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At least 415 records · Page 23Linked to original sources

PubMed2005

A phase II study of external beam radiotherapy combined with permanent source brachytherapy for intermediate-risk, clinically localized adenocarcinoma of the prostate: preliminary results of RTOG P-0019.

PURPOSE: To estimate the rate of acute and late Grade 3-5 genitourinary and gastrointestinal toxicity after treatment with external beam radiotherapy and permanent source brachytherapy in a multi-institutional, cooperative group setting. METHODS AND MATERIALS: All patients were treated with external beam radiotherapy (45 Gy in 25 fractions), followed 2-6 weeks later by an interstitial implant using 125I to deliver an additional 108 Gy. Late genitourinary toxicity was graded according to the Common Toxicity Criteria Version 2.0, and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring system was used for all other toxicity. RESULTS: A total of 138 patients from 28 institutions were entered on this study. Acute toxicity information was available in 131 patients, and 127 patients were analyzable for late toxicity. Acute Grade 3 toxicity was documented in 10 of 131 patients (7.6%). No Grade 4 or 5 acute toxicity has been observed. The 18-month month estimate of late Grade 3 genitourinary and gastrointestinal toxicity was 3.3% (95% confidence interval, 0.1-6.5). No late Grade 4 or 5 toxicity has been observed. CONCLUSIONS: The acute and late morbidity observed in this multi-institutional, cooperative group study is consistent with previous reports from single institutions with significant prostate brachytherapy experience.

Adenocarcinoma↗

PubMedDate not supplied

Effect of endotoxin on canine colonic motility and transit.

Diarrhea is a common problem in patients who have episodes of sepsis and are being fed enterally. Endotoxemia results in gastrointestinal motor dysfunction characterized by slowed gastric emptying and rapid intestinal transit; however, the effect of endotoxin on colonic motility is unknown. The aim of our study was to determine the effects of a single sublethal dose of endotoxin on colonic motility and transit. Seven dogs underwent construction of a 50 cm colonic Thiry-Vella fistula. Five manometry catheters were sewn into the colonic lumen at 8 cm intervals along the fistula. Following recovery, the fistula was perfused with an isotonic solution at 2.9 ml/min, and fasting and postprandial colonic motility was determined. Liquid transit was assessed by bolus of a nonabsorbable marker instilled into the proximal end of the Thiry-Vella fistula. Recordings of gastrointestinal contractile activity were made digitally to determine contractile frequencies and motility indexes. Following completion of the baseline studies, each dog was given a single dose of E. coli lipopolysaccharide, 200 microgram/kg intravenously, and studies were repeated daily for the next 3 days. Endotoxin doubled the fasting colonic contractile frequency on postendotoxin day 1 and also increased motility indexes on that same day. Fasting motility indexes and contractile activity were decreased on postendotoxin days 2 and 3. The postprandial frequency of contractions and motility indexes were decreased on postendotoxin day 3. Fasting colonic liquid transit was rapid on postendotoxin day 1, whereas postprandial liquid transit was rapid on both postendotoxin days 1 and 2. Endotoxin temporarily speeds liquid transit and increases both the frequency and strength of colonic contractions. These effects may contribute to the diarrhea that occurs during episodes of sepsis.

Animals↗

PubMed1991

Esophageal motility in children with Hirschsprung's disease.

Esophageal motility was studied in 12 children with Hirschsprung's disease to see if extracolonic motor dysfunction was present in this disorder. Manometric tracings were compared with those from eight children with idiopathic megacolon and from 10 children without esophageal disease or constipation. Amplitude of esophageal contraction waves was significantly higher in children with Hirschsprung's disease than in the other two groups. Swallows that were followed by simultaneous contractions or double-peaked waves were also more common in the group with Hirschsprung's disease (subjects with Hirschsprung's disease, subjects with megacolon, and controls; 57%, 10%, and 8%, respectively). Lower esophageal sphincter characteristics did not differ among the three groups. The increase in simultaneous contractions and double-peaked waves persisted in those children who were reexamined following surgery for Hirschsprung's disease, whereas wave amplitudes fell to a level similar to that observed in the other groups. These data suggest that gastrointestinal motor dysfunction in persons with Hirschsprung's disease is not restricted to the colon, and that some of the observed abnormalities in esophageal motility do not reflect nonspecific responses to megacolon or colonic obstruction.

