The aim of this study was to determine to what extent human migrating motor complex (MMC)-related secretory phenomena are influenced by a recently discovered period of duodenal retroperistalsis during late phase III. A constant-flow... more
The aim of this study was to determine to what extent human migrating motor complex (MMC)-related secretory phenomena are influenced by a recently discovered period of duodenal retroperistalsis during late phase III. A constant-flow perfusion technique was used to measure gastric appearance of acid, bicarbonate, pepsin, bilirubin, IgA, and duodenally infused [14C]polyethylene glycol (PEG) 4000 in 12 healthy volunteers. Interdigestive gastroduodenal motility was recorded by digital manometry. During late antral phase II and III, the gastric lumen was acidified ( P < 0.005 phase III vs. phase I) together with a marked increase in luminal pepsin output (3.1 ± 1.2 during phase III vs. 0.25 ± 0.08 kU/5 min in phase I, P < 0.01), followed by a realkalinization due to a simultaneous reduction of acid secretion and a duodenogastric reflux, aided by retrograde peristalsis, of bicarbonate and IgA but not of bilirubin, at the end of antral phase III ( P < 0.05 phase III vs. phase I va...
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The aim of the study is to determine the effects of selective cardiac receptor unloading on vascular resistance and net fluid transport in the small intestine. In anesthetized cats, cardiac receptors were unloaded by positive pressure... more
The aim of the study is to determine the effects of selective cardiac receptor unloading on vascular resistance and net fluid transport in the small intestine. In anesthetized cats, cardiac receptors were unloaded by positive pressure ventilation (PPV). Arterial baroreceptor activity was artificially maintained constant. To test if the observed responses were due to a vagal reflex, experiments were performed both in animals with intact vagal nerves (n = 9) and after bilateral cervical vagotomy (n = 8). PPV-induced decreases in central blood volume (CBV) significantly increased intestinal vascular resistance (IVR) and net fluid absorption rate and decreased the transmural potential difference (PD). Cervical vagotomy per se also increased IVR and absorption rate and decreased PD. In vagotomized animals, decreases in CBV had no consistent effects on IVR, net fluid absorption rate, or PD. The results are compatible with cardiac receptor modulation of both blood flow and fluid absorption...
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The aim of the study was to investigate the role of cardiac mechanoreceptors in the reflex regulation of intestinal blood flow and fluid transport. Feline cardiac mechanoreceptor activity was modified with two noninvasive techniques:... more
The aim of the study was to investigate the role of cardiac mechanoreceptors in the reflex regulation of intestinal blood flow and fluid transport. Feline cardiac mechanoreceptor activity was modified with two noninvasive techniques: positive-pressure ventilation (PPV) and inspiratory resistance breathing (IRB). A jejunal segment with intact vascular and nervous supply was isolated and exposed to cholera toxin as a model for intestinal secretion. The results revealed that PPV induced a pronounced intestinal vasoconstriction and a marked inhibition of choleraic secretion. IRB had the opposite effects. The responses were well correlated with changes in central blood volume and either markedly reduced or abolished by vagotomy, intestinal alpha-adrenoreceptor blockade, or postganglionic mesenteric denervation. The results indicate that cardiac mechanoreceptors with vagal afferents may mediate the observed reflex responses, and hence this receptor station may be of importance in the norm...
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The rate of net water uptake from the feline small intestine has been investigated during control conditions, during graded infusions of the vasodilator drug isopropylnoradrenaline, and during electrical stimulation of the regional... more
The rate of net water uptake from the feline small intestine has been investigated during control conditions, during graded infusions of the vasodilator drug isopropylnoradrenaline, and during electrical stimulation of the regional sympathetic nerve fibres to the gut. Net water absorption rate was largely unaffected by intestinal vasodilatation. The fraction of the absorbate transported via the lymphatics remained also constrant at 20-40% of the total absorption regardless of blood flow rate. Stimulating the sympathetic nerve fibres to the small intestine increased, however, net water absorption rate. The increase was particularly pronounced when blood pressure was kept constant during the period of stimulation. The absorption rate was on an average almost doubled at a stimulation frequency of 8 Hz during constant pressure conditions. The mechanism(s) explaining this nervous control of water absorption are tentatively discussed.
