, while the correlation noise and its correlation time can slow down the extinction process of the population system. With respect to SNR, the multiplicative noise always weakens the SR effect, while noise correlation time plays a dual role in motivating the SR phenomenon. Meanwhile, time-delay mainly plays a negative role in stimulating the SR phenomenon. Conversely, it could motivate the SR effect to increase the strength of the cross-correlation noise in the SNR-β plot, while the increase of additive noise intensity will firstly excite SR, and then suppress the SR effect.
Transition to adulthood: delays and unmet needs among adolescents and young adults with asthma.
Scal, Peter; Davern, Michael; Ireland, Marjorie; Park, Kyong
2008-04-01
To examine the effect of the transition to adulthood on financial and non-financial barriers to care in youth with asthma. With National Health Interview Survey data from 2000 to 2005, we examined delays and unmet needs because of financial and non-financial barriers, evaluating the effect of adolescent (age, 12-17 years; n = 1539) versus young adult age (age, 18-24 years; N = 833), controlling for insurance, usual source of care, and sociodemographic characteristics. We also simulated the effects of providing public insurance to uninsured patients and a usual source of care to patients without one. More young adults than adolescents encountered financial barriers resulting in delays (18.6% versus 8%, P < .05) and unmet needs (26.6% versus 11.4%, P < .05), although delays caused by non-financial barriers were similar (17.3% versus 14.9%, P = not significant). In logistic models young adults were more likely than adolescents to report delays (odds ratio [OR], 1.45; 95% CI, 1.02-2.08) and unmet needs (OR, 1.8; 95% CI, 1.29-2.52) caused by financial barriers. Delays and unmet needs for care caused by financial reasons are significantly higher for young adults than they are for adolescents with asthma.
Gendered transitions to adulthood by college field of study in the United States
Han, Siqi; Tumin, Dmitry; Qian, Zhenchao
2017-01-01
BACKGROUND Field of study may influence the timing of transitions to the labor market, marriage, and parenthood among college graduates. Research to date has yet to study how field of study is associated with the interweaving of these transitions in the USA. OBJECTIVE The current study examines gendered influences of college field of study on transitions to a series of adult roles, including full-time work, marriage, and parenthood. METHODS We use Cox proportional hazards models and multinomial logistic regression to examine gendered associations between field of study and the three transitions among college graduates of the NLSY97 (National Longitudinal Survey of Youth) cohort. RESULTS Men majoring in STEM achieve early transitions to full-time work, marriage, and parenthood; women majoring in STEM show no significant advantage in finding full-time work and delayed marriage and childbearing; women in business have earlier transitions to full-time work and marriage than women in other fields, demonstrating an advantage similar to that of men in STEM. CONCLUSIONS The contrast between men and women in STEM shows that transition to adulthood remains gendered; the contrast between women in STEM and women in business illustrates that a prestigious career may not necessarily delay family formation. PMID:29075146
Microbial mineral colonization across a subsurface redox transition zone
Converse, Brandon J.; McKinley, James P.; Resch, Charles T.; ...
2015-08-28
Here our study employed 16S rRNA gene amplicon pyrosequencing to examine the hypothesis that chemolithotrophic Fe(II)-oxidizing bacteria (FeOB) would preferentially colonize the Fe(II)-bearing mineral biotite compared to quartz sand when the minerals were incubated in situ within a subsurface redox transition zone (RTZ) at the Hanford 300 Area site in Richland, WA, USA. The work was motivated by the recently documented presence of neutral-pH chemolithotrophic FeOB capable of oxidizing structural Fe(II) in primary silicate and secondary phyllosilicate minerals in 300 Area sediments and groundwater (Benzine et al., 2013). Sterilized portions of sand+biotite or sand alone were incubated in situ formore » 5 months within a multilevel sampling (MLS) apparatus that spanned a ca. 2-m interval across the RTZ in two separate groundwater wells. Parallel MLS measurements of aqueous geochemical species were performed prior to deployment of the minerals. Contrary to expectations, the 16S rRNA gene libraries showed no significant difference in microbial communities that colonized the sand+biotite vs. sand-only deployments. Both mineral-associated and groundwater communities were dominated by heterotrophic taxa, with organisms from the Pseudomonadaceae accounting for up to 70% of all reads from the colonized minerals. These results are consistent with previous results indicating the capacity for heterotrophic metabolism (including anaerobic metabolism below the RTZ) as well as the predominance of heterotrophic taxa within 300 Area sediments and groundwater. Although heterotrophic organisms clearly dominated the colonized minerals, several putative lithotrophic (NH 4 +, H 2, Fe(II), and HS - oxidizing) taxa were detected in significant abundance above and within the RTZ. Such organisms may play a role in the coupling of anaerobic microbial metabolism to oxidative pathways with attendant impacts on elemental cycling and redox-sensitive contaminant behavior in the vicinity of the RTZ.« less
Sun, Xiaojuan; Perc, Matjaž; Kurths, Jürgen
2017-05-01
In this paper, we study effects of partial time delays on phase synchronization in Watts-Strogatz small-world neuronal networks. Our focus is on the impact of two parameters, namely the time delay τ and the probability of partial time delay p delay , whereby the latter determines the probability with which a connection between two neurons is delayed. Our research reveals that partial time delays significantly affect phase synchronization in this system. In particular, partial time delays can either enhance or decrease phase synchronization and induce synchronization transitions with changes in the mean firing rate of neurons, as well as induce switching between synchronized neurons with period-1 firing to synchronized neurons with period-2 firing. Moreover, in comparison to a neuronal network where all connections are delayed, we show that small partial time delay probabilities have especially different influences on phase synchronization of neuronal networks.
Ye, Feng; Chen, Yixing; Xia, Lu; Lian, Jiabian; Yang, Shuyu
2018-03-04
There is increasing evidence that glycolysis is involved in cancer progression. Aldolase is a glycolytic enzyme that catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. Disruption of the aldolase genes also plays a role in the progression of multiple types of cancer. However, the underlying mechanism of the action of aldolases in colon cancer progression remains elusive. In this study, aldolase A expression was investigated and found to be upregulated along with human colon cancer progression and metastasis at both the mRNA and protein levels in human colon cancer tissues. In addition, silencing aldolase A suppressed colon cancer cell proliferation and invasion and inhibited the EMT phenotype. Aldolase A protein expression in colon cancer was related to tumor location, tumor clinical stage and survival. Kaplan-Meier analysis showed that high aldolase A protein expression was associated with an unfavorable outcome. Moreover, aldolase A affected the development of colon cancer not only by affecting the glucose metabolism but also by interacting with the HIF-1 and other EMT-related signaling pathways; silencing aldolase A resulted in the reduced activity of these signaling pathways. These results indicate that aldolase A has additional non-glycolytic functions in transcriptional EMT regulation and may therefore have potential as a therapeutic target or a biomarker for identifying patients at risk for poorer survival. Copyright © 2018 Elsevier Inc. All rights reserved.
Colonic spirochetosis in animals and humans.
Smith, James L
2005-07-01
Colonic spirochetosis is a disease caused by the gram-negative bacteria Brachyspira aalborgi and Brachyspira pilosicoli. B. pilosicoli induces disease in both humans and animals, whereas B. aalborgi affects only humans and higher primates. Symptoms in humans include diarrhea, rectal bleeding, and abdominal cramps. Colonic spirochetosis is common in third world countries; however, in developed countries, the disease is observed mainly in homosexual males. Terminally ill patients infected with Brachyspira are particularly at risk for developing spirochetemia. Diarrhea, poor growth performance, and decreased feed-to-gain efficiency is seen in pigs with colonic spirochetosis. The disease in chickens is characterized by delayed and/or reduced egg production, diarrhea, poor feed conversion, and retarded growth. Thus, colonic spirochetosis can represent a serious economic loss in the swine and poultry industries. The organisms are transmitted by the fecal-oral route, and several studies have demonstrated that human, primate, pig, dog, or bird strains of B. pilosicoli can be transmitted to pigs, chickens, and mice. B. pilosicoli may be a zoonotic pathogen, and although it has not been demonstrated, there is a possibility that both B. pilosicoli and B. aalborgi can be transferred to humans via contact with the feces of infected animals, meat from infected animals, or food contaminated by food handlers. Neither B. pilosicoli nor B. aalborgi has been well characterized in terms of basic cellular functions, pathogenicity, or genetics. Studies are needed to more thoroughly understand these Brachyspira species and their disease mechanisms.
Report #09-P-0128, March 25, 2009. Lack of compliance with established project management procedures resulted in transitional problems in 2005 that delayed ICTS development and negatively affected contractor performance.
Rail Transit Winterization Technology and Systems Operations Study
DOT National Transportation Integrated Search
1980-09-01
The severe winters of 1977-1978 and 1978-1979 caused all snowbelt transit systems to experience a variety of problems which resulted in impaired service ranging from systems delays to complete system shutdowns. The scope of this report includes a sum...
Xu, Lin; Yu, Wenkui; Jiang, Jun; Li, Ning
2014-12-30
To explore the effect of pectin, a kind of soluble dietary fiber, on colonic transit time (CTT), clinical symptoms and gut microbiota in adults with slow-transit constipation. A total of 80 patients with slow-transit constipation were selected between June 2011 and December 2013. For this randomized controlled trial, we evaluated the efficacy of pectin on intestinal transit time and other indices of constipation in adults with slow-transit constipation. They were randomized to receive either pectin or placebo. Treatment consisted of 4-week supplementation with 24 g/d pectin (fiber group) or maltodextrin (placebo group). Before and after 4-week treatment, CTT, constipation symptoms and fecal bacterial population were compared between groups. CTT of the fiber group after treatment was lower than those of fiber group before treatment and those in the placebo group ((60.2 ± 11.2) h vs (80.3 ± 9.5), (79.4 ± 11.7) h, P < 0.01). Constipation score of the fiber group after treatment also decreased than those of fiber group before treatment and those in the placebo group (both P < 0.05). Bifidobacterium sp. and Lactobacillus sp. evidently increased (lg copies/g:8.26 ± 0.83 vs 6.42 ± 1.07 and 6.48 ± 0.82, 6.83 ± 0.77 vs 5.85 ± 0.64 and 5.91 ± 0.73; all P < 0.05) and total Clostridium sp. significantly decreased (9.07 ± 0.63 vs 9.74 ± 0.81 and 9.66 ± 0.43, P < 0.05) in the fiber group after treatment versus the placebo group. No significant adverse effects were reported. Four-week soluble dietary fiber use accelerates colon transit time and alleviates clinical symptoms in patients with slow-transit constipation. Additionally, supplementary fiber offers protective effects on gut microbiota by increasing the population of healthy microflora.
Colon Transit Time Test in Korean Children with Chronic Functional Constipation
Yoo, Ha Yeong; Kim, Mock Ryeon; Park, Hye Won; Son, Jae Sung
2016-01-01
Purpose Each ethnic group has a unique life style, including diets. Life style affects bowel movement. The aim of this study is to describe the results of colon transit time (CTT) tests in Korean children who had chronic functional constipation based on highly refined data. Methods One hundred ninety (86 males) out of 415 children who performed a CTT test under the diagnosis of chronic constipation according to Rome III criteria at Konkuk University Medical Center from January 2006 through March 2015 were enrolled in this study. Two hundreds twenty-five children were excluded on the basis of CTT test result, defecation diary, and clinical setting. Shapiro-Wilk and Mann-Whitney U, and chi-square tests were used for statistical analysis. Results The median value and interquartile range (IQR) of CTT was 54 (37.5) hours in Encopresis group, and those in non-encopresis group was 40.2 (27.9) hours (p<0.001). The frequency of subtype between non-encopresis group and encopresis was statistically significant (p=0.002). The non-encopresis group (n=154, 81.1%) was divided into normal transit subgroup (n=84, 54.5%; median value and IQR of CTT=26.4 [9.6] hours), outlet obstruction subgroup (n=18, 11.7%; 62.4 [15.6] hours), and slow transit subgroup (n=52, 33.8%; 54.6 [21.0] hours]. The encopresis group (n=36, 18.9%) was divided into normal transit subgroup (n=8, 22.2%; median value and IQR of CTT=32.4 [9.9] hours), outlet obstruction subgroup (n=8, 22.2%; 67.8 [34.8] hours), and slow transit subgroup (n=20, 55.6%; 59.4 [62.7]hours). Conclusion This study provided the basic pattern and value of the CTT test in Korean children with chronic constipation. PMID:27064388
Zhang, Chunhong; Xu, Yangjie; Wang, Haowen; Li, Gang; Yan, Han; Fei, Zhenghua; Xu, Yunsheng; Li, Wenfeng
2018-04-01
The objective of this study was to investigate the effect and the mechanism by which curcumin reverses irinotecan-induced chemotherapy resistance in colon cancer. Construction of irinotecan-resistant colon cancer model LoVo/CPT-11R cells was performed by increasing drug concentration. The Cell Counting Kit-8 assay was used to detect inhibition of proliferation; cell morphology was observed by an optical microscope. Quantitative RT-PCR and western blotting were performed to detect molecular marker expressions during epithelial-mesenchymal transition (EMT); drug-resistant cells were treated with curcumin at different concentrations and Cell Counting Kit-8 was reperformed to detect cell proliferation after treatments. Drug-resistant cells were then divided into four groups: control group, irinotecan group, curcumin group, and irinotecan+curcumin group; quantitative RT-PCR and western blotting were performed to detect molecular marker expressions during epithelial-mesenchymal transition. Flow cytometry was used to detect cell apoptosis after grouping, and apoptosis-related protein was detected by western blotting. LoVo/CPT-11R cells could survive in culture medium containing irinotecan at 60 μg/ml and the drug-resistance index was 5.69; the drug-resistant cells had a larger volume than normal cells and were poorly connected to each other. E-cadherin expression was downregulated, whereas vimentin and N-cadherin expressions were upregulated. After curcumin treatment, drug-resistant cell proliferation was significantly inhibited; in the curcumin+irinotecan treatment group, E-cadherin expression was upregulated, whereas vimentin and N-cadherin expressions were downregulated. Curcumin could significantly increase cell apoptosis. EMT is involved in the development of irinotecan resistance and curcumin can reverse this drug resistance through reversion of the EMT process.
Williams, S; Horner, J; Orton, E; Green, M; McMullen, S; Mobasheri, A; Freeman, S L
2015-01-01
Reasons for performing study A change in management from pasture to stabling is a risk factor for equine colic. Objectives To investigate the effect of a management change from pasture with no controlled exercise to stabling with light exercise on aspects of gastrointestinal function related to large colon impaction. The hypothesis was that drinking water intake, faecal output, faecal water content and large intestinal motility would be altered by a transition from a pastured to a stabled regime. Study design Within-subject management intervention trial involving changes in feeding and exercise using noninvasive techniques. Methods Seven normal horses were evaluated in a within-subjects study design. Horses were monitored while at pasture 24 h/day, and for 14 days following a transition to a stabling regime with light controlled exercise. Drinking water intake, faecal output and faecal dry matter were measured. Motility of the caecum, sternal flexure and left colon (contractions/min) were measured twice daily by transcutaneous ultrasound. Mean values were pooled for the pastured regime and used as a reference for comparison with stabled data (Days 1–14 post stabling) for multilevel statistical analysis. Results Drinking water intake was significantly increased (mean ± s.d. pasture 2.4 ± 1.8 vs. stabled 6.4 ± 0.6 l/100 kg bwt/day), total faecal output was significantly decreased (pasture 4.62 ± 1.69 vs. stabled 1.81 ± 0.5 kg/100 kg bwt/day) and faecal dry matter content was significantly increased (pasture 18.7 ± 2.28 vs. stabled 27.2 ± 1.93% DM/day) on all days post stabling compared with measurements taken at pasture (P<0.05). Motility was significantly decreased in all regions of the large colon collectively on Day 2 post stabling (-0.76 contractions/min), and in the left colon only on Day 4 (-0.62 contractions/min; P<0.05). Conclusions There were significant changes in large intestinal motility patterns and parameters relating to gastrointestinal water balance during a transition from pasture to stabled management, particularly during the first 5 days. PMID:24528106
Barlow, Amanda J.; Dixon, Jill; Dixon, Michael; Trainor, Paul A.
2013-01-01
Hirschsprung disease (HSCR) is a human congenital disorder, defined by the absence of ganglia from variable lengths of the colon. These ganglia comprise the enteric nervous system (ENS) and are derived from migratory neural crest cells (NCCs). The inheritance of HSCR is complex, often non-Mendelian and characterized by variable penetrance. Although extensive research has identified many key players in the pathogenesis of Hirschsprung disease, a large number of cases remain genetically undefined. Therefore, additional unidentified genes or modifiers must contribute to the etiology and pathogenesis of Hirschsprung disease. We have discovered that Tcof1 may be one such modifier. Haploinsufficiency of Tcof1 in mice results in a reduction of vagal NCCs and their delayed migration along the length of the gut during early development. This alone, however, is not sufficient to cause colonic aganglionosis as alterations in the balance of NCC proliferation and differentiation ensures NCC colonize the entire length of the gut of Tcof1+/− mice by E18.5. In contrast, Tcof1 haploinsufficiency is able to sensitize Pax3+/− mice to colonic aganglionosis. Although, Pax3 heterozygous mice do not show ENS defects, compound Pax3;Tcof1 heterozygous mice exhibit cumulative apoptosis which severely reduces the NCC population that migrates into the foregut. In addition, the proliferative capacity of these NCC is also diminished. Taken together with the opposing effects of Pax3 and Tcof1 on NCC differentiation, the synergistic haploinsufficiency of Tcof1 and Pax3 results in colonic aganglionosis in mice and may contribute to the pathogenesis of Hirschsprung disease. PMID:23283078
Barlow, Amanda J; Dixon, Jill; Dixon, Michael; Trainor, Paul A
2013-03-15
Hirschsprung disease (HSCR) is a human congenital disorder, defined by the absence of ganglia from variable lengths of the colon. These ganglia comprise the enteric nervous system (ENS) and are derived from migratory neural crest cells (NCCs). The inheritance of HSCR is complex, often non-Mendelian and characterized by variable penetrance. Although extensive research has identified many key players in the pathogenesis of Hirschsprung disease, a large number of cases remain genetically undefined. Therefore, additional unidentified genes or modifiers must contribute to the etiology and pathogenesis of Hirschsprung disease. We have discovered that Tcof1 may be one such modifier. Haploinsufficiency of Tcof1 in mice results in a reduction of vagal NCCs and their delayed migration along the length of the gut during early development. This alone, however, is not sufficient to cause colonic aganglionosis as alterations in the balance of NCC proliferation and differentiation ensures NCC colonize the entire length of the gut of Tcof1(+/-) mice by E18.5. In contrast, Tcof1 haploinsufficiency is able to sensitize Pax3(+/-) mice to colonic aganglionosis. Although, Pax3 heterozygous mice do not show ENS defects, compound Pax3;Tcof1 heterozygous mice exhibit cumulative apoptosis which severely reduces the NCC population that migrates into the foregut. In addition, the proliferative capacity of these NCC is also diminished. Taken together with the opposing effects of Pax3 and Tcof1 on NCC differentiation, the synergistic haploinsufficiency of Tcof1 and Pax3 results in colonic aganglionosis in mice and may contribute to the pathogenesis of Hirschsprung disease.
Inhibition of JNK Sensitizes Hypoxic Colon Cancer Cells to DNA Damaging Agents
Vasilevskaya, Irina A.; Selvakumaran, Muthu; Hierro, Lucia Cabal; Goldstein, Sara R.; Winkler, Jeffrey D.; O'Dwyer, Peter J.
2015-01-01
Purpose We showed previously that in HT29 colon cancer cells, modulation of hypoxia-induced stress signaling affects oxaliplatin cytotoxicity. To further study the significance of hypoxia-induced signaling through JNK, we set out to investigate how modulation of kinase activities influences cellular responses of hypoxic colon cancer cells to cytotoxic drugs. Experimental design In a panel of cell lines we investigated effects of pharmacological and molecular inhibition of JNK on sensitivity to oxaliplatin, SN-38 and 5-FU. Combination studies for the drugs and JNK inhibitor CC-401 were carried out in vitro and in vivo. Results Hypoxia-induced JNK activation was associated with resistance to oxaliplatin. CC-401 in combination with chemotherapy demonstrates synergism in colon cancer cell lines, though synergy is not always hypoxia-specific. A more detailed analysis focused on HT29 and SW620 (responsive), and HCT116 (non-responsive) lines. In HT29 and SW620 cells CC-401 treatment results in greater DNA damage in the sensitive cells. In vivo, potentiation of bevacizumab, oxaliplatin, and the combination by JNK inhibition was confirmed in HT29-derived mouse xenografts, where tumor growth delay was greater in the presence of CC-401. Finally, stable introduction of a dominant negative JNK1, but not JNK2, construct into HT29 cells rendered them more sensitive to oxaliplatin under hypoxia, suggesting differing input of JNK isoforms in cellular responses to chemotherapy. Conclusions These findings demonstrate that signaling through JNK is a determinant of response to therapy in colon cancer models, and support the testing of JNK inhibition to sensitize colon tumors in the clinic. PMID:26023085
Sharpe, John P; Magnotti, Louis J; Weinberg, Jordan A; Shahan, Charles P; Cullinan, Darren R; Marino, Katy A; Fabian, Timothy C; Croce, Martin A
2014-04-01
For more than a decade, operative decisions (resection plus anastomosis vs diversion) for colon injuries, at our institution, have followed a defined management algorithm based on established risk factors (pre- or intraoperative transfusion requirements of more than 6 units packed RBCs and/or presence of significant comorbid diseases). However, this management algorithm was originally developed for patients managed with a single laparotomy. The purpose of this study was to evaluate the applicability of this algorithm to destructive colon injuries after abbreviated laparotomy (AL) and to determine whether additional risk factors should be considered. Consecutive patients over a 17-year period with colon injuries after AL were identified. Nondestructive injuries were managed with primary repair. Destructive wounds were resected at the initial laparotomy followed by either a staged diversion (SD) or a delayed anastomosis (DA) at the subsequent exploration. Outcomes were evaluated to identify additional risk factors in the setting of AL. We identified 149 patients: 33 (22%) patients underwent primary repair at initial exploration, 42 (28%) underwent DA, and 72 (49%) had SD. Two (1%) patients died before re-exploration. Of those undergoing DA, 23 (55%) patients were managed according to the algorithm and 19 (45%) were not. Adherence to the algorithm resulted in lower rates of suture line failure (4% vs 32%, p = 0.03) and colon-related morbidity (22% vs 58%, p = 0.03) for patients undergoing DA. No additional specific risk factors for suture line failure after DA were identified. Adherence to an established algorithm, originally defined for destructive colon injuries after single laparotomy, is likewise efficacious for the management of these injuries in the setting of AL. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.
Singh, Anurag Kumar; Xia, Weiliang; Riederer, Brigitte; Juric, Marina; Li, Junhua; Zheng, Wen; Cinar, Ayhan; Xiao, Fang; Bachmann, Oliver; Song, Penghong; Praetorius, Jeppe; Aalkjaer, Christian; Seidler, Ursula
2013-04-15
Duodenal epithelial cells need efficient defence strategies during gastric acidification of the lumen, while colonic mucosa counteracts damage by pathogens by building up a bacteria-free adherent mucus layer. Transport of HCO3(-) is considered crucial for duodenal defence against acid as well as for mucus release and expansion, but the transport pathways involved are incompletely understood. This study investigated the significance of the electroneutral Na(+)-HCO3(-) cotransporter NBCn1 for duodenal defence against acid and colonic mucus release. NBCn1 was localized to the basolateral membrane of duodenal villous enterocytes and of colonic crypt cells, with predominant expression in goblet cells. Duodenal villous enterocyte intracellular pH was studied before and during a luminal acid load by two-photon microscopy in exteriorized, vascularly perfused, indicator (SNARF-1 AM)-loaded duodenum of isoflurane-anaesthetized, systemic acid-base-controlled mice. Acid-induced HCO3(-) secretion was measured in vivo by single-pass perfusion and pH-stat titration. After a luminal acid load, NBCn1-deficient duodenocytes were unable to recover rapidly from intracellular acidification and could not respond adequately with protective HCO3(-) secretion. In the colon, build-up of the mucus layer was delayed, and a decreased thickness of the adherent mucus layer was observed, suggesting that basolateral HCO3(-) uptake is essential for optimal release of mucus. The electroneutral Na(+)-HCO3(-) cotransporter NBCn1 displays a differential cellular distribution in the murine intestine and is essential for HCO3(-)-dependent mucosal protective functions, such as recovery of intracellular pH and HCO3(-) secretion in the duodenum and secretion of mucus in the colon.