Adolescent↗

PubMed1987

Colonic motility, autonomic function, and gastrointestinal hormones under psychological stress on irritable bowel syndrome.

Effects of an artificial mental stress on colonic motility, autonomic nervous system, and gastrointestinal hormones were examined in patients with irritable bowel syndrome (IBS). The subjects were 20 patients with typical IBS and 12 controls. A transducer was inserted to the sigmoid colon from the anus for measuring colonic intraluminal pressure, and mirror drawing test was loaded as psychological stress. At the same time, coefficient of variation of R-R interval on ECG (CV-RR) was measured and the levels of plasma catecholamines, gastrin, glucagon, and motilin were assessed. Colonic motility showed a significant increase in the IBS patients during the stress compared with that in controls (p less than 0.01). Motilin also increased significantly in the IBS patients after the stress (p less than 0.01). CV-RR and motilin revealed positive relationship with colonic motility alteration in the IBS patients although no significant change was detected in controls. These phenomena are thought to be due to autonomic nervous dysfunction and/or gastrointestinal hormonal derrangments induced by psychological stress. It is suggested that organ specificity of the alimentary tract for the stress exists in this disease.

Adolescent↗

PubMed1995

Neuromuscular diseases of the gastrointestinal tract. Specific disorders that often get a nonspecific diagnosis.

Gastrointestinal motor dysfunction, intestinal pseudo-obstruction syndromes, and hollow visceral neuropathy and myopathy were previously considered functional bowel diseases but are now recognized to be organic disorders. They may alter the muscle of the intestinal wall or the nerves of the myenteric plexus, or both. Their symptoms of chronic unexplained abdominal pain, abdominal distention and bloating, early satiety, nausea, vomiting, and alternating diarrhea and constipation are the most common and perhaps the most difficult problems encountered by gastroenterologists. New intestinal recording devices assess motility and allow objective classification of neuromuscular disease, permitting accurate diagnosis and better treatment.

Digestive System↗

PubMed2000

Intolerance to intragastric enteral nutrition in critically ill patients: complications and management.

Compared with parenteral nutrition, early administration of enteral nutrition (EN) to critically ill patients improves clinical outcomes and reduces infection rates. Intragastric EN often is complicated by intolerance, as indicated by elevated volumes of aspirated gastric residuals. Conflicting data are available for the volume of residual that represents intolerance, but most clinicians use 150-200 ml to signify gastrointestinal motility dysfunction. Intolerance is associated with mortality. Data support an association between intragastric EN and aspiration pneumonia, but little information is available regarding the contributory effect of intolerance. Transpyloric migration of the feeding tube may facilitate tolerance but does not reduce the likelihood of aspiration pneumonia. Prokinetic agents (cisapride, erythromycin, metoclopramide) promote gastric emptying. Results of most studies are limited because patients did not receive or tolerated intragastric EN. Metoclopramide is the agent of choice for treating intolerance. Further studies are necessary before prokinetic drugs can be recommended for preventing intragastric EN-associated aspiration pneumonia.

Critical Illness↗

PubMed2004

Secretin as a treatment for autism: a review of the evidence.

Secretin is used in the United States for diagnosis of pancreatic gastrointestinal (GI) dysfunction and disease. Repeated therapeutic use has not been approved. Widespread interest in secretin as a treatment for autism followed media reports of behavioral improvements in an autistic child who received the hormone during a GI diagnostic procedure. International demand for secretin soared in the absence of experimental evidence of its efficacy for autism. This review presents a brief history of secretin's rise to popularity and summarizes research on secretin as a treatment for autism. Seventeen studies are reviewed comparing the effects of secretin forms, dosage levels, and dosing intervals on outcome measures with approximately 600 children. Twelve of 13 placebo-controlled studies failed to demonstrate the differential efficacy of secretin. Implications for advocating treatment in the absence of empirical evidence are discussed.

Autistic Disorder↗

PubMed2005

Methylisogermabullone isolated from radish roots stimulates small bowel motility via activation of acetylcholinergic receptors.