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The sympathetic reflex response to mechanical ventilation with PEEP was studied in conscious human volunteers (n = 8). Muscle sympathetic nerve activity (MSNA) was measured from the peroneal nerve, calf blood flow, forearm venous plasma... more
The sympathetic reflex response to mechanical ventilation with PEEP was studied in conscious human volunteers (n = 8). Muscle sympathetic nerve activity (MSNA) was measured from the peroneal nerve, calf blood flow, forearm venous plasma catecholamines, blood pressure, heart rate, airway pressure, and end-tidal CO2 (%) during spontaneous breathing and during mechanical ventilation with 0-20 cmH2O PEEP. MSNA increased (P less than 0.01) during PEEP ventilation, from 22 bursts.min-1 at spontaneous breathing to 39 bursts.min-1 at 20 PEEP. This increase in MSNA was accompanied by an increase (P less than 0.01) in calf vascular resistance (CVR) from 35 PRU100 at spontaneous breathing to 48 PRU100 at 15 PEEP with no further increase at 20 PEEP. Venous plasma norepinephrine concentrations increased (P less than 0.01) during PEEP ventilation from 0.19 ng.ml-1 at spontaneous breathing to 0.31 ng.ml-1 at 20 PEEP, whereas plasma epinephrine and dopamine were less than 0.03 ng.ml-1 during the ex...
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Splanchnic nerve stimulation (SNS) in cats leads to a jejunal vasoconstriction and to an enhancement of jejunal net fluid absorption. We tested the possibility that the sympathetic fibers to the transporting epithelium might use a... more
Splanchnic nerve stimulation (SNS) in cats leads to a jejunal vasoconstriction and to an enhancement of jejunal net fluid absorption. We tested the possibility that the sympathetic fibers to the transporting epithelium might use a ganglionic transmission mechanism different from the one utilized by the jejunal vasoconstrictor nerves. The splanchnic nerves were stimulated before and after a dose of hexamethonium sufficient to entirely block the intestinal vasoconstrictor fibers. However, SNS still increased net fluid absorption in these hexamethonium-treated animals. The hexamethonium-resistant increase in fluid absorption during SNS was a neurogenic effect on the jejunal segment, as it was eliminated by mesenteric denervation and could be reproduced by stimulation of the nerves surrounding the superior mesenteric artery. These data indicate that the rate of jejunal fluid absorption may be regulated by sympathetic fibers functionally distinct from the intestinal vasoconstrictor nerves.
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Research Interests: Biology, Medicine, Humans, Intestinal Mucosa, Female, and 14 moreMale, Mechanoreceptors, Clinical Sciences, Middle Aged, Atrophy, Adult, Gut, Gastrointestinal motility, Muscle contraction, Biological markers, Small Intestine, Case Control Studies, Low pass filter, and Paediatrics and reproductive medicine
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Small intestinal movements depend on the composition of the chyme with mixing predominating at high nutrient levels and propulsion being prevalent at low nutrient levels. The mechanisms coupling nutrients to motility are unknown. We used... more
Small intestinal movements depend on the composition of the chyme with mixing predominating at high nutrient levels and propulsion being prevalent at low nutrient levels. The mechanisms coupling nutrients to motility are unknown. We used computer analysis of video recordings of isolated guinea-pig duodenum, jejunum and ileum to examine movements induced by a fatty acid, decanoic acid. Increasing intraluminal pressure past a threshold using control saline consistently evoked propulsive reflexes: lumen-occluding constrictions appeared at the oral end propagating at 20.4 +/- 2.4 mm s(-1) (mean +/-s.d., jejunum) to the anal end before being repeated until the intraluminal pressure was returned to control. Subthreshold pressure increases sometimes evoked a transient series of constrictions appearing at the oral end and propagating anally at 18.4 +/- 4.7 mm s(-1) (jejunum). At basal pressures, decanoic acid dose-dependently induced motor activity consisting of 40-60 s episodes of constric...
Research Interests: Biological Sciences, Smooth muscle, Fatty acids, Female, Animals, and 15 moreMale, Jejunum, Eating, Enteric Nervous System, Pressure, Guinea Pig, Fatty Acid, Gastrointestinal motility, Muscle contraction, Sodium Chloride, Video Recording, Ileum, Duodenum, Medical and Health Sciences, and Guinea pigs
Interdigestive pain relieved by food is a common feature of ulcer disease. We tested the hypothesis that the duodenal bulb is intermittently acidified in association with phase III of the interdigestive motility cycle, and tried to... more
Interdigestive pain relieved by food is a common feature of ulcer disease. We tested the hypothesis that the duodenal bulb is intermittently acidified in association with phase III of the interdigestive motility cycle, and tried to quantify the balance between acid and duodenal bicarbonate secretion during this particular period. The experiments were performed in Helicobacter-negative healthy volunteers. Gastric and duodenal luminal pH was measured with a triple antimon electrode before, during, and after phase III of the migrating motor complex. Gastric acid secretion rate was measured in real time with a perfusion system and duodenal bicarbonate secretion was estimated from a continuous recording of the transmucosal potential difference (PD) in the duodenal bulb. No significant changes in bulb pH occurred before, during, or after phase III. During the studied time window, the stomach produced 2.24 +/- 0.55 mmol of acid at a peak pH of 1.74 +/- 0.10. Basal HCO3- secretion calculate...