Nath, Bipul; Nath, Lila Kanta
2013-11-01
The present study was aimed at designing a microflora triggered colon-targeted drug delivery system (MCDDS) based on swellable polysaccharide, Sterculia gum in combination with biodegradable polymers with a view to target azathioprine (AZA) in the colon for the treatment of IBD with reduced systemic toxicity. The microflora degradation study of gum was investigated in rat cecal medium. The polysaccharide tablet was coated to different film thicknesses with blends of chitosan/Eudragit RLPO and over coated with Eudragit L00 to provide acid and intestinal resistance. Swelling and drug release studies were carried out in simulated gastric fluid (SGF) (pH 1.2), simulated intestinal fluid (SIF) (pH 6.8) and simulated colonic fluid (SCF) (pH 7.4 under anaerobic environment), respectively. Drug release study in SCF revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudragit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that, the optimized MCDDS was fitted well into first order model and apparent lag time was found to be 6 h, followed by Higuchi spherical matrix release. The degradation of chitosan was the rate-limiting factor for drug release in the colon. In-vivo study in rabbit shows delayed T(max), prolonged absorption time, decreased C(max) and absorption rate constant (Ka) indicating reduced systemic toxicity of the drug as compared to other dosage forms.
Growth Control in Colon Epithelial Cells: Gadolinium Enhances Calcium-Mediated Growth Regulation
Attili, Durga; Jenkins, Brian; Aslam, Muhammad Nadeem; Dame, Michael K.
2013-01-01
Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1–5 µM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet. PMID:23008064
Ebigbo, Alanna; Probst, Andreas; Römmele, Christoph; Messmann, Helmut
2018-05-01
The endoscopic submucosal dissection (ESD) of cancerous and precancerous lesions in the gastrointestinal (GI) tract is an effective but difficult-to-learn procedure, especially for Western endoscopists. We developed a step-up training protocol and evaluated its outcome on a single endoscopist using specific performance measures. The training protocol included a 12-month period of 50 observational and supervised ESD cases as well as 24 animal procedures. After completion of the protocol, ESD competency was evaluated in the first 30 independent ESD cases. Majority of lesions were located in the stomach and rectum. Performance measures included R0-resection rate, complication rate and resection speed. R0 resection rate was 93 %, complication rate was 7 % and median resection speed was 6,77 cm 2 /h. 1 case of delayed perforation with subsequent hemicolectomy occurred in the descending colon. The ESD step-up training protocol used in this study on a single endoscopist showed excellent outcomes for lesions in the rectum and stomach. However, ESD training in the upper colon remains a challenge.
β -delayed γ decay of P 26 : Possible evidence of a proton halo
Pérez-Loureiro, D.; Wrede, C.; Bennett, M. B.; ...
2016-06-01
Background: Measurements of β decay provide important nuclear structure information that can be used to probe isospin asymmetries and inform nuclear astrophysics studies. Purpose: To measure the β-delayed γ decay of 26P and compare the results with previous experimental results and shell-model calculations. Method: A 26P fast beam produced using nuclear fragmentation was implanted into a planar germanium detector. Its β-delayed γ-ray emission was measured with an array of 16 high-purity germanium detectors. Positrons emitted in the decay were detected in coincidence to reduce the background. Results: The absolute intensities of 26P β-delayed γ-rays were determined. A total of sixmore » new β-decay branches and 15 new γ-ray lines have been observed for the first time in 26P β-decay. A complete β-decay scheme was built for the allowed transitions to bound excited states of 26Si. ft values and Gamow-Teller strengths were also determined for these transitions and compared with shell model calculations and the mirror β-decay of 26Na, revealing significant mirror asymmetries. Conclusions: A very good agreement with theoretical predictions based on the USDB shell model is observed. The significant mirror asymmetry observed for the transition to the first excited state (δ=51(10)%) may be evidence for a proton halo in 26P.« less
NASA Astrophysics Data System (ADS)
Sun, Xiaojuan; Perc, Matjaž; Kurths, Jürgen
2017-05-01
In this paper, we study effects of partial time delays on phase synchronization in Watts-Strogatz small-world neuronal networks. Our focus is on the impact of two parameters, namely the time delay τ and the probability of partial time delay pdelay, whereby the latter determines the probability with which a connection between two neurons is delayed. Our research reveals that partial time delays significantly affect phase synchronization in this system. In particular, partial time delays can either enhance or decrease phase synchronization and induce synchronization transitions with changes in the mean firing rate of neurons, as well as induce switching between synchronized neurons with period-1 firing to synchronized neurons with period-2 firing. Moreover, in comparison to a neuronal network where all connections are delayed, we show that small partial time delay probabilities have especially different influences on phase synchronization of neuronal networks.
ERIC Educational Resources Information Center
Lyons, Guy Kevin
2014-01-01
Students face many challenges in the transition to high school. From pressures of high-stakes testing for graduation to transitioning to the high school environment, many diversions can delay or even stop a student's path to graduation. Ninth-grade students are at a pivotal point in their educational careers, and a successful transition to high…
Transition to Turbulence in curved pipe
NASA Astrophysics Data System (ADS)
Hashemi, Amirreza; Loth, Francis
2014-11-01
Studies have shown that transitional turbulence in a curved pipe is delayed significantly compared with straight pipes. These analytical, numerical and experimental studies employed a helical geometry that is infinitely long such that the effect of the inlet and outlet can be neglected. The present study examined transition to turbulence in a finite curved pipe with a straight inlet/outlet and a 180 degrees curved pipe with a constant radius of curvature and diameter (D). We have employed the large scale direct numerical simulation (DNS) by using the spectral element method, nek5000, to simulate the flow field within curved pipe geometry with different curvature radii and Reynolds numbers to determine the point of the transition to turbulence. Long extensions for the inlet (5D) and outlet (20D) were used to diminish the effect of the boundary conditions. Our numerical results for radius of curvatures of 1.5D and 5D show transition turbulence is near Re = 3000. This is delayed compared with a straight pipe (Re = 2200) but still less that observed for helical geometries (Reynolds number less than 5000). Our research aims to describe the critical Reynolds number for transition to turbulence for a finite curved pipe at various curvature radii.
An Experimental Investigation of Hypergolic Ignition Delay of Hydrogen Peroxide with Fuel Mixtures
NASA Technical Reports Server (NTRS)
Blevins, John A.; Gostowski, Rudy; Chianese, Silvio
2003-01-01
An experimental investigation of hypergolicity and ignition delay of fuel mixtures with hydrogen peroxide is presented. Example results of high speed photography and schleiren from drop tests are shown. Also, a discussion of the sensitivity to experimental parameters such as drop size and subsequent uncertainty considerations of ignition delay results is presented. It is shown that using the described setup on the mixtures presented, the precision uncertainty is on the order of 6% of average ignition delay and 5% of average decomposition delay. This represents sufficient repeatability for first order discrimination of ignition delay for propellant development and screening. Two mixtures, each using commonly available amines and transition metal compounds, are presented as examples that result in ignition delays on the order of 10 milliseconds.
Chandrasekar, A; Rakkiyappan, R; Cao, Jinde
2015-10-01
This paper studies the impulsive synchronization of Markovian jumping randomly coupled neural networks with partly unknown transition probabilities via multiple integral approach. The array of neural networks are coupled in a random fashion which is governed by Bernoulli random variable. The aim of this paper is to obtain the synchronization criteria, which is suitable for both exactly known and partly unknown transition probabilities such that the coupled neural network is synchronized with mixed time-delay. The considered impulsive effects can be synchronized at partly unknown transition probabilities. Besides, a multiple integral approach is also proposed to strengthen the Markovian jumping randomly coupled neural networks with partly unknown transition probabilities. By making use of Kronecker product and some useful integral inequalities, a novel Lyapunov-Krasovskii functional was designed for handling the coupled neural network with mixed delay and then impulsive synchronization criteria are solvable in a set of linear matrix inequalities. Finally, numerical examples are presented to illustrate the effectiveness and advantages of the theoretical results. Copyright © 2015 Elsevier Ltd. All rights reserved.
Liu, Lu; Shang, Fei; Morgan, Matthew J; King, Denis W; Lubowski, David Z; Burcher, Elizabeth
2009-04-01
Tachykinins are important neurotransmitters regulating intestinal motility. Slow transit constipation (STC) represents an extreme colonic dysmotility with unknown etiology that predominantly affects women. We examined whether the tachykinin system is involved in the pathogenesis of STC. Isolated sigmoid colon circular muscle from female STC and control patients was studied using functional and quantitative reverse transcriptase-polymerase chain reaction methods. A possible alteration of neurotransmission was investigated by electrical field stimulation (EFS) and ganglionic stimulation by dimethylphenylpiperazinium (DMPP). Substance P (SP)-mediated contractions in circular muscle strips were significantly diminished in STC compared with age-matched control (P < 0.001). In contrast, contractile responses to neurokinin A, the selective tachykinin NK(2) receptor agonist, [Lys(5),MeLeu(9),Nle(10)]NKA(4-10), and acetylcholine were unaltered in STC. The reduced responses to SP in STC were fully restored by indomethacin, partially reversed by tetrodotoxin (TTX), but unaffected by atropine or hexamethonium. The restoration by indomethacin was blocked by the NK(1) receptor antagonist CP99994 [(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine] and TTX. In STC colonic muscle, there was a significant increase of NK(1) receptor mRNA expression, but no difference in NK(2) mRNA level. DMPP generated biphasic responses, relaxation at lower and contraction at higher concentrations. Although the responses to DMPP were similar in STC and control, an altered contractile pattern in response to EFS was observed in STC circular muscle. In conclusion, we postulate that the diminished contractile response to SP in STC is due to an increased release of inhibitory prostaglandins through activation of up-regulated NK(1) receptors. Our results also indicate some malfunction of the enteric nervous system in STC.
Colon delivery of budesonide: evaluation of chitosan-chondroitin sulfate interpolymer complex.
Kaur, Gurpreet; Rana, Vikas; Jain, Subheet; Tiwary, Ashok K
2010-03-01
The present study was aimed at formulating tablets comprising of coating susceptible to microbial enzyme degradation for releasing budesonide in the colon. Tablets prepared by using Avicel pH 102 as diluent and Eudragit L100-55 as binder were coated to a weight gain of 10% w/w employing aqueous mixtures containing chitosan (CH) and chondroitin sulfate (CS). The interpolymer complex between CH and CS was characterized using Fourier transform infrared (FTIR) and differential scanning calorimetery (DSC) studies. The tablets were evaluated for release of budesonide through in vitro in vivo studies. Formation of bonds between -COO(-) and -OSO3(-) groups of CS and -NH3+ groups of CH was evident in the FTIR spectra of these interpolymer complexed (IPC) films. The DSC thermograms of these films revealed one endothermic transition between 190 degrees C and 205 degrees C, suggesting the formation of new bonds in the IPC. The pH sensitive swelling exhibited by these films was observed to be a function of CH concentration. Tablets coated with aqueous mixtures containing 40:60 or 50:50 ratio of CH/CS totally prevented the release of budesonide in pH 1.2 buffer. The peaks (FTIR) and endothermic transitions (DSC) characteristic of interpolymer complexation were observed to remain unaffected after sequential exposure of the films to pH 1.2 and pH 7.4 buffer IP. This proved the versatility of these IPC films for colon delivery. C (max) of 1,168.99 and 1,174.2 ng/mL, respectively, at 12 and 8 h post-oral dosing of tablets coated with 40:60 or 50:50 ratio of CH/CS was observed in rats. The aqueous CH/CS (40:60) coating could provide a facile method for delivering budesonide to the colon.
Wellman, Tyler J.; Winkler, Tilo; Vidal Melo, Marcos F.
2015-01-01
18F-FDG-PET is increasingly used to assess pulmonary inflammatory cell activity. However, current models of pulmonary 18F-FDG kinetics do not account for delays in 18F-FDG transport between the plasma sampling site and the lungs. We developed a three-compartment model of 18F-FDG kinetics that includes a delay between the right heart and the local capillary blood pool, and used this model to estimate regional pulmonary perfusion. We acquired dynamic 18F-FDG scans in 12 mechanically ventilated sheep divided into control and lung injury groups (n=6 each). The model was fit to tracer kinetics in three isogravitational regions-of-interest to estimate regional lung transport delays and regional perfusion. 13NN bolus infusion scans were acquired during a period of apnea to measure regional perfusion using an established reference method. The delayed input function model improved description of 18F-FDG kinetics (lower Akaike Information Criterion) in 98% of studied regions. Local transport delays ranged from 2.0–13.6s, averaging 6.4±2.9s, and were highest in non-dependent regions. Estimates of regional perfusion derived from model parameters were highly correlated with perfusion measurements based on 13NN-PET (R2=0.92, p<0.001). By incorporating local vascular transports delays, this model of pulmonary 18F-FDG kinetics allows for simultaneous assessment of regional lung perfusion, transit times, and inflammation. PMID:25940652
Song, Guohe; Xiao, Chao; Yan, Dongwang; Zhong, Lin; Sun, Xing; Wang, Xiaoliang; Yu, Fudong; Yu, Yang; Tang, Huamei; Peng, Zhihai
2016-01-01
P21 protein (Cdc42/Rac)-activated kinase 7 (PAK7) can promote neurite outgrowth, induce microtubule stabilization, and activate cell survival signaling pathways. PAK7 expression was found to increase with colon carcinoma progression, but the prognostic value, clinical significance, and underlying mechanisms have not been explored. In my study, the expression of PAK7 was up-related at both the transcriptional and the translational levels in colon tumors compared to that in adjacent normal colon tissue. Patients with PAK7-positive tumors had a lower rate of overall survival (OS) and metastasis-free survival (MFS) (log-rank test, P < 0.001). A Cox proportional hazards model showed that PAK7 expression was an independent prognostic factor for OS (hazard ration [HR], 2.08; 95% confidence interval [CI], 1.16-3.73; P = 0.004) and MFS (HR, 2.88; 95% CI, 1.53-5.42; P < 0.001) in patients with colon cancer. Patients with tumors that were over-expressing PAK7 experienced metastasis, and died within a significantly shorter time after surgery (P < 0.001). Knockdown of PAK7 by a specific short hairpin RNA (shRNA) significantly suppressed the progression of epithelial to mesechymal transition (EMT), migration, and invasion of colon cancer cells in vitro and tumor growth in vivo. However, overexpression of PAK7 significantly promoted these processes. These findings indicate that aberrant PAK7 expression is associated with the occurrence of metastasis and poor clinical outcomes of human colon cancer by promoting the EMT, and the assessment of PAK7 expression might be helpful in predicting metastasis and prognostication for patients with colon cancer. PMID:27323857
Yasuda, S; Fujii, H; Yamamoto, K; Nakagawa, M; Watanabe, I; Nakano, H
1992-01-01
For the purpose of making a functional assessment of colostomy irrigation, eight patients were examined. Group A was composed of four patients whose experience of irrigation was less than one year. Group B was composed of four patients who had undergone irrigation for more than two years. The capacity of the remnant colon was determined by a barium enema. Next, 74 MBq of milking technetium 99 diethylene triamine penta-acetic acid (99mTc-DTPA) was instilled with a predetermined amount of water (37 degrees C). A dynamic scan was performed for 45 min. The mean evacuation time of Groups A and B were 6 min 56 s +/- 2 min 33 s and 13 min 27 s +/- 10 min 50 s, respectively. The mean half emptying time of Groups A and B were 142.5 s +/- 7.9 s and 309.0 s +/- 181.9 s. The results suggest that the remnant colon may be habituated with irrigation. Colostomy irrigation which uses a single instillation of a measured volume of tepid water is recommended.
Shyer and larger bird species show more reduced fear of humans when living in urban environments.
delBarco-Trillo, Javier
2018-04-01
As the natural habitats of many species are degraded or disappear, there is scope for these species to be established in urban habitats. To ease the establishment and maintenance of urban populations of more species we need to better understand what degree of phenotypical change to expect as different species transition into urban environments. During the first stages of urban colonization, behavioural changes such as an increase in boldness are particularly important. A consistent response in urban populations is to decrease the distance at which individuals flee from an approaching human (flight initiation distance, or FID). Performing a phylogenetic generalized least-squares (PGLS) analysis on 130 avian species, I found that the largest changes in FID between rural and urban populations occur in species that are larger-bodied and naturally shy (higher rural FID), two phenotypic traits that are not normally associated with urban colonizers. More unlikely species may thus be able to colonize urban environments, especially if we design cities in ways that promote such urban colonizations. © 2018 The Author(s).
Patel, B A
2014-02-01
Mechanical stimulation of the mucosal epithelium results in increased serotonin (5-HT) release from enterochromaffin (EC) cells. Little is known about how this process varies in different regions of the intestinal tract; however, purines are felt to play a role. We studied the relationship between mechanical stimulation, adenosine triphosphate (ATP), and 5-HT release from ileal and colonic mucosal tissue. Amperometric recordings of ATP and 5-HT were carried out using an ATP biosensor and boron-doped diamond microelectrode. Levels of extracellular ATP and 5-HT were monitored using high performance liquid chromatography. Under basal conditions, 5-HT levels were significantly decreased in the ileum (p < 0.001) but not the colon in the presence of the P2 antagonist suramin (100 μM). Ecto-ATPase inhibitor ARL67156 (10 μM) elevated ATP levels in the ileum and colon (both p < 0.001), but only 5-HT levels in the ileum (p < 0.001). Exogenous ATP increased 5-HT release in the presence of tetrodotoxin in the ileum (p < 0.001), but had not effect in the colon. Mechanical stimulation increased levels of 5-HT in the ileum (p < 0.001) and colon (p < 0.01), but levels returned to baseline in the presence of suramin and MRS2179 in the ileum. The onset of 5-HT release was delayed following mechanical stimulation. The rise time of the ATP response was quicker than that of 5-HT during mechanical stimulation. During mechanical stimulation of the mucosal epithelium, ATP mediates 5-HT release from EC cells in the ileum, but not the colon. Mucosal 5-HT signaling following mechanical stimulation is varied in different regions of the intestinal tract. © 2013 John Wiley & Sons Ltd.
Hope in Africa?: social representations of world history and the future in six African countries.
Cabecinhas, Rosa; Liu, James H; Licata, Laurent; Klein, Olivier; Mendes, Júlio; Feijó, João; Niyubahwe, Aline
2011-10-01
Data on social representations of world history have been collected everywhere in the world except sub-Saharan Africa. Two studies using open-ended data involving university students from six African countries fill this gap. In Study 1, nominations from Cape Verde and Mozambique for the most important events in world history in the past 1000 years were dominated by war and politics, recency effects, and Western-centrism tempered by African sociocentrism on colonization and independence. The first three findings replicated previous research conducted in other parts of the world, but the last pattern contrasted sharply with European data. Study 2 employed a novel method asking participants how they would begin the narration of world history, and then to describe a major transition to the present. Participants most frequently wrote about the evolution of humanity out of Africa, followed by war and then colonization as a beginning, and then replicated previous findings with war, colonization, and technology as major transitions to the present. Finally, when asked about how they foresaw the future, many participants expressed hope for peace and cooperation, especially those facing more risk of collective violence (Burundi and Congo). A colonial/liberation narrative was more predominant in the data from former Portuguese colonies (Angola, Cape Verde, and Guinea-Bissau) than from former Belgian colonies (Burundi and Congo).
Gastrointestinal transit in nonobese diabetic mouse: an animal model of human diabetes type 1.
El-Salhy, M
2001-01-01
Gastrointestinal transit (GI) in the nonobese diabetic (NOD) mouse, an animal model of human diabetes type 1, was examined in animals with short- (duration 1-5 days) and long-term (duration 28-35 days) diabetes. Blood glucose level, serum insulin concentration, and gut neuroendocrine peptide content were also measured. GI was significantly rapid in NOD mice with long-term diabetes (LTD), but was not correlated with blood glucose level, serum insulin concentration, or pancreatic insulin content. GI was correlated with duodenal secretin content, but not with the content of other neuroendocrine peptides in the different segments investigated. Whereas antral vasoactive intestinal peptide (VIP) content in NOD mice with LTD was significantly higher, colonic VIP was lower in NOD mice with short-term diabetes (STD). In the duodenum, whereas the concentration of secretin in NOD mice with both STD and LTD was lower, the gastrin content was higher. Duodenal somatostatin content in NOD mice with LTD was lower. In colon, the content of galanin in NOD mice with LTD was higher than in controls. The decreased content of secretin may be among the factors that cause rapid GI in NOD mice with LTD. Changes in the antral content of VIP, duodenal somatostatin, and colonic galanin in NOD mice with LTD may cause low intestinal secretion and, together with rapid GI, give rise to diarrhoea, which is a common symptom in diabetes.
Kennedy, Jonathan D; Borregaard, Michael K; Jønsson, Knud A; Holt, Ben; Fjeldså, Jon; Rahbek, Carsten
2017-01-01
Regional variation in clade richness can be vast, reflecting differences in the dynamics of historical dispersal and diversification among lineages. Although it has been proposed that dispersal into new biogeographic regions may facilitate diversification, to date there has been limited assessment of the importance of this process in the generation, and maintenance, of broad-scale biodiversity gradients. To address this issue, we analytically derive biogeographic regions for a global radiation of passerine birds (the Corvides, c. 790 species) that are highly variable in the geographic and taxonomic distribution of species. Subsequently, we determine rates of historical dispersal between regions, the dynamics of diversification following regional colonization, and spatial variation in the distribution of species that differ in their rates of lineage diversification. The results of these analyses reveal spatiotemporal differences in the build-up of lineages across regions. The number of regions occupied and the rate of transition between regions both predict family richness well, indicating that the accumulation of high clade richness is associated with repeated expansion into new geographic areas. However, only the largest family (the Corvidae) had significantly heightened rates of both speciation and regional transition, implying that repeated regional colonization is not a general mechanism promoting lineage diversification among the Corvides. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.
Colonic transit time and pressure based on Bernoulli's principle.
Uno, Yoshiharu
2018-01-01
Variations in the caliber of human large intestinal tract causes changes in pressure and the velocity of its contents, depending on flow volume, gravity, and density, which are all variables of Bernoulli's principle. Therefore, it was hypothesized that constipation and diarrhea can occur due to changes in the colonic transit time (CTT), according to Bernoulli's principle. In addition, it was hypothesized that high amplitude peristaltic contractions (HAPC), which are considered to be involved in defecation in healthy subjects, occur because of cecum pressure based on Bernoulli's principle. A virtual healthy model (VHM), a virtual constipation model and a virtual diarrhea model were set up. For each model, the CTT was decided according to the length of each part of the colon, and then calculating the velocity due to the cecum inflow volume. In the VHM, the pressure change was calculated, then its consistency with HAPC was verified. The CTT changed according to the difference between the cecum inflow volume and the caliber of the intestinal tract, and was inversely proportional to the cecum inflow volume. Compared with VHM, the CTT was prolonged in the virtual constipation model, and shortened in the virtual diarrhea model. The calculated pressure of the VHM and the gradient of the interlocked graph were similar to that of HAPC. The CTT and HAPC can be explained by Bernoulli's principle, and constipation and diarrhea may be fundamentally influenced by flow dynamics.
Film coatings for oral pulsatile release.
Maroni, Alessandra; Zema, Lucia; Loreti, Giulia; Palugan, Luca; Gazzaniga, Andrea
2013-12-05
Pulsatile delivery is generally intended as a release of the active ingredient that is delayed for a programmable period of time to meet particular chronotherapeutic needs and, in the case of oral administration, also target distal intestinal regions, such as the colon. Most oral pulsatile delivery platforms consist in coated formulations wherein the applied polymer serves as the release-controlling agent. When exposed to aqueous media, the coating initially performs as a protective barrier and, subsequently, undergoes a timely failure based on diverse mechanisms depending on its physico-chemical and formulation characteristics. Indeed, it may be ruptured because of the gradual expansion of the core, swell and/or erode due to the glassy-rubbery polymer transition or become permeable thus allowing the drug molecules to diffuse outwards. Otherwise, when the coating is a semipermeable membrane provided with one or more orifices, the drug is released through the latter as a result of an osmotic water influx. The vast majority of pulsatile delivery systems described so far have been prepared by spray-coating, which offers important versatility and feasibility advantages over other techniques such as press- and dip-coating. In the present article, the design, manufacturing and performance of spray-coated pulsatile delivery platforms is thus reviewed. Copyright © 2013 Elsevier B.V. All rights reserved.
Wu, Florence T H; Lee, Christina R; Bogdanovic, Elena; Prodeus, Aaron; Gariépy, Jean; Kerbel, Robert S
2015-06-01
Angiopoietin-1 (Ang1) activation of Tie2 receptors on endothelial cells (ECs) reduces adhesion by tumor cells (TCs) and limits junctional permeability to TC diapedesis. We hypothesized that systemic therapy with Vasculotide (VT)-a purported Ang1 mimetic, Tie2 agonist-can reduce the extravasation of potentially metastatic circulating TCs by similarly stabilizing the host vasculature. In vitro, VT and Ang1 treatments impeded endothelial hypermeability and the transendothelial migration of MDA-MB-231∙LM2-4 (breast), HT29 (colon), or SN12 (renal) cancer cells to varying degrees. In mice, VT treatment inhibited the transit of TCs through the pulmonary endothelium, but not the hepatic or lymphatic endothelium. In the in vivo LM2-4 model, VT monotherapy had no effect on primary tumors, but significantly delayed distant metastatic dissemination to the lungs. In the post-surgical adjuvant treatment setting, VT therapeutically complemented sunitinib therapy, an anti-angiogenic tyrosine kinase inhibitor which limited the local growth of residual disease. Unexpectedly, detailed investigations into the putative mechanism of action of VT revealed no evidence of Tie2 agonism or Tie2 binding; alternative mechanisms have yet to be determined. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.
Snake River fall Chinook salmon life history investigations, annual report 2008
Tiffan, Kenneth F.; Connor, William P.; Bellgraph, Brian J.; Buchanan, Rebecca A.
2010-01-01
In 2009, we used radio and acoustic telemetry to evaluate the migratory behavior, survival, mortality, and delay of subyearling fall Chinook salmon in the Clearwater River and Lower Granite Reservoir. We released a total of 1,000 tagged hatchery subyearlings at Cherry Lane on the Clearwater River in mid August and we monitored them as they passed downstream through various river and reservoir reaches. Survival through the free-flowing river was high (>0.85) for both radio- and acoustic-tagged fish, but dropped substantially as fish delayed in the Transition Zone and Confluence areas. Estimates of the joint probability of migration and survival through the Transition Zone and Confluence reaches combined were similar for both radio- and acoustic-tagged fish, and ranged from about 0.30 to 0.35. Estimates of the joint probability of delaying and surviving in the combined Transition Zone and Confluence peaked at the beginning of the study, ranging from 0.323 ( SE =NA; radio-telemetry data) to 0.466 ( SE =0.024; acoustic-telemetry data), and then steadily declined throughout the remainder of the study. By the end of October, no live tagged juvenile salmon were detected in either the Transition Zone or the Confluence. As estimates of the probability of delay decreased throughout the study, estimates of the probability of mortality increased, as evidenced by the survival estimate of 0.650 ( SE =0.025) at the end of October (acoustic-telemetry data). Few fish were detected at Lower Granite Dam during our study and even fewer fish passed the dam before PIT-tag monitoring ended at the end of October. Five acoustic-tagged fish passed Lower Granite Dam in October and 12 passed the dam in November based on detections in the dam tailrace; however, too few detections were available to calculate the joint probabilities of migrating and surviving or delaying and surviving. Estimates of the joint probability of migrating and surviving through the reservoir was less than 0.2 based on acoustic-tagged fish. Migration rates of tagged fish were highest in the free-flowing river (median range = 36 to 43 km/d) but were generally less than 6 km/d in the reservoir reaches. In particular, median migration rates of radio-tagged fish through the Transition Zone and Confluence were 3.4 and 5.2 km/d, respectively. Median migration rate for acoustic-tagged fish though the Transition Zone and Confluence combined was 1 km/d.
Bacterial growth, flow, and mixing shape human gut microbiota density and composition.
Arnoldini, Markus; Cremer, Jonas; Hwa, Terence
2018-03-13
The human gut microbiota is highly dynamic, and host physiology and diet exert major influences on its composition. In our recent study, we integrated new quantitative measurements on bacterial growth physiology with a reanalysis of published data on human physiology to build a comprehensive modeling framework. This can generate predictions of how changes in different host factors influence microbiota composition. For instance, hydrodynamic forces in the colon, along with colonic water absorption that manifests as transit time, exert a major impact on microbiota density and composition. This can be mechanistically explained by their effect on colonic pH which directly affects microbiota competition for food. In this addendum, we describe the underlying analysis in more detail. In particular, we discuss the mixing dynamics of luminal content by wall contractions and its implications for bacterial growth and density, as well as the broader implications of our insights for the field of gut microbiota research.
The quest for a unified view of bacterial land colonization
Wu, Hao; Fang, Yongjun; Yu, Jun; Zhang, Zhang
2014-01-01
Exploring molecular mechanisms underlying bacterial water-to-land transition represents a critical start toward a better understanding of the functioning and stability of the terrestrial ecosystems. Here, we perform comprehensive analyses based on a large variety of bacteria by integrating taxonomic, phylogenetic and metagenomic data, in the quest for a unified view that elucidates genomic, evolutionary and ecological dynamics of the marine progenitors in adapting to nonaquatic environments. We hypothesize that bacterial land colonization is dominated by a single-gene sweep, that is, the emergence of dnaE2 derived from an early duplication event of the primordial dnaE, followed by a series of niche-specific genomic adaptations, including GC content increase, intensive horizontal gene transfer and constant genome expansion. In addition, early bacterial radiation may be stimulated by an explosion of land-borne hosts (for example, plants and animals) after initial land colonization events. PMID:24451209
Prieto, Daniel; Román, Elvira; Alonso-Monge, Rebeca; Pla, Jesús
2017-01-01
The transcriptional regulator Wor1 has been shown to induce the GUT transition, an environmentally triggered process that increases the fitness of Candida albicans in the mouse gastrointestinal tract. We have developed strains where the expression of this gene is driven from the strong and tightly regulated tetracycline promoter. These cells retain the main characteristics reported for GUT cells albeit they show defects in the initial stages of colonization. They also show a differential colonization along the gastrointestinal tract compared to isogenic strains, which is probably caused by their susceptibility to bile salts. We also show that WOR1 overexpressing cells have an altered metabolic activity, as revealed by a different susceptibility to inhibitors of respiration, and an enhanced adhesion to the mouse mucosa. We propose that this may contribute to their long-term favored ability to colonize the gastrointestinal tract. PMID:28955659
Prieto, Daniel; Román, Elvira; Alonso-Monge, Rebeca; Pla, Jesús
2017-01-01
The transcriptional regulator Wor1 has been shown to induce the GUT transition, an environmentally triggered process that increases the fitness of Candida albicans in the mouse gastrointestinal tract. We have developed strains where the expression of this gene is driven from the strong and tightly regulated tetracycline promoter. These cells retain the main characteristics reported for GUT cells albeit they show defects in the initial stages of colonization. They also show a differential colonization along the gastrointestinal tract compared to isogenic strains, which is probably caused by their susceptibility to bile salts. We also show that WOR1 overexpressing cells have an altered metabolic activity, as revealed by a different susceptibility to inhibitors of respiration, and an enhanced adhesion to the mouse mucosa. We propose that this may contribute to their long-term favored ability to colonize the gastrointestinal tract.
Can't afford a baby? Debt and young Americans.
Nau, Michael; Dwyer, Rachel E; Hodson, Randy
2015-12-01
This article explores the role of personal debt in the transition to parenthood. We analyze data from the National Longitudinal Study of Youth-1997 cohort and find that for the generation coming of age in the 2000s, student loans delay fertility for women, particularly at very high levels of debt. Home mortgages and credit card debt, in contrast, appear to be precursors to parenthood. These results indicate that different forms of debt have different implications for early adulthood transitions: whereas consumer loans or home mortgages immediately increase access to consumption goods, there is often a significant delay between the accrual and realization of benefits for student loans. The double-edged nature of debt as both barrier and facilitator to life transitions highlights the importance of looking at debt both as a monetary issue and also as a carrier of social meanings.
Clocking and Synchronization Circuits in Multiprocessor Systems
1989-04-01
18 3.4 Inter -chip Clocking Strategies...may occur when two or more of the switches make transitions at different times during the inter - val during which those inputs are being processed...increased without any fruitful computation. The sources of the inter -chip clock skew are the electromagnetic propagation delay, the buffer delay within
The Induction of Emergent Relations in Children with Severe Cognitive and Language Delays
ERIC Educational Resources Information Center
Howarth, Matthew
2012-01-01
In three experiments I sought to experimentally test a source of emergent relations defined as transitivity by Stimulus Equivalence theory or as combinatorial entailment in Relational Frame Theory. In Experiment I, the participants were 4 children diagnosed with autism who also demonstrated significant cognitive and language delays, who were…
Observations of long delays to detonation in propellant for tests with marginal card gaps
NASA Technical Reports Server (NTRS)
Olinger, B.
1980-01-01
Using the large-scale card gap tests with pin and high-speed framing camera techniques, VRP propellant, and presumably others, were found to transit to detonation at marginal gaps after a long delay. In addition, manganin-constantan gauge measurements were made in the card gap stack.
Zangaro, Waldemar; Rostirola, Leila Vergal; de Souza, Priscila Bochi; de Almeida Alves, Ricardo; Lescano, Luiz Eduardo Azevedo Marques; Rondina, Artur Berbel Lírio; Nogueira, Marco Antonio; Carrenho, Rosilaine
2013-04-01
The influence of plant functional groups and moderate seasonality on arbuscular mycorrhizal (AM) fungal status (root colonization and spore density) was investigated during 13 consecutive months in a chronosequence of succession in southern Brazil, consisting of grassland field, scrub vegetation, secondary forest and mature forest, in a region of transition from tropical to subtropical zones. AM root colonization and spore density decreased with advancing succession and were highest in early successional sites with grassland and scrub vegetation, intermediary in the secondary forest and lowest in the mature forest. They were little influenced by soil properties, but were sufficiently influenced by the fine root nutrient status and fine root traits among different functional plant groups. AM root colonization and spore density were higher during the favourable plant growth season (spring and summer) than during the less favourable plant growth season (autumn and winter). Spore density displayed significant seasonal variation at all sites, whilst root colonization displayed significant seasonal variation in grassland, scrub and secondary forest, but not in mature forest. The data suggest that (1) different plant functional groups display different relationships with AM fungi, influencing their abundance differentially; (2) plant species from early successional phases are more susceptible to AM root colonization and maintain higher AM sporulation than late successional species; (3) fine root traits and nutrient status influence these AM fungal attributes; and (4) higher AM spore production and root colonization is associated with the season of higher light incidence and temperature, abundant water in soil and higher plant metabolic activity.
Effect of colectomy on gastric emptying in idiopathic slow-transit constipation.
Hemingway, D M; Finlay, I G
2000-09-01
Gastric emptying is delayed in patients with idiopathic slow-transit constipation (ISTC). Gastric emptying was measured before and after colectomy and ileorectal anastomosis in patients with ISTC to determine whether the abnormality persists after operation. Twelve patients undergoing colectomy for severe ISTC had solid-phase gastric emptying measured after an overnight fast. All 12 had an uncomplicated subtotal colectomy and ileorectal anastomosis; 11 had an excellent functional outcome. In ten of these patients gastric emptying was repeated within 3 months of operation. Seven patients (including the remaining two) had the study performed at 1 year. All 12 patients had severely delayed gastric emptying before operation. Gastric emptying remained delayed in the ten patients who underwent an early postoperative gastric emptying study. Six of seven patients assessed at 1 year had improved gastric emptying, of whom four had returned to normal. Functional outcome did not relate to gastric emptying. Patients with ISTC have delayed gastric emptying. In some patients this returns to normal after colectomy, but is persistent in others. This may have implications for our understanding of ISTC.
Vocal effort modulates the motor planning of short speech structures
NASA Astrophysics Data System (ADS)
Taitz, Alan; Shalom, Diego E.; Trevisan, Marcos A.
2018-05-01
Speech requires programming the sequence of vocal gestures that produce the sounds of words. Here we explored the timing of this program by asking our participants to pronounce, as quickly as possible, a sequence of consonant-consonant-vowel (CCV) structures appearing on screen. We measured the delay between visual presentation and voice onset. In the case of plosive consonants, produced by sharp and well defined movements of the vocal tract, we found that delays are positively correlated with the duration of the transition between consonants. We then used a battery of statistical tests and mathematical vocal models to show that delays reflect the motor planning of CCVs and transitions are proxy indicators of the vocal effort needed to produce them. These results support that the effort required to produce the sequence of movements of a vocal gesture modulates the onset of the motor plan.
Feng, Ze-Meng; Li, Tie-Jun; Wu, Li; Xiao, Ding-Fu; Blachier, Francois; Yin, Yu-Long
2015-01-01
Background The Chinese have been undergone rapid transition to a high-fat diet-consuming lifestyle, while monosodium L-glutamate (MSG) is widely used as a daily food additive. It has been reported that fat alters the composition of intestinal microbiota. However, little information is available on the effects of oral MSG on intestinal microbiota, and no study was done focusing on the interaction effect of fat and MSG with respect to intestinal microbiota. The present study thus aimed to determine the effects of MSG and/or fat on intestinal microbiota, and also to identify possible interactions between these two nutrients. Methods Four iso-nitrogenous and iso-caloric diets were provided to growing pigs. The microbiota from jejunum, ileum, cecum, and colon were analyzed. Results Our results show that both MSG and fat clearly increased the intestinal microbiota diversity. MSG and fat modified the composition of intestinal microbiota, particularly in the colon. Both MSG and fat promoted the colonization of microbes related to energy extraction in gastrointestinal tract via different ways. MSG promoted the colonization of Faecalibacterium prausnitzii and Roseburia, while fat increased the percentage of Prevotella in colon and other intestinal segments. Conclusion Our results will help to understand how individual or combined dietary changes modify the microbiota composition to prevent obesity. PMID:25791341
Feng, Ze-Meng; Li, Tie-Jun; Wu, Li; Xiao, Ding-Fu; Blachier, Francois; Yin, Yu-Long
2015-01-01
The Chinese have been undergone rapid transition to a high-fat diet-consuming lifestyle, while monosodium L-glutamate (MSG) is widely used as a daily food additive. It has been reported that fat alters the composition of intestinal microbiota. However, little information is available on the effects of oral MSG on intestinal microbiota, and no study was done focusing on the interaction effect of fat and MSG with respect to intestinal microbiota. The present study thus aimed to determine the effects of MSG and/or fat on intestinal microbiota, and also to identify possible interactions between these two nutrients. Four iso-nitrogenous and iso-caloric diets were provided to growing pigs. The microbiota from jejunum, ileum, cecum, and colon were analyzed. Our results show that both MSG and fat clearly increased the intestinal microbiota diversity. MSG and fat modified the composition of intestinal microbiota, particularly in the colon. Both MSG and fat promoted the colonization of microbes related to energy extraction in gastrointestinal tract via different ways. MSG promoted the colonization of Faecalibacterium prausnitzii and Roseburia, while fat increased the percentage of Prevotella in colon and other intestinal segments. Our results will help to understand how individual or combined dietary changes modify the microbiota composition to prevent obesity.
Streptococcus mitis: walking the line between commensalism and pathogenesis.
Mitchell, J
2011-04-01
Streptococcus mitis is a viridans streptococcus and a normal commensal of the human oropharynx. However, S. mitis can escape from this niche and cause a variety of infectious complications including infective endocarditis, bacteraemia and septicaemia. It uses a variety of strategies to effectively colonize the human oropharynx. These include expression of adhesins, immunoglobulin A proteases and toxins, and modulation of the host immune system. These various colonization factors allow S. mitis to compete for space and nutrients in the face of its more pathogenic oropharyngeal microbial neighbours. However, it is likely that in vulnerable immune-compromised patients S. mitis will use the same colonization and immune modulation factors as virulence factors promoting its opportunistic pathogenesis. The recent publication of a complete genome sequence for S. mitis strain B6 will allow researchers to thoroughly investigate which genes are involved in S. mitis host colonization and pathogenesis. Moreover, it will help to give insight into where S. mitis fits in the complicated oral microbiome. This review will discuss the current knowledge of S. mitis factors involved in host colonization, their potential role in virulence and what needs to be done to fully understand how a an oral commensal successfully transitions to a virulent pathogen. © 2011 John Wiley & Sons A/S.
Dispersal-competition tradeoff in microbiomes in the quest for land colonization.
Dini-Andreote, Francisco; van Elsas, Jan Dirk; Olff, Han; Salles, Joana Falcão
2018-06-21
Ancestor microbes started colonizing inland habitats approximately 2.7 to 3.5 billion years ago. With some exceptions, the key physiological adaptations of microbiomes associated with marine-to-land transitions have remained elusive. This is essentially caused by the lack of suitable systems that depict changes in microbiomes across sufficiently large time scales. Here, we investigate the adaptive routes taken by microbiomes along a contemporary gradient of land formation. Using functional trait-based metagenomics, we show that a switch from a microbial 'dispersal' to a 'competition' response modus best characterizes the microbial trait changes during this eco-evolutionary trajectory. The 'dispersal' modus prevails in microbiomes at the boundary sites between land and sea. It encompasses traits conferring cell chemosensory and motile behaviors, thus allowing the local microbes to exploit short-lived nutritional patches in high-diffusion microhabitats. A systematic transition towards the 'competition' modus occurs progressively as the soil matures, which is likely due to forces of viscosity or strain that favor traits for competition and chemical defense. Concomitantly, progressive increases in the abundances of genes encoding antibiotic resistance and complex organic substrate degradation were found. Our findings constitute a novel perspective on the ecology and evolution of microbiome traits, tracking back one of the most seminal transitions in the evolutionary history of life.
Legacy Effect of Amazonian Drought Delays the Season Transition from Dry to Wet
NASA Astrophysics Data System (ADS)
Shi, M.; Liu, J.; Wong, S.; Worden, J. R.; Fisher, J.; Frankenberg, C.
2017-12-01
The long-term drought effect on forest coverage, so-called legacy effect, has been observed in ground and remote sensing measurements. Drought and forest loss may amplify each other through vegetation-atmosphere feedbacks. In this study, we investigate the impact of the reduced growth of southern Amazonian forest from the 2005 drought on dry-to-wet season transition and its variations in 2005 and 2006. We quantified the vegetation-atmosphere feedbacks with the Community Atmosphere Model version 5 (CAM5) with a control and a sensitivity experiments. We further investigate the mechanism of vegetation-atmosphere feedbacks with data-constrained evapotranspiration (ET) and HDO/H2O observations from the Scanning Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY) and from the Tropospheric Emission Spectrometer (TES). Our results show that the dry season end (DSE) in southern Amazonian forest was delayed by 15 days in 2005 and by 25 days in 2006 with drought induced leaf carbon pool reduction. The postponed DSE is triggered by the reduced evapotranspiration (ET), but amplified by change of large-scale circulation. The reduction of ET and its delaying effect on dry-wet season transition is further confirmed with SCIAMACHY and TES HDO/H2O measurements.
DOT National Transportation Integrated Search
2011-08-01
This report documents an investigation into the transportation project development process in the : context of the implementation of bus rapid transit systems on the State Highway System as well as such : systems being part of the Federal New Starts ...
Kansas Early Childhood Research Institute on Transitions. Final Report.
ERIC Educational Resources Information Center
Rice, Mabel L.; O'Brien, Marion
This final report describes research projects and other activities of the Kansas Early Childhood Research Institute (KECRI), a multi-investigator, cross-disciplinary Institute focusing on successful transitions for young (birth to age 8) children with disabilities or developmental delays. Interventions were developed, evaluated, and disseminated…
Life in the Transition Economies.
ERIC Educational Resources Information Center
Lopus, Jane
1998-01-01
Reports on interviews conducted with Ukrainian teachers who were asked whether they and others they know are better, or worse, off since Ukrainian independence. Addresses inflation, private enterprise, delayed salaries, and new freedoms. Provides insights into the effects of the transition on people's lives and hopes for the future. (DSK)
Control of amplitude chimeras by time delay in oscillator networks
NASA Astrophysics Data System (ADS)
Gjurchinovski, Aleksandar; Schöll, Eckehard; Zakharova, Anna
2017-04-01
We investigate the influence of time-delayed coupling in a ring network of nonlocally coupled Stuart-Landau oscillators upon chimera states, i.e., space-time patterns with coexisting partially coherent and partially incoherent domains. We focus on amplitude chimeras, which exhibit incoherent behavior with respect to the amplitude rather than the phase and are transient patterns, and we show that their lifetime can be significantly enhanced by coupling delay. To characterize their transition to phase-lag synchronization (coherent traveling waves) and other coherent structures, we generalize the Kuramoto order parameter. Contrasting the results for instantaneous coupling with those for constant coupling delay, for time-varying delay, and for distributed-delay coupling, we demonstrate that the lifetime of amplitude chimera states and related partially incoherent states can be controlled, i.e., deliberately reduced or increased, depending upon the type of coupling delay.
Modeling of delays in PKPD: classical approaches and a tutorial for delay differential equations.
Koch, Gilbert; Krzyzanski, Wojciech; Pérez-Ruixo, Juan Jose; Schropp, Johannes
2014-08-01
In pharmacokinetics/pharmacodynamics (PKPD) the measured response is often delayed relative to drug administration, individuals in a population have a certain lifespan until they maturate or the change of biomarkers does not immediately affects the primary endpoint. The classical approach in PKPD is to apply transit compartment models (TCM) based on ordinary differential equations to handle such delays. However, an alternative approach to deal with delays are delay differential equations (DDE). DDEs feature additional flexibility and properties, realize more complex dynamics and can complementary be used together with TCMs. We introduce several delay based PKPD models and investigate mathematical properties of general DDE based models, which serve as subunits in order to build larger PKPD models. Finally, we review current PKPD software with respect to the implementation of DDEs for PKPD analysis.
Urgent surgery for complicated colonic diverticula.
Funariu, Gheorghe; Binţinţan, Vasile; Seicean, Radu
2006-03-01
The AIM of this retrospective study was to evaluate the emergency surgical treatment of life-threatening complications of colonic diverticula. In the last 11 years, 22 of 101 patients with colonic diverticula (22.1%) underwent urgent surgery for acute complications: perforated gangrenous diverticulitis with generalized peritonitis (n=8) or pericolic abscess (n=8), acute bowel obstruction (n=4) and severe diverticular bleeding (n=2). In all patients with diffuse peritonitis or acute obstruction the indication for surgery was decided on clinical basis and the complicated diverticula were recognized only intra-operatively. Emergency surgical strategy differed according to the type of complication and the biologic condition of the patient: segmental colectomy and primary anastomosis for diverticular perforation (n=4), colonic stenosis (n=3) or diverticular bleeding (n=2); Hartmann resection with late reconnecting anastomosis in patients with diverticular perforation (n=5) or colonic obstruction (n=1); diverticulectomy with peritoneal drainage (n=2) and colostomy and drainage followed by secondary colectomy (n=5) for diverticular perforations in patients with poor general condition. Only one patient (4.5%) died post-operatively of multiple organ failure from generalized peritonitis. There was no anastomotic leakage in patients with primary anastomosis. Six patients (27.2%) developed wound infection. Hospital stay ranged between 11 and 60 days, significantly longer in cases with two-stage operations. Primary colectomy with immediate or delayed anastomosis is the best surgical procedure for acute divericular complications in patients with good biologic status. Two-stage operations such as colostomy and drainage coupled with late colectomy remain the viable alternative in patients with advanced disease and critical biologic condition.
Rapid genetic restoration of a keystone species exhibiting delayed demographic response.
Cosentino, Bradley J; Schooley, Robert L; Bestelmeyer, Brandon T; McCarthy, Alison J; Sierzega, Kevin
2015-12-01
Genetic founder effects are often expected when animals colonize restored habitat in fragmented landscapes, but empirical data on genetic responses to restoration are limited. We examined the genetic response of banner-tailed kangaroo rats (Dipodomys spectabilis) to landscape-scale grassland restoration in the Chihuahuan Desert of New Mexico, USA. Dipodomys spectabilis is a grassland specialist and keystone species. At sites treated with herbicide to remove shrubs, colonization by D. spectabilis is slow and populations persist at low density for ≥10 years (≥6 generations). Persistence at low density and low gene flow may cause strong founder effects. We compared genetic structure of D. spectabilis populations between treated sites and remnant grasslands, and we examined how the genetic response to restoration depended on treatment age, area, and connectivity to source populations. Allelic richness and heterozygosity were similar between treated sites and remnant grasslands. Allelic richness at treated sites was greatest early in the restoration trajectory, and genetic divergence did not differ between recently colonized and established populations. These results indicated that founder effects during colonization of treated sites were weak or absent. Moreover, our results suggested founder effects were not mitigated by treatment area or connectivity. Dispersal is negatively density-dependent in D. spectabilis, and we hypothesize that high gene flow may occur early in the restoration trajectory when density is low. Our study shows genetic diversity can be recovered more rapidly than demographic components of populations after habitat restoration and that founder effects are not inevitable for animals colonizing restored habitat in fragmented landscapes. © 2015 John Wiley & Sons Ltd.
Ramond, Cyrille; Bandeira, Antonio; Berthault, Claire; Pereira, Pablo; Cumano, Ana; Burlen-Defranoux, Odile
2015-01-01
Characterizing thymic settling progenitors is important to understand the pre-thymic stages of T cell development, essential to devise strategies for T cell replacement in lymphopenic patients. We studied thymic settling progenitors from murine embryonic day 13 and 18 thymi by two complementary in vitro and in vivo techniques, both based on the “hanging drop” method. This method allowed colonizing irradiated fetal thymic lobes with E13 and/or E18 thymic progenitors distinguished by CD45 allotypic markers and thus following their progeny. Colonization with mixed populations allows analyzing cell autonomous differences in biologic properties of the progenitors while colonization with either population removes possible competitive selective pressures. The colonized thymic lobes can also be grafted in immunodeficient male recipient mice allowing the analysis of the mature T cell progeny in vivo, such as population dynamics of the peripheral immune system and colonization of different tissues and organs. Fetal thymic organ cultures revealed that E13 progenitors developed rapidly into all mature CD3+ cells and gave rise to the canonical γδ T cell subset, known as dendritic epithelial T cells. In comparison, E18 progenitors have a delayed differentiation and were unable to generate dendritic epithelial T cells. The monitoring of peripheral blood of thymus-grafted CD3-/- mice further showed that E18 thymic settling progenitors generate, with time, larger numbers of mature T cells than their E13 counterparts, a feature that could not be appreciated in the short term fetal thymic organ cultures. PMID:26131754
O-antigen and Core Carbohydrate of Vibrio fischeri Lipopolysaccharide
Post, Deborah M. B.; Yu, Liping; Krasity, Benjamin C.; Choudhury, Biswa; Mandel, Mark J.; Brennan, Caitlin A.; Ruby, Edward G.; McFall-Ngai, Margaret J.; Gibson, Bradford W.; Apicella, Michael A.
2012-01-01
Vibrio fischeri exists in a symbiotic relationship with the Hawaiian bobtail squid, Euprymna scolopes, where the squid provides a home for the bacteria, and the bacteria in turn provide camouflage that helps protect the squid from night-time predators. Like other Gram-negative organisms, V. fischeri expresses lipopolysaccharide (LPS) on its cell surface. The structure of the O-antigen and the core components of the LPS and their possible role in colonization of the squid have not previously been determined. In these studies, an O-antigen ligase mutant, waaL, was utilized to determine the structures of these LPS components and their roles in colonization of the squid. WaaL ligates the O-antigen to the core of the LPS; thus, LPS from waaL mutants lacks O-antigen. Our results show that the V. fischeri waaL mutant has a motility defect, is significantly delayed in colonization, and is unable to compete with the wild-type strain in co-colonization assays. Comparative analyses of the LPS from the wild-type and waaL strains showed that the V. fischeri LPS has a single O-antigen repeat composed of yersiniose, 8-epi-legionaminic acid, and N-acetylfucosamine. In addition, the LPS from the waaL strain showed that the core structure consists of l-glycero-d-manno-heptose, d-glycero-d-manno-heptose, glucose, 3-deoxy-d-manno-octulosonic acid, N-acetylgalactosamine, 8-epi-legionaminic acid, phosphate, and phosphoethanolamine. These studies indicate that the unusual V. fischeri O-antigen sugars play a role in the early phases of bacterial colonization of the squid. PMID:22247546
The Colonization History of Juniperus brevifolia (Cupressaceae) in the Azores Islands
Rumeu, Beatriz; Caujapé-Castells, Juli; Blanco-Pastor, José Luis; Jaén-Molina, Ruth; Nogales, Manuel; Elias, Rui B.; Vargas, Pablo
2011-01-01
Background A central aim of island biogeography is to understand the colonization history of insular species using current distributions, fossil records and genetic diversity. Here, we analyze five plastid DNA regions of the endangered Juniperus brevifolia, which is endemic to the Azores archipelago. Methodology/Principal Findings The phylogeny of the section Juniperus and the phylogeographic analyses of J. brevifolia based on the coalescence theory of allele (plastid) diversity suggest that: (1) a single introduction event likely occurred from Europe; (2) genetic diversification and inter-island dispersal postdated the emergence of the oldest island (Santa Maria, 8.12 Ma); (3) the genetic differentiation found in populations on the islands with higher age and smaller distance to the continent is significantly higher than that on the younger, more remote ones; (4) the high number of haplotypes observed (16), and the widespread distribution of the most frequent and ancestral ones across the archipelago, are indicating early diversification, demographic expansion, and recurrent dispersal. In contrast, restriction of six of the seven derived haplotypes to single islands is construed as reflecting significant isolation time prior to colonization. Conclusions/Significance Our phylogeographic reconstruction points to the sequence of island emergence as the key factor to explain the distribution of plastid DNA variation. The reproductive traits of this juniper species (anemophily, ornithochory, multi-seeded cones), together with its broad ecological range, appear to be largely responsible for recurrent inter-island colonization of ancestral haplotypes. In contrast, certain delay in colonization of new haplotypes may reflect intraspecific habitat competition on islands where this juniper was already present. PMID:22110727
Samuelsson, A; Isaksson, B; Hanberger, H; Olhager, E
2014-01-01
Between 2006 and 2011, 11 patients with Serratia marcescens sepsis and 47 patients colonized due to the spread of various clones were observed. These recurrent clusters brought about interventions to reduce spread between patients. To evaluate the effect of stepwise interventions to prevent S. marcescens colonization/sepsis and to analyse risk factors for late-onset sepsis (LOS). An open retrospective observational study was performed to evaluate the interventions. A retrospective case-control study was performed to analyse the risk factors for LOS. S. marcescens sepsis and colonization decreased after the stepwise adoption of hygiene interventions. Low gestational age, low birth weight, indwelling central venous or umbilical catheter, and ventilator treatment were identified as risk factors for LOS. Compliance with basic hygiene guidelines was the only intervention monitored continuously from late 2007. Compliance increased gradually to a steady high level in early 2009. There was a decrease in S. marcescens LOS, clustering after the second quarter of 2008. After the first quarter of 2009, S. marcescens colonization decreased. It was not possible to identify the specific effects of each intervention, but it is likely that an update of the hospital's antibiotic policy affected the occurrence of S. marcescens LOS. The delayed effect of interventions on S. marcescens colonization was probably due to the time it takes for new routines to have an effect, illustrated by the gradual increase in compliance with basic hygiene guidelines. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
Time and pH dependent colon specific, pulsatile delivery of theophylline for nocturnal asthma.
Mastiholimath, V S; Dandagi, P M; Jain, S Samata; Gadad, A P; Kulkarni, A R
2007-01-02
In this study, investigation of an oral colon specific, pulsatile device to achieve time and/or site specific release of theophylline, based on chronopharmaceutical consideration. The basic design consists of an insoluble hard gelatin capsule body, filled with eudragit microcapsules of theophylline and sealed with a hydrogel plug. The entire device was enteric coated, so that the variability in gastric emptying time can be overcome and a colon-specific release can be achieved. The theophylline microcapsules were prepared in four batches, with Eudragit L-100 and S-100 (1:2) by varying drug to polymer ratio and evaluated for the particle size, drug content and in vitro release profile and from the obtained results; one better formulation was selected for further fabrication of pulsatile capsule. Different hydrogel polymers were used as plugs, to maintain a suitable lag period and it was found that the drug release was controlled by the proportion of polymers used. In vitro release studies of pulsatile device revealed that, increasing the hydrophilic polymer content resulted in delayed release of theophylline from microcapsules. The gamma scintigraphic study pointed out the capability of the system to release drug in lower parts of GIT after a programmed lag time for nocturnal asthma. Programmable pulsatile, colon-specific release has been achieved from a capsule device over a 2-24h period, consistent with the demands of chronotherapeutic drug delivery.
The induction of apoptosis and autophagy by Wasabia japonica extract in colon cancer.
Hsuan, Shu-Wen; Chyau, Charng-Cherng; Hung, Hsiao-Yu; Chen, Jing-Hsien; Chou, Fen-Pi
2016-03-01
Wasabia japonica (wasabi) has been shown to exhibit properties of detoxification, anti-inflammation and the induction of apoptosis in cancer cells. This study aimed to investigate the molecular mechanism of the cytotoxicity of wasabi extract (WE) in colon cancer cells to evaluate the potential of wasabi as a functional food for chemoprevention. Colo 205 cells were treated with different doses of WE, and the cytotoxicity was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide. Apoptosis and autophagy were detected by 4',6-diamidino-2-phenylindole, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbo-yanine iodide and staining for acidic vascular organelles (AVOs), along with Western blotting. The results demonstrated that WE induced the extrinsic pathway and mitochondrial death machinery through the activation of TNF-α, Fas-L, caspases, truncated Bid and cytochrome C. WE also induced autophagy by decreasing the phosphorylation of Akt and mTOR and promoting the expression of microtubule-associated protein 1 light chain 3-II and AVO formation. An in vivo xenograft model verified that tumor growth was delayed by WE treatment. Our studies revealed that WE exhibits anti-colon cancer properties through the induction of apoptosis and autophagy. These results provide support for the application of WE as a chemopreventive functional food and as a prospective treatment of colon cancer.
Time-delayed reaction-diffusion fronts
NASA Astrophysics Data System (ADS)
Isern, Neus; Fort, Joaquim
2009-11-01
A time-delayed second-order approximation for the front speed in reaction-dispersion systems was obtained by Fort and Méndez [Phys. Rev. Lett. 82, 867 (1999)]. Here we show that taking proper care of the effect of the time delay on the reactive process yields a different evolution equation and, therefore, an alternate equation for the front speed. We apply the new equation to the Neolithic transition. For this application the new equation yields speeds about 10% slower than the previous one.
The effects of daikenchuto (DKT) on propulsive motility in the colon.
Wood, Michael J; Hyman, Neil H; Mawe, Gary M
2010-11-01
The purpose of this study is to examine the use of daikenchuto (DKT), a traditional Japanese medicine, as a potential treatment for opiate-induced slowing of intestinal transit in an isolated guinea pig colon model of motility. Isolated segments of distal guinea pig colon were mounted in a perfusion chamber and imaged with a digital video camera interfaced with a computer. Fecal pellets were inserted into the oral end of the colonic segment and the rates of propulsive motility over a 3 to 4 cm segment of colon were determined in the presence and absence of test compounds. In addition, intracellular recordings were obtained from intact circular muscle, and the responsiveness of inhibitory and excitatory junction potentials to DKT was evaluated. The addition of D-Ala2, N-Me-Phe4, Gly-ol5 (DAMGO), a selective μ-receptor agonist, caused a concentration dependent decrease in colon motility. Naloxone did not affect basal activity, but partially restored motility in the DAMGO treated preparations. DKT (1 × 10(-4)-3 × 10(-4)g/mL) also reversed the inhibitory effect of DAMGO treated colon in a concentration dependent manner. At higher concentrations (1 × 10(-3)-3 × 10(-3)g/mL), however, this effect was lost. Motility slowed even further when naloxone and DKT were combined with noticeable disruptions in spatiotemporal patterns. Interestingly, when added alone, DKT resulted in reverse peristalsis of the pellet. In electrophysiologic studies DKT inhibited both excitatory and inhibitory junction potentials. DKT appears to be as effective as naloxone in restoring motility in DAMGO treated colon. These two agents, however, do not appear to have an additive effect. When used on untreated colon segments, DKT appears to cause disruptions in the intrinsic reflex circuit of the gut resulting in a disruption of neuromuscular communication. Copyright © 2010 Elsevier Inc. All rights reserved.
The Effects of Daikenchuto (DKT) on Propulsive Motility in the Colon
Wood, MJ; Hyman, N; Mawe, GM
2010-01-01
Purpose The purpose of this study is to examine the use of daikenchuto (DKT), a traditional Japanese medicine, as a potential treatment for opiate-induced slowing of intestinal transit in an isolated guinea-pig colon model of motility. Methods Isolated segments of distal guinea-pig colon were mounted in a perfusion chamber and imaged with a digital video camera interfaced with a computer. Fecal pellets were inserted into the oral end of the colonic segment and the rates of propulsive motility over a 3-4 cm segment of colon were determined in the presence and absence of test compounds. In addition, intracellular recordings were obtained from intact circular muscle, and the responsiveness of inhibitory and excitatory junction potentials to DKT was evaluated. Results The addition of DAMGO (D-Ala2, N-Me-Phe4, Gly-ol5), a selective mu-receptor agonist, caused a concentration dependent decrease in colon motility. Naloxone did not affect basal activity, but partially restored motility in the DAMGO treated preparations. DKT (1×10-4 – 3×10-4 g/ml) also reversed the inhibitory effect of DAMGO treated colon in a concentration dependent manner. At higher concentrations (1×10-3 – 3×10-3 g/ml), however, this effect was lost. Motility slowed even further when naloxone and DKT were combined with noticeable disruptions in spatiotemporal patterns. Interestingly, when added alone, DKT resulted in reverse peristalsis of the pellet. In electrophysiological studies DKT inhibited both excitatory and inhibitory junction potentials. Conclusions DKT appears to be as effective as naloxone in restoring motility in DAMGO treated colon. These two agents, however, do not appear to have an additive effect. When used on untreated colon segments, DKT appears to cause disruptions in the intrinsic reflex circuit of the gut resulting in a disruption of neuromuscular communication. PMID:19631346
Optimization of chitosan nanoparticles for colon tumors using experimental design methodology.
Jain, Anekant; Jain, Sanjay K
2016-12-01
Purpose Colon-specific drug delivery systems (CDDS) can improve the bio-availability of drugs through the oral route. A novel formulation for oral administration using ligand coupled chitosan nanoparticles bearing 5-Flurouracil (5FU) encapsulated in enteric coated pellets has been investigated for CDDS. Method The effect of polymer concentration, drug concentration, stirring time and stirring speed on the encapsulation efficiency, and size of nanoparticles were evaluated. The best (or optimum) formulation was obtained by response surface methodology. Using the experimental data, analysis of variance has been carried out to evolve linear empirical models. Using a new methodology, polynomial models have been evolved and the parametric analysis has been carried out. In order to target nanoparticles to the hyaluronic acid (HA) receptors present on colon tumors, HA coupled nanoparticles were tested for their efficacy in vivo. The HA coupled nanoparticles were encapsulated in pellets and were enteric coated to release the drug in the colon. Results Drug release studies under conditions of mimicking stomach to colon transit have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine. The relatively high local drug concentration with prolonged exposure time provides a potential to enhance anti-tumor efficacy with low systemic toxicity for the treatment of colon cancer. Conclusions Conclusively, HA coupled nanoparticles can be considered as the potential candidate for targeted drug delivery and are anticipated to be promising in the treatment of colorectal cancer.
Vincent, Caroline; Miller, Mark A; Edens, Thaddeus J; Mehrotra, Sudeep; Dewar, Ken; Manges, Amee R
2016-03-14
Clostridium difficile infection (CDI) is the leading infectious cause of nosocomial diarrhea. Hospitalized patients are at increased risk of developing CDI because they are exposed to C. difficile spores through contact with the hospital environment and often receive antibiotics and other medications that can disrupt the integrity of the indigenous intestinal microbiota and impair colonization resistance. Using whole metagenome shotgun sequencing, we examined the diversity and composition of the fecal microbiota in a prospective cohort study of 98 hospitalized patients. Four patients had asymptomatic C. difficile colonization, and four patients developed CDI. We observed dramatic shifts in the structure of the gut microbiota during hospitalization. In contrast to CDI cases, asymptomatic patients exhibited elevated relative abundance of potentially protective bacterial taxa in their gut at the onset of C. difficile colonization. Use of laxatives was associated with significant reductions in the relative abundance of Clostridium and Eubacterium; species within these genera have previously been shown to enhance resistance to CDI via the production of secondary bile acids. Cephalosporin and fluoroquinolone exposure decreased the frequency of Clostridiales Family XI Incertae Sedis, a bacterial family that has been previously associated with decreased CDI risk. This study underscores the detrimental impact of antibiotics as well as other medications, particularly laxatives, on the intestinal microbiota and suggests that co-colonization with key bacterial taxa may prevent C. difficile overgrowth or the transition from asymptomatic C. difficile colonization to CDI.
DOT National Transportation Integrated Search
2017-04-01
The main objective of this project is to develop and conduct limited testing of novel sensors using Bluetooth technology : (BT) to estimate OD demands and station wait times for users of public transit stations. The NYU research team tested the : fea...
Novel MRI tests of orocecal transit time and whole gut transit time: studies in normal subjects
Chaddock, G; Lam, C; Hoad, C L; Costigan, C; Cox, E F; Placidi, E; Thexton, I; Wright, J; Blackshaw, P E; Perkins, A C; Marciani, L; Gowland, P A; Spiller, R C
2014-01-01
Background Colonic transit tests are used to manage patients with Functional Gastrointestinal Disorders. Some tests used expose patients to ionizing radiation. The aim of this study was to compare novel magnetic resonance imaging (MRI) tests for measuring orocecal transit time (OCTT) and whole gut transit time (WGT), which also provide data on colonic volumes. Methods 21 healthy volunteers participated. Study 1: OCTT was determined from the arrival of the head of a meal into the cecum using MRI and the Lactose Ureide breath test (LUBT), performed concurrently. Study 2: WGT was assessed using novel MRI marker capsules and radio-opaque markers (ROMs), taken on the same morning. Studies were repeated 1 week later. Key Results OCTT measured using MRI and LUBT was 225 min (IQR 180–270) and 225 min (IQR 165–278), respectively, correlation rs = 0.28 (ns). WGT measured using MRI marker capsules and ROMs was 28 h (IQR 4–50) and 31 h ± 3 (SEM), respectively, correlation rs = 0.85 (p < 0.0001). Repeatability assessed using the intraclass correlation coefficient (ICC) was 0.45 (p = 0.017) and 0.35 (p = 0.058) for MRI and LUBT OCTT tests. Better repeatability was observed for the WGT tests, ICC being 0.61 for the MRI marker capsules (p = 0.001) and 0.69 for the ROM method (p < 0.001) respectively. Conclusions & Inferences The MRI WGT method is simple, convenient, does not use X-ray and compares well with the widely used ROM method. Both OCTT measurements showed modest reproducibility and the MRI method showed modest inter-observer agreement. PMID:24165044
Kapur, Raj P
2016-10-01
Submucosal nerve hypertrophy is a feature of the transition zone in Hirschsprung disease and has been used as a primary diagnostic feature of transition zone pull-through for patients with persistent obstructive symptoms after their initial surgery. Most published criteria for identification of hypertrophy rely on a nerve diameter of greater than 40μm, based primarily on data from a relatively small number of infants with Hirschsprung disease and controls. The validity of these objective measures has not been validated in appropriate controls for post-pull-through patients. The primary pull-through specimens and post pull-through biopsies +/- redo pull-through resections from a series of 9 patients with Hirschsprung disease were reviewed to assess the prevalence of submucosal nerves >40μm in diameter and 400× microscopic fields containing two or more such nerves. Similar data from multiple colonic locations were collected from a series of 40 non-Hirschsprung autopsy and surgical controls. The overwhelming majority of Hirschsprung patients harbored submucosal nerves >40μm in their post-pull-through specimens independent of other features of transition zone pathology, and despite normal innervation at the proximal margins of their initial resections. Measurement of submucosal nerve diameters in autopsy and surgical non-Hirschsprung control samples indicated that nerves >40μm are normal in the distal rectum after 1year of age and are found in more proximal colon at older ages. These results suggest that diagnostic criteria currently used to recognize submucosal nerve hypertrophy in the neorectum after a pull-through for Hirschsprung disease are not justified and should not be regarded as definitive evidence for transition zone pull-through. Copyright © 2016 Elsevier Inc. All rights reserved.
Wellman, Tyler J; Winkler, Tilo; Vidal Melo, Marcos F
2015-11-01
¹⁸F-FDG-PET is increasingly used to assess pulmonary inflammatory cell activity. However, current models of pulmonary ¹⁸F-FDG kinetics do not account for delays in ¹⁸F-FDG transport between the plasma sampling site and the lungs. We developed a three-compartment model of ¹⁸F-FDG kinetics that includes a delay between the right heart and the local capillary blood pool, and used this model to estimate regional pulmonary perfusion. We acquired dynamic ¹⁸F-FDG scans in 12 mechanically ventilated sheep divided into control and lung injury groups (n = 6 each). The model was fit to tracer kinetics in three isogravitational regions-of-interest to estimate regional lung transport delays and regional perfusion. ¹³NN bolus infusion scans were acquired during a period of apnea to measure regional perfusion using an established reference method. The delayed input function model improved description of ¹⁸F-FDG kinetics (lower Akaike Information Criterion) in 98% of studied regions. Local transport delays ranged from 2.0 to 13.6 s, averaging 6.4 ± 2.9 s, and were highest in non-dependent regions. Estimates of regional perfusion derived from model parameters were highly correlated with perfusion measurements based on ¹³NN-PET (R² = 0.92, p < 0.001). By incorporating local vascular transports delays, this model of pulmonary ¹⁸F-FDG kinetics allows for simultaneous assessment of regional lung perfusion, transit times, and inflammation.
Time of One's Own: Employment, Leisure, and Delayed Transition to Motherhood in Japan
ERIC Educational Resources Information Center
Nomaguchi, Kei M.
2006-01-01
Recent theoretical work suggests that the increase in women's sense of entitlement to leisure has become a key to understanding delay in childbearing in industrialized countries. Using data from the Japanese Panel Study of Consumer Life, the author examines the relationship between leisure time and childbearing among Japanese married women in a…
ERIC Educational Resources Information Center
Ullery, Mary Anne; Katz, Lynne
2017-01-01
This article examined transition rates of young children (n = 102) from an early intervention program at the Linda Ray Intervention Program (LRIP) who had documented developmental delays and co-occurring prenatal drug exposure often coupled with verified child maltreatment. Findings indicated that there was significant group improvement from…
The Role of Resilience, Delayed Gratification and Stress in Predicting Academic Performance
ERIC Educational Resources Information Center
Cheng, Vivienne; Catling, Jonathan
2015-01-01
Transition to university is an important and potentially stressful life event for students. Previous studies have shown that resilience, delay of gratification and stress can affect the academic performance of students. However, none have shown the effect of these factors in predicting academic performance, hence the current study aimed to look at…
Transition Control with Dielectric Barrier Discharge Plasmas
2013-01-01
release; distribution is unlimited. of transition is observed . For higher applied body forces, the transition delay effect is enhanced, but care has...REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public reporting burden for this collection of information is estimated to average 1 ...currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1 . REPORT DATE (DD-MM-YYYY) 3 January 2013 2. REPORT TYPE
Can't afford a baby? Debt and young Americans☆
Nau, Michael; Dwyer, Rachel E.; Hodson, Randy
2016-01-01
This article explores the role of personal debt in the transition to parenthood. We analyze data from the National Longitudinal Study of Youth-1997 cohort and find that for the generation coming of age in the 2000s, student loans delay fertility for women, particularly at very high levels of debt. Home mortgages and credit card debt, in contrast, appear to be precursors to parenthood. These results indicate that different forms of debt have different implications for early adulthood transitions: whereas consumer loans or home mortgages immediately increase access to consumption goods, there is often a significant delay between the accrual and realization of benefits for student loans. The double-edged nature of debt as both barrier and facilitator to life transitions highlights the importance of looking at debt both as a monetary issue and also as a carrier of social meanings. PMID:28090131
Di Domenico, Enea Gino; Farulla, Ilaria; Prignano, Grazia; Gallo, Maria Teresa; Vespaziani, Matteo; Cavallo, Ilaria; Sperduti, Isabella; Pontone, Martina; Bordignon, Valentina; Cilli, Laura; De Santis, Alessandra; Di Salvo, Fabiola; Pimpinelli, Fulvia; Lesnoni La Parola, Ilaria; Toma, Luigi; Ensoli, Fabrizio
2017-01-01
Bacterial biofilm is a major factor in delayed wound healing and high levels of biofilm production have been repeatedly described in multidrug resistant organisms (MDROs). Nevertheless, a quantitative correlation between biofilm production and the profile of antimicrobial drug resistance in delayed wound healing remains to be determined. Microbial identification, antibiotic susceptibility and biofilm production were assessed in 135 clinical isolates from 87 patients. Gram-negative bacteria were the most represented microorganisms (60.8%) with MDROs accounting for 31.8% of the total isolates. Assessment of biofilm production revealed that 80% of the strains were able to form biofilm. A comparable level of biofilm production was found with both MDRO and not-MDRO with no significant differences between groups. All the methicillin-resistant Staphylococcus aureus (MRSA) and 80% of Pseudomonas aeruginosa MDR strains were found as moderate/high biofilm producers. Conversely, less than 17% of Klebsiella pneumoniae extended-spectrum beta-lactamase (ESBL), Escherichia coli-ESBL and Acinetobacter baumannii were moderate/high biofilm producers. Notably, those strains classified as non-biofilm producers, were always associated with biofilm producer bacteria in polymicrobial colonization. This study shows that biofilm producers were present in all chronic skin ulcers, suggesting that biofilm represents a key virulence determinant in promoting bacterial persistence and chronicity of ulcerative lesions independently from the MDRO phenotype. PMID:28513576
NASA Astrophysics Data System (ADS)
Proctor, K. W.; Montgomery, Q. W.; Prairie, J. C.
2016-02-01
Marine snow aggregates play a fundamental role in the marine carbon cycle. Since marine snow aggregates are larger and thus sink faster than individual phytoplankton, aggregates often dominate carbon flux. Previous studies have shown that marine snow aggregates will significantly decrease their settling velocity when passing through sharp density transitions within the ocean, a phenomenon defined as delayed settling. Given the importance of aggregate settling to carbon export, these small-scale changes in aggregate settling dynamics may have significant impacts on the efficiency of the biological pump. However, there is still a lack of knowledge about how different physical properties of aggregates can affect this delayed settling. In this study, we investigated the effect of phytoplankton growth phase on delayed settling behavior. Using phytoplankton cultures stopped at four different growth phases, we formed marine snow aggregates in the laboratory in rotating cylindrical tanks. We then observed individual aggregates as they settled through a stratified tank. We will present data which illustrates that aggregates experience greatly reduced settling rates when passing through sharp density gradients and that the growth phase of the phytoplankton used to form these aggregates has a significant effect on this delayed settling behavior. A thorough understanding of the impact of phytoplankton growth phase on the delayed settling behavior of marine snow will offer insight into the way phytoplankton growth phase may influence the efficiency of the biological pump, carbon flux, and the carbon cycle as a whole.
Long noncoding RNA BC200 regulates cell growth and invasion in colon cancer.
Wu, Kaiming; Xu, Kaiwu; Liu, Kuanzhi; Huang, Jiehong; Chen, Jianhui; Zhang, Jian; Zhang, Ning
2018-06-01
Colon cancer is the third most commonly diagnosed and deadly cancer worldwide. Efforts have been made to characterize its pathological mechanisms and to explore new therapeutic targets of this disease. Aberrant expression of long noncoding RNAs (lncRNAs) has been associated with the pathogenesis of colon cancer. In the current study, we aimed to define the biological mechanism of the lncRNA BC200 in colon cancer. Here, we found that expression of BC200 was up-regulated in colon cancer tissues as compared with adjacent non-cancerous tissues. The BC200 level was positively correlated with advanced TNM stage. The Kaplan-Meier method indicated that the cumulative survival rate was significantly lower in patients with high BC200 expression than in those with low BC200 expression. Interestingly, we found that knockdown of BC200 inhibited proliferation of HCT-116 and HT29 colon cancer cell lines and reduce the expression of cell proliferation markers, such as Ki-67 and PCNA. In addition, silencing of BC200 could induce obvious G0/G1 arrest and cause apoptosis in HCT-116 and HT29 cells and reduced the expression of cyclin D1, cyclin E, and c-Myc through inhibiting the expression of β-catenin. Importantly, we found that knockdown of BC200 reduced invasion of HCT-116 and HT29 cells and epithelial-mesenchymal transition (EMT) by reducing the expression of MMP-2 and MMP-9. Mechanistically, silencing of BC200 significantly reduced the phosphorylation of STAT3. Overall, the findings presented here suggest that lncRNA BC200 may serve as a novel oncogene and a new therapeutic target for colon cancer. Copyright © 2018. Published by Elsevier Ltd.
CARMA3 is overexpressed in colon cancer and regulates NF-{kappa}B activity and cyclin D1 expression
DOE Office of Scientific and Technical Information (OSTI.GOV)
Miao, Zhifeng; Zhao, Tingting; Wang, Zhenning
2012-09-07
Highlights: Black-Right-Pointing-Pointer CARMA3 expression is elevated in colon cancers. Black-Right-Pointing-Pointer CARMA3 promotes proliferation and cell cycle progression in colon cancer cells. Black-Right-Pointing-Pointer CARMA3 upregulates cyclinD1 through NF-{kappa}B activation. -- Abstract: CARMA3 was recently reported to be overexpressed in cancers and associated with the malignant behavior of cancer cells. However, the expression of CARMA3 and its biological roles in colon cancer have not been reported. In the present study, we analyzed the expression pattern of CARMA3 in colon cancer tissues and found that CARMA3 was overexpressed in 30.8% of colon cancer specimens. There was a significant association between CARMA3 overexpression andmore » TNM stage (p = 0.0383), lymph node metastasis (p = 0.0091) and Ki67 proliferation index (p = 0.0035). Furthermore, knockdown of CARMA3 expression in HT29 and HCT116 cells with high endogenous expression decreased cell proliferation and cell cycle progression while overexpression of CARMA3 in LoVo cell line promoted cell proliferation and facilitated cell cycle transition. Further analysis showed that CARMA3 knockdown downregulated and its overexpression upregulated cyclin D1 expression and phospho-Rb levels. In addition, we found that CARMA3 depletion inhibited p-I{kappa}B levels and NF-{kappa}B activity and its overexpression increased p-I{kappa}B expression and NF-{kappa}B activity. NF-{kappa}B inhibitor BAY 11-7082 reversed the role of CARMA3 on cyclin D1 upregulation. In conclusion, our study found that CARMA3 is overexpressed in colon cancers and contributes to malignant cell growth by facilitating cell cycle progression through NF-{kappa}B mediated upregulation of cyclin D1.« less
Lan, Annaïg; Andriamihaja, Mireille; Blouin, Jean-Marc; Liu, Xinxin; Descatoire, Véronique; Desclée de Maredsous, Caroline; Davila, Anne-Marie; Walker, Francine; Tomé, Daniel; Blachier, François
2015-01-01
We have previously shown that high-protein (HP) diet ingestion causes marked changes in the luminal environment of the colonic epithelium. This study aimed to evaluate the impact of such modifications on small intestinal and colonic mucosa, two segments with different transit time and physiological functions. Rats were fed with either normal protein (NP; 14% protein) or HP (53% protein) isocaloric diet for 2 weeks, and parameters related to intestinal mucous-secreting cells and to several innate/adaptive immune characteristics (myeloperoxidase activity, cytokine and epithelial TLR expression, proportion of immune cells in gut-associated lymphoid tissues) were measured in the ileum and colon. In ileum from HP animals, we observed hyperplasia of mucus-producing cells concomitant with an increased expression of Muc2 at both gene and protein levels, reduction of mucosal myeloperoxidase activity, down-regulation of Tlr4 gene expression in enterocytes and down-regulation of mucosal Th cytokines associated with CD4+ lymphocyte reduction in mesenteric lymph nodes. These changes coincided with an increased amount of acetate in the ileal luminal content. In colon, HP diet ingestion resulted in a lower number of goblet cells at the epithelial surface but increased goblet cell number in colonic crypts together with an increased Muc3 and a slight reduction of Il-6 gene expression. Our data suggest that HP diet modifies the goblet cell distribution in colon and, in ileum, increases goblet cell activity and decreases parameters related to basal gut inflammatory status. The impact of HP diet on intestinal mucosa in terms of beneficial or deleterious effects is discussed. Copyright © 2015 Elsevier Inc. All rights reserved.
Zheng, Xiaodan; Xie, Jianlan; Zhou, Xiaoge
2015-01-01
Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disease (LPD) is not uncommon in China, but gastrointestinal involvement is very rare. We report on an immunocompetent patient with EBV-associated T-cell LPD of the colon. The 26-year-old man was initially misdiagnosed with ulcerative colitis (UC). A colon biopsy revealed the presence of small to medium-sized lymphoid cells infiltrating the intestinal wall. The neoplastic cells expressed CD3, CD5, and granzyme B, not CD56. EBV-encoded small ribonucleic acid was detected in the tumor cells of the colon as well as the lymph node, and the T-cell receptor gene rearrangement result displayed δ gene monoclonal rearrangement. The patient died 2 moths after the diagnosis. The clinical course of EBV-associated T-cell LPD is aggressive and the prognosis is poor, the wrong diagnosis may delay treatment. Therefore, we should be very careful to prevent misdiagnosis. When patients have multiple intestinal ulcers that are not typical of UC and the clinical course is unusual, although morphology looks like inflammatory change, pathologist should consider the possibility of EBV-associated LPD. The treatment strategy and prognosis of these two diseases are different.
Tchirikov, Michael; Zhumadilov, Zhaxybay; Winarno, Andreas Suhartoyo; Haase, Roland; Buchmann, Jörg
2017-01-01
Bacterial infection is one of the main causes of preterm premature rupture of membranes (PPROM) leading to preterm delivery, pulmonary hypoplasia, sepsis and joint deformities. Expectant management, broad-spectrum antibiotics and antenatal corticosteroids are routinely used in this condition with very limited success to prevent bacteremia, chorioamnionitis, funisitis and intra-amniotic infection syndrome. Here, we report a case in which we attempted to treat PPROM at 26+3 weeks of gestation with anhydramnion colonized by multiresistant Klebsiella. A perinatal port system was implanted subcutaneously at 28+0 weeks of gestation, enabling long-term continuous lavage of the amniotic cavity with a hypotonic aqueous composition similar to human amniotic fluid combined with intra-amniotic antibiotic application. The patient gave birth to a preterm female infant at 31+1 weeks without any signs of infection. The girl was discharged with a weight of 2,730 g in very good condition. In the follow-up examinations at 5 months and 1 year of age, there was no apparent neurological disturbance, developmental delay or Klebsiella colonization. © 2015 The Author(s) Published by S. Karger AG, Basel.
Cavalcanti, Natália Silva; da Silva, Lorena Luryann Cartaxo; da Silva, Leonardo Sales; da Fonseca, Luiz Antonio Cavalcante; Alexandre, Cristianne da Silva
2013-01-01
Enterovesical fistula are pathological connections between the bladder and pelvic intestinal segments. It consists of a rare complication of neoplastic and inflammatory pelvic disorders, in addition to iatrogenic or traumatic injuries, and correlates with both high morbidity and mortality indexes. Male patient, 61 years old, admitted at the hospital clinics featuring abdominal pain and distension, vomiting and fecal retention. Patient's pathological precedents include high blood pressure, diabetes mellitus, vesical dysfunction and recurrent urinary tract infection on the past three years. Magnetic resonance imaging of abdomen and pelvis revealed enterovesical fistula in association with colon diverticular disease of the sigmoid. Management of choice consisted of partial colectomy with bowel lowering and partial cystectomy with surgical double-J stent insertion. Although consisting of a gastrointestinal primary affection, patients with enterovesical fistula usually search for medical help charging urinary tract features. In this particular case, our patient was admitted with gastrointestinal symptoms, reasoned by diagnostic delay, as the patient had already attended at multiple centers with urinary symptoms. Despite being an unusual affection, recurrent urinary tract infection associated with colon diverticular disease must always be considered at differential diagnosis of recurrent urinary tract infection as it concurs with high morbidity and mortality.
Management of Pneumocystis jirovecii Pneumonia in Kidney Transplantation to Prevent Further Outbreak
Goto, Norihiko; Futamura, Kenta; Okada, Manabu; Yamamoto, Takayuki; Tsujita, Makoto; Hiramitsu, Takahisa; Narumi, Shunji; Watarai, Yoshihiko
2015-01-01
The outbreak of Pneumocystis jirovecii pneumonia (PJP) among kidney transplant recipients is emerging worldwide. It is important to control nosocomial PJP infection. A delay in diagnosis and treatment increases the number of reservoir patients and the number of cases of respiratory failure and death. Owing to the large number of kidney transplant recipients compared to other types of organ transplantation, there are greater opportunities for them to share the same time and space. Although the use of trimethoprim-sulfamethoxazole (TMP-SMX) as first choice in PJP prophylaxis is valuable for PJP that develops from infections by trophic forms, it cannot prevent or clear colonization, in which cysts are dominant. Colonization of P. jirovecii is cleared by macrophages. While recent immunosuppressive therapies have decreased the rate of rejection, over-suppressed macrophages caused by the higher levels of immunosuppression may decrease the eradication rate of colonization. Once a PJP cluster enters these populations, which are gathered in one place and uniformly undergoing immunosuppressive therapy for kidney transplantation, an outbreak can occur easily. Quick actions for PJP patients, other recipients, and medical staff of transplant centers are required. In future, lifelong prophylaxis may be required even in kidney transplant recipients. PMID:26609250
Colonic transit time and pressure based on Bernoulli’s principle
Uno, Yoshiharu
2018-01-01
Purpose Variations in the caliber of human large intestinal tract causes changes in pressure and the velocity of its contents, depending on flow volume, gravity, and density, which are all variables of Bernoulli’s principle. Therefore, it was hypothesized that constipation and diarrhea can occur due to changes in the colonic transit time (CTT), according to Bernoulli’s principle. In addition, it was hypothesized that high amplitude peristaltic contractions (HAPC), which are considered to be involved in defecation in healthy subjects, occur because of cecum pressure based on Bernoulli’s principle. Methods A virtual healthy model (VHM), a virtual constipation model and a virtual diarrhea model were set up. For each model, the CTT was decided according to the length of each part of the colon, and then calculating the velocity due to the cecum inflow volume. In the VHM, the pressure change was calculated, then its consistency with HAPC was verified. Results The CTT changed according to the difference between the cecum inflow volume and the caliber of the intestinal tract, and was inversely proportional to the cecum inflow volume. Compared with VHM, the CTT was prolonged in the virtual constipation model, and shortened in the virtual diarrhea model. The calculated pressure of the VHM and the gradient of the interlocked graph were similar to that of HAPC. Conclusion The CTT and HAPC can be explained by Bernoulli’s principle, and constipation and diarrhea may be fundamentally influenced by flow dynamics. PMID:29670388
Influence of Sensor Ingestion Timing on Consistency of Temperature Measures
2009-01-01
volunteers orally ingested an ITS (VitalSense Jonah Ingestible Capsule ; Minimitter Inc.). From 1300 to 1700 h, volunteers per- formed structured...emptying and gastrointes- tinal transit. Clin Investig. 1992;70(6):487–91. 24. Rao SS, Welcher K, Zimmerman B, Stumbo P. Is coffee a colonic stimulant? Eur J
Democracy, Human Rights and the Role of Teachers
ERIC Educational Resources Information Center
Kang, Soon-Won
2007-01-01
This paper focuses on the historical review of neo-liberalism in Korean education with relevance to human rights education and teachers movement. In transition to post-colonial society, Korea confronts polarization of education. From the first stage just after the independence from Japanese Colonization in 1945 to the fifth present stage, Korean…
Severe splenic rupture after colorectal endoscopic submucosal dissection
Herreros de Tejada, Alberto; Giménez-Alvira, Luis; Van den Brule, Enrique; Sánchez-Yuste, Rosario; Matallanos, Pilar; Blázquez, Esther; Calleja, Jose L; Abreu, Luis E
2014-01-01
Splenic rupture (SR) after colonoscopy is a very rare but potentially serious complication. Delayed diagnosis is common, and may increase morbidity and mortality associated. There is no clear relation between SR and difficult diagnostic or therapeutic procedures, but it has been suggested that loop formation and excessive torquing might be risk factors. This is a case of a 65-year-old woman who underwent endoscopic submucosal dissection (ESD) for lateral spreading tumor in the descending colon, and 36 h afterwards presented symptoms and signs of severe hypotension due to SR. Standard splenectomy was completed and the patient recovered uneventfully. Colorectal ESD is usually a long and position-demanding technique, implying torquing and loop formation. To our knowledge this is the first case of SR after colorectal ESD reported in the literature. Endoscopists performing colorectal ESD in the left colon must be aware of this potential complication. PMID:25071360
Preventive Effects of Cocoa and Cocoa Antioxidants in Colon Cancer
Martín, María Angeles; Goya, Luis; Ramos, Sonia
2016-01-01
Colorectal cancer is one of the main causes of cancer-related mortality in the developed world. Carcinogenesis is a multistage process conventionally defined by the initiation, promotion and progression stages. Natural polyphenolic compounds can act as highly effective antioxidant and chemo-preventive agents able to interfere at the three stages of cancer. Cocoa has been demonstrated to counteract oxidative stress and to have a potential capacity to interact with multiple carcinogenic pathways involved in inflammation, proliferation and apoptosis of initiated and malignant cells. Therefore, restriction of oxidative stress and/or prevention or delayed progression of cancer stages by cocoa antioxidant compounds has gained interest as an effective approach in colorectal cancer prevention. In this review, we look over different in vitro and in vivo studies that have identified potential targets and mechanisms whereby cocoa and their flavonoids could interfere with colonic cancer. In addition, evidence from human studies is also illustrated. PMID:28933386
NASA Astrophysics Data System (ADS)
Wang, Zhefu; Wang, Liang; Fu, Song
2017-09-01
Sensitivity analyses and non-linear parabolized stability equations are solved to provide a computational assessment of the potential use of a Dielectric Barrier Discharge (DBD) plasma actuator for a prolonging laminar region in swept Hiemenz flow. The derivative of the kinetic energy with respect to the body force is deduced, and its components in different directions are defined as sensitivity functions. The results of sensitivity analyses and non-linear parabolized stability equations both indicate that the introduction of a body force as the plasma actuator at the bottom of a crossflow vortex can mitigate instability to delay flow transition. In addition, the actuator is more effective when placed more upstream until the neutral point. In fact, if the actuator is sufficiently close to the neutral point, it is likely to act as a strong disturbance over-riding the natural disturbance and dominating transition. Different operating voltages of the DBD actuators are tested, resulting in an optimal practice for transition delay. The results demonstrate that plasma actuators offer great potential for transition control.
Shiga, Takeki; Suzuki, Hiroyuki; Yamamoto, Ayumi; Yamamoto, Hiroaki; Yamamoto, Kazuo
2010-01-01
Previously, we have shown that phenyl hydroquinone, a hepatic metabolite of the Ames test-negative carcinogen o-phenylphenol, efficiently induced aneuploidy in Saccharomyces cerevisiae by arresting the cell cycle at the G2/M transition as a result of the activation of the Hog1 (p38 MAPK homolog)-Swe1 (Wee1 homolog) pathway. In this experiment, we examined the aneuploidy forming effects of hydroquinone, a benzene metabolite, since both phenyl hydroquinone and hydroquinone are Ames-test negative carcinogens and share similar molecular structures. As was seen in phenyl hydroquinone, hydroquinone induced aneuploidy in yeast by delaying the cell cycle at the G2/M transition. Deficiencies in SWE1 and HOG1 abolished the hydroquinone-induced delay at the G2/M transition and aneuploidy formation. Furthermore, Hog1 was phosphorylated by hydroquinone, which may stabilize Swe1. These data indicate that the hydroquinone-induced G2/M transition checkpoint, which is activated by the Hog1-Swe1 pathway, plays a role in the formation of aneuploidy.
ERIC Educational Resources Information Center
Ivy, Sarah E.; Hooper, Jonathan D.
2015-01-01
Introduction: Many students with adventitious vision loss or progressive vision loss need to transition from print to braille as a primary literacy medium. It is important that this transition is handled efficiently so that the student can have continued access to a literacy medium and make progress in the core curriculum. For this study, we used…
West, Christine; Stanisz, Andrew M; Wong, Annette; Kunze, Wolfgang A
2016-12-28
To investigate the capacity of Saccharomyces cerevisiae ( S. cerevisiae ) and Saccharomyces boulardii ( S. boulardii ) yeasts to reverse or to treat acute stress-related intestinal dysmotility. Adult Swiss Webster mice were stressed for 1 h in a wire-mesh restraint to induce symptoms of intestinal dysmotility and were subsequently killed by cervical dislocation. Jejunal and colon tissue were excised and placed within a tissue perfusion bath in which S. cerevisiae , S. boulardii , or their supernatants were administered into the lumen. Video recordings of contractility and gut diameter changes were converted to spatiotemporal maps and the velocity, frequency, and amplitude of propagating contractile clusters (PCC) were measured. Motility pre- and post-treatment was compared between stressed animals and unstressed controls. S. boulardii and S. cerevisiae helped to mediate the effects of stress on the small and large intestine. Restraint stress reduced jejunal transit velocity (mm/s) from 2.635 ± 0.316 to 1.644 ± 0.238, P < 0.001 and jejunal transit frequency (Hz) from 0.032 ± 0.008 to 0.016 ± 0.005, P < 0.001. Restraint stress increased colonic transit velocity (mm/s) from 0.864 ± 0.183 to 1.432 ± 0.329, P < 0.001 and frequency to a lesser degree. Luminal application of S. boulardii helped to restore jejunal and colonic velocity towards the unstressed controls; 1.833 ± 0.688 to 2.627 ± 0.664, P < 0.001 and 1.516 ± 0.263 to 1.036 ± 0.21, P < 0.001, respectively. S. cerevisiae also had therapeutic effects on the stressed gut, but was most apparent in the jejunum. S. cerevisiae increased PCC velocity in the stressed jejunum from 1.763 ± 0.397 to 2.017 ± 0.48, P = 0.0031 and PCC frequency from 0.016 ± 0.009 to 0.027 ± 0.007, P < 0.001. S. cerevisiae decreased colon PCC velocity from 1.647 ± 0.187 to 1.038 ± 0.222, P < 0.001. Addition of S. boulardii or S. cerevisiae supernatants also helped to restore motility to unstressed values in similar capacity. There is a potential therapeutic role for S. cerevisiae and S. boulardii yeasts and their supernatants in the treatment of acute stress-related gut dysmotility.
West, Christine; Stanisz, Andrew M; Wong, Annette; Kunze, Wolfgang A
2016-01-01
AIM To investigate the capacity of Saccharomyces cerevisiae (S. cerevisiae) and Saccharomyces boulardii (S. boulardii) yeasts to reverse or to treat acute stress-related intestinal dysmotility. METHODS Adult Swiss Webster mice were stressed for 1 h in a wire-mesh restraint to induce symptoms of intestinal dysmotility and were subsequently killed by cervical dislocation. Jejunal and colon tissue were excised and placed within a tissue perfusion bath in which S. cerevisiae, S. boulardii, or their supernatants were administered into the lumen. Video recordings of contractility and gut diameter changes were converted to spatiotemporal maps and the velocity, frequency, and amplitude of propagating contractile clusters (PCC) were measured. Motility pre- and post-treatment was compared between stressed animals and unstressed controls. RESULTS S. boulardii and S. cerevisiae helped to mediate the effects of stress on the small and large intestine. Restraint stress reduced jejunal transit velocity (mm/s) from 2.635 ± 0.316 to 1.644 ± 0.238, P < 0.001 and jejunal transit frequency (Hz) from 0.032 ± 0.008 to 0.016 ± 0.005, P < 0.001. Restraint stress increased colonic transit velocity (mm/s) from 0.864 ± 0.183 to 1.432 ± 0.329, P < 0.001 and frequency to a lesser degree. Luminal application of S. boulardii helped to restore jejunal and colonic velocity towards the unstressed controls; 1.833 ± 0.688 to 2.627 ± 0.664, P < 0.001 and 1.516 ± 0.263 to 1.036 ± 0.21, P < 0.001, respectively. S. cerevisiae also had therapeutic effects on the stressed gut, but was most apparent in the jejunum. S. cerevisiae increased PCC velocity in the stressed jejunum from 1.763 ± 0.397 to 2.017 ± 0.48, P = 0.0031 and PCC frequency from 0.016 ± 0.009 to 0.027 ± 0.007, P < 0.001. S. cerevisiae decreased colon PCC velocity from 1.647 ± 0.187 to 1.038 ± 0.222, P < 0.001. Addition of S. boulardii or S. cerevisiae supernatants also helped to restore motility to unstressed values in similar capacity. CONCLUSION There is a potential therapeutic role for S. cerevisiae and S. boulardii yeasts and their supernatants in the treatment of acute stress-related gut dysmotility. PMID:28082805
Williams, S; Horner, J; Orton, E; Green, M; McMullen, S; Mobasheri, A; Freeman, S L
2015-01-01
A change in management from pasture to stabling is a risk factor for equine colic. To investigate the effect of a management change from pasture with no controlled exercise to stabling with light exercise on aspects of gastrointestinal function related to large colon impaction. The hypothesis was that drinking water intake, faecal output, faecal water content and large intestinal motility would be altered by a transition from a pastured to a stabled regime. Within-subject management intervention trial involving changes in feeding and exercise using noninvasive techniques. Seven normal horses were evaluated in a within-subjects study design. Horses were monitored while at pasture 24 h/day, and for 14 days following a transition to a stabling regime with light controlled exercise. Drinking water intake, faecal output and faecal dry matter were measured. Motility of the caecum, sternal flexure and left colon (contractions/min) were measured twice daily by transcutaneous ultrasound. Mean values were pooled for the pastured regime and used as a reference for comparison with stabled data (Days 1-14 post stabling) for multilevel statistical analysis. Drinking water intake was significantly increased (mean ± s.d. pasture 2.4 ± 1.8 vs. stabled 6.4 ± 0.6 l/100 kg bwt/day), total faecal output was significantly decreased (pasture 4.62 ± 1.69 vs. stabled 1.81 ± 0.5 kg/100 kg bwt/day) and faecal dry matter content was significantly increased (pasture 18.7 ± 2.28 vs. stabled 27.2 ± 1.93% DM/day) on all days post stabling compared with measurements taken at pasture (P<0.05). Motility was significantly decreased in all regions of the large colon collectively on Day 2 post stabling (-0.76 contractions/min), and in the left colon only on Day 4 (-0.62 contractions/min; P<0.05). There were significant changes in large intestinal motility patterns and parameters relating to gastrointestinal water balance during a transition from pasture to stabled management, particularly during the first 5 days. © 2014 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
Atomic clouds as spectrally selective and tunable delay lines for single photons from quantum dots
NASA Astrophysics Data System (ADS)
Wildmann, Johannes S.; Trotta, Rinaldo; Martín-Sánchez, Javier; Zallo, Eugenio; O'Steen, Mark; Schmidt, Oliver G.; Rastelli, Armando
2015-12-01
We demonstrate a compact, spectrally selective, and tunable delay line for single photons emitted by quantum dots. This is achieved by fine-tuning the wavelength of the optical transitions of such "artificial atoms" into a spectral window in which a cloud of natural atoms behaves as a slow-light medium. By employing the ground-state fine-structure-split exciton confined in an InGaAs/GaAs quantum dot as a source of single photons at different frequencies and the hyperfine-structure-split D1 transition of Cs-vapors as a tunable delay medium, we achieve a differential delay of up 2.4 ns on a 7.5-cm-long path for photons that are only 60 μ eV (14.5 GHz) apart. To quantitatively explain the experimental data, we develop a theoretical model that accounts for both the inhomogeneous broadening of the quantum-dot emission lines and the Doppler broadening of the atomic lines. The concept we proposed here may be used to implement time-reordering operations aimed at erasing the "which-path" information that deteriorates entangled-photon emission from excitons with finite fine-structure splitting.
Constipation: evaluation and treatment of colonic and anorectal motility disorders.
Rao, Satish S C
2007-09-01
This article focuses on the colonic and anorectal motility disturbances that are associated with chronic constipation and their management. Functional chronic constipation consists of three overlapping subtypes: slow transit constipation, dyssynergic defecation, and irritable bowel syndrome with constipation. The Rome criteria may serve as a useful guide for making a clinical diagnosis of functional constipation. Today, an evidence-based approach can be used to treat patients with chronic constipation. The availability of specific drugs for the treatment of chronic constipation, such as tegaserod and lubiprostone, has enhanced the therapeutic armamentarium for managing these patients. Randomized controlled trials have also established the efficacy of biofeedback therapy in the treatment of dyssynergic defecation.
Mosińska, Paula; Fichna, Jakub; Storr, Martin
2015-06-28
Chronic idiopathic constipation is a common disorder of the gastrointestinal tract that encompasses a wide profile of symptoms. Current treatment options for chronic idiopathic constipation are of limited value; therefore, a novel strategy is necessary with an increased effectiveness and safety. Recently, the inhibition of the ileal bile acid transporter has become a promising target for constipation-associated diseases. Enhanced delivery of bile acids into the colon achieves an accelerated colonic transit, increased stool frequency, and relief of constipation-related symptoms. This article provides insight into the mechanism of action of ileal bile acid transporter inhibitors and discusses their potential clinical use for pharmacotherapy of constipation in chronic idiopathic constipation.
Hydrogen jet combustion in a scramjet combustor with the rearwall-expansion cavity
NASA Astrophysics Data System (ADS)
Zhang, Yan-Xiang; Wang, Zhen-Guo; Sun, Ming-Bo; Yang, Yi-Xin; Wang, Hong-Bo
2018-03-01
This study is carried out to experimentally investigate the combustion characteristics of the hydrogen jet flame stabilized by the rearwall-expansion cavity in a model scramjet combustor. The flame distributions are characterized by the OH* spontaneous emission images, and the dynamic features of the flames are studied through the high speed framing of the flame luminosity. The combustion modes are further analyzed based on the visual flame structure and wall pressure distributions. Under the present conditions, the combustion based on the rearwall-expansion cavity appears in two distinguished modes - the typical cavity shear-layer stabilized combustion mode and the lifted-shear-layer stabilized combustion mode. In contrast with the shear-layer stabilized mode, the latter holds stronger flame. The transition from shear-layer stabilized combustion mode to lifted-shear-layer stabilized mode usually occurs when the equivalence ratio is high enough. While the increases of the offset ratio and upstream injection distance both lead to weaker jet-cavity interactions, cause longer ignition delay, and thus delay the mode transition. The results reveal that the rearwall-expansion cavity with an appropriate offset ratio should be helpful in delaying mode transition and preventing thermal choke, and meanwhile just brings minor negative impact on the combustion stability and efficiency.
Li, Meng Amy; Amaral, Paulo P; Cheung, Priscilla; Bergmann, Jan H; Kinoshita, Masaki; Kalkan, Tüzer; Ralser, Meryem; Robson, Sam; von Meyenn, Ferdinand; Paramor, Maike; Yang, Fengtang; Chen, Caifu; Nichols, Jennifer; Spector, David L; Kouzarides, Tony; He, Lin; Smith, Austin
2017-01-01
Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) linc1281, hereafter Ephemeron (Eprn), that modulates the dynamics of exit from naïve pluripotency. Eprn deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression. In the absence of Eprn, Lin28a expression is reduced which results in persistence of let-7 microRNAs, and the up-regulation of de novo methyltransferases Dnmt3a/b is delayed. Dnmt3a/b deletion retards ES cell transition, correlating with delayed Nanog promoter methylation and phenocopying loss of Eprn or Lin28a. The connection from lncRNA to miRNA and DNA methylation facilitates the acute extinction of naïve pluripotency, a pre-requisite for rapid progression from preimplantation epiblast to gastrulation in rodents. Eprn illustrates how lncRNAs may introduce species-specific network modulations. DOI: http://dx.doi.org/10.7554/eLife.23468.001 PMID:28820723
Experimental investigation of self-induced transparency and pulse delay in ruby.
NASA Technical Reports Server (NTRS)
Asher, I. M.
1972-01-01
We have investigated the self-induced transparency effect in ruby over a range of input energies which range from linear absorption to full transparency. The transmission, pulse delay, and pulse broadening were studied as a function of input energy. The transition region is narrower than that found in similar studies of the CO2/SF6 system; this is consistent with predictions based on ensembles of two-level systems. Included are the first pulse-delay and pulse-broadening curves to be obtained for the ruby system.
Gorgun, Emre; Benlice, Cigdem; Abbas, Maher A; Steele, Scott
2018-07-01
Need for colon sparing interventions for premalignant lesions not amenable to conventional endoscopic excision has stimulated interest in advanced endoscopic approaches. The aim of this study was to report a single institution's experience with these techniques. A retrospective review was conducted of a prospectively collected database of all patients referred between 2011 and 2015 for colorectal resection of benign appearing deemed endoscopically unresectable by conventional endoscopic techniques. Patients were counseled for endoscopic submucosal dissection (ESD) with possible combined endoscopic-laparoscopic surgery (CELS) or alternatively colorectal resection if unable to resect endoscopically or suspicion for cancer. Lesion characteristic, resection rate, complications, and outcomes were evaluated. 110 patients were analyzed [mean age 64 years, female gender 55 (50%), median body mass index 29.4 kg/m 2 ]. Indications for interventions were large polyp median endoscopic size 3 cm (range 1.5-6.5) and/or difficult location [cecum (34.9%), ascending colon (22.7%), transverse colon (14.5%), hepatic flexure (11.8%), descending colon (6.3%), sigmoid colon (3.6%), rectum (3.6%), and splenic flexure (2.6%)]. Lesion morphology was sessile (N = 98, 93%) and pedunculated (N = 12, 7%). Successful endoscopic resection rate was 88.2% (N = 97): ESD in 69 patients and CELS in 28 patients. Complication rate was 11.8% (13/110) [delayed bleeding (N = 4), perforation (N = 3), organ-space surgical site infection (SSI) (N = 2), superficial SSI (N = 1), and postoperative ileus (N = 3)]. Out of 110 patients, 13 patients (11.8%) required colectomy for technical failure (7 patients) or carcinoma (6 patients). During a median follow-up of 16 months (range 6-41 months), 2 patients had adenoma recurrence. Advanced endoscopic surgery appears to be a safe and effective alternative to colectomy for patients with complex premalignant lesions deemed unresectable with conventional endoscopic techniques.
Håkansson, Åsa; Bränning, Camilla; Molin, Göran; Adawi, Diya; Hagslätt, Marie-Louise; Jeppsson, Bengt; Nyman, Margareta; Ahrné, Siv
2012-01-01
Long-term colonic inflammation promotes carcinogenesis and histological abnormalities of the liver, and colorectal tumours frequently arise in a background of dysplasia, a precursor of adenomas. Altered colonic microbiota with an increased proportion of bacteria with pro-inflammatory characteristics, have been implicated in neoplastic progression. The composition of the microbiota can be modified by dietary components such as probiotics, polyphenols and dietary fibres. In the present study, the influence of probiotics in combination with blueberry husks on colorectal carcinogenesis and subsequent liver damage was evaluated. Colorectal tumours were induced in rats by cyclic treatment with dextran sulphate sodium (DSS). Blueberry husks and a mixture of three probiotic strains (Bifidobacterium infantis DSM 15159, Lactobacillus gasseri, DSM 16737 and Lactobacillus plantarum DSM 15313) supplemented a basic diet fortified with oats. The condition of the rats was monitored using a disease activity index (DAI). A qualitative and quantitative histological judgement was performed on segments of distal colon and rectum and the caudate lobe of the liver. The formation of short-chain fatty acids, bacterial translocation, the inflammatory reaction and viable count of lactobacilli and Enterobaceriaceae were addressed. Blueberry husks with or without probiotics significantly decreased DAI, and significantly reduced the number of colonic ulcers and dysplastic lesions. With a decreased proportion of blueberry husk in the diet, the probiotic supplement was needed to achieve a significant decrease in numbers of dysplastic lesions. Probiotics decreased faecal viable count of Enterobacteriaceae and increased that of lactobacilli. Blueberry husks with or without probiotics lowered the proportion of butyric acid in distal colon, and decreased the haptoglobin levels. Probiotics mitigated hepatic injuries by decreasing parenchymal infiltration and the incidence of stasis and translocation. The results demonstrate a dietary option for use of blueberry husks and probiotics to delay colonic carcinogenesis and hepatic injuries in the rat model. PMID:22457771
Low-FODMAP vs regular rye bread in irritable bowel syndrome: Randomized SmartPill® study.
Pirkola, Laura; Laatikainen, Reijo; Loponen, Jussi; Hongisto, Sanna-Maria; Hillilä, Markku; Nuora, Anu; Yang, Baoru; Linderborg, Kaisa M; Freese, Riitta
2018-03-21
To compare the effects of regular vs low-FODMAP rye bread on irritable bowel syndrome (IBS) symptoms and to study gastrointestinal conditions with SmartPill ® . Our aim was to evaluate if rye bread low in FODMAPs would cause reduced hydrogen excretion, lower intraluminal pressure, higher colonic pH, different transit times, and fewer IBS symptoms than regular rye bread. The study was a randomized, double-blind, controlled cross-over meal study. Female IBS patients ( n = 7) ate study breads at three consecutive meals during one day. The diet was similar for both study periods except for the FODMAP content of the bread consumed during the study day. Intraluminal pH, transit time, and pressure were measured by SmartPill, an indigestible motility capsule. Hydrogen excretion (a marker of colonic fermentation) expressed as area under the curve (AUC) (0-630 min) was [median (range)] 6300 (1785-10800) ppm∙min for low-FODMAP rye bread and 10 635 (4215-13080) ppm∙min for regular bread ( P = 0.028). Mean scores of gastrointestinal symptoms showed no statistically significant differences but suggested less flatulence after low-FODMAP bread consumption ( P = 0.063). Intraluminal pressure correlated significantly with total symptom score after regular rye bread (ρ = 0.786, P = 0.036) and nearly significantly after low-FODMAP bread consumption (ρ = 0.75, P = 0.052). We found no differences in pH, pressure, or transit times between the breads. Gastric residence of SmartPill was slower than expected. SmartPill left the stomach in less than 5 h only during one measurement (out of 14 measurements in total) and therefore did not follow on par with the rye bread bolus. Low-FODMAP rye bread reduced colonic fermentation vs regular rye bread. No difference was found in median values of intraluminal conditions of the gastrointestinal tract.
Gallium-67 complexes as radioactive markers to assess gastric and colonic transit
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bellen, J.C.; Chatterton, B.E.; Penglis, S.
1995-03-01
Constipation and gastroparesis are gastrointestinal tract disorders that can be assessed by using radioactive markers in conjunction with scintigraphic techniques. Indium-111-DTPA is the radiopharmaceutical of choice for treating colonic transit in constipated patients, but it is an expensive product and its availability has been unreliable. Indium-113m-DTPA was the tracer used in our study to determine the liquid gastric emptying rate in dual-isotope solid-liquid emptying studies, however, cessation of the {sup 113}Sn/{sup 113m}In generator production makes it unavailable. Thus, development of alternative tracers to {sup 111}In-DTPA and {sup 113m}In-DTPA was essential. Gallium-67-citrate and {sup 67}Ga-EDTA were compared to {sup 111}In-DTPA tomore » assess their efficacy for exclusive retention in the GI tract. These markers were orally administered into rats and their three-day cumulative fecal excretion, urine excretion and carcass retention were measured. An in vitro gastric emptying model was used to determine liquid phase partitioning of {sup 113m}In-DTPA, {sup 67}Ga-citrate and {sup 67}Ga-EDTA at 37{degrees}. Gallium-67-citrate was predominantly excreted in the feces (97.2% {+-} 0.2%) after three days, with negligible urine excretion (0.1% {+-} 0.0%) and carcass retention (0.6% {+-} 0.2%). These results are analogous to those obtained for {sup 111}In-DTPA for fecal excretion (96.7% {+-} 2.6%), urine excretion (0.6% {+-} 0.0%) and retention in the carcass (0.2% {+-} 0.0%). Gallium-67-EDTA showed similar partitioning in the liquid phase of the gastric emptying model compared with {sup 113m}In-DTPA. Gallium-67-citrate is an economical and readily available alternative to {sup 111}In-DTPA as a colonic transit radiopharmaceutical. Gallium-67-EDTA is also an alternative to {sup 113m}In-DTPA for assessing liquid-phase emptying in a dual-isotope solid/liquid gastric emptying study. 17 refs., 3 figs., 2 tabs.« less
Maitz, Charles A.; Khan, Aslam A.; Kueffer, Peter J.; ...
2017-08-01
Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. We implanted mice with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH 3(CH 2) 15–7,8-C 2B 9H 11] in the lipid bilayer and encapsulated Na 3[1-(2`-B 10H 9)-2-NH 3B 10H 8] within the liposomal core. Mice were irradiated 30 hours after the second injection inmore » a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. In spite of relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.« less
Colonization of disturbed trees by the southern pine bark beetle guild (Coleoptera: Scolytidae)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Flamm, R.O.; Pulley, P.E.; Coulson, R.N.
1993-02-01
The southern pine bark beetle guild [Dendroctonus frontalis Zimmermann, D. terebrans (Olivier), Ips calligraphus (Germar), I. grandicollis (Eichhoff), and I. avulsus (Eichhoff)] uses disturbed hosts as habitat for establishment of within-tree populations. The process of colonization of disturbed hosts was examined. Using a procedure designed to emulate effects of a lightning strike, pines were severely disturbed. Response was characterized by measuring beetle populations that (1) arrived at the trees and (2) successfully attacked the trees. Establishment of within-tree populations was characterized by measuring length of egg gallery excavated by attacking adults. The time delay between arrival and attack for D.more » frontalis and I. calligraphus was also calculated. Attack densities of both species became asymptotic as arrival increased. The percentage of arriving beetles that attacked ranged from 9 to 41 for D. frontalis and from 8 to 59 for I. calligraphus. Numbers of beetles that arrived at the tree but did not attack ranged from 2.7 to 50.2 beetles per dm[sup 2] for D. frontalis and from 0.2 to 10.0 beetles per dm[sup 2] for I. calligraphus. Most D. frontalis and I. calligraphus attacked on the day they arrived. The delay between arrival and attack was longer for I. calligraphus than the D. frontalis. Egg gallery excavated by D. frontalis increased throughout the study. Eventually, the Ips species were excluded from the lower half of the hole. The low attack densities observed in this study illustrate the significance of disturbed trees in providing refuges for enzootic levels of bark beetles. The aggregation behavior of beetle populations colonizing disturbed hosts supported the contention that these trees serve as foci for initiation of infestations. Furthermore, in disturbed pines, small numbers of beetles were capable of overcoming host defense systems.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Maitz, Charles A.; Khan, Aslam A.; Kueffer, Peter J.
Boron neutron capture therapy (BNCT) was performed at the University of Missouri Research Reactor in mice bearing CT26 colon carcinoma flank tumors and the results were compared with previously performed studies with mice bearing EMT6 breast cancer flank tumors. We implanted mice with CT26 tumors subcutaneously in the caudal flank and were given two separate tail vein injections of unilamellar liposomes composed of cholesterol, 1,2-distearoyl-sn-glycer-3-phosphocholine, and K[nido-7-CH 3(CH 2) 15–7,8-C 2B 9H 11] in the lipid bilayer and encapsulated Na 3[1-(2`-B 10H 9)-2-NH 3B 10H 8] within the liposomal core. Mice were irradiated 30 hours after the second injection inmore » a thermal neutron beam for various lengths of time. The tumor size was monitored daily for 72 days. In spite of relatively lower tumor boron concentrations, as compared to EMT6 tumors, a 45 minute neutron irradiation BNCT resulted in complete resolution of the tumors in 50% of treated mice, 50% of which never recurred. Median time to tumor volume tripling was 38 days in BNCT treated mice, 17 days in neutron-irradiated mice given no boron compounds, and 4 days in untreated controls. Tumor response in mice with CT26 colon carcinoma was markedly more pronounced than in previous reports of mice with EMT6 tumors, a difference which increased with dose. The slope of the dose response curve of CT26 colon carcinoma tumors is 1.05 times tumor growth delay per Gy compared to 0.09 times tumor growth delay per Gy for EMT6 tumors, indicating that inherent radiosensitivity of tumors plays a role in boron neutron capture therapy and should be considered in the development of clinical applications of BNCT in animals and man.« less
Schenk, John J; Rowe, Kevin C; Steppan, Scott J
2013-11-01
Why some clades are more species-rich than others is a central question in macroevolution. Most hypotheses explaining exceptionally diverse clades involve the emergence of an ecological opportunity caused by a major biogeographic transition or evolution of a key innovation. The radiation of muroid rodents is an ideal model for testing theories of diversification rates in relation to biogeography and ecological opportunity because the group is exceptionally species-rich (comprising nearly one-third of all mammal species), it is ecologically diverse, and it has colonized every major landmass except New Zealand and Antarctica, thus providing multiple replicate radiations. We present an extension of the conventional ecological opportunity model to include a geographic incumbency effect, develop the largest muroid phylogeny to date, and use this phylogeny to test the new model. The nearly 300-species phylogeny based on four nuclear genes is robustly resolved throughout. Consistent with the fossil record, we identified Eurasia as the most likely origin of the group and reconstructed five to seven colonizations of Africa, five of North America, four of Southeast Asia, two of South America, two of Sahul, one of Madagascar, and eight to ten recolonizations of Eurasia. We accounted for incomplete taxon sampling by using multiple statistical methods and identified three corroborated regions of the tree with significant shifts in diversification rates. In several cases, higher rates were associated with the first colonization of a continental area, but most colonizations were not followed by bursts of speciation. We found strong evidence for diversification consistent with the ecological opportunity model (initial burst followed by density-dependent slowdown) in the first colonization of South America and partial support for this model in the first colonization of Sahul. Primary colonizers appear to inhibit the ultimate diversity of secondary colonizers, a pattern of incumbency that is consistent with ecological opportunity, but they did not inhibit initial diversification rates of secondary colonizers. These results indicate that ecological opportunity may be a general but weak process in muroids and one that requires specific circumstances to lead to an adaptive radiation. The total land area, length of time between colonizations, and rank of colonizations did not influence the diversification rates of primary colonizers. Models currently employed to test ecological opportunity do a poor job of explaining muroid diversity. In addition, the various rate-shift metrics identified different clades, suggesting that caution should be used when only one is applied, and we discuss which methods are most appropriate to address different questions of diversification.
Multi-state models for colon cancer recurrence and death with a cured fraction.
Conlon, A S C; Taylor, J M G; Sargent, D J
2014-05-10
In cancer clinical trials, patients often experience a recurrence of disease prior to the outcome of interest, overall survival. Additionally, for many cancers, there is a cured fraction of the population who will never experience a recurrence. There is often interest in how different covariates affect the probability of being cured of disease and the time to recurrence, time to death, and time to death after recurrence. We propose a multi-state Markov model with an incorporated cured fraction to jointly model recurrence and death in colon cancer. A Bayesian estimation strategy is used to obtain parameter estimates. The model can be used to assess how individual covariates affect the probability of being cured and each of the transition rates. Checks for the adequacy of the model fit and for the functional forms of covariates are explored. The methods are applied to data from 12 randomized trials in colon cancer, where we show common effects of specific covariates across the trials. Copyright © 2013 John Wiley & Sons, Ltd.
Analysis of 178 penetrating stomach and small bowel injuries.
Salim, Ali; Teixeira, Pedro G R; Inaba, Kenji; Brown, Carlos; Browder, Timothy; Demetriades, Demetrios
2008-03-01
Surgical site infections (SSIs), such as wound infection, fascial dehiscence, and intraabdominal abscess, commonly occur following penetrating abdominal trauma. However, most of the literature involves penetrating colon injuries. There are few reports describing complications following penetrating stomach and small bowel injuries. Based on the hypothesis that SSIs are commonly found following penetrating stomach and small bowel trauma, a prospective observational study was performed at an academic Level I trauma center from March 1, 2004 until August 31, 2006. The subjects were patients who had sustained a penetrating injury to the stomach or small bowel. Patients were followed for the development of an SSI, defined as wound infection, fascial dehiscence, or intraabdominal abscess. A total of 178 patients were admitted with penetrating stomach or small bowel injuries over the 29-month period. There were 121 (68%) gunshot injuries and 57 (32%) stab wounds. Associated intraabdominal injuries occurred in 74% of patients. Overall, SSIs occurred in 20% of cases. Risk factors for SSI included associated duodenal or colon injury, whereas time to operating room, blood loss, and type and duration of antibiotic use were not. When associated colon injuries were excluded, SSIs occurred in 16% of patients with gastric injuries and 13% of those with small bowel injuries. SSIs commonly follow penetrating stomach and small bowel trauma. Risk factors for SSI include associated duodenal or colon injury. Delay to operating room, blood loss, and type and length of antibiotic prophylaxis were not associated with an increased risk of SSI.
Arthikala, Manoj-Kumar; Sánchez-López, Rosana; Nava, Noreide; Santana, Olivia; Cárdenas, Luis; Quinto, Carmen
2014-05-01
The reactive oxygen species (ROS) generated by respiratory burst oxidative homologs (Rbohs) are involved in numerous plant cell signaling processes, and have critical roles in the symbiosis between legumes and nitrogen-fixing bacteria. Previously, down-regulation of RbohB in Phaseolus vulgaris was shown to suppress ROS production and abolish Rhizobium infection thread (IT) progression, but also to enhance arbuscular mycorrhizal fungal (AMF) colonization. Thus, Rbohs function both as positive and negative regulators. Here, we assessed the effect of enhancing ROS concentrations, by overexpressing PvRbohB, on the P. vulgaris--rhizobia and P. vulgaris--AMF symbioses. We estimated superoxide concentrations in hairy roots overexpressing PvRbohB, determined the status of early and late events of both Rhizobium and AMF interactions in symbiont-inoculated roots, and analyzed the nodule ultrastructure of transgenic plants overexpressing PvRbohB. Overexpression of PvRbohB significantly enhanced ROS production, the formation of ITs, nodule biomass, and nitrogen-fixing activity, and increased the density of symbiosomes in nodules, and the density and size of bacteroides in symbiosomes. Furthermore, PvCAT, early nodulin, PvSS1, and PvGOGAT transcript abundances were elevated in these nodules. By contrast, mycorrhizal colonization was reduced in roots that overexpressed RbohB. Overexpression of PvRbohB augmented nodule efficiency by enhancing nitrogen fixation and delaying nodule senescence, but impaired AMF colonization. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.
Sanitation of wallboard colonized with Stachybotrys chartarum.
Price, D L; Ahearn, D G
1999-07-01
Sections (8 cm2) of unused, nonsterile gypsum wallboard (dry wall) were inoculated with varying densities (10(4) to approximately 10(8)/ml) of conidia from 14- to 21-day cultures of Stachybotrys chartarum grown on cellulose agar. The sections were permitted to air dry and were placed into vessels with 86% or 92% RH and incubated at 22-25 degrees C for up to 12 weeks. The moisture content of the dryboard increased from near 10% to over 35%. Selected sections with confluent surface growth, mainly of S. chartarum, were obtained within 3 weeks. Sections were cleaned with a quaternary or quaternary and chlorine dioxide or a concentrated oxygen-saline solution and treated, in some cases, with a preservative system and returned to humidity vessels. Reemergence of S. chartarum from inoculated and treated surfaces occurred within 5 weeks only with sections treated with the quaternary alone. Other fungi, mostly species of Aspergillus, Chaetomium and Penicillium, slowly colonized (between 9-12 weeks) at least some areas of most treated surfaces and most uninoculated control surfaces. Stachybotrys chartarum was also found on several sections of uninoculated controls. Sections treated with a quaternary/acrylic and placed in a dynamic challenging chamber remained visually free of colonized fungi for over 90 days. These studies indicate that control samples of uninstalled wallboard, available from local distributors, can contain a baseline bioburden, including S. chartarum, that will colonize surfaces under high humidity conditions. Sanitation and preservation treatment of the wallboard can markedly delay regrowth of these fungi, particularly of S. chartarum.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Shanwen; Zhu, Jing; Zuo, Shuai
1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been reported to inhibit proliferation and migration of multiple types of cancer cells. However, the mechanism underlying its anti-metastasis effect is not fully illustrated. In this study, the effect of 1,25(OH)2D3 on TGF-β1/β2-induced epithelial–mesenchymal transition (EMT) is tested in colon cancer cells. The results suggest that 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased invasion and migration of in SW-480 and HT-29 cells. 1,25(OH)2D3 also inhibited the cadherin switch in SW-480 and HT-29 cells. TGF-β1/β2-induced increased expression of EMT-related transcription factors was also inhibited by 1,25(OH)2D3. 1,25(OH)2D3 also inhibited the secretion of MMP-2 and MMP-9 and increased expression of F-actinmore » induced by TGF-β1/β2 in SW-480 cells. Taken together, this study suggests that the suppression of EMT might be one of the mechanisms underlying the anti-metastasis effect of 1,25(OH)2D3 in colon cancer cells. - Highlights: • TGF-β1/β2-induced model of EMT was used in this study to test the effect of 1,25(OH)2D3 on EMT in colon cancer cells. • 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased migration and invasion. • 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased level of EMT-related transcription factors. • 1,25(OH)2D3 inhibited TGF-β1/β2-induced increased expression of F-actin in SW-480 cells.« less
Webber, Alyson F; Heath, Julie A; Fischer, Richard A
2013-01-01
Habitat use has important consequences for avian reproductive success and survival. In coastal areas with recreational activity, human disturbance may limit use of otherwise suitable habitat. Snowy plovers Charadrius nivosus have a patchy breeding distribution along the coastal areas on the Florida Panhandle, USA. Our goal was to determine the relative effects of seasonal human disturbance and habitat requirements on snowy plover habitat use. We surveyed 303 sites for snowy plovers, human disturbance, and habitat features between January and July 2009 and 2010. We made multiple visits during three different sampling periods that corresponded to snowy plover breeding: pre-breeding, incubation, and brood-rearing and used multi-season occupancy models to examine whether human disturbance, habitat features, or both influenced site occupancy, colonization (probability of transition from an unoccupied site to an occupied site), and extinction (probability of transition from an occupied site to an unoccupied site). Snowy plover site occupancy and colonization was negatively associated with human disturbance and site extinction was positively associated with human disturbance. Interdune vegetation had a negative effect on occupancy and colonization, indicating that plovers were less likely to use areas with uniform, dense vegetation among dunes. Also, dune shape, beach debris, and access to low-energy foraging areas influenced site occupancy, colonization, and extinction. Plovers used habitat based on beach characteristics that provided stage-specific resource needs; however, human disturbance was the strongest predictor of site occupancy. In addition, vegetation plantings used to enhance dune rehabilitation may negatively impact plover site occupancy. Management actions that decrease human disturbance, such as symbolic fencing and signage, may increase the amount of breeding habitat available to snowy plovers on the Florida Panhandle and in other areas with high human activity. The specific areas that require this protection may vary across snowy plover life history stages. PMID:23610630
Flahou, Bram; Haesebrouck, Freddy; Pasmans, Frank; D'Herde, Katharina; Driessen, Ann; Van Deun, Kim; Smet, Annemieke; Duchateau, Luc; Chiers, Koen; Ducatelle, Richard
2010-11-22
"Helicobacter (H.) heilmannii" type 1 is the most prevalent gastric non-H. pylori Helicobacter species in humans suffering from gastric disease. It has been shown to be identical to H. suis, a bacterium which is mainly associated with pigs. To obtain better insights into the long-term pathogenesis of infections with this micro-organism, experimental infections were carried out in different rodent models. Mongolian gerbils and mice of two strains (BALB/c and C57BL/6) were infected with H. suis and sacrificed at 3 weeks, 9 weeks and 8 months after infection. Gastric tissue samples were collected for PCR analysis, histological and ultrastructural examination. In gerbils, bacteria mainly colonized the antrum and a narrow zone in the fundus near the forestomach/stomach transition zone. In both mice strains, bacteria colonized the entire glandular stomach. Colonization with H. suis was associated with necrosis of parietal cells in all three animal strains. From 9 weeks after infection onwards, an increased proliferation rate of mucosal epithelial cells was detected in the stomach regions colonized with H. suis. Most gerbils showed a marked lymphocytic infiltration in the antrum and in the forestomach/stomach transition zone, becoming more pronounced in the course of time. At 8 months post infection, severe destruction of the normal antral architecture at the inflamed sites and development of mucosa-associated lymphoid tissue (MALT) lymphoma-like lesions were observed in some gerbils. In mice, the inflammatory response was less pronounced than in gerbils, consisting mainly of mononuclear cell infiltration and being most severe in the fundus. H. suis causes death of parietal cells, epithelial cell hyperproliferation and severe inflammation in mice and Mongolian gerbil models of human gastric disease. Moreover, MALT lymphoma-like lesions were induced in H. suis-infected Mongolian gerbils. Therefore, the possible involvement of this micro-organism in human gastric disease should not be neglected.
ERIC Educational Resources Information Center
Camberis, Anna-Lisa; McMahon, Catherine A.; Gibson, Frances L.; Boivin, Jacky
2014-01-01
In the context of the trend toward delayed parenthood, this study examines whether older maternal age is associated with greater psychological maturity and whether greater psychological maturity provides any adaptive benefit during the transition to motherhood. A sample of 240 predominantly English-speaking Australian women in a metropolitan area…
Kansas Early Childhood Research Institute on Transitions: Executive Summary.
ERIC Educational Resources Information Center
Rice, Mabel L.; O'Brien, Marion
This executive summary reviews activities over the past 5 years of the Kansas Early Childhood Research Institute (KECRI). The Institute has addressed transition issues faced by infants and young children (and their families) who have a disability or are at risk for developmental delay. KECRI goals are stated and the importance and impact of the…
Extreme hydroclimatic events and their socio-economic consequences
NASA Astrophysics Data System (ADS)
Ghil, Michael
2017-04-01
This talk will quickly summarize some earlier work reported in [1,2] and then focus on recent work in progress. The former will include two complementary views on the classical, 1300-year long Nile River records. The latter will cover studies of damage propagation in production-and-supply networks [3,4]. Here we use Boolean delay equations (BDEs), a semi-discrete type of dynamical systems [5], to explore the effect of network topology and of the delays in the supply on network resilience. [1] M. Ghil et al., Nonlin. Processes Geophys. (2011) [2] M. Chavez, M. Ghil & J. Urrutia Fucugauchi, Extreme Events: Observations, Modeling and Economics, Geophys. Monograph 214, AGU & Wiley (2015) [3] B. Coluzzi et al., Intl. J. Bifurcation Chaos (2011) [4] C. Colon & M. Ghil, Chaos, submitted (2017) [5] M. Ghil et al., Physica D (2008)
Pathogenesis of Acute and Delayed Corneal Lesions After Ocular Exposure to Sulfur Mustard Vapor
2012-03-01
using a vapor cup delivery system. The transition from acute to delayed injury was characterized by clinical, histological, and ultrastructural metrics...These data demonstrate a system-based approach combining ultrastructural analysis , histochemistry, and molecular evaluation that links architectural...predictive of the 11% of corneas that underwent asymptomatic recovery. Ultrastructural comparison of asymptomatic and MGK corneas at 8 weeks indicates that MGK
ERIC Educational Resources Information Center
Harris, Aimee; Foster, T. Mary; Levine, Joshua; Temple, William
2012-01-01
Domestic hens responded under multiple fixed-ratio fixed-ratio schedules with equal fixed ratios. One component provided immediate reinforcement and the other provided reinforcement after a delay, signaled by the offset of the key light. The components were presented quasi-randomly so that all four possible transitions occurred in each session.…
Accounting for Laminar Run & Trip Drag in Supersonic Cruise Performance Testing
NASA Technical Reports Server (NTRS)
Goodsell, Aga M.; Kennelly, Robert A.
1999-01-01
An improved laminar run and trip drag correction methodology for supersonic cruise performance testing was derived. This method required more careful analysis of the flow visualization images which revealed delayed transition particularly on the inboard upper surface, even for the largest trip disks. In addition, a new code was developed to estimate the laminar run correction. Once the data were corrected for laminar run, the correct approach to the analysis of the trip drag became evident. Although the data originally appeared confusing, the corrected data are consistent with previous results. Furthermore, the modified approach, which was described in this presentation, extends prior historical work by taking into account the delayed transition caused by the blunt leading edges.
Characterisation of colonic dysplasia-like epithelial atypia in murine colitis
Randall-Demllo, Sarron; Fernando, Ruchira; Brain, Terry; Sohal, Sukhwinder Singh; Cook, Anthony L; Guven, Nuri; Kunde, Dale; Spring, Kevin; Eri, Rajaraman
2016-01-01
AIM To determine if exacerbation of pre-existing chronic colitis in Winnie (Muc2 mutant) mice induces colonic dysplasia. METHODS Winnie mice and C57BL6 as a genotype control, were administered 1% w/v dextran sulphate sodium (DSS) orally, followed by drinking water alone in week-long cycles for a total of three cycles. After the third cycle, mice were killed and colonic tissue collected for histological and immunohistochemical evaluation. Inflammation and severity of dysplasia in the colonic mucosa were assessed in H&E sections of the colon. Epithelial cell proliferation was assessed using Ki67 and aberrant β-catenin signalling assessed with enzyme-based immunohistochemistry. Extracted RNA from colonic segments was used for the analysis of gene expression using real-time quantitative PCR. Finally, the distribution of Cxcl5 was visualised using immunohistochemistry. RESULTS Compared to controls, Winnie mice exposed to three cycles of DSS displayed inflammation mostly confined to the distal-mid colon with extensive mucosal hyperplasia and regenerative atypia resembling epithelial dysplasia. Dysplasia-like changes were observed in 100% of Winnie mice exposed to DSS, with 55% of these animals displaying changes similar to high-grade dysplasia, whereas high-grade changes were absent in wild-type mice. Occasional penetration of the muscularis mucosae by atypical crypts was observed in 27% of Winnie mice after DSS. Atypical crypts however displayed no evidence of oncogenic nuclear β-catenin accumulation, regardless of histological severity. Expression of Cav1, Trp53 was differentially regulated in the distal colon of Winnie relative to wild-type mice. Expression of Myc and Ccl5 was increased by DSS treatment in Winnie only. Furthermore, increased Ccl5 expression correlated with increased complexity in abnormal crypts. While no overall difference in Cxcl5 mucosal expression was observed between treatment groups, epithelial Cxcl5 protein appeared to be diminished in the atypical epithelium. CONCLUSION Alterations to the expression of Cav1, Ccl5, Myc and Trp53 in the chronically inflamed Winnie colon may influence the transition to dysplasia. PMID:27729740
El Oufir, L; Flourié, B; Bruley des Varannes, S; Barry, J L; Cloarec, D; Bornet, F; Galmiche, J P
1996-06-01
To investigate whether transit time could influence H2 consuming flora and certain indices of colonic bacterial fermentation. Eight healthy volunteers (four methane excretors and four non-methane excretors) were studied for three, three week periods during which they received a controlled diet alone (control period), and then the same diet with cisapride or loperamide. At the end of each period, mean transit time (MTT) was estimated, an H2 lactulose breath test was performed, and stools were analysed. In the control period, transit time was inversely related to faecal weight, sulphate reducing bacteria counts, concentrations of total short chain fatty acids (SCFAs), propionic and butyric acids, and H2 excreted in breath after lactulose ingestion. Conversely, transit time was positively related to faecal pH and tended to be related to methanogen counts. Methanogenic bacteria counts were inversely related to those of sulphate reducing bacteria and methane excretors had slower MTT and lower sulphate reducing bacteria counts than non-methane excretors. Compared with the control period, MTT was significantly shortened (p < 0.05) by cisapride and prolonged (p < 0.05) by loperamide (73 (11) hours, 47 (5) hours and 147 (12) hours for control, cisapride, and loperamide, respectively, mean (SD)). Cisapride reduced transit time was associated with (a) a significant rise in faecal weight, sulphate reducing bacteria, concentrations of total SCFAs, and propionic and butyric acids and breath H2 as well as (b) a significant fall in faecal pH and breath CH4 excretion, and (c) a non-significant decrease in the counts of methanogenic bacteria. Reverse relations were roughly the same during the loperamide period including a significant rise in the counts of methanogenic bacteria and a significant fall in those of sulphate reducing bacteria. Transit time differences between healthy volunteers are associated with differences in H2 consuming flora and certain indices of colonic fermentation. Considering the effects of some fermentation products on intestinal morphology and function, these variations may be relevant to the pathogenesis of colorectal diseases.
El Oufir, L; Flourié, B; Bruley des Varannes, S; Barry, J L; Cloarec, D; Bornet, F; Galmiche, J P
1996-01-01
BACKGROUND/AIMS: To investigate whether transit time could influence H2 consuming flora and certain indices of colonic bacterial fermentation. METHODS: Eight healthy volunteers (four methane excretors and four non-methane excretors) were studied for three, three week periods during which they received a controlled diet alone (control period), and then the same diet with cisapride or loperamide. At the end of each period, mean transit time (MTT) was estimated, an H2 lactulose breath test was performed, and stools were analysed. RESULTS: In the control period, transit time was inversely related to faecal weight, sulphate reducing bacteria counts, concentrations of total short chain fatty acids (SCFAs), propionic and butyric acids, and H2 excreted in breath after lactulose ingestion. Conversely, transit time was positively related to faecal pH and tended to be related to methanogen counts. Methanogenic bacteria counts were inversely related to those of sulphate reducing bacteria and methane excretors had slower MTT and lower sulphate reducing bacteria counts than non-methane excretors. Compared with the control period, MTT was significantly shortened (p < 0.05) by cisapride and prolonged (p < 0.05) by loperamide (73 (11) hours, 47 (5) hours and 147 (12) hours for control, cisapride, and loperamide, respectively, mean (SD)). Cisapride reduced transit time was associated with (a) a significant rise in faecal weight, sulphate reducing bacteria, concentrations of total SCFAs, and propionic and butyric acids and breath H2 as well as (b) a significant fall in faecal pH and breath CH4 excretion, and (c) a non-significant decrease in the counts of methanogenic bacteria. Reverse relations were roughly the same during the loperamide period including a significant rise in the counts of methanogenic bacteria and a significant fall in those of sulphate reducing bacteria. CONCLUSIONS: Transit time differences between healthy volunteers are associated with differences in H2 consuming flora and certain indices of colonic fermentation. Considering the effects of some fermentation products on intestinal morphology and function, these variations may be relevant to the pathogenesis of colorectal diseases. PMID:8984026
Progranulin regulates neurogenesis in the developing vertebrate retina.
Walsh, Caroline E; Hitchcock, Peter F
2017-09-01
We evaluated the expression and function of the microglia-specific growth factor, Progranulin-a (Pgrn-a) during developmental neurogenesis in the embryonic retina of zebrafish. At 24 hpf pgrn-a is expressed throughout the forebrain, but by 48 hpf pgrn-a is exclusively expressed by microglia and/or microglial precursors within the brain and retina. Knockdown of Pgrn-a does not alter the onset of neurogenic programs or increase cell death, however, in its absence, neurogenesis is significantly delayed-retinal progenitors fail to exit the cell cycle at the appropriate developmental time and postmitotic cells do not acquire markers of terminal differentiation, and microglial precursors do not colonize the retina. Given the link between Progranulin and cell cycle regulation in peripheral tissues and transformed cells, we analyzed cell cycle kinetics among retinal progenitors following Pgrn-a knockdown. Depleting Pgrn-a results in a significant lengthening of the cell cycle. These data suggest that Pgrn-a plays a dual role during nervous system development by governing the rate at which progenitors progress through the cell cycle and attracting microglial progenitors into the embryonic brain and retina. Collectively, these data show that Pgrn-a governs neurogenesis by regulating cell cycle kinetics and the transition from proliferation to cell cycle exit and differentiation. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc. Develop Neurobiol 77: 1114-1129, 2017. © 2017 The Authors. Developmental Neurobiology Published by Wiley Periodicals, Inc.
Golf-course and funnel energy landscapes: Protein folding concepts in martensites
NASA Astrophysics Data System (ADS)
Shankaraiah, N.
2017-06-01
We use protein folding energy landscape concepts such as golf course and funnel to study re-equilibration in athermal martensites under systematic temperature quench Monte Carlo simulations. On quenching below a transition temperature, the seeded high-symmetry parent-phase austenite that converts to the low-symmetry product-phase martensite, through autocatalytic twinning or elastic photocopying, has both rapid conversions and incubation delays in the temperature-time-transformation phase diagram. We find the rapid (incubation delays) conversions at low (high) temperatures arises from the presence of large (small) size of golf-course edge that has the funnel inside for negative energy states. In the incubating state, the strain structure factor enters into the Brillouin-zone golf course through searches for finite transitional pathways which close off at the transition temperature with Vogel-Fulcher divergences that are insensitive to Hamiltonian energy scales and log-normal distributions, as signatures of dominant entropy barriers. The crossing of the entropy barrier is identified through energy occupancy distributions, Monte Carlo acceptance fractions, heat emission, and internal work.
Impact of age at onset for children with renal failure on education and employment transitions.
Lewis, Helen; Arber, Sara
2015-01-01
Previous medical research has shown that children with end-stage renal failure experience delay or underachievement of key markers of transition to adulthood. This article analyses 35 qualitative interviews with end-stage renal failure patients, aged 20-30 years, first diagnosed at 0-19 years of age, to explore how far delayed or underachievement in education and employment is related to their age at onset of end-stage renal failure. This study shows how unpredictable failures of renal replacement therapies, comorbidities and/or side effects of treatment in the early life course often coincided with critical moments for education and employment. Entering school, college, work-related training or employment, and disclosing health status or educational underachievement to an employer, were particularly critical, and those who were ill before puberty became progressively more disadvantaged in terms of successful transition into full-time employment, compared with those first diagnosed after puberty. © The Author(s) 2014.
Lorenzo, Melissa; Stolte-Dijkstra, Irene; van Rheenen, Patrick; Smith, Ronald Garth; Scheers, Tom; Walia, Jagdeep S
2018-06-01
KIAA2022 is an X-linked intellectual disability (XLID) syndrome affecting males more severely than females. Few males with KIAA2022 variants and XLID have been reported. We present a clinical report of two unrelated males, with two nonsense KIAA2022 pathogenic variants, with profound intellectual disabilities, limited language development, strikingly similar autistic behavior, delay in motor milestones, and postnatal growth restriction. Patient 1, 19-years-old, has long ears, deeply set eyes with keratoconus, strabismus, a narrow forehead, anteverted nares, café-au-lait spots, macroglossia, thick vermilion of the upper and lower lips, and prognathism. He has gastroesophageal reflux, constipation with delayed rectosigmoid colonic transit time, difficulty regulating temperature, several musculoskeletal issues, and a history of one grand mal seizure. Patient 2, 10-years-old, has mild dysmorphic features, therapy resistant vomiting with diminished motility of the stomach, mild constipation, cortical visual impairment with intermittent strabismus, axial hypotonia, difficulty regulating temperature, and cutaneous mastocytosis. Genetic testing identified KIAA2022 variant c.652C > T(p.Arg218*) in Patient 1, and a novel nonsense de novo variant c.2707G > T(p.Glu903*) in Patient 2. We also summarized features of all reported males with KIAA2022 variants to date. This report not only adds knowledge of a novel pathogenic variant to the KIAA2022 variant database, but also likely extends the spectrum by describing novel dysmorphic features and medical conditions including macroglossia, café-au-lait spots, keratoconus, severe cutaneous mastocytosis, and motility problems of the GI tract, which may help physicians involved in the care of patients with this syndrome. Lastly, we describe the power of social media in bringing families with rare medical conditions together. © 2018 Wiley Periodicals, Inc.
Deboer, Mark D; Li, Yongli
2011-01-01
In boys, inflammatory bowel disease often results in delayed puberty associated with decreased bone mineral density and decreased linear growth. Our goal was to investigate whether pubertal timing and levels of leptin differed between prepubertal male mice with colitis and food-restricted (FR) mice maintained at a similar weight. We induced colitis in 32-d-old male mice using dextran sodium sulfate (DSS), resulting in 10 d of worsening colitis. We followed up these mice for separation of the prepuce from the glans penis as a marker of pubertal progression. Compared with free-feeding control mice, DSS and FR mice had significantly lower weight on d 7-10 of treatment. DSS mice had later puberty than control and FR mice. DSS mice also had smaller testes, lower FSH levels, increased systemic cytokines, and increased colonic inflammation by histology. Leptin levels were similar between DSS and FR mice, whereas both had decreases in leptin compared with controls. We conclude that DSS colitis causes delayed puberty in sexually immature male mice beyond what is seen among FR mice of similar weight, food intake, and leptin levels. These experiments provide support for the hypothesis that pubertal delay in colitis is influenced by factors beyond poor weight gain alone.
Boundary-Layer Transition on a Slender Cone in Hypervelocity Flow with Real Gas Effects
NASA Astrophysics Data System (ADS)
Jewell, Joseph Stephen
The laminar to turbulent transition process in boundary layer flows in thermochemical nonequilibrium at high enthalpy is measured and characterized. Experiments are performed in the T5 Hypervelocity Reflected Shock Tunnel at Caltech, using a 1 m length 5-degree half angle axisymmetric cone instrumented with 80 fast-response annular thermocouples, complemented by boundary layer stability computations using the STABL software suite. A new mixing tank is added to the shock tube fill apparatus for premixed freestream gas experiments, and a new cleaning procedure results in more consistent transition measurements. Transition location is nondimensionalized using a scaling with the boundary layer thickness, which is correlated with the acoustic properties of the boundary layer, and compared with parabolized stability equation (PSE) analysis. In these nondimensionalized terms, transition delay with increasing CO2 concentration is observed: tests in 100% and 50% CO2, by mass, transition up to 25% and 15% later, respectively, than air experiments. These results are consistent with previous work indicating that CO2 molecules at elevated temperatures absorb acoustic instabilities in the MHz range, which is the expected frequency of the Mack second-mode instability at these conditions, and also consistent with predictions from PSE analysis. A strong unit Reynolds number effect is observed, which is believed to arise from tunnel noise. NTr for air from 5.4 to 13.2 is computed, substantially higher than previously reported for noisy facilities. Time- and spatially-resolved heat transfer traces are used to track the propagation of turbulent spots, and convection rates at 90%, 76%, and 63% of the boundary layer edge velocity, respectively, are observed for the leading edge, centroid, and trailing edge of the spots. A model constructed with these spot propagation parameters is used to infer spot generation rates from measured transition onset to completion distance. Finally, a novel method to control transition location with boundary layer gas injection is investigated. An appropriate porous-metal injector section for the cone is designed and fabricated, and the efficacy of injected CO2 for delaying transition is gauged at various mass flow rates, and compared with both no injection and chemically inert argon injection cases. While CO2 injection seems to delay transition, and argon injection seems to promote it, the experimental results are inconclusive and matching computations do not predict a reduction in N factor from any CO2 injection condition computed.
Thomson, Merran A; Yoder, Bradley A; Winter, Vicki T; Giavedoni, Luis; Chang, Ling Yi; Coalson, Jacqueline J
2006-11-01
Using the 125-day baboon model of bronchopulmonary dysplasia treated with prenatal steroid and exogenous surfactant, we hypothesized that a delay of extubation from low tidal volume positive pressure ventilation to nasal continuous positive airway pressure at 5 days (delayed nasal continuous positive airway pressure group) would not induce more lung injury when compared with baboons aggressively weaned to nasal continuous positive airway pressure at 24 hours (early nasal continuous positive airway pressure group), because both received positive pressure ventilation. After delivery by cesarean section at 125 days (term: 185 days), infants received 2 doses of Curosurf (Chiesi Farmaceutica S.p.A., Parma, Italy) and daily caffeine citrate. The delay in extubation to 5 days resulted in baboons in the delayed nasal continuous positive airway pressure group having a lower arterial to alveolar oxygen ratio, high PaCO2, and worse respiratory function. The animals in the delayed nasal continuous positive airway pressure group exhibited a poor respiratory drive that contributed to more reintubations and time on mechanical ventilation. A few animals in both groups developed necrotizing enterocolitis and/or sepsis, but infectious pneumonias were not documented. Cellular bronchiolitis and peribronchiolar alveolar wall thickening were more frequently seen in the delayed nasal continuous positive airway pressure group. Bronchoalveolar lavage levels of interleukin-6, interleukin-8, monocyte chemotactic protein-1, macrophage inflammatory protein-1 alpha, and growth-regulated oncogene-alpha were significantly increased in the delayed nasal continuous positive airway pressure group. Standard and digital morphometric analyses showed no significant differences in internal surface area and nodal measurements between the groups. Platelet endothelial cell adhesion molecule vascular staining was not significantly different between the 2 nasal continuous positive airway pressure groups. Volutrauma and/or low-grade colonization of airways secondary to increased reintubations and ventilation times are speculated to play causative roles in the delayed nasal continuous positive airway pressure group findings.
Primary repair of civilian colon injuries is safe in the damage control scenario.
Kashuk, Jeffry L; Cothren, C Clay; Moore, Ernest E; Johnson, Jeffrey L; Biffl, Walter L; Barnett, Carlton C
2009-10-01
Although the safety of primary repair/anastomosis for civilian colon injuries after standard laparotomy (SL) has been established, recent civilian and military reports have questioned the advisability of this technique in the patient requiring damage control laparotomy (DL). We hypothesized that, even in the high-risk DL group, primary repair could be safely used after patient stabilization and that the open abdomen would facilitate the safety of this procedure. All patients admitted to our level 1 trauma center with a colon injury over a 7-year period were reviewed from a prospectively collected database. Patients were categorized as having undergone either SL or DL at initial operation. Primary variables of interest were as follows: injury patterns; method of primary repair (suture repair, resection and primary anastomosis, resection and delayed anastomosis); diversion techniques (planned diversion or diversion for anastomotic dehiscence); and colon-related morbidity and mortality. High-risk status in the DL group was identified by the following physiologic variables: mean injury severity score (ISS), red blood cell (RBC) transfusions, ventilator days, and intensive care unit (ICU) duration of stay. During the study period, 309 patients had colonic wounds identified at laparotomy. Of these 309 patients, 280 (91%) underwent SL, of which 277 (98.9%) had primary colonic repair/anastomosis. In the SL group, 1 (0.3%) patient required diversion for subsequent leak and 2 (0.6%) patients had planned diversion The remaining 29 hemodynamically unstable patients required DL. Mean +/- standard deviation indices of injury severity in this group included: ISS = 36.2 +/- 15.8, RBC = 28.7 +/- 25.4 units, ventilator days = 20.1 +/- 16.3, ICU duration of stay = 29.5 +/- 21.6 days. Of the 29 patients in the DL group, 21 (72%) had bowel continuity successfully reestablished in 2.6 +/- 2 days after initial attempts at primary suture repair or resection/anastomosis. A total of 4 (16.6%) patients in this group developed colon-related complications, 3 of whom were treated with subsequent diversion before definitive abdominal closure. One patient developed a late leak. (day 43). Another 4 (13.8%) patients had planned diversion for injuries that were considered to be high risk for leak at subsequent reexploration. There were no colon-related deaths in either group. Primary repair of colon injuries appears safe in the majority of patients after DL. Although it is associated with a higher leak rate than SL, the open abdomen affords careful inspection of abdominal contents at reexploration to identify patients who require subsequent diversion.
Biomagnetic techniques for evaluating gastric emptying, peristaltic contraction and transit time
la Roca-Chiapas, Jose María De; Cordova-Fraga, Teodoro
2011-01-01
Biomagnetic techniques were used to measure motility in various parts of the gastrointestinal (GI) tract, particularly a new technique for detecting magnetic markers and tracers. A coil was used to enhance the signal from a magnetic tracer in the GI tract and the signal was detected using a fluxgate magnetometer or a magnetoresistor in an unshielded room. Estimates of esophageal transit time were affected by the position of the subject. The reproducibility of estimates derived using the new biomagnetic technique was greater than 85% and it yielded estimates similar to those obtained using scintigraphy. This technique is suitable for studying the effect of emotional state on GI physiology and for measuring GI transit time. The biomagnetic technique can be used to evaluate digesta transit time in the esophagus, stomach and colon, peristaltic frequency and gastric emptying and is easy to use in the hospital setting. PMID:22025978
Biomagnetic techniques for evaluating gastric emptying, peristaltic contraction and transit time.
la Roca-Chiapas, Jose María De; Cordova-Fraga, Teodoro
2011-10-15
Biomagnetic techniques were used to measure motility in various parts of the gastrointestinal (GI) tract, particularly a new technique for detecting magnetic markers and tracers. A coil was used to enhance the signal from a magnetic tracer in the GI tract and the signal was detected using a fluxgate magnetometer or a magnetoresistor in an unshielded room. Estimates of esophageal transit time were affected by the position of the subject. The reproducibility of estimates derived using the new biomagnetic technique was greater than 85% and it yielded estimates similar to those obtained using scintigraphy. This technique is suitable for studying the effect of emotional state on GI physiology and for measuring GI transit time. The biomagnetic technique can be used to evaluate digesta transit time in the esophagus, stomach and colon, peristaltic frequency and gastric emptying and is easy to use in the hospital setting.
Peroxiredoxin 5 promotes the epithelial-mesenchymal transition in colon cancer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ahn, Hye-Mi; Yoo, Jin-Woo; College of Natural Sciences, Kyungpook National University, Daegu
Globally, colorectal cancer (CRC) is common cause of cancer-related deaths. The high mortality rate of patients with colon cancer is due to cancer cell invasion and metastasis. Initiation of the epithelial-to-mesenchymal transition (EMT) is essential for the tumorigenesis. Peroxiredoinxs (PRX1-6) have been reported to be overexpressed in various tumor tissues, and involved to be responsible for tumor progression. However, the exact role of PRX5 in colon cancer remains to be investigated enhancing proliferation and promoting EMT properties. In this study, we constructed stably overexpressing PRX5 and suppressed PRX5 expression in CRC cells. Our results revealed that PRX5 overexpression significantly enhancedmore » CRC cell proliferation, migration, and invasion. On the other hand, PRX5 suppression markedly inhibited these EMT properties. PRX5 was also demonstrated to regulate the expression of two hallmark EMT proteins, E-cadherin and Vimentin, and the EMT-inducing transcription factors, Snail and Slug. Moreover, in the xenograft mouse model, showed that PRX5 overexpression enhances tumor growth of CRC cells. Thus, our findings first provide evidence in CRC that PRX5 promotes EMT properties by inducing the expression of EMT-inducing transcription factors. Therefore, PRX5 can be used as a predictive biomarker and serves as a putative therapeutic target for the development of clinical treatments for human CRC. - Highlights: • PRX5 promoted colorectal cancer cell proliferation. • PRX5 enhanced EMT properties in colorectal cancer. • PRX5 mediated the EMT by inducing the expression of Snail and Slug. • PRX5 promoted tumor growth of colorectal cancer cells.« less
Fecal weight, colon cancer risk, and dietary intake of nonstarch polysaccharides (dietary fiber)
Cummings, J H; Bingham, S A; Heaton, K W; Eastwood, M A
1992-12-01
Low fecal weight and slow bowel transit time are thought to be associated with bowel cancer risk, but few published data defining bowel habits in different communities exist. Therefore, data on stool weight were collected from 20 populations in 12 countries to define this risk more accurately, and the relationship between stool weight and dietary intake of nonstarch polysaccharides (NSP) (dietary fiber) was quantified. In 220 healthy U.K. adults undertaking careful fecal collections, median daily stool weight was 106 g/day (men, 104 g/day; women, 99 g/day; P = 0.02) and whole-gut transit time was 60 hours (men, 55 hours; women, 72 hours; P = 0.05); 17% of women, but only 1% of men, passed < 50 g stool/day. Data from other populations of the world show average stool weight to vary from 72 to 470 g/day and to be inversely related to colon cancer risk (r = -0.78). Meta-analysis of 11 studies in which daily fecal weight was measured accurately in 26 groups of people (n = 206) on controlled diets of known NSP content shows a significant correlation between fiber intake and mean daily stool weight (r = 0.84). Stool weight in many Westernized populations is low (80-120 g/day), and this is associated with increased colon cancer risk. Fecal output is increased by dietary NSP. Diets characterized by high NSP intake (approximately 18 g/day) are associated with stool weights of 150 g/day and should reduce the risk of bowel cancer.
Swidsinski, Alexander; Loening-Baucke, Vera; Schulz, Stefan; Manowsky, Julia; Verstraelen, Hans; Swidsinski, Sonja
2016-02-01
Sections of fecal cylinders were analyzed using fluorescence in situ hybridization targeting 180 bacterial groups. Samples were collected from three groups of women (N=20 each) treated for bacterial vaginosis with ciprofloxacin+metronidazole. Group A only received the combined antibiotic regimen, whereas the A/Sb group received concomitant Saccharomyces boulardii CNCM I-745 treatment, and the A_Sb group received S. boulardii prophylaxis following the 14-day antibiotic course. The number of stool cylinders analyzed was 188 out of 228 in group A, 170 out of 228 in group A/Sb, and 172 out of 216 in group A_Sb. The colonic biomass was organized into a separate mucus layer with no bacteria, a 10-30μm broad unstirred transitional layer enriched with bacteria, and a patchy fermentative area that mixed digestive leftovers with bacteria. The antibiotics suppressed bacteria mainly in the fermentative area, whereas abundant bacterial clades retreated to the transitional mucus and survived. As a result, the total concentration of bacteria decreased only by one order. These effects were lasting, since the overall recovery of the microbial mass, bacterial diversity and concentrations were still below pre-antibiotic values 4 months after the end of antibiotic treatment. Sb-prophylaxis markedly reduced antibiotic effects and improved the recovery rates. Since the colon is a sophisticated bioreactor, the study indicated that the spatial anatomy of its biomass was crucial for its function. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.
Slater, B J; Varma, J S; Gillespie, J I
1997-02-01
The underlying pathophysiology of idiopathic slow transit constipation (ISTC) remains unclear. At present, there is little evidence to implicate a smooth muscle myopathy in the aetiology of this condition. This study compared the effect of cisapride on the cholinergic response of colonic muscle strips from patients with this condition with that of control tissue. Isometric tension production was recorded from circular smooth muscle strips taken from five patients undergoing colectomy for ISTC in response to cumulative concentrations of carbachol (100 nmol/1-100 mumol/l) alone and in the presence of cisapride 400 nmol/l. Similar dose-response activity was obtained for a control group consisting of six patients undergoing resection for colorectal carcinoma. In the absence of cisapride, smooth muscle from patients with carcinoma exhibited a significantly lower sensitivity to cholinergic stimulation (agonist concentration required to produce half-maximal activation (EC50) 4.83 mumol/l) than that from patients with ISTC (EC50 1.63 mumol/l, P = 0.036), and also a greater maximal frequency of the oscillatory activity associated with the increase in isometric tension (0.070 versus 0.049 Hz, P = 0.035). Cisapride had no effect on the sensitivity to carbachol of the carcinoma tissue but brought about a significant reduction in the sensitivity of smooth muscle from patients with ISTC (EC50 3.24 mumol/l, P = 0.043). These findings indicate that colonic smooth muscle from patients with ISTC is hypersensitive to cholinergic stimulation and suggest the existence of a smooth muscle myopathy in this condition.
Pallarés, Susana; Arribas, Paula; Bilton, David T; Millán, Andrés; Velasco, Josefa; Ribera, Ignacio
2017-10-01
Transitions from fresh to saline habitats are restricted to a handful of insect lineages, as the colonization of saline waters requires specialized mechanisms to deal with osmotic stress. Previous studies have suggested that tolerance to salinity and desiccation could be mechanistically and evolutionarily linked, but the temporal sequence of these adaptations is not well established for individual lineages. We combined molecular, physiological and ecological data to explore the evolution of desiccation resistance, hyporegulation ability (i.e., the ability to osmoregulate in hyperosmotic media) and habitat transitions in the water beetle genus Enochrus subgenus Lumetus (Hydrophilidae). We tested whether enhanced desiccation resistance evolved before increases in hyporegulation ability or vice versa, or whether the two mechanisms evolved in parallel. The most recent ancestor of Lumetus was inferred to have high desiccation resistance and moderate hyporegulation ability. There were repeated shifts between habitats with differing levels of salinity in the radiation of the group, those to the most saline habitats generally occurring more rapidly than those to less saline ones. Significant and accelerated changes in hyporegulation ability evolved in parallel with smaller and more progressive increases in desiccation resistance across the phylogeny, associated with the colonization of meso- and hypersaline waters during global aridification events. All species with high hyporegulation ability were also desiccation-resistant, but not vice versa. Overall, results are consistent with the hypothesis that desiccation resistance mechanisms evolved first and provided the physiological basis for the development of hyporegulation ability, allowing these insects to colonize and diversify across meso- and hypersaline habitats. © 2017 John Wiley & Sons Ltd.
Two waves of colonization straddling the K-Pg boundary formed the modern reef fish fauna.
Price, S A; Schmitz, L; Oufiero, C E; Eytan, R I; Dornburg, A; Smith, W L; Friedman, M; Near, T J; Wainwright, P C
2014-05-22
Living reef fishes are one of the most diverse vertebrate assemblages on Earth. Despite its prominence and ecological importance, the origins and assembly of the reef fish fauna is poorly described. A patchy fossil record suggests that the major colonization of reef habitats must have occurred in the Late Cretaceous and early Palaeogene, with the earliest known modern fossil coral reef fish assemblage dated to 50 Ma. Using a phylogenetic approach, we analysed the early evolutionary dynamics of modern reef fishes. We find that reef lineages successively colonized reef habitats throughout the Late Cretaceous and early Palaeogene. Two waves of invasion were accompanied by increasing morphological convergence: one in the Late Cretaceous from 90 to 72 Ma and the other immediately following the end-Cretaceous mass extinction. The surge in reef invasions after the Cretaceous-Palaeogene boundary continued for 10 Myr, after which the pace of transitions to reef habitats slowed. Combined, these patterns match a classic niche-filling scenario: early transitions to reefs were made rapidly by morphologically distinct lineages and were followed by a decrease in the rate of invasions and eventual saturation of morphospace. Major alterations in reef composition, distribution and abundance, along with shifts in climate and oceanic currents, occurred during the Late Cretaceous and early Palaeogene interval. A causal mechanism between these changes and concurrent episodes of reef invasion remains obscure, but what is clear is that the broad framework of the modern reef fish fauna was in place within 10 Myr of the end-Cretaceous extinction.
Morphofunctional changes underlying intestinal dysmotility in diabetic RIP-I/hIFNβ transgenic mice
Domènech, Anna; Pasquinelli, Gianandrea; De Giorgio, Roberto; Gori, Alessandra; Bosch, Fàtima; Pumarola, Martí; Jiménez, Marcel
2011-01-01
The pathogenetic mechanisms underlying gastrointestinal dysmotility in diabetic patients remain poorly understood, although enteric neuropathy, damage to interstitial cells of Cajal (ICC) and smooth muscle cell injury are believed to play a role. The aim of this study was to investigate the morphological and functional changes underlying intestinal dysmotility in RIP-I/hIFNβ transgenic mice treated with multiple very low doses of streptozotocin (20 mg/kg, i.p., 5 days). Compared with vehicle-treated mice, streptozotocin-treated animals developed type 1 diabetes mellitus, with sustained hyperglycaemia for 3.5 months, polyphagia, polydipsia and increased faecal output without changes in faecal water content (metabolic cages). Diabetic mice had a longer intestine, longer ileal villi and wider colonic crypts (conventional microscopy) and displayed faster gastric emptying and intestinal transit. Contractility studies showed selective impaired neurotransmission in the ileum and mid-colon of diabetic mice. Compared with controls, the ileal and colonic myenteric plexus of diabetic mice revealed ultrastructural features of neuronal degeneration and HuD immunohistochemistry on whole-mount preparations showed 15% reduction in neuronal numbers. However, no immunohistochemical changes in apoptosis-related markers were noted. Lower absolute numbers of neuronal nitric oxide synthase- and choline acetyltransferase-immunopositive neurons and enhanced vasoactive intestinal polypeptide and substance P immunopositivity were observed. Ultrastructural and immunohistochemical analyses did not reveal changes in the enteric glial or ICC networks. In conclusion, this model of diabetic enteropathy shows enhanced intestinal transit associated with intestinal remodelling, including neuroplastic changes, and overt myenteric neuropathy. Such abnormalities are likely to reflect neuroadaptive and neuropathological changes occurring in this diabetic model. PMID:22050417
Two waves of colonization straddling the K–Pg boundary formed the modern reef fish fauna
Price, S. A.; Schmitz, L.; Oufiero, C. E.; Eytan, R. I.; Dornburg, A.; Smith, W. L.; Friedman, M.; Near, T. J.; Wainwright, P. C.
2014-01-01
Living reef fishes are one of the most diverse vertebrate assemblages on Earth. Despite its prominence and ecological importance, the origins and assembly of the reef fish fauna is poorly described. A patchy fossil record suggests that the major colonization of reef habitats must have occurred in the Late Cretaceous and early Palaeogene, with the earliest known modern fossil coral reef fish assemblage dated to 50 Ma. Using a phylogenetic approach, we analysed the early evolutionary dynamics of modern reef fishes. We find that reef lineages successively colonized reef habitats throughout the Late Cretaceous and early Palaeogene. Two waves of invasion were accompanied by increasing morphological convergence: one in the Late Cretaceous from 90 to 72 Ma and the other immediately following the end-Cretaceous mass extinction. The surge in reef invasions after the Cretaceous–Palaeogene boundary continued for 10 Myr, after which the pace of transitions to reef habitats slowed. Combined, these patterns match a classic niche-filling scenario: early transitions to reefs were made rapidly by morphologically distinct lineages and were followed by a decrease in the rate of invasions and eventual saturation of morphospace. Major alterations in reef composition, distribution and abundance, along with shifts in climate and oceanic currents, occurred during the Late Cretaceous and early Palaeogene interval. A causal mechanism between these changes and concurrent episodes of reef invasion remains obscure, but what is clear is that the broad framework of the modern reef fish fauna was in place within 10 Myr of the end-Cretaceous extinction. PMID:24695431
Revival of oscillations from deaths in diffusively coupled nonlinear systems: Theory and experiment
NASA Astrophysics Data System (ADS)
Zou, Wei; Sebek, Michael; Kiss, István Z.; Kurths, Jürgen
2017-06-01
Amplitude death (AD) and oscillation death (OD) are two structurally different oscillation quenching phenomena in coupled nonlinear systems. As a reverse issue of AD and OD, revival of oscillations from deaths attracts an increasing attention recently. In this paper, we clearly disclose that a time delay in the self-feedback component of the coupling destabilizes not only AD but also OD, and even the AD to OD transition in paradigmatic models of coupled Stuart-Landau oscillators under diverse death configurations. Using a rigorous analysis, the effectiveness of this self-feedback delay in revoking AD is theoretically proved to be valid in an arbitrary network of coupled Stuart-Landau oscillators with generally distributed propagation delays. Moreover, the role of self-feedback delay in reviving oscillations from AD is experimentally verified in two delay-coupled electrochemical reactions.
NASA Astrophysics Data System (ADS)
Andreev, R. B.; Butylkin, V. S.; Evtiushkin, V. A.; Fisher, P. S.; Khabarov, V. V.
1983-03-01
The threshold of stimulated Raman scattering was lowered by filling an optical delay line with hydrogen. Pumping was by a tunable neodymium laser. Lens-prism combinations were used as phase correctors in the delay line. The dependences of the energy of the Stokes component on the pump energy determined experimentally for different numbers of transits through the delay line were compared with the results of a calculation allowing for the losses in the components of this line. When the frequency conversion was by a factor of at least 2 and the tuning range was wide (tens of percent), the optimal performance was obtained from the optical delay line when total-internal-reflection prisms and lenses were combined in a single component and oriented at the Brewster angle.
NASA Astrophysics Data System (ADS)
Andreev, R. B.; Butylkin, V. S.; Evtyushkin, V. A.; Fisher, P. S.; Khabarov, V. V.
1983-03-01
The threshold of stimulated Raman scattering was lowered by filling an optical delay line with hydrogen. Pumping was by a tunable neodymium laser. Lens-prism combinations were used as phase correctors in the delay line. The dependences of the energy of the Stokes component on the pump energy determined experimentally for different numbers of transits through the delay line were compared with the results of a calculation allowing for the losses in the components of this line. When the frequency conversion was by a factor of at least 2 and the tuning range was wide (tens of percent), the optimal performance was obtained from the optical delay line when total-internal-reflection prisms and lenses were combined in a single component and oriented at the Brewster angle.
Revival of oscillations from deaths in diffusively coupled nonlinear systems: Theory and experiment.
Zou, Wei; Sebek, Michael; Kiss, István Z; Kurths, Jürgen
2017-06-01
Amplitude death (AD) and oscillation death (OD) are two structurally different oscillation quenching phenomena in coupled nonlinear systems. As a reverse issue of AD and OD, revival of oscillations from deaths attracts an increasing attention recently. In this paper, we clearly disclose that a time delay in the self-feedback component of the coupling destabilizes not only AD but also OD, and even the AD to OD transition in paradigmatic models of coupled Stuart-Landau oscillators under diverse death configurations. Using a rigorous analysis, the effectiveness of this self-feedback delay in revoking AD is theoretically proved to be valid in an arbitrary network of coupled Stuart-Landau oscillators with generally distributed propagation delays. Moreover, the role of self-feedback delay in reviving oscillations from AD is experimentally verified in two delay-coupled electrochemical reactions.
Anismus in patients with normal and slow transit constipation.
Miller, R; Duthie, G S; Bartolo, D C; Roe, A M; Locke-Edmunds, J; Mortensen, N J
1991-06-01
This study examined differences in anorectal function, with particular reference to anismus, which might explain why some patients with intractable constipation have slow and others have normal whole gut transit times. Twenty-four patients were studied; 13 with slow transit (all female, median age 32 years, range 16-52 years) and 11 with normal transit (eight women, three men, median age 37 years, range 21-60 years). Videoproctography with synchronous sphincteric electromyography and anorectal manometry was performed. There were no differences between the two groups, suggesting that slow transit constipation is not secondary to any abnormality in anorectal function and may therefore be a primary disorder of colonic motility. There was no correlation between electromyographic evidence of anismus (pelvic floor contraction on defaecation) and the ability of the patient to evacute the rectum or symptoms of obstructed defaecation. Electromyography findings alone can be misleading and should be related to proctographic evidence of incomplete rectal evacuation before functional anismus can be said to be present.
Neonatal small left colon syndrome in the offspring of diabetic mothers-an analysis of 105 children.
Ellis, Helen; Kumar, Rajendra; Kostyrka, Ben
2009-12-01
Neonatal small left colon syndrome (NSLCS) is considered a rare cause of neonatal intestinal obstruction, with few documented cases in the English literature. Maternal diabetes has been reported in 40% to 50% of the published cases of NSLCS. Currently, the incidence of maternal diabetes is increasing, but there has been no study to ascertain the incidence and significance of NSLCS in this population. This review aims to assess the current significance of NSLCS and its association with maternal diabetes. This was a retrospective review of 105 offspring of diabetic mothers who were admitted during the period 2004 to 2008 to our neonatal unit with special emphasis on associated NSLCS. There were 6 cases of intestinal obstruction in this group of 105 children. Five children, including a pair of twins, had classic features of NSLCS as demonstrated in the contrast enema with an abrupt transition at the splenic flexure and a narrow left colon. Conservative treatment was successful in all, negating the need for further invasive investigation. The sixth child had rectosigmoid Hirschprung disease. During the study period, there were no other cases of NSLCS in the nondiabetic population. Neonatal small left colon syndrome is the most common cause of intestinal obstruction in offspring of diabetic mothers. Neonatal small left colon syndrome can be confidently diagnosed in this population based on the classic clinical and radiologic findings. The incidence of NSLCS can be expected to increase as the incidence of maternal diabetes increases.
Klerks, M M; van Gent-Pelzer, M; Franz, E; Zijlstra, C; van Bruggen, A H C
2007-08-01
This paper describes the physiological and molecular interactions between the human-pathogenic organism Salmonella enterica serovar Dublin and the commercially available mini Roman lettuce cv. Tamburo. The association of S. enterica serovar Dublin with lettuce plants was first determined, which indicated the presence of significant populations outside and inside the plants. The latter was evidenced from significant residual concentrations after highly efficient surface disinfection (99.81%) and fluorescence microscopy of S. enterica serovar Dublin in cross sections of lettuce at the root-shoot transition region. The plant biomass was reduced significantly compared to that of noncolonized plants upon colonization with S. enterica serovar Dublin. In addition to the physiological response, transcriptome analysis by cDNA amplified fragment length polymorphism analysis also provided clear differential gene expression profiles between noncolonized and colonized lettuce plants. From these, generally and differentially expressed genes were selected and identified by sequence analysis, followed by reverse transcription-PCR displaying the specific gene expression profiles in time. Functional grouping of the expressed genes indicated a correlation between colonization of the plants and an increase in expressed pathogenicity-related genes. This study indicates that lettuce plants respond to the presence of S. enterica serovar Dublin at physiological and molecular levels, as shown by the reduction in growth and the concurrent expression of pathogenicity-related genes. In addition, it was confirmed that Salmonella spp. can colonize the interior of lettuce plants, thus potentially imposing a human health risk when processed and consumed.