We have previously reported that extract of radish roots exhibits an increase in gastrointestinal motility through the activation of muscarinic acetylcholine (ACh) receptors. Based on the stimulatory activity-guided fractionation on rat ileal segments, this study isolated methylisogermabullone (MIGB, C23H31O5NS, MW 433) from methanol extracts of radish roots. MIGB caused a significant increase of the isolated rat ileal contraction in a concentration-dependent manner (23-693 microM), and the pattern of MIGB-induced ileal contraction was different in the time course to that produced by ACh. The EC50 value of MIGB, to produce 50% maximum ileal contraction, was estimated to be 45.5 microM. MIGB (230 microM)-induced ileal contractions were enhanced by pretreatment of segments with ACh (0.1 microM). Ileal contractions produced by MIGB (230 microM) or ACh (0.1 microM) at submaximal concentration were partially inhibited by pretreatment of hexamethonium (0.1 mM), a ganglionic blocker, whereas they were almost completely abolished by atropine (10 microM). Oral administration of MIGB to mice stimulated the small intestinal transit of charcoal in a dose-dependent manner (10-100 mg kg(-1)), and MIGB (100 mg kg(-1))-induced stimulation of small intestinal transit was significantly attenuated by co-administration of atropine (50 mg kg(-1)). Taken together, these results demonstrate that MIGB isolated from radish roots stimulates the small bowel motility through the activation of ACh receptors. These findings suggest that MIGB may become a potential regulatory agent for therapeutic intervention in dysfunction of gastrointestinal motility.

Alkenes↗

PubMed2005

Plasticity of the enteric nervous system during intestinal inflammation.

Inflammation of the bowel causes structural and functional changes to the enteric nervous system (ENS). While morphological alterations to the ENS are evident in some inflammatory conditions, it appears that relatively subtle modifications to the neurophysiology of enteric microcircuits may play a role in gastrointestinal (GI) dysfunction. These include changes to the excitability and synaptic properties of enteric neurones. The response of the ENS to inflammation varies according to the site and type of inflammation, with the functional consequences depending on the nature of the inflammatory stimulus. It has become clear that inflammation at one site can produce changes that occur at remotes sites in the GI tract. Immunohistochemical data from patients with inflammatory bowel disease (IBD) and animal models indicate that inflammation alters the neurochemical content of some functional classes of enteric neurones. A growing body of evidence supports an active role for enteric glia in neuronal and neuroimmune communication in the GI tract, particularly during inflammation. In conclusion, plasticity of the ENS is a feature of intestinal inflammation. Elucidation of the mechanisms whereby inflammation alters enteric neural control of GI functions may lead to novel treatments for IBD.

Animals↗

PubMed2005

Gastrointestinal ischemia-reperfusion injury is lectin complement pathway dependent without involving C1q.

Complement activation plays an important role in local and remote tissue injury associated with gastrointestinal ischemia-reperfusion (GI/R). The role of the classical and lectin complement pathways in GI/R injury was evaluated using C1q-deficient (C1q KO), MBL-A/C-deficient (MBL-null), complement factor 2- and factor B-deficient (C2/fB KO), and wild-type (WT) mice. Gastrointestinal ischemia (20 min), followed by 3-h reperfusion, induced intestinal and lung injury in C1q KO and WT mice, but not in C2/fB KO mice. Addition of human C2 to C2/fB KO mice significantly restored GI/R injury, demonstrating that GI/R injury is mediated via the lectin and/or classical pathway. Tissue C3 deposition in C1q KO and WT, but not C2/fB KO, mice after GI/R demonstrated that complement was activated in C1q KO mice. GI/R significantly increased serum alanine aminotransferase, gastrointestinal barrier dysfunction, and neutrophil infiltration into the lung and gut in C1q KO and WT, but not C2/fB KO, mice. MBL-null mice displayed little gut injury after GI/R, but lung injury was present. Addition of recombinant human MBL (rhuMBL) to MBL-null mice significantly increased injury compared with MBL-null mice after GI/R and was reversed by anti-MBL mAb treatment. However, MBL-null mice were not protected from secondary lung injury after GI/R. These data demonstrate that C2 and MBL, but not C1q, are necessary for gut injury after GI/R. Lung injury in mice after GI/R is MBL and C1q independent, but C2 dependent, suggesting a potential role for ficolins in this model.

Alanine Transaminase↗

PubMed2006

[Influence of scald on the cytoskeleton of colonic smooth muscle cells of the rats].

OBJECTIVE: To investigate the changes in the morphology and cytoskeleton (CSL) content of the CSL in the colonic smooth muscle cells (SMCs) of rats in early postscald stage, so as to elucidate the mechanism of dysfunction of gastrointestinal motility. METHODS: Seventy Wistar rats were randomly divided into normal control (n = 10, without scald) , and scald ( n = 60, with 10 cm x 7 cm wound inflicted on the back) groups. The colonic smooth muscle tissue of 10 normal rats and scalded rats were harvested at 1, 3, 6, 12, 24 and 48 postscald hours( PSH) and divided into two parts: one for histologic examination, and the other for the detection of CSL changes in the colonic smooth muscle tissue by flowcytometry method. RESULTS: The electron microscope examination showed that the arrangement of cytoskeleton of SMC of the scalded rats during 1 to 3 PSH was disordered, and sparse, and the condensed area was uneven, with fragmentation. But the morphology and distribution of CSL gradually restored to normal state during 6 to 12 PSH, and it approached that of normal group at 48 PSH. The CSL content in the colonic smooth muscle tissue of scalded rats was obviously increased at 1 PSH (610+/-23) , decreased thereafter, evidently lower than that in control group at 3 PSH (92+/-17) , and then it started to increase at 12 PSH, exceeding the normal value at 24 PSH, and continued to rise until 48 PSH. There was significant difference in CSL content in the colonic smooth muscle tissue of the rats between scald and control group ( P < 0.05 or 0. 01). CONCLUSION: Changes in the morphology and CSL content in the colonic smooth muscle tissue can be observed at early stage after a scald, which imply the kinetic balance between damage and repair in the body. In addition, changes in CSL content in the colonic smooth muscle tissue may be important factors in producing colonic dysfunction, damage of intestinal wall structure, and dynamic abnormalities of the colonic smooth muscle.

Actins↗

PubMed2006

[Influence of lipopolysaccharide and burn sera on ion channels in smooth muscle cells of colon of guinea pig].

OBJECTIVE: To investigate the influence of lipopolysaccharide (LPS) and burn sera on potassium channels (Kca) in smooth muscle cells of colon of guinea pig so as to elucidate the molecular mechanism of gastrointestinal motility dysfunction after severe burns. METHODS: Single smooth muscle cells were isolated from the taenia coli of guinea pig with enzyme digestion. The standard patch clamp technique was employed to record the single KCa channel currents of smooth muscle cell after challenged by LPS and burn serum. Data were recorded and analyzed by P clamp 6.04 software, and the probability of open (PO), mean open time (OT), mean close time (CT) and current amplitude (CA) were determined. Subsequently, LPS in the concentration of 20, 40, 60, 80 and 100 mg/L, respectively, and normal serum and burn serum in the concentration of 10% were respectively added into medium to examine the influence of the two clamps and sera on the KCa activity. RESULTS: In hyperkalemic solution, the KCa conductance of colonic smooth muscle cells of the guinea pig was (271 +/- 7) pS, indicating it was an ionic channel with high conductivity. Subsequent to depolarization of the membrane, inner-cellular calcium level was increased, and channel PO was also increased, which could be blocked by 1 mmol/L tetraethylammonium (TEA) outside the membrane chaff. As 40 mmol/L TEA inside the membrane chaff did not show such effect, it was proved to be KCa current. The activity of the channel as determined with two kinds of clamps was increased in a dose dependent manner with LPS challenge when the concentration of calcium was 0 mol/L. The KCa activity and PO of the channel was increased obviously when the concentration of LPS was above 40 mg/L (P < 0.05 or 0.01), and it could not be reversed after irrigation with non-LPS medium. By using the two kinds of patch clamps, the KCa were activated by burn sera, but not normal sera. CONCLUSION: Both LPS and burn sera can lead to inhibition of the gastrointestinal motility by activation of KCa channels.

Animals↗

PubMed2004

Decreased interstitial cells of Cajal in the sigmoid colon of patients with slow transit constipation.

BACKGROUND AND AIMS: Slow transit constipation (STC) is a colonic motor disorder that is characterized by measurably delayed movement of materials through the colon. Although abnormalities in the neuronal networks of the colon have been demonstrated in patients with STC, the etiology of STC remains unclear. Interstitial cells of Cajal (ICC) have been shown to be the pacemaker cells of the intestine and have been implied in the pathogenesis of a number of gastrointestinal motility dysfunctions, including idiopathic STC. This study aimed to determine the normal distribution of ICC within the colon of the Chinese and also to determine if ICC are decreased in Chinese STC patients. PATIENTS AND METHODS: Twelve patients with STC and eight age-matched normal controls were studied. Specimens of sigmoid colon were obtained immediately after resection. ICC were identified with a monoclonal antibody to c-kit by an indirect immunofluorescence method. Immunostained tissues were examined with a laser scanning confocal microscope and the area occupied by ICC was calculated with an image analysis system. RESULTS: ICC were located in the external muscle layers including myenteric plexus (MP) and submucosal border (SMB). Two types of Kit-positive ICC were observed: bipolar cells characterized by one or two long processes and multipolar cells characterized by long stellate processes extending in various directions. A higher percentage of ICC was present in the MP regions and circular muscle (CM) layers compared with the SMB and longitudinal muscle (LM) layers. Tissues from STC patients showed a considerable decrease in the number of ICC located in the four regions (ICC-LM, ICC-MP, ICC-CM, ICC-SMB), especially the ICC-SMB, in which ICC almost completely disappeared. CONCLUSIONS: Similar distribution of ICC was observed in the normal sigmoid colon of the Chinese. Decreased area of c-kit+ ICC may play an important role in the pathophysiology of STC. It remains to be determined whether the loss of ICC is primary or secondary to another lesion.

Adult↗

PubMed2003

Colonic transit time and rectoanal videomanometry in Parkinson's disease.

BACKGROUND: Constipation is a prominent lower gastrointestinal tract dysfunction that occurs frequently in Parkinson's disease (PD). OBJECTIVE: To investigate colonic transport and dynamic rectoanal behaviour during filling and defecation in patients with PD. METHODS: Colonic transit time (CTT) and rectoanal videomanometry analyses were performed in 12 patients with PD (10 men and 2 women; mean age, 68 years, mean duration of disease, five years; mean Hoehn and Yahr grade, 3; decreased stool frequency (<3 times a week) in six, difficulty in stool expulsion in eight) and 10 age matched normal control subjects (7 men and 3 women; mean age, 62 years; decreased stool frequency in two, difficulty in stool expulsion in two). RESULTS: In the PD patients, CTT was significantly prolonged in the rectosigmoid segment (p<0.05) and total colon (p<0.01) compared with the control subjects. At the resting state, anal closure and squeeze pressures of PD patients were lower than those in control subjects, though not statistically significant. However, the PD patients showed a smaller increase in abdominal pressure on coughing (p<0.01) and straining (p<0.01). The sphincter motor unit potentials of the patients were normal. During filling, PD patients showed normal rectal volumes at first sensation and maximum desire to defecate, and normal rectal compliance. However, they showed smaller amplitude in phasic rectal contraction (p<0.05), which was accompanied by an increase in anal pressure that normally decreased, together with leaking in two patients. During defecation, most PD patients could not defecate completely with larger post-defecation residuals (p<0.01). PD patients had weak abdominal strain and smaller rectal contraction on defecation than those in control subjects, though these differences were not statistically significant. However, the PD patients had larger anal contraction on defecation (p<0.05), evidence of paradoxical sphincter contraction on defecation (PSD). CONCLUSIONS: Slow colonic transit, decreased phasic rectal contraction, weak abdominal strain, and PSD were all features in our PD patients with frequent constipation.

Adult↗

PubMed1987

Demonstration of myenteric plexus abnormalities in genetic diseases by a microdissection technique: preliminary studies.

Eighty-eight specimens of esophagus, small intestine, or colon from 45 patients, predominantly infants and children, with 30 different genetic diseases were analyzed by a microdissection technique for the following abnormalities of the Auerbach (myenteric) plexus: (1) abnormality of the pattern of the nervous network of the plexus, (2) abnormal fraction of neural tissue in the plane of the plexus, (3) abnormal size or appearance of the cytoplasm of the neurons of the plexus, and (4) abnormal number of neurons in