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In 17 healthy volunteers, we studied the dynamics of secretory immunoglobulin A (SIgA) release in the proximal small intestine (distal duodenum and proximal jejunum), using a modified triple-lumen perfusion technique. Secretory data were... more
In 17 healthy volunteers, we studied the dynamics of secretory immunoglobulin A (SIgA) release in the proximal small intestine (distal duodenum and proximal jejunum), using a modified triple-lumen perfusion technique. Secretory data were related to the current phase of the migrating motor complex (MMC), as recorded by manometry. In both segments, luminal SIgA output changed cyclically, with peak outputs occurring at the end of the MMC cycle (late phase II). These MMC-related changes were due to two factors: cyclic inflow of SIgA from more proximal sites, and a cyclic release of SIgA from the test segment that correlated in time with an increase in epithelial fluid secretion. Cyclic intestinal SIgA release may thus be another secretory component of the MMC. The data are compatible with the hypothesis that motility and SIgA release are linked by motility-activated chloride secretion from the intestinal crypts.
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Human gastric interdigestive acid and bicarbonate outputs vary cyclically in association with the migrating motor complex (MMC). These phenomena were studied in 26 healthy volunteers by constant-flow gastric perfusion, with continuous... more
Human gastric interdigestive acid and bicarbonate outputs vary cyclically in association with the migrating motor complex (MMC). These phenomena were studied in 26 healthy volunteers by constant-flow gastric perfusion, with continuous recording of pH and Pco2 in mixed gastric effluent and concomitant open-tip manometry of gastroduodenal motility. Stable acid and bicarbonate outputs were registered during less than 50% of the MMC cycle. Acid secretion started to increase 71 +/- 3% into the cycle, with maximum output during antral phase III. Bicarbonate output increased biphasically 1) 40 +/- 5% into the cycle, coinciding with reflux of bile, and 2) at the end of duodenal phase III when the aspirate was devoid of bile. The bicarbonate peak associated with phase III was abolished by atropine (0.01 mg/kg iv, n = 8) and by pyloric occlusion (n = 9) but remained unchanged after omeprazole (n = 10). The acid peak was abolished by both atropine and omeprazole. It is concluded that the MMC-r...
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The aim of the study was to investigate the effects of dopamine on the intestinal mucosal blood flow and transport function. Dopamine was infused intravenously at 20 micrograms X kg-1 X min-1 in anesthetized cats. Total and intramural... more
The aim of the study was to investigate the effects of dopamine on the intestinal mucosal blood flow and transport function. Dopamine was infused intravenously at 20 micrograms X kg-1 X min-1 in anesthetized cats. Total and intramural blood flow in an isolated jejunal segment was measured by a combined drop-flow and 85Kr clearance technique. Net fluid transport was recorded by two independent perfusion methods. Unidirectional sodium transport was estimated from luminal 22Na disappearance. Dopamine induced a pronounced mucosal vasodilatation up to 400% of control values. Concomitantly, net fluid and sodium absorption increased by 50%. The effect on sodium transport was due to a pronounced decrease in tissue-to-lumen sodium flux, a pattern similar to the one seen on alpha-adrenergic stimulation. The effect of dopamine on blood flow was unaffected by phentolamine, 1 mg X kg-1, whereas the absorptive response was abolished. The findings indicate that dopamine induces a mucosal vasodilat...
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In 22 healthy volunteers distal duodenal fluid absorption was related to the interdigestive motility cycle. Fluid absorption was measured with a triple-lumen perfusion technique, and motility was registered with a low-compliance... more
In 22 healthy volunteers distal duodenal fluid absorption was related to the interdigestive motility cycle. Fluid absorption was measured with a triple-lumen perfusion technique, and motility was registered with a low-compliance pneumohydraulic system. Pancreatic and biliary secretions were estimated by measurement of bilirubin and amylase release into the duodenal segment. Duodenal fluid absorption rate changed during the interdigestive motility cycle; the highest absorption rate was registered during phase I (low-motor activity) and absorption rate then decreased in parallel with increasing motor activity during phase II (r = -0.69, P less than 0.001). In late phase II a net fluid secretion was frequently registered, together with an increased release of bilirubin into the duodenal lumen. This pattern was seen during perfusion with both glucose-containing (30 mM) and glucose-free solutions. The results show that duodenal fluid absorption rate changes markedly during the interdiges...
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The bicarbonate ion seems to play a crucial role in mucosal acid-base regulation by generating a pH gradient that is regarded as a &#39;first line of defense&#39; against acid back-diffusion. The aim of this study was to determine... more
The bicarbonate ion seems to play a crucial role in mucosal acid-base regulation by generating a pH gradient that is regarded as a &#39;first line of defense&#39; against acid back-diffusion. The aim of this study was to determine the effects of hypovolemia on gastric mucosal buffering capacity, as reflected by luminal HCO3- release, in human volunteers. Central hypovolemia was induced by lower-body negative pressure (LBNP), and HCO3- release was measured by using a perfusion system based on continuous recording of the pH and PCO2 of gastric aspirate. The response to LBNP was related to concomitant cardiovascular effects, to gastric pH, and to the current phase of the migrating motor complex (MMC). At an acid gastric pH, LBNP induced a slight but statistically significant reduction in luminal HCO3- release (-27 +/- 10%, p &lt; 0.05). The magnitude of the response was significantly correlated with the degree of reflex tachycardia. A larger and less variable response (-78 +/- 4%, p &lt; 0.01 versus control group) was seen when luminal pH was increased by ranitidine pretreatment. The effect of LBNP on HCO3- release was statistically significant only during the early and middle parts of the MMC cycle. The results indicate that hypotension may reduce gastric mucosal buffering capacity, probably by activation of a sympathetic reflex. The magnitude of this response seems to depend on: 1) the degree of baroreceptor unloading; 2) luminal pH; and 3) the current phase of the MMC.
Research Interests: Humans, Hemodynamics, Blood Pressure, Female, Male, and 6 moreClinical Sciences, Middle Aged, Adult, Pulse, Gastric mucosa, and Bicarbonates
The present paper describes and evaluates a methodologic approach for registration of the fast, interdigestive, motility-related changes in gastric acid and bicarbonate outputs seen in man. The technique is based on continuous gastric... more
The present paper describes and evaluates a methodologic approach for registration of the fast, interdigestive, motility-related changes in gastric acid and bicarbonate outputs seen in man. The technique is based on continuous gastric luminal perfusion and measurements of pH and PCO2 in gastric effluent and concomitant intragastric/duodenal manometry. Fourteen healthy volunteers participated. Direct acid secretory estimations from pH recordings, corrected for hydrogen ion activity, correlated closely with values obtained by conventional titration. After intragastric infusion of bicarbonate, 96 +/- 5% of the newly measured steady-state value was registered virtually instantaneously provided that corrections for the PCO2 electrode time constant and the perfusion/aspiration time were made. In the neutral pH range (pH 5-7), practically full quantitative recovery of intragastrically infused bicarbonate was obtained. In the acid pH interval (pH 2-5) the recovery was significantly lower (53 +/- 6%; p &lt; 0.01). With an aspirate without air admixture and during high perfusion rates (31 and 46 ml/min), full recovery of bicarbonate was obtained also at an acid pH, whereas a reduced perfusion rate (16 ml/min) significantly (p &lt; 0.05) reduced the recovery rate. With the pH/PCO2 technique both acid and bicarbonate assessments have a close to on-line time resolution. Acid output is measured accurately, but the method potentially underestimates actual bicarbonate levels in the acid pH range, a combined effect of diffusion of CO2 into air bubbles in the aspirate and into the gastric mucosa from the lumen. A high gastric perfusion rate minimizes this source of error. The pH/PCO2 technique is well suited for studies of the interaction between secretion and motility in the human stomach.
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In six human volunteers we studied the effects of hypovolemia on the secretory activity of the gastric mucosa. The secretion of acid and HCO3 from the stomach was calculated from continuous measurements of pH and Pco2 in gastric effluent.... more
In six human volunteers we studied the effects of hypovolemia on the secretory activity of the gastric mucosa. The secretion of acid and HCO3 from the stomach was calculated from continuous measurements of pH and Pco2 in gastric effluent. Gastric secretion was stimulated by sham feeding (SF), and cardiac filling pressure was decreased by pooling blood in the lower extremities (lower body negative pressure (LBNP]. LBNP at -20 mmHg had no significant effects on systemic arterial pressure or heart rate but increased plasma norepinephrine concentration by 48 +/- 6% (p less than 0.001). Both the acid and the alkaline responses to SF were significantly attenuated during LBNP (-38 +/- 8%, p less than 0.01, and -55 +/- 14%, p less than 0.05, respectively). Analysis of the relationship between acid and HCO3 secretion in individual experiments suggested a relatively more pronounced inhibition of HCO3 secretion. The results imply that a decreased responsiveness of the gastric mucosa may be one component of the cardiovascular reflex adaptation to hypovolemia. A downregulation of active secretion will lead to smaller metabolic demands from the secreting cells and may thereby help to maintain a vasoconstriction in the gastric mucosa.
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The relationship between interdigestive gastric motility and secretion was studied in eight healthy volunteers. Acid and bicarbonate output rates were measured with a high time resolution, using a perfusion system based on continuous... more
The relationship between interdigestive gastric motility and secretion was studied in eight healthy volunteers. Acid and bicarbonate output rates were measured with a high time resolution, using a perfusion system based on continuous registration of pH and PCO2 of gastric effluent. Antral pressure was measured by manometry. The total duration of the interdigestive motility cycle (time between two phase-III complexes) was 96 +/- 12 min (mean +/- SE). In late migrating motor complex phase II, acid output, bicarbonate output, and bile reflux increased significantly. Acid secretion reached a peak in association with motor phase III. The gastric lumen was then rapidly alkalinized; this phenomenon was due to a simultaneous decrease in acid secretion and a short-lasting (15 +/- 2 min, mean +/- SE) phasic increase in bicarbonate output, which was not associated with bile reflux (bilirubin). After these phase-III-related events both acid and bicarbonate output rates reached a relatively stable level during phase I and early phase II. This period of stability constituted 47 +/- 3% (acid) and 41 +/- 6% (bicarbonate, means +/- SE), respectively, of the cycle. The peak to base line output ratio was 6.6 +/- 1.2 (p &lt; 0.001) for acid and 2.8 +/- 0.3 (p &lt; 0.001) for bicarbonate (means +/- SE). The results show a marked variability in acid and bicarbonate output rates during the interdigestive motility cycle. The magnitude of this variability has previously been underestimated owing to poor time resolution of the secretion measurements. If not taken into account, these &#39;spontaneous&#39; secretory variations may constitute a considerable source of error in gastric secretion studies.
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The pathophysiology of intestinal inflammation and diarrhoea is complex and involves the arachidonic acid cascade. Prostaglandins induce chloride secretion in healthy subjects and in patients with coeliac disease. Leukotrienes (LTs) are... more
The pathophysiology of intestinal inflammation and diarrhoea is complex and involves the arachidonic acid cascade. Prostaglandins induce chloride secretion in healthy subjects and in patients with coeliac disease. Leukotrienes (LTs) are also known inflammatory mediators which have been shown to stimulate ion secretion in ileum and colon of rats and rabbits. The aim of this study was to determine the effects of leukotrienes C(4) (LTC(4)) and D(4) (LTD(4)) in normal and atrophic intestinal mucosa in children. Routine paediatric intestinal biopsies were obtained from 109 children. Sixty-seven control biopsies and 42 biopsies from children with different stages of coeliac disease were mounted in a modified Ussing chamber. Potential difference (Pd) was measured continuously and tissue resistance (R(t)) and the generated current (I(m)) were calculated. In morphologically normal mucosa of duodenum, LTC(4) and LTD(4) increased Pd and I(m) in a dose-dependent manner. The increase was more pronounced in the distal than in the proximal part, similar to the response to prostaglandin E(2). The induced current was chloride-mediated, since replacement of Cl(-) with SO(4)(2-) in the bathing solution eliminated the response to the LTs. The LTC(4)-induced secretion was significantly decreased in atrophic mucosa, but the response was partially restored after preincubation with the cyclooxygenase inhibitor indomethacin. The results showed that LTC(4) and LTD(4) are secretagogues in the duodenal mucosa from healthy children by inducing a net chloride secretion. Restoration of the response in coeliac disease by cyclooxygenase inhibition suggests interactions between the different pathways of the arachidonic cascade in the intestinal mucosa.
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The immunologic reactivity of the gastric mucosa is poorly understood. The origin and dynamics of immunoglobulin A (IgA) occurring in the gastric lumen were investigated in healthy, Helicobacter pylori-negative volunteers. Gastroduodenal... more
The immunologic reactivity of the gastric mucosa is poorly understood. The origin and dynamics of immunoglobulin A (IgA) occurring in the gastric lumen were investigated in healthy, Helicobacter pylori-negative volunteers. Gastroduodenal manometric motility recordings were combined with gastric luminal perfusion, enabling calculation of gastric acid output and analysis of the total IgA output. Acid output and total IgA correlated with the migrating motility complexes (MMC). The gastric IgA release showed maximal values in association with gastric motility phase III (maximal motor activity) and lowest values during phases I and II (none or irregular motor activity). The IgA output correlated with neither swallowed saliva (as indicated by amylase in the gastric perfusate) nor duodenogastric reflux (as indicated by gastric occurrence of bilirubin and/or duodenally infused PEG4000). Stimulation of gastric acid secretion by sham feeding during phase II-like motor activity (n = 6) induced a rapid and transient doubling of IgA output. There was no significant correlation between gastric acid secretion and gastric IgA release. Substantial amounts of IgA are released into the human stomach, most likely originating from the gastric mucosa. The up-regulation of IgA release in association with the activity front of the MMC and anticipatory to food intake suggests a neuroendocrine control of gastric mucosal immune responses.
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The aim of the study was to characterize the epithelial transport properties of the distal duodenal mucosa in untreated coeliac disease. The study was performed in 20 patients and in 22 healthy controls. Net fluid and bicarbonate... more
The aim of the study was to characterize the epithelial transport properties of the distal duodenal mucosa in untreated coeliac disease. The study was performed in 20 patients and in 22 healthy controls. Net fluid and bicarbonate transport was measured with a triple-lumen perfusion technique. Interdigestive motility was recorded by manometry, and the transmural potential difference (PD) was measured as an indicator of electrogenic anion secretion. In the patients a net fluid secretion was seen (-1.04 +/- 0.26 versus 0.12 +/- 0.11 ml/min x 10 cm in the controls; p &lt; 0.01), and there was no significant net bicarbonate absorption (5.6 +/- 3.4 versus 27.5 +/- 4.4 mumol/min x 10 cm in the controls; p &lt; 0.001). The epithelial transport rate varied with the interdigestive motility; a shift in the secretory direction was seen in late phase II of the migrating motor complex (MMC). Moreover, the MMC-related PD curve was significantly displaced in the lumen-negative direction (p &lt; 0.001 versus controls). The results suggest that in untreated coeliac disease, active chloride secretion is enhanced, and Na+/H+ exchange is reduced. This remodelled mucosa still seems to respond to neurogenic stimuli, as suggested by the presence of MMC-related changes in secretion rate.
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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(+)... more
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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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... more
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 &lt; 0.05) and the PD decline after phase III was significantly prolonged in the jejunum (P &lt; 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.
Research Interests: Physiology, Gastroenterology, Humans, Fasting, Intestinal Mucosa, and 15 moreCeliac Disease, Clinical Medicine, Female, Male, Jejunum, Irritable Bowel Syndrome, Clinical Sciences, Middle Aged, Adult, Neuronal Activity, Gastrointestinal motility, Physiopathology, Neurosciences, Duodenum, and Motor activity
The clinical course of ulcerative colitis (UC) is unpredictable. The need for reliable biomarkers to reflect disease severity and predict disease course is therefore large. We investigated whether cytokines in mucosal tissue and serum... more
The clinical course of ulcerative colitis (UC) is unpredictable. The need for reliable biomarkers to reflect disease severity and predict disease course is therefore large. We investigated whether cytokines in mucosal tissue and serum reflect clinical disease severity at the onset of UC and predict the future disease course. We prospectively monitored 102 patients from the onset of UC during 3 years, and they were followed up yearly for clinical and biochemical disease severity. Rectal biopsies were obtained from healthy controls and patients with UC. Serum and stool samples were obtained from patients with UC. Total mRNA from biopsies was analyzed with real-time PCR. Cytokine levels in serum were determined using Luminex or ELISA. Mucosal mRNA expression of IL-17A was 99.8 times higher while IFN-γ and IL-13 expression was increased 12.4 and 6.7 times, respectively, in patients relative to controls. Serum IL-17A correlated with clinical disease severity at the onset. Also, contrary to a number of other parameters, serum IL-17A at the onset predicted the clinical and biochemical course of the disease, as reflected by the Mayo score, number × severity of flares, and fecal calprotectin levels, respectively, during 3 years after the onset of the disease. None of these associations were found with mucosal cytokines at the onset. Serum IL-17A levels of treatment-naive patients with UC reflect clinical disease severity at the onset of the disease and also predicted the disease course over the following 3 years. Thus, serum IL-17A may be valuable in the clinical management of patients with UC at the onset of the disease.
Research Interests: Prospective studies, Humans, Intestinal Mucosa, Ulcerative colitis, Female, and 13 moreMale, Follow-up studies, Clinical Sciences, Adult, Prognosis, Biological markers, Cross Sectional Studies, Enzyme Linked Immunosorbent Assay, Inflammatory Bowel Diseases, Case Control Studies, Interleukin, Interferon gamma, and Severity of Illness Index
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Gastroenterology, Volume 120, Issue 5, Pages A224, April 2001, Authors:Anna Gunnarsdottir; Einar S. Bjomsson; Gisela Ringstrom; Magnus Simren; Per-Ove Stotzer; Hasse Abrahamsson; Rolf Olsson. Gastroenterology - Click ...
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... Regionalt HTA-arbete kan ge bra genomslag i vården: Goda exempel från Västra Götaland. Auteur(s) / Author(s). BERGH Christina ; ALOPAEUS Eva ; JIVEGARD Lennart ; SAMUELSSON Ola ; SJÖVALL Henrik ; STRANDELL Annika ; SVANBERG Therese ;... more
... Regionalt HTA-arbete kan ge bra genomslag i vården: Goda exempel från Västra Götaland. Auteur(s) / Author(s). BERGH Christina ; ALOPAEUS Eva ; JIVEGARD Lennart ; SAMUELSSON Ola ; SJÖVALL Henrik ; STRANDELL Annika ; SVANBERG Therese ; Revue / Journal Title ...
To assess the levels of gut peptides involved in gastrointestinal motor, secretory and sensory function in colonic biopsies in irritable bowel syndrome (IBS) patients and healthy controls. We studied 34 patients with IBS and 15 subjects... more
To assess the levels of gut peptides involved in gastrointestinal motor, secretory and sensory function in colonic biopsies in irritable bowel syndrome (IBS) patients and healthy controls. We studied 34 patients with IBS and 15 subjects without gastrointestinal symptoms. The predominant bowel pattern in the IBS patients was constipation in 17 patients (IBS-C) and diarrhoea in 17 patients (IBS-D). With radioimmunoassay, the levels of vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY) and peptide YY (PYY) were analysed in biopsies from the descending colon and ascending colon obtained during colonoscopy. The IBS patients had lower levels of PYY in the descending colon than the controls, but the levels in the ascending colon did not differ. The NPY levels were lower in IBS-D than in IBS-C, both in the ascending colon and in the descending colon. Low levels of VIP were more common in IBS patients, but mean levels did not differ between groups. No group differences were observed for substance P. The levels of VIP, substance P and NPY were higher in the ascending colon than in the descending colon, whereas the opposite pattern was seen for PYY. IBS patients demonstrate lower levels of PYY in the descending colon than controls. Colonic NPY levels differ between IBS subgroups based on the predominant bowel pattern. These findings may reflect the pathophysiology of IBS and the symptom variation within the IBS population.
Research Interests: Gastroenterology, Biopsy, Pathophysiology, Diarrhea, Humans, and 15 moreConstipation, Female, Male, Clinical Sciences, Aged, Middle Aged, Adult, Neuropeptide Y, Vasoactive Intestinal Peptide, Substance P, Colon, Neurosciences, Case Control Studies, Neuropeptide, and Paediatrics and reproductive medicine
The understanding of the mechanisms for increased immune activation in subgroups of patients with irritable bowel syndrome (IBS) is incomplete. We hypothesized that monocytes are more activated in patients with IBS than in the healthy... more
The understanding of the mechanisms for increased immune activation in subgroups of patients with irritable bowel syndrome (IBS) is incomplete. We hypothesized that monocytes are more activated in patients with IBS than in the healthy population. We therefore examined activation phenotype and cytokine secretion of blood monocytes. Blood samples from 74 patients with IBS and 30 controls were obtained. The activation phenotype of CD11cCD14 monocytes and cytokine secretion in serum and in peripheral blood mononuclear cells cultured with or without lipopolysaccharide was determined. Gastrointestinal and psychological symptom severity and quality of life were assessed using validated questionnaires. Monocytes from patients demonstrated an increased expression of toll-like receptor (TLR) 2, whereas the expression on monocytes of TLR4, HLA-DR, CD40, CD80 and CD86 was comparable in patients and controls. The expression of activation markers on monocytes did not correlate with gastrointestinal or extracolonic symptom severity, but the expressions of TLR2, HLA-DR and CD86 were associated with less severe psychological symptoms and better social and physical well-being. Cytokine secretion in serum and peripheral blood mononuclear cell cultures was comparable in patients and controls. A subgroup of patients (15%) who had TLR2 and HLA-DR expression intensity above the level seen in controls reported less severe psychosocial symptoms. Patients with IBS have increased expression of TLR2 on monocytes and the activation level on monocytes correlates with less severe psychological symptoms and better quality of life. Thus, our data implicate less importance of psychosocial factors and increased importance of immunological parameters for symptom generation in a subgroup of patients with IBS.
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Research Interests:
Research Interests:
The migrating motor complex (MMC) is a cyclic motor pattern with several phases enacted over the entire length of the small intestine. This motor pattern is initiated and coordinated by the enteric nervous system and modulated by... more
The migrating motor complex (MMC) is a cyclic motor pattern with several phases enacted over the entire length of the small intestine. This motor pattern is initiated and coordinated by the enteric nervous system and modulated by extrinsic factors. Because in vitro preparations of the MMC do not exist, it has not been possible to determine the intrinsic nerve circuits that manage this motor pattern. We have used computer simulation to explore the possibility that the controlling circuit is the network of AH/Dogiel type II (AH) neurons. The basis of the model is that recurrent connections between AH neurons cause local circuits to enter a high-firing-rate state that provides the maximal motor drive observed in phase III of the MMC. This also drives adjacent segments of the network causing slow migration. Delayed negative feedback within the circuit, provided by activity-dependent synaptic depression, forces the network to return to rest after passage of phase III. The anal direction ...
Research Interests: Physiology, Algorithms, Neural Networks, Neural Network, Models, and 15 moreComputer Simulation, Computer Model, Negative Feedback, Medical Physiology, Enteric Nervous System, Synaptic Depression, Digestive System, SYNAPSES, Codebook Excitation, Gastrointestinal motility, Pattern Generation, Axons, Small Intestine, Excitatory Postsynaptic Potentials, and Excitation
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Research Interests: Nonparametric Statistics, Diarrhea, Humans, Chronic Disease, Female, and 15 moreMale, Mechanoreceptors, Jejunum, Medical Physiology, Enteric Nervous System, Intestinal absorption, Aged, Middle Aged, Digestive System, Adult, ACTA, Gastrointestinal motility, Reference Values, Case Control Studies, and Chlorides
... Scand J Gastroent 16: 377-384. CASSUTO, J., JODAL, M., TUTTLE, R. & LUNDGREN, 0. 5-hydroxytryptamine and cholera secretion: physiological and pharmacological studies in cats and rats. ... Klin Wschr 29/39: 706-707. LANDER, S.... more
... Scand J Gastroent 16: 377-384. CASSUTO, J., JODAL, M., TUTTLE, R. & LUNDGREN, 0. 5-hydroxytryptamine and cholera secretion: physiological and pharmacological studies in cats and rats. ... Klin Wschr 29/39: 706-707. LANDER, S. & WALLENTIN, I. 1964. ...
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The hemodynamic response in the parallel-coupled vascular sections of the cat small intestine were studied before, during and after a two hour period of hemorrhage (about 30 per cent of estimated blood volume). Fluid and electrolyte... more
The hemodynamic response in the parallel-coupled vascular sections of the cat small intestine were studied before, during and after a two hour period of hemorrhage (about 30 per cent of estimated blood volume). Fluid and electrolyte transport and villous tissue osmolality were also measured. Biopsies for histology were taken at the end of all experiments. The animals were divided in two groups, undamaged and damaged, according to the degree of mucosal damage observed. The hemodynamic reactions were investigated with a method that made it possible to study total intestinal, absorptive site (&quot;villous&quot;), nonabsorptive site (&quot;crypt&quot;) and muscle layer blood flows. Total intestinal blood flow was lower in the damaged as compared to the undamaged group during hypovolemia. No difference in absorptive site blood flow was observed between the two groups during hypovolemia. Furthermore, no decrease of red blood cell flow in the &quot;villi&quot; was recorded in either group after hemorrhage. Consequently, mucosal lesions developed despite an unchanged oxygen transport capacity to the villi. The pathophysiology of the mucosal lesions is briefly discussed. Net fluid and sodium absorption was after hemorrhage increased in the undamaged group reflecting a decrease in the tissue to lumen transport of sodium. After retransfusion net fluid and sodium absorption returned to control. In the damaged group, however, net fluid and sodium absorption was decreased after hemorrhage. The increased rate of fluid and electrolyte transport observed in the undamaged small intestine after hemorrhage, is proposed to be an important mechanism for fluid replacement after hemorrhage.