| 1. |
- Boden, K., et al.
(author)
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Swallowing and respiratory pattern in young healthy individuals recorded with high temporal resolution
- 2009
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:11, s. 1163-1163
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Journal article (peer-reviewed)abstract
- P>The coordination of swallowing and respiration is essential for a safe swallow. Swallowing consists of several subsecond events. To study this, it is important to use modalities with high temporal resolution. In this study, we have examined young healthy individuals with simultaneous videofluoroscopy, videomanometry and respiratory recording, all with high temporal resolution. The onset of 13 predetermined swallowing and respiratory events and the surrounding respiratory phase pattern were studied in different body positions and during different respiratory drives. An increased respiratory drive was induced by breathing 5% CO2. The results demonstrated a highly repeatable and fixed temporal coordination of the swallowing pattern despite body position and respiratory drive. Previous studies have demonstrated a period of centrally controlled apnoea during swallowing. This apnoea period has a variable length, varying from 1 to 5 s. During increased respiratory drive, we could demonstrate a significantly shorter period of apnoea during swallowing, mainly due to an earlier resumption of respiration. The high temporal recordings in this study have revealed that swallowing during expiration is present basically in all healthy individuals. This swallowing respiratory pattern seems to be appropriate for a safe swallow. This knowledge will be used as a reference for future studies on how swallowing and respiratory coordination might be altered due to ageing and diseases.
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| 2. |
- Borg, Julia, et al.
(author)
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Oxytocin reduces satiety scores without affecting the volume of nutrient intake or gastric emptying rate in healthy subjects.
- 2011
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In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 23:1
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Journal article (peer-reviewed)abstract
- Background Oxytocin is expressed throughout the gastrointestinal tract and is released in response to a fatty meal. Administration of an oxytocin receptor antagonist prolongs the gastric emptying rate. The aim of this study was to examine the effect of oxytocin on gastric accommodation, gastric emptying time, and satiety after food intake. Methods Ten healthy subjects participated in a slow satiety drinking test with a liquid meal. Every 5min the subjects scored their sensation of satiety using a visual analogue scale (VAS) until maximum satiety was reached and the amount of liquid intake was determined. Twelve subjects participated in a gastric emptying test. They were given a standardized meal containing 20 radio-opaque markers, after which fluoroscopy was performed and VAS was scored every hour. Both tests were performed four times during infusions of saline and three different oxytocin concentrations. Blood was collected for oxytocin concentration measurements. Key Results There were no differences in the volume of nutrient intake at maximum satiety between the three doses of oxytocin and saline. However, lower satiety scores at maximum satiety were seen after oxytocin infusion (P=0.031), with 40mUmin(-1) being the most effective dosage (P=0.013), and this was also true 30min after finishing the meal (P=0.032). There was no difference in gastric emptying time between saline and oxytocin. The oxytocin concentration in plasma was increased proportional to the oxytocin infusions. Conclusions & Inferences Infusion of oxytocin reduces satiety without affecting the volume of nutrient intake or gastric emptying in healthy subjects.
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| 3. |
- Cedborg, A. I. Hardemark, et al.
(author)
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Breathing and swallowing in normal man - effects of changes in body position, bolus types, and respiratory drive
- 2010
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 22:11, s. 1201-1201
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Journal article (peer-reviewed)abstract
- Background Coordination of breathing and swallowing is essential for airway protection and dyscoordination may cause morbidity and mortality. Methods Using a recently developed technique for high accuracy respiratory measurements of airflow during swallowing, we investigated the effects of body position (upright vs left lateral), bolus type (spontaneously swallowed saliva vs water), and respiratory drive (normo- vs hypercapnia) on coordination of breathing and swallowing in 32 healthy volunteers. Key Results Swallows were in all cases (100%) proceded by expiration and 98% were also followed by expiration, regardless of body position, bolus type, or respiratory drive. While the endpoint of postswallow apnea correlated well to the endpoint of pharyngeal swallowing, duration of preswallow apnea was highly variable. In a small fraction of swallows followed by inspiration (3%), the expiratory phase before swallowing and duration of postswallow apnea was significantly longer. Body position and respiratory drive affected the increase in upper esophageal sphincter tone during inspiration. Increased respiratory drive also reduced swallowing frequency and shortened duration of preswallow apnea. Water swallows had longer duration of preswallow apnea. Conclusions & Inferences Swallowing occurs during the expiratory phase of respiration, and the fraction of swallows preceded and followed by expiration approach 100% in healthy humans. This integration between breathing and swallowing remains unchanged regardless of body position, bolus characteristics, or respiratory drive. Our results provide a platform for future studies aiming at understanding how this integration is changed by aging, diseases, and drugs.
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| 4. |
- Ekblad, Eva, et al.
(author)
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Cocaine- and amphetamine-regulated transcript: distribution and function in rat gastrointestinal tract.
- 2003
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 15:5, s. 545-557
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Journal article (peer-reviewed)abstract
- Cocaine- and amphetamine-regulated transcript (CART) peptide, originally isolated from brain, is also expressed in the peripheral nervous system. The distribution, origin and projections of CART-expressing enteric neurones by immunocytochemistry and in situ hybridization in rat gastrointestinal (GI) tract were studied. Possible motor functions of CART were studied in vitro using longitudinal muscle strips from stomach, ileum and colon. Cocaine- and amphetamine-regulated transcript peptide was found in numerous myenteric neurones throughout the GI tract while CART-expressing submucous neurones were scarce. Cocaine- and amphetamine-regulated transcript was also expressed in the antral gastrin cells. Myenteric CART-expressing neurones in both small and large intestine issued short descending projections. In atrophic ileum, CART mRNA-expressing neurones increased in number while neurones containing CART peptide decreased. In hypertrophied ileum, no change in CART peptide or CART mRNA containing myenteric neurones was detected. Cocaine- and amphetamine-regulated transcript 55-102 (10-9-10-7 mol L-1) did not induce any contractile or relaxatory responses in the muscle strips, neither did it affect responses induced by vasoactive intestinal peptide, pituitary adenylate cyclase-activating peptide or neuronal stimulation. In colonic, but not in ileal, strips addition of CART attenuated nitric oxide (NO) donor-induced relaxations. Although CART does not seem to play a pivotal role in classic neurotransmission to the longitudinal muscle, it may serve a modulatory role in NO transmission. It may, moreover, be involved in intestinal adaptation, and an additional hormonal role is also possible.
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| 5. |
- Knowles, C H, et al.
(author)
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Quantitation of cellular components of the enteric nervous system in the normal human gastrointestinal tract - report on behalf of the Gastro 2009 International Working Group.
- 2011
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 23:2, s. 115-124
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Journal article (peer-reviewed)abstract
- Background Patients with gastrointestinal neuromuscular diseases may undergo operative procedures that yield tissue appropriate to diagnosis of underlying neuromuscular pathology. Critical to accurate diagnosis is the determination of limits of normality based on the study of control human tissues. Although robust diagnostic criteria exist for many qualitative alterations in the neuromuscular apparatus, these do not include quantitative values due to lack of adequate control data. Purpose The aim of this report was to summarize all relevant available published quantitative data for elements of the human enteric nervous system (neuronal cell bodies, glial cells, and nerve fibers) from the perspective of the practicing pathologist. Forty studies meeting inclusion criteria were systematically reviewed with data tabulated in detail and discussed in the context of methodological variations and limitations. The results reveal a lack of concordance between observations of different investigators resulting in data insufficient to produce robust normal ranges. This diversity highlights the need to standardize the way pathologists collect, process, and quantitate neuronal and glial elements in enteric neuropathologic samples, as suggested by recent international guidelines on gastrointestinal neuromuscular pathology.
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| 6. |
- Knowles, C H, et al.
(author)
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Safety and diagnostic yield of laparoscopically assisted full-thickness bowel biospy
- 2008
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 20:7, s. 774-779
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Journal article (peer-reviewed)abstract
- Advances in minimally invasive surgery have made laparoscopy and full-thickness bowel biopsy possible in the investigation of patients with suspected gastrointestinal neuromuscular disorders. The safety and diagnostic yield of this investigation have not been formally reported. A prospective study was undertaken of 124 patients with clinico-physiological diagnoses of chronic intestinal pseudo-obstruction, enteric dysmotility and severe irritable bowel syndrome undergoing LFTB in three European teaching centres with expertise in the management of gastrointestinal neuromuscular disorders. Perioperative data were collected including complications. Diagnostic yield was expressed as proportion with well-established specific neuromuscular abnormalities based on a protocol of routine and immunohistochemical techniques. The majority of patients underwent a laparoscopically assisted procedure with extracorporeal biopsy. Median operating time was 50 min, conversion rate 2% and length of stay 1 day. There was an 8% readmission rate for obstructive symptoms but minimal other morbidity and no mortality. Overall specific diagnostic yield was 81%, being high for jejunal biopsies (89%) but low for a small number of ileal and colonic biopsies. Laparoscopy and full-thickness biopsy of the bowel appears acceptable in terms of safety. It should be performed in a jejunal site to achieve a high diagnostic yield.
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| 7. |
- Ohlsson, Bodil, et al.
(author)
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Effects of long-term treatment with oxytocin in chronic constipation; a double blind, placebo-controlled pilot trial.
- 2005
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In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1350-1925 .- 1365-2982. ; 17:5, s. 697-704
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Journal article (peer-reviewed)abstract
- BACKGROUND: Oxytocin and its receptor have been found throughout the gastrointestinal (GI) tract, where it affects gut function. Clinically, we have noticed an improvement of bowel habits during lactation in constipated women. The aim of this study was to examine whether oxytocin has an effect on bowel symptoms and psychological well being in women with refractory constipation. METHODS: Fifty-nine women with refractory constipation were included in a double blind, multicentre study. After a 2-week run-in period, they were randomly allocated to nasal inhalation of either placebo or oxytocin treatment twice daily for 13 weeks, followed by a 2 weeks, posttreatment period. The patients completed a questionnaire every day concerning bowel habits, abdominal pain and discomfort, and Gastrointestinal Symptoms Rating Scale (GSRS) and Psychological General Well-being (PGWB) twice during the study; namely, during the baseline period and at the end of the treatment period. RESULTS: Both oxytocin and placebo led to improvement of the constipation according to the GSRS and led to improvement in the sensation of incomplete evacuation and anorectal obstruction, without significant differences between the groups. Abdominal pain and discomfort responded weakly to oxytocin, with no effect of the placebo. In a subgroup of patients with IBS and concomitant depression, a weak improvement in depressed mood was observed after oxytocin administartion. CONCLUSION: Nasal administration of oxytocin had no significant advantage over placebo concerning an effect on constipation. However, it seems to have a positive effect on abdominal pain and discomfort and depressed mood. These findings should be further explored.
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| 8. |
- Ohlsson, Bodil, et al.
(author)
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Oxytocin stimulates colonic motor activity in healthy women.
- 2004
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In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1350-1925 .- 1365-2982. ; 16:2, s. 233-40
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Journal article (peer-reviewed)abstract
- The effects of oxytocin in the gastrointestinal tract are unclear. The aim of this study was to examine the effect of infusion of oxytocin on colonic motility and sensitivity in healthy women. Fourteen healthy women were investigated twice. A 6-channel perfusion catheter, with three recording points (2 cm apart) proximally and three recording points distally to a barostat balloon, was inserted to the splenic flexure. An intestinal feeding tube was placed in the mid-duodenum. A 90-min duodenal lipid infusion of 3 kcal min(-1) was administered. Thirty minutes after the start of the lipid infusion, the subject randomly received either 20 or 40 mU min(-1) of oxytocin, or isotonic saline as intravenous infusions for 90 min. Meanwhile, the colonic motility was recorded. During the last 30 min of oxytocin and saline infusion, the visceral sensitivity to balloon distensions was examined. During lipid infusion the number of antegrade contractions per hour was 0.7 +/- 0.3 after saline and 3.9 +/- 1.4 after oxytocin (P = 0.03), indicating more pronounced lumen-occlusive contractile activity after oxytocin administration. Some of these consisted of high-amplitude (> 103 mmHg in amplitude) antegrade contractions. Lipid infusion evoked a decrease of the balloon volume, reflecting increased colonic tone, but there was no difference between saline and oxytocin. Sensory thresholds did not differ significantly between saline and oxytocin. Infusion of oxytocin stimulates antegrade peristaltic contractions in stimulated colon in healthy women. The effects of oxytocin on colonic motor activity deserve to be further explored, especially in patients with colonic peristaltic dysfunction.
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| 9. |
- Simpson, J., et al.
(author)
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Post inflammatory damage to the enteric nervous system in diverticular disease and its relationship to symptoms
- 2009
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:8, s. 847-847
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Journal article (peer-reviewed)abstract
- Some patients with colonic diverticula suffer recurrent abdominal pain and exhibit visceral hypersensitivity, though the mechanism is unclear. Prior diverticulitis increases the risk of being symptomatic while experimental colitis in animals increases expression of neuropeptides within the enteric nervous system (ENS) which may mediate visceral hypersensitivity. Our aim was to determine the expression of neuropeptides within the ENS in diverticulitis (study 1) and in patients with symptomatic disease (study 2). Study 1 - Nerves in colonic resection specimens with either acute diverticulitis (AD, n = 16) or chronic diverticulitis (CD, n = 16) were assessed for neuropeptide expression recording % area staining with protein gene product (PGP9.5), substance P (SP), neuropeptide K (NPK), pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP) and galanin. Study 2 - Seventeen symptomatic and 15 asymptomatic patients with colonic diverticula underwent flexible sigmoidoscopy and multiple peridiverticular mucosal biopsies. Study 1- Neural tissue, as assessed by PGP staining was increased to a similar degree in circular muscle in both AD and CD. The CD specimens showed significant increases in the immunoreactivity of SP, NPK and galanin in both mucosal and circular muscle layer compared with controls. Study 2 - Mucosal histology was normal and PGP9.5 staining was similar between groups however patients with symptomatic diverticular disease demonstrated significantly higher levels of SP, NPK, VIP, PACAP and galanin within the mucosal plexus. Patients with symptomatic diverticular disease exhibit increased neuropeptides in mucosal biopsies which may reflect resolved prior inflammation, as it parallels the changes seen in acute and chronic diverticulitis.
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| 10. |
- Simpson, J, et al.
(author)
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Prolonged elevation of galanin and tachykinin expression in mucosal and myenteric enteric nerves in trinitrobenzene sulphonic acid colitis
- 2008
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 20:4, s. 392-406
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Journal article (peer-reviewed)abstract
- Diverticulitis causes recurrent abdominal pain associated with increased mucosal expression of mucosal galanin and substance P (SP). We studied changes in mucosal and myenteric plexus neuropeptides in adult rats using a model of colonic inflammation, trinitrobenzenesulphonic acid colitis. We assessed the effects on the pan-neuronal markers protein gene product 9.5 (PGP9.5) and neurofilament protein, as well as specific neuropeptides at 1, 2, 3, 4, 6, 8, 10 and 14 weeks. Following the acute injury there was macroscopic resolution of inflammation but minor microscopic abnormalities persisted. Percent area stained of mucosal PGP9.5 fell initially but average levels on days 21 and 28 levels were significantly elevated (P < 0.001), returning to normal by day 42. Percent area staining of PGP9.5 in the muscle rose immediately and remained significantly elevated at 70 days (P < 0.001). SP, neuropeptide K and galanin followed a similar overall pattern. SP to PGP9.5 ratio was significantly increased in the muscle both acutely (days 1-28) and in the long term (days 70 and 98), whereas the galanin to PGP9.5 ratio was significantly increased in the mucosa throughout the study. Low-grade chronic inflammation after an acute initial insult causes a persistent increase in the expression of galanin in the mucosa and SP in muscle layer.
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| 11. |
- Rao, S S C, et al.
(author)
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Evaluation of gastrointestinal transit in clinical practice: position paper of the American and European Neurogastroenterology and Motility Societies.
- 2011
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In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 23:1, s. 8-23
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Research review (peer-reviewed)abstract
- Background Disorders of gastrointestinal (GI) transit and motility are common, and cause either delayed or accelerated transit through the stomach, small intestine or colon, and affect one or more regions. Assessment of regional and/or whole gut transit times can provide direct measurements and diagnostic information to explain the cause of symptoms, and plan therapy. Purpose Recently, several newer diagnostic tools have become available. The American and European Neurogastroenterology and Motility Societies undertook this review to provide guidelines on the indications and optimal methods for the use of transit measurements in clinical practice. This was based on evidence of validation including performance characteristics, clinical significance, and strengths of various techniques. The tests include measurements of: gastric emptying with scintigraphy, wireless motility capsule, and (13) C breath tests; small bowel transit with breath tests, scintigraphy, and wireless motility capsule; and colonic transit with radioopaque markers, wireless motility capsule, and scintigraphy. Based on the evidence, consensus recommendations are provided for each technique and for the evaluations of regional and whole gut transit. In summary, tests of gastrointestinal transit are available and useful in the evaluation of patients with symptoms suggestive of gastrointestinal dysmotility, since they can provide objective diagnosis and a rational approach to patient management.
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| 12. |
- Tack, J, et al.
(author)
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Diagnosis and treatment of chronic constipation--a European perspective.
- 2011
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In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 23:8, s. 697-710
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Research review (peer-reviewed)abstract
- BACKGROUND: Although constipation can be a chronic and severe problem, it is largely treated empirically. Evidence for the efficacy of some of the older laxatives from well-designed trials is limited. Patients often report high levels of dissatisfaction with their treatment, which is attributed to a lack of efficacy or unpleasant side-effects. Management guidelines and recommendations are limited and are not sufficiently current to include treatments that became available more recently, such as prokinetic agents in Europe. PURPOSE: We present an overview of the pathophysiology, diagnosis, current management and available guidelines for the treatment of chronic constipation, and include recent data on the efficacy and potential clinical use of the more newly available therapeutic agents. Based on published algorithms and guidelines on the management of chronic constipation, secondary pathologies and causes are first excluded and then diet, lifestyle, and, if available, behavioral measures adopted. If these fail, bulk-forming, osmotic, and stimulant laxatives can be used. If symptoms are not satisfactorily resolved, a prokinetic agent such as prucalopride can be prescribed. Biofeedback is recommended as a treatment for chronic constipation in patients with disordered defecation. Surgery should only be considered once all other treatment options have been exhausted.
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| 13. |
- Wixner, Jonas, et al.
(author)
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Gastric emptying in hereditary transthyretin amyloidosis : the impact of autonomic neuropathy
- 2012
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In: Neurogastroenterology and Motility. - : Wiley-Blackwell. - 1350-1925 .- 1365-2982. ; 24:12, s. 1111-e568
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Journal article (peer-reviewed)abstract
- Background: Gastrointestinal (GI) complications are common in hereditary transthyretin amyloidosis and an autonomic dysfunction has been considered to explain these symptoms. The aim of this study was to investigate the impact of autonomic neuropathy on gastric emptying in hereditary transthyretin amyloidosis and to relate these findings to nutritional status, GI symptoms, gender, and age at disease onset.Methods: Gastric emptying was evaluated with gastric emptying scintigraphy. Spectral analysis of the heart rate variability and cardiovascular responses after tilt test were used to assess the autonomic function. The nutritional status was evaluated with the modified body mass index (s-albumine x BMI).Key Results: Gastric retention was found in about one-third of the patients. A weak correlation was found between the scintigraphic gastric emptying rate and both the sympathetic (rs = -0.397, P < 0.001) and parasympathetic function (rs = -0.282, P = 0.002). The gastric emptying rate was slower in those with lower or both upper and lower GI symptoms compared with those without symptoms (median T50 123 vs 113 min, P = 0.042 and 192 vs 113 min, P = 0.003, respectively). Multiple logistic regression analysis showed that age of onset (OR 0.10, CI 0.020.52) and sympathetic dysfunction (OR 0.23, CI 0.100.51), but not gender (OR 0.76, CI 0.311.84) and parasympathetic dysfunction (OR 1.81, CI 0.724.56), contributed to gastric retention.Conclusions and Inferences: Gastric retention is common in hereditary transthyretin amyloidosis early after onset. Autonomic neuropathy only weakly correlates with gastric retention and therefore additional factors must be involved.
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| 14. |
- Andersson, S., et al.
(author)
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Gastric electrical stimulation for intractable vomiting in patients with chronic intestinal pseudoobstruction
- 2006
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In: Neurogastroenterology and motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 18:9, s. 823-30
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Journal article (peer-reviewed)abstract
- Gastric electrical stimulation (GES) is effective for medically refractory nausea and vomiting in patients with idiopathic or diabetic gastroparesis (DGP). We studied whether GES has similar effects in chronic intestinal pseudoobstruction (CIP). Patients referred for chronic small bowel (SB) motor dysfunction requiring parenteral nutrition and having a weekly vomiting frequency (WVF) >/=7 refractory to prokinetics and antiemetics were included. Patients were implanted for high-frequency GES 12 stimuli min(-1), laparoscopy being the first-line implantation procedure. Results were compared with those obtained in 11 DGP patients. Three patients with familial CIP and one patient with postsurgical CIP fulfilled the criteria. Gastric emptying was delayed in two and was normal in two patients. SB transit time was markedly delayed. Laparoscopy was used in three patients, one patient required laparotomy. During GES, WVF decreased from 24 (mean) before GES to 6.9 at 12 months and 7.5 at last visit. Vomiting reduction was 50-90% at last visit. For the DGP patients, WVF decreased from 23 before GES to 3.5 at 12 months and 3.5 (P < 0.01) at last visit. In patients with CIP and medically refractory vomiting, GES seems to have an anti-vomiting effect comparable to that seen in patients with severe DGP. GES should be considered as a therapeutic option for these patients.
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| 15. |
- Bucinskaite, V, et al.
(author)
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Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat
- 2009
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:9, s. 978-e78
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Journal article (peer-reviewed)abstract
- The vagus nerve plays a role in mediating effects of the two glucagon-like peptides GLP-1 and GLP-2 on gastrointestinal growth, functions and eating behaviour. To obtain electrophysiological and molecular evidence for the contribution of afferent pathways in chemoreception from the gastrointestinal tract, afferent mass activity in the ventral gastric branch of the vagus nerve and gene expression of GLP-1 receptors and GLP-2 receptors in the nodose ganglion were examined in Sprague–Dawley rats. Intravenous administration of GLP-1 (30–1000 pmol kg−1), reaching high physiological plasma concentrations, increased vagal afferent mass activity peaking (13–52% above basal level, P < 0.05) 3–5 min after injection. Repeated administration of GLP-1 (1000 pmol kg−1; five times, 15 min intervals) elicited similar responses. Pretreatment with GLP-1 receptor antagonist exendin(9-39)amide (500 pmol kg−1) abolished the GLP-1 response to doses 30–300 pmol kg−1 but had no effect on the vagal response to gastric distension. For comparison, GLP-2 (1000 pmol kg−1) had no effect on vagal afferent activity. Vagal chemoreception of GLP-1 is supported by expression of the GLP-1 receptor gene in the nodose ganglion. However, the GLP-2 receptor was also expressed. To conclude, our results show that peripherally administered GLP-1, differently from GLP-2, activates vagal afferents, with no evidence of desensitisation. The GLP-1 effect was blocked by exendin(9-39)amide, suggesting that GLP-1 receptors on vagal afferent nerves mediate sensory input from the gastrointestinal tract or pancreas; either directly or indirectly via the release of another mediator. GLP-2 receptors appear not be functionally expressed on vagal afferents.
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| 16. |
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| 17. |
- Delbro, Dick
(author)
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Do neuro-humoral signaling molecules participate in colorectal carcinogenesis/cancer progression?
- 2012
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In: Neurogastroenterology and Motility. - : Wiley-Blackwell. - 1350-1925 .- 1365-2982. ; 24:2, s. 96-99
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Journal article (peer-reviewed)abstract
- Signaling molecules in the gastrointestinal (GI) tract, as released from intrinsic, or extrinsic neurons, or from local endocrine cells may serve as positive or negative growth factors, and it has been suggested that such could participate also in colorectal carcinogenesis/cancer progression. Sporadic colorectal cancer arises from an initially benign adenoma, which, in turn, develops from the stem cell compartment, located in the bottom of the crypts of the colorectal mucosa. It was recently demonstrated in rat that intrinsic denervation of the colon appeared to be protective against chemically induced carcinogenesis. Of the various GI signaling molecules, noradrenaline (NA) and substance P (SP) may be of particular importance as growth factors involved in colorectal cancer. In the current issue of Neurogastroenterology and Motility, Graf et al. demonstrate that in benign, human colon polyps, there was a loss of innervation compared with adjacent mucosa, affecting efferent, noradrenergic, as well as sensory, SP-ergic fibers, while there was an increase in SP-immunoreactive non-neuronal cells in the polyps. The results obtained could suggest that loss of mucosal innervation, due to e.g. luminal, pro-inflammatory stimuli, could result in unbalanced pro-tumorigenic stimulation of the stem cell region by non-neuronal SP. The current findings may be important for the further understanding of the development of sporadic colorectal cancer.
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| 18. |
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| 19. |
- Edholm, T., et al.
(author)
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Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis
- 2010
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 22:11, s. 1191-e315
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Journal article (peer-reviewed)abstract
- Background Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are major incretins with important effects on glucoregulatory functions. The aim of this study was to investigate effects of GIP and GLP-1 on gastric emptying and appetite after a mixed meal, and effects on insulin secretion and glucose disposal in humans. Methods Randomized crossover single-blind study in 17 healthy volunteers receiving GIP (2 or 5 pmol kg−1 min−1, n = 8), GLP-1 (0.75 pmol kg−1 min−1, n = 9) or NaCl for 180 min with a radionuclide-labeled omelette and fruit punch (370 kcal). Outcome measures were gastric emptying rate, insulinogenic index, hunger, satiety, desire to eat, and prospective food consumption. Blood was analyzed for GIP, GLP-1, glucagon, C-peptide, peptide YY (PYY) and ghrelin. Key Results Glucose-dependent insulinotropic polypeptide 2 and 5 pmol kg−1 min−1 decreased gastric half-emptying time from 128.5 ± 34.0 min in controls to 93.3 ± 6.3 and 85.2 ± 11.0 min (P < 0.05). Glucose-dependent insulinotropic polypeptide 5 pmol kg−1 min−1 decreased postprandial glucose (P < 0.001) and insulin (P < 0.05) with increased insulinogenic index. Glucose-dependent insulinotropic polypeptide had no effects on hunger, desire to eat, satiety or prospective consumption. Glucagon-like peptide-1 0.75 pmol kg−1 min−1 increased half-emptying time from 76.6 ± 7.6 min to 329.4 ± 71.6 (P < 0.01). Glucagon-like peptide-1 decreased plasma glucose and insulin (both P < 0.05–0.001), and increased insulinogenic index markedly. Hunger, desire to eat and prospective consumption were decreased (P < 0.05), and satiety borderline increased (P < 0.06). Conclusion & Inferences The incretin effect of GIP and GLP-1 differs as GLP-1 exerts a strong glucoregulatory incretin through inhibition of gastric emptying, which GIP does not. Thus, GLP-1 as incretin mimetic may offer unique benefits in terms of weight loss in treatment of type 2 diabetes.
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| 20. |
- Edholm, T, et al.
(author)
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The incretin hormones GIP and GLP-1 in diabetic rats : effects on insulin secretion and small bowel motility
- 2009
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:3, s. 313-321
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Journal article (peer-reviewed)abstract
- Incretin hormones often display inhibitory actions on gut motility. The aim of this study was to investigate if altered responsiveness to glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) as regards insulin release and small bowel motility could bring further clarity to the pathophysiology of diabetes in the Goto-Kakizaki (GK) rat. The isolated perfused pancreas was studied in male GK and Wistar rats (controls) under euglycemic and hyperglycemic conditions. Glucose-dependent insulinotropic peptide (10 nmol L−1) or GLP-1 (10 nmol L−1) were added to the medium and perfusate was collected and analysed for insulin. Moreover, GK and Wistar rats were supplied with bipolar electrodes in the small bowel and myoelectric activity was recorded during intravenous administration of GIP (1–400 pmol kg−1 min−1) or GLP-1 (0.1–20 pmol kg−1 min−1). Finally, tissue was collected from GK and Wistar rats for RNA extraction. Under euglycemia, GIP and GLP-1 stimulated the initial insulin response by 10-fold in GK rats (P < 0.05). At later hyperglycemia, the insulin response to GIP and GLP-1 was blunted to about one-third compared with controls (P < 0.05). In the bowel GLP-1 was about 2.6–16.7 times more potent than GIP in abolishing the migrating myoelectric complex in the GK and control rats. Polymerase chain reaction (PCR) showed GIP and GLP-1 receptor gene expression in pancreatic islets and in small bowel. The initially high, but later low insulin responsiveness to stimulation with GIP and GLP-1 along with inhibition of small bowel motility in the GK rat indicates a preserved incretin response on motility in diabetes type 2.
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| 21. |
- Ejskjaer, N., et al.
(author)
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Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis : a randomized, placebo-controlled study
- 2010
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 22:10, s. 1069-1077
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Journal article (peer-reviewed)abstract
- Background Gastroparesis, a chronic disorder of abnormal gastric motility, is common in patients with diabetes mellitus. A synthetic, selective ghrelin receptor agonist, TZP-101, is in clinical development for treatment of gastroparesis. This double-blind, randomized, placebo-controlled study evaluated the safety and efficacy of multiple TZP-101 doses in patients with moderate to severe symptomatic diabetic gastroparesis. Methods Patients were admitted to the hospital and adaptively randomized to receive a single 30-min intravenous infusion of 20, 40, 80, 160, 320, or 600 μg kg−1 TZP-101, (n = 57) or placebo, (n = 19) for four consecutive days. Symptoms were evaluated daily with the patient-rated Gastroparesis Cardinal Symptom Index (GCSI) and Gastroparesis Symptom Assessment (GSA). Clinicians rated gastroparesis symptoms on treatment day 4. Key Results The 80 μg kg−1 dose was identified as the most effective dose. On day 4, there was statistically significant improvement compared with placebo in the severity of GCSI Loss of Appetite and Vomiting scores for that dose group (P = 0.034 and P = 0.006). In addition, at the 80 μg kg−1 dose, the proportion of patients with at least 50% improvement in vomiting score was significantly different (P = 0.019) compared with placebo. Meal-related GSA scores for Postprandial fullness were significantly improved in the 80 μg kg−1 TZP-101 group compared with placebo (P = 0.012). Clinicians rated the 80 μg kg−1 group better improved than placebo for overall symptom assessment (P = 0.047). Safety profiles were similar in the placebo and TZP-101 groups and all doses were well-tolerated.
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| 22. |
- Falkén, Y., et al.
(author)
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Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans
- 2010
-
In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 22:6, s. e192-e200
-
Journal article (peer-reviewed)abstract
- Background Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis during a 6-h infusion in humans. Methods Ghrelin (15 pmol kg−1 min−1) or saline was infused intravenously for 360 min after intake of radio-opaque markers, acetaminophen, and lactulose after a standardized breakfast in 12 male volunteers. Gastric emptying, orocecal transit, colonic transit, postprandial plasma concentrations of glucose, insulin, glucagon-like peptide-1 (GLP-1), and peptide YY were assessed. In vitro studies of gastrointestinal muscle contractility were performed. Key Results The gastric emptying rate was faster for ghrelin compared to saline (P = 0.002) with a shorter half-emptying time (50.3 ± 3.9 vs 59.9 ± 4.4 min, P = 0.004). There was no effect of ghrelin on orocecal or colonic transit. Postprandial elevations of plasma glucose, insulin, and GLP-1 occurred 15 min earlier and were higher with ghrelin. The insulinogenic index did not change during ghrelin infusion. Basal in vitro contractility was unaffected by ghrelin. Conclusions & Inferences The effect of a 6-h ghrelin infusion on gastrointestinal motility is limited to the stomach without affecting orocecal or colonic transit. Plasma glucose, insulin, and GLP-1 are elevated postprandially, probably as a result of the hastened gastric emptying. Changes in glucose homeostasis as a consequence of stimulated gastric emptying and hormone release, need to be taken into account in the use of pharmacological stimulants for the treatment of motility disorders.
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| 23. |
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| 24. |
- Frøkjaer, J B, et al.
(author)
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Esophageal distension parameters as potential biomarkers of impaired gastrointestinal function in diabetes patients.
- 2012
-
In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 24:11
-
Journal article (peer-reviewed)abstract
- Gastrointestinal (GI) symptoms, such as nausea, vomiting, bloating, postprandial fullness, and abdominal pain, are frequent in patients with diabetes mellitus (DM). The pathogenesis is complex and multi-factorial. To determine easy accessible and valid biomarkers for disordered GI function in DM patients, we aimed to study esophageal mechanical parameters and their relation to symptoms typically arising from the digestive tract.
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| 25. |
- Hellström, Per M., 1954-
(author)
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Faces of ghrelin--research for the 21st century.
- 2009
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:1, s. 2-5
-
Journal article (peer-reviewed)abstract
- In this issue of Neurogastroenterology and Motility we find three new articles on different aspects of ghrelin, dealing with physiological and pathophysiological actions of the peptide. For the reader this is food for thoughts: Does this peptide do everything? Ghrelin is a gut peptide hormone well established to stimulate motility throughout most parts of the gastrointestinal (GI) tract and appetite. Ghrelin has been linked to various GI regulatory mechanisms, the most evident being hunger, over-eating and obesity. In this setting ghrelin has been studied under physiological conditions converging on obesity as a pathophysiological process where the peptide has been employed as an interesting tool for studying the development of obesity. With a widespread distribution of ghrelin receptors on various immune cells, it has been assumed that ghrelin also possesses immunoregulatory properties, thus also being of interest in intestinal inflammation research. Anti-inflammatory effects of exogenous ghrelin have been claimed in experimental colitis in mice. Further studies on this concept using ghrelin gene knock-out mice, however, show an increased inflammatory activity in experimental colitis in wild-type mice pointing to ghrelin as an enhancer of the inflammatory course of the disease. Taken together, recent studies on ghrelin indicate that the peptide is not only a regulatory agent in pathophysiological processes, but also participates in pathological disease conditions with actions that seem to even involve genetic mechanisms.
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| 26. |
- Hellström, P. M., et al.
(author)
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GLP-1 suppresses gastrointestinal motility and inhibits the migrating motor complex in healthy subjects and patients with irritable bowel syndrome
- 2008
-
In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 20:6, s. 649-659
-
Journal article (peer-reviewed)abstract
- Glucagon-like peptide-1 (GLP-1) is released after food intake to act as an incretin. GLP-1 also inhibits gastric emptying and increases satiety. In rats, GLP-1 inhibits small bowel motility. Our aim was to study the effects of GLP-1 on gastrointestinal motility in healthy subjects and patients with irritable bowel syndrome (IBS). Antro-duodeno-jejunal manometry was carried out during a 4-h control period with saline, followed by a 4-h period with intravenous GLP-1 (healthy: 0.7 and 1.2 pmol kg-1 min-1 (n = 16), IBS, 1.2 and 2.5 pmol kg-1 min-1 (n = 14). Plasma was analysed for GLP-1 and gut hormones, and gut tissue expression of GLP-1 receptor was studied. In healthy subjects, GLP-1 0.7 pmol kg-1 min-1 reduced the migrating motor complexes (MMCs) from a median of 2 (range 2-3) to 0.5 (0-2), and motility index from 4.9 ± 0.1 to 4.3 ± 0.3 ln ∑(mmHg*s min-1) in jejunum, while GLP-1 1.2 pmol kg -1 min-1 diminshed MMCs from 2 (2-3) to 1.5 (1-2.5), and motility index from 5.2 ± 0.2 to 4.4 ± 0.2. In IBS patients, GLP-1 1.2 pmol kg-1 min-1 reduced the MMCs from 2.5 (2-3.5) to 1 (0-1.5) without affecting motility index. At 2.5 pmol kg-1 min -1 GLP-1 decreased MMCs from 2 (1.5-3) to 1 (0.5-1.5), and motility index from 5.2 ± 0.2 to 4.0 ± 0.5. Motility responses to GLP-1 were similar in antrum and duodenum. Presence of the GLP-1 receptor in the gut was verified by reverse transcriptase PCR. In conclusion, the gut peptide GLP-1 decreases motility in the antro-duodeno-jejunal region and inhibits the MMC in healthy subjects and IBS patients. © 2008 The Authors.
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| 27. |
- Holmén, Nathalie, 1979, et al.
(author)
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CD4+CD25+ regulatory T cells in irritable bowel syndrome patients.
- 2007
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In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1350-1925. ; 19:2, s. 119-25
-
Journal article (peer-reviewed)abstract
- The aetiology of the irritable bowel syndrome (IBS) is incompletely understood. A low-grade colonic inflammation is frequently seen, but it is unclear to what extent this phenomenon contributes to the pathophysiology of IBS. CD4(+)CD25(+) regulatory T cells (Treg) are implicated to play an important role in suppressing intestinal inflammation. We, therefore, examined whether the intestinal inflammatory process in IBS patients is the result of an altered function and/or frequency of CD25(+) Treg cells. Patients with IBS (n = 34), fulfilling the Rome II criteria, were compared with controls (n = 26). The suppressive activity of blood CD25(+) Treg cells was determined and the frequency of colonic and blood CD25(+) Treg cells was analysed by flow cytometry. The expression of the Treg marker, FOXP3 mRNA, in colonic biopsies was determined by reverse transcription-polymerase chain reaction. Blood CD25(+) Treg cells from IBS patients suppressed the proliferation of blood CD4(+)CD25(low/-) T cells. Similar frequencies of CD25(+) Treg cells were recorded in mucosa and blood of IBS patients and controls. FOXP3 mRNA was equally expressed in the colonic mucosa of patients with IBS and controls. In conclusion, the low-grade intestinal inflammation recorded in patients with IBS is not associated with an altered function or frequency of CD25(+) Treg cells.
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| 28. |
- Jerndal, P, et al.
(author)
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Gastrointestinal-specific anxiety: an important factor for severity of GI symptoms and quality of life in IBS.
- 2010
-
In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 22:6
-
Journal article (peer-reviewed)abstract
- Gastrointestinal (GI)-specific anxiety (GSA) has been proposed to influence symptom severity and quality of life (QOL) in patients with irritable bowel syndrome (IBS). The Visceral Sensitivity Index (VSI) is a recently developed, reliable and valid measure of GSA. Our aim was to evaluate the association between GSA, GI symptom severity, and QOL in IBS patients.
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| 29. |
- Karling, Pontus, et al.
(author)
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No difference in symptoms of irritable bowel syndrome between healthy subjects and patients with recurrent depression in remission
- 2007
-
In: Neurogastroenterology and Motility. - Oxford : Blackwell. - 1350-1925 .- 1365-2982. ; 19:11, s. 896-904
-
Journal article (peer-reviewed)abstract
- There is bidirectional comorbidity between anxiety/depression and irritable bowel syndrome (IBS). To investigate the prevalence of IBS symptoms, and factors associated with gastrointestinal symptoms in patients with recurrent depressive disorder. Patients (n = 95) with recurrent type of major depression according to DSM-IV criteria and sex- and age-matched controls (n = 190) were sent questionnaires investigating symptoms of IBS [Gastrointestinal Symptom Rating Scale (GSRS)-IBS] and symptoms of anxiety and depression [Hospital Anxiety and Depression Scale (HADS)]. Medical records were checked over a 10-year period for chronic somatic symptoms or diseases. Seventy-three patients with unipolar disorder (mean age 63.6 years SD 13.8; range 23–86 years) and 156 controls (mean age 59.2 years SD 11.6, range 21–85 years) responded. Patients with recurrent depression had higher GSRS-IBS scores and showed a strong correlation between symptoms of IBS and anxiety-depression (rs = 0.54; P < 0.001). IBS symptoms were also associated with multiple pain symptoms, higher health-seeking behaviour and selective-serotonin-reuptake inhibitor intake. However, patients with recurrent depression (n = 46) in remission (HADS-Depression score <8) did not have more symptoms of IBS than controls (GSRS-IBS median score 6.0 vs 6.5; P = 0.46). There is a strong association between symptoms of IBS and symptoms of anxiety and depression, whereas depressive patients in remission do not have more IBS symptoms than controls.
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| 30. |
- Keita, Åsa V, et al.
(author)
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Stress-induced barrier disruption of the follicle-associated epithelium involves corticotropin-releasing hormone, vasoactive intestinal peptide and mast cells
- 2010
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 22:7, s. 770-e222
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Journal article (peer-reviewed)abstract
- Background The follicle-associated epithelium (FAE) is specialized in uptake and sampling of luminal antigens and bacteria. We previously showed that stress increased FAE permeability in rats. An increased uptake may alter antigen exposure in Peyers patches leading to intestinal disease. The aim of this study was to elucidate mechanisms involved in the acute stress-induced increase in FAE permeability. Methods Rats were pretreated i.p. with corticotropin-releasing hormone receptor (CRH-R) antagonist, neurokinin receptor 1 (NK-1R) antagonist, atropine, the mast cell stabilizer doxantrazole (DOX), or NaCl, and submitted to 1-h acute water avoidance stress. FAE tissues were mounted in Ussing chambers for measurements of permeability to 51Cr-EDTA, horseradish peroxidase (HRP) and chemically killed Escherichia coli K-12. Further, FAE segments were exposed in vitro in chambers to CRH, substance P (SP), carbachol, and DOX. Neurotransmitter- and receptor distribution was studied by immunohistochemistry. Key Results Stress-induced increases in uptake across FAE of HRP and E. coli were reduced by DOX, CRH-R antagonist and atropine, whereas the NK-1R antagonist decreased 51Cr-EDTA permeability. Exposure to CRH and carbachol increased HRP and E. coli passage, whereas SP increased bacterial and 51Cr-EDTA permeability. DOX counteracted all of these effects. Immunohistochemistry revealed CRH, acetylcholine, SP, and their receptors on mast cells within the Peyers patches, subepithelial dome, and adjacent villi. Conclusions & Inferences Corticotropin-releasing hormone and acetylcholine signaling affect mainly transcellular permeability while SP seems more selective toward the paracellular pathways. Our findings may be of importance for the understanding of the pathogenesis of stress-related intestinal disorders.
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| 31. |
- Keita, Åsa V., et al.
(author)
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The intestinal barrier and its regulation by neuroimmune factors
- 2010
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In: Neurogastroenterology and Motility. - : Blackwell Publishing Ltd. - 1350-1925 .- 1365-2982. ; 22:7, s. 718-733
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Research review (peer-reviewed)abstract
- Background The ability to control uptake across the mucosa and protect from damage of harmful substances from the lumen is defined as intestinal barrier function. A disturbed barrier dysfunction has been described in many human diseases and animal models, for example, inflammatory bowel disease, irritable bowel syndrome, and intestinal hypersensitivity. In most diseases and models, alterations are seen both of the paracellular pathway, via the tight junctions, and of the transcellular routes, via different types of endocytosis. Recent studies of pathogenic mechanisms have demonstrated the important role of neuroimmune interaction with the epithelial cells in the regulation of barrier function. Neural impulses from extrinsic vagal and/or sympathetic efferent fibers or intrinsic enteric nerves influence mucosal barrier function via direct effects on epithelial cells or via interaction with immune cells. For example, by nerve-mediated activation by corticotropin-releasing hormone or cholinergic pathways, mucosal mast cells release a range of mediators with effects on transcellular, and/or paracellular permeability (for example, tryptase, TNF-alpha, nerve growth factor, and interleukins). Purpose In this review, we discuss current physiological and pathophysiological aspects of the intestinal barrier and, in particular, its regulation by neuroimmune factors.
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| 32. |
- Larsson, Marie H, 1972, et al.
(author)
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Elevated motility-related transmucosal potential difference in the upper small intestine in the irritable bowel syndrome.
- 2007
-
In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1350-1925. ; 19:10, s. 812-20
-
Journal article (peer-reviewed)abstract
- The pathophysiology of irritable bowel syndrome (IBS) is complex and incompletely known. Very little has been studied regarding the role of submucous neuronal activity. We therefore measured small intestinal transmural potential difference (PD, reflecting mainly electrogenic chloride secretion), and its linkage with fasting motor activity [migrating motor complex (MMC)] in controls (n = 16) and patients with IBS [n = 23, 14 diarrhoea predominant (d-IBS) and nine constipation predominant (c-IBS)]. Transmural-PD and its relation to MMC phase III was measured by modified multilumen manometry for 3 h in the fasting state using one jejunal and one duodenal infusion line as flowing electrodes. The amplitude and duration of motor phase III was similar in controls and IBS patients, but the propagation speed of phase III was higher in IBS patients. In IBS patients, maximal PD during MMC phase III was significantly elevated in both the duodenum and jejunum (P < 0.05) and the PD decline after phase III was significantly prolonged in the jejunum (P < 0.01). The PD elevation was seen in both duodenum and jejunum in d-IBS patients, but only in the jejunum in the c-IBS patients. On the basis of previous modelling studies, we propose that the enhanced secretion may reflect disturbed enteric network behaviour in some patients with IBS.
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| 33. |
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| 34. |
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| 35. |
- Sanger, G J, et al.
(author)
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GSK962040 : a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility
- 2009
-
In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:6, s. 657-664, e30-31
-
Journal article (peer-reviewed)abstract
- There is an urgent clinical need for a safe, efficacious stimulant of gastric emptying; current therapies include erythromycin (an antibiotic with additional properties which preclude chronic use) and metoclopramide (a 5-hydroxytryptamine type 4 receptor agonist and an antagonist at brain D2 receptors, associated with movement disorders). To move away from the complex motilide structure of erythromycin, a small molecule motilin receptor agonist, GSK962040, was identified and characterized. The compound was evaluated using recombinant human receptors, rabbit and human isolated stomach preparations known to respond to motilin and in vivo, by measuring its ability to increase defecation in conscious rabbits. At the human motilin receptor, the pEC50 (the negative logarithm to base 10 of the EC50 value, the concentration of agonist that produces 50% of the maximal response) values for GSK962040 and erythromycin as agonists were, respectively, 7.9 and 7.3; GSK962040 had no significant activity at a range of other receptors (including ghrelin), ion channels and enzymes. In rabbit gastric antrum, GSK962040 300 nmol L−1–10 μmol L−1 caused a prolonged facilitation of the amplitude of cholinergically mediated contractions, to a maximum of 248 ± 47% at 3 μmol L−1. In human-isolated stomach, GSK962040 10 μmol L−1, erythromycin 10 μmol L−1 and [Nle13]-motilin 100 nmol L−1, each caused muscle contraction of similar amplitude. In conscious rabbits, intravenous doses of 5 mg kg−1 GSK962040 or 10 mg kg−1 erythromycin significantly increased faecal output over a 2-h period. Together, these data show that GSK962040, a non-motilide structure, selectively activates the motilin receptor. Simplification of the structural requirements to activate this receptor greatly facilitates the design of potentially new medicines for gastroparesis.
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| 36. |
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| 37. |
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| 38. |
- Simrén, Magnus, 1966, et al.
(author)
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High interdigestive and postprandial motilin levels in patients with the irritable bowel syndrome.
- 2005
-
In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1350-1925. ; 17:1, s. 51-7
-
Journal article (peer-reviewed)abstract
- Motilin shows cyclic variation with the different phases of the migrating motor complex (MMC). Altered motilin levels have been found in irritable bowel syndrome (IBS) patients, but in these studies motilin levels were analysed without the knowledge of the phases of MMC. We included 13 healthy controls (HC) and 24 patients with IBS [12 diarrhoea-predominant (IBS-D) and 12 constipation-predominant (IBS-C)]. We performed interdigestive and postprandial antroduodenojejunal manometry and blood samples for analysis of motilin were drawn. Group differences in plasma levels of motilin were analysed during mid-phase II, just before the start of phase III (pre-III), during phase I, immediately before the meal and 30 and 60 min after the 500 kcal mixed meal. Higher motilin levels were observed in IBS vs HC in both the interdigestive and postprandial periods (P < 0.05). No significant differences between IBS-C and IBS-D were observed. The cyclic variation of motilin during MMC and the meal response was similar in IBS and controls. IBS patients, irrespective of the predominant bowel habit, demonstrate higher motilin levels than HCs in all phases of the MMC and also after a meal. These findings may bear some pathophysiological importance in IBS and relate to the gastrointestinal dysmotility often seen in these patients.
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| 39. |
- Simrén, Magnus, 1966, et al.
(author)
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Nutrient-dependent enhancement of rectal sensitivity in irritable bowel syndrome (IBS).
- 2007
-
In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1350-1925. ; 19:1, s. 20-9
-
Journal article (peer-reviewed)abstract
- Food-related gastrointestinal symptoms are common in irritable bowel syndrome (IBS), but the mechanisms behind this are unclear. Enhanced colorectal sensitivity after duodenal lipid administration in IBS patients has been demonstrated. However, the effects of a regular meal on colorectal sensitivity in these patients and the importance of the composition of the meal are not known. On two separate days, 10 IBS patients and 11 controls randomly received a liquid meal (800 kcal), containing 60% calories from fat (fatty meal) or carbohydrate (carbohydrate meal). Using a barostat rectal sensitivity was assessed during four separate distension sequences before, immediately after and 30 and 60 min after the meal. In the patients, the discomfort (P = 0.04) and the pain thresholds (P = 0.007) were gradually reduced after the fatty meal, whereas only a tendency in the same direction was seen after the carbohydrate meal. In patients VAS ratings for pain increased after the fatty meal (P = 0.03), but not after carbohydrates. In the controls, sensory thresholds were not affected by the meals. In IBS, a liquid meal enhances rectal sensitivity, and this seems to be partly nutrient dependent as a fatty meal has more pronounced effects than a carbohydrate meal. This might be of relevance for their postprandial symptoms.
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| 40. |
- Simrén, Magnus, 1966, et al.
(author)
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The places to be for neurogastroenterologists.
- 2012
-
In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 24:6, s. 501-2
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Journal article (other academic/artistic)
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| 41. |
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| 42. |
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| 43. |
- Vanhoutvin, S. A. L. W., et al.
(author)
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The effects of butyrate enemas on visceral perception in healthy volunteers
- 2009
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In: Neurogastroenterology and Motility. - : Wiley-Blackwell Publishing Inc.. - 1350-1925 .- 1365-2982. ; 21:9, s. 952-e76
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Journal article (peer-reviewed)abstract
- Fermentation of dietary fibres by colonic microbes leads to the production of short chain fatty acids (mainly propionate, butyrate and acetate), which are utilized by the colonic mucosa. Previous studies showed positive effects of butyrate on parameters of oxidative stress, inflammation and apoptosis. Recent studies in rats, however, showed that butyrate increased visceral sensitivity. The aim of this study was to determine the effects of physiologically relevant concentrations of butyrate on visceral perception in healthy human subjects. Eleven healthy volunteers participated in this randomized double-blind, placebo controlled cross-over study. The study consisted of three periods of 1 week each, in which the volunteers daily self-administered rectal enemas containing 100, 50 mmol L(-1) butyrate, or placebo (saline) prior to sleeping. A rectal barostat measurement was performed at the start and the end of each test period for the measurement of pain, urge and discomfort. Butyrate treatment resulted in a dose-dependent reduction of pain, urge and discomfort throughout the entire pressure range of the protocol. At a pressure of 4 mmHg, 50 and 100 mmol L(-1) butyrate concentrations resulted in a 23.9% and 42.1% reduction of pain scores, respectively, and the discomfort scores decreased by 44.2% and 69.0% respectively. At a pressure of 67 mmHg, 50 and 100 mmol L(-1) of butyrate decreased the pain scores by 23.8% and 42%, respectively, and discomfort scores 1.9% and 5.2% respectively. Colonic administration of butyrate, at physiologically relevant concentrations, dose-dependently decreases visceral sensitivity in healthy volunteers.
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| 44. |
- Walter, Susanna A., et al.
(author)
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Pre-experimental stress in patients with irritable bowel syndrome : high cortisol values already before symptom provocation with rectal distensions
- 2006
-
In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 18:12, s. 1069-1077
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Journal article (peer-reviewed)abstract
- Stress is known to affect symptoms of irritable bowel syndrome (IBS) probably by an alteration of visceral sensitivity. We studied the impact of maximal tolerable rectal distensions on cortisol levels in patients with IBS, chronic constipation and controls, and evaluated the effect of the experimental situation per se. In twenty-four IBS patients, eight patients with chronic constipation and 15 controls salivary cortisol was measured before and after repetitive maximal tolerable rectal balloon distensions and at similar times in their usual environment. Rectal sensitivity thresholds were determined. IBS patients but not controls and constipation patients had higher cortisol levels both before and after the experiment compared with similar times on an ordinary day in their usual environment (P = 0.0034 and 0.0002). There was no difference in salivary cortisol level before compared with after rectal distensions. The IBS patients had significantly lower thresholds for first sensation, urge and maximal tolerable distension than controls (P = 0.0247, 0.0001 and <0.0001) and for urge and maximal tolerable distension than patients with constipation (P = 0.006 and 0.013). IBS patients may be more sensitive to expectancy stress than controls and patients with constipation according to salivary cortisol. Rectal distensions were not associated with a further significant increase in cortisol levels.
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| 45. |
- Walter, Susanna A., et al.
(author)
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Sympathetic (electrodermal) activity during repeated maximal rectal distensions in patients with irritable bowel syndrome and constipation
- 2008
-
In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 20:1, s. 43-52
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Journal article (peer-reviewed)abstract
- Irritable bowel syndrome (IBS) is associated with visceral hypersensitivity, stress and autonomic dysfunction. Sympathetic activity during repeated events indicates excitatory or inhibitory mechanisms such as sensitization or habituation. We investigated skin conductance (SC) during repetitive rectal distensions at maximal tolerable pressure in patients with IBS and chronic constipation. Twenty-seven IBS patients, 13 constipation patients and 18 controls underwent two sets of isobaric rectal distensions. First, maximal tolerable distension was determined and then it was repeated five times. Skin conductance was measured continuously. Subjective symptom assessment remained steady in all groups. The baseline values of SC were higher in IBS patients than in patients with constipation and significantly lower in constipation patients than in controls. The maximal SC response to repetitive maximal distensions was higher in IBS patients compared with constipation patients. The amplitude of the initial SC response decreased successively with increased number of distensions in patients with IBS and constipation but not in controls. Irritable bowel syndrome and constipation patients habituated to maximal repetitive rectal distensions with decreasing sympathetic activity. Irritable bowel syndrome patients had higher sympathetic reactivity and baseline activity than constipation patients. A lower basal SC in constipation patients compared with controls suggests an inhibition of the sympathetic drive in constipation patients.
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| 46. |
- Walter, Susanna, et al.
(author)
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Anorectal function in patients with collagenous colitis in active and clinically quiescent phase, in comparison with healthy controls
- 2010
-
In: Neurogastroenterology and Motility. - : Blackwell Publishing Ltd. - 1350-1925 .- 1365-2982. ; 22:5, s. 534-
-
Journal article (peer-reviewed)abstract
- Background Collagenous colitis (CC) is characterized by chronic watery diarrhea, a macroscopically normal colonic mucosa but typical microscopic inflammation. Chronic mucosal inflammation of the colon and rectum has earlier been associated with altered visceral sensitivity, but anorectal function has never been reported in cases of CC. Methods Fifteen patients with CC in active phase recorded their symptoms. The severity of inflammation was determined in mucosal biopsies. Anorectal function was assessed and compared with that of 15 healthy volunteers of corresponding age and matched for gender. After 6 weeks of budesonide treatment when the patients were in clinical remission anorectal function was re-assessed. Key Results All patients had inflammation also in rectum. Patients in active phase had, during rectal balloon distension a higher rectal sensory threshold for the feeling of first sensation, compared with controls (P = 0.02). There were no differences in rectal sensory threshold for the feeling of urgency or maximum distension, between patients with CC in active phase and healthy controls. Rectal volume at first sensation was significantly greater in patients than in controls (P = 0.02), but there were no differences at urgency or maximum distension. Twelve of 15 patients completed 6 weeks of budesonide treatment and all went into clinical remission. No differences in anorectal function were measured when patients had active disease, compared with clinical remission. Conclusions andamp; Inferences Collagenous colitis was not associated with rectal hypersensitivity or disturbed anal function despite rectal inflammation. On the contrary, the sensation threshold for light rectal pressure was elevated in patients with active CC.
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| 47. |
- Wang, X.-Y., et al.
(author)
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Ultrastructural injury to interstitial cells of Cajal and communication with mast cells in Crohn's disease
- 2007
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 19:5, s. 349-364
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Journal article (peer-reviewed)abstract
- Crohn's disease associated dysmotility has been attributed to fibrosis and damage to enteric nerves but injury to interstitial cells of Cajal (ICC) could also be involved. We assessed ICC in specimens obtained from patients with Crohn's disease and determined the relation between ICC and the inflammatory infiltrate, particularly mast cells (MC) using quantitative immunohistochemistry and electron microscopy. Ultrastructural injury to ICC was patchy in all ICC subtypes but ICC-Auerbach's plexus (AP) showed damage more frequently, i.e. swelling of mitochondria, decreased electron density, autophagosomes and partial depletion of the cytoplasm. Light microscopy confirmed a significant decrease in c-kit immunoreactivity for ICC-AP and an increased number of MC in the muscularis externa. Electron microscopy showed MC exhibiting piecemeal degranulation and making frequent and selective membrane-to-membrane contact with all types of injured ICC which suggests chronic release of granule content to affect ICC. Extent of ICC injury was not associated with duration of the disease. In conclusion, ultrastructural injury and loss of ICC-AP is evident in Crohn's disease. Epidemiological and morphological data suggest that ICC have the capacity to regenerate in spite of the chronic insult. The muscularis hosts a marked number of MC that exhibit piecemeal degranulation associated with ICC and may facilitate ICC maintenance. © 2007 The Authors.
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| 48. |
- Woods, CM, et al.
(author)
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Selective iNOS inhibition enhances spontaneous gallbladder motility in the Australian possum
- 2007
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 19:6, s. 497-503
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Journal article (peer-reviewed)abstract
- Gallbladder inflammation is a common and painful disease. Inducible nitric oxide synthase (iNOS) plays a major role in inflammatory diseases, and iNOS inhibitors are being developed as therapeutic agents. Reports are inconsistent regarding iNOS expression in normal gallbladder. The aim of this study was to determine the effect of iNOS inhibition on spontaneous gallbladder motility. mRNA extracted from normal possum gallbladders was analysed by PCR. Gallbladder contractility was evaluated using a highly selective iNOS inhibitor AR-C102222AA (AR-C) in in vitro muscle strips (0.1-10 000 μm) and in vivo (0.1-30 μmol kg-1) experiments. Gene expression analysis revealed the presence of iNOS mRNA in normal gallbladder (n = 3). In vitro, AR-C (0.1-1000 μmol L-1) produced a concentration-dependent increase in spontaneous gallbladder contractile activity and basal tension (P < 0.05, n = 6). The maximum effect was a 1.8-fold increase in activity and 2.1-fold increase in basal tension. Pretreatment of muscle strips with tetrodotoxin (1 μmol L -1) did not block the AR-C-induced response (n = 5). In vivo, AR-C (30 μmol kg-1, i.v.) increased gallbladder contraction frequency (P < 0.05, n = 8). These data suggest that iNOS is continually expressed in the normal gallbladder, which presumably releases low levels of nitric oxide and in turn may modulate spontaneous gallbladder motility. AR-C may be a beneficial treatment for patients suffering from acute cholecystitis. © 2007 The Authors.
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| 49. |
- Öhman, Lena, 1967, et al.
(author)
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B-cell activation in patients with irritable bowel syndrome (IBS).
- 2009
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In: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society. - : Wiley. - 1365-2982. ; 21:6
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Journal article (peer-reviewed)abstract
- Patients with irritable bowel syndrome (IBS) may have a low grade immune activation. However, little is known about the properties of B cells of IBS patients. We therefore investigated activation level and antigen presenting phenotype of blood B cells of IBS patients. We also examined B-cell responses to lipopolysaccharide (LPS) and probiotic bacteria. Blood samples were obtained from 74 IBS patients and 30 healthy subjects. Peripheral blood mononuclear cells were isolated and stimulated with LPS or an UV-light inactivated bacterial cocktail consisting of the probiotic Gram-positive strains; Lactobacillus paracasei ssp. paracasei 19, Lactobacillus acidophilus La5, Bifidobacterium lactis B612. The phenotype of CD19(+) B cells was investigated by flow cytometry before and after 72 h cell culture. Furthermore, IBS symptom severity was assessed. B cells isolated from blood of IBS patients displayed an amplified activation level as demonstrated by increased cell surface expression of IgG, and also the costimulatory molecules CD80 and CD86. Expression of antigen presenting HLA-DR and costimulatory molecule CD40 on B cells was, however comparable in IBS patients and controls. B cells of IBS patients displayed an impaired ability to increase expression of CD80, but not CD86, in response to both LPS as well as probiotic bacteria stimulations. To conclude, blood B cells of IBS patients have an increased activation level. Bacterial component induced expression of the costimulatory molecule CD80, regarded as important for tolerance induction, is impaired. These data suggest that B-cell antigen presentation in IBS patients is associated with altered capacity of providing costimulation to T cells.
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| 50. |
- Aguilera-Lizarraga, J., et al.
(author)
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Expression of immune-related genes in rectum and colon descendens of Irritable Bowel Syndrome patients is unrelated to clinical symptoms
- 2019
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In: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 31:6
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Journal article (peer-reviewed)abstract
- Background: Mucosal immune activation has been postulated to play an important role in the pathogenesis of irritable bowel syndrome (IBS). However, data are conflicting and often based on small patient cohorts. Here, we aimed to evaluate the gene expression of a large set of immune-related genes in mucosal biopsies from IBS patients and healthy volunteers (HV). Methods: A total of 171 IBS patients and 127 HV were included in the study. Rectum biopsies were collected from a cohort of 70 HV and 77 IBS patients (Rome III) and colon descendens biopsies from another cohort of 57 HV and 94 IBS patients (Rome II). Gene expression was assessed using OpenArray technology, and validated questionnaires were used to evaluate clinical characteristics (GI symptoms, somatization, anxiety, and depression). Key Results: A subset of IBS patients (33%) with increased immune activation in the colon descendens was identified using multivariate analysis and displayed increased gene expression of IL1B (3-fold change), prostaglandin synthase PTGS2 (2.1-fold change), and the G-protein-coupled receptor MRGPRX2 (10.7-fold change). Clinical characteristics in this subgroup were however similar to the rest of the patient cohort. Analysis of rectal biopsies failed to identify such subgroup of “immuno-active” IBS patients in the other patient cohort. Conclusion: A subset of IBS patients reveals evidence of immune activation in the colon descendens, but not in the rectum; however, gene expression is unrelated to clinical symptoms. To what extent this subgroup might however respond to anti-inflammatory therapy remains to be investigated. © 2019 John Wiley & Sons Ltd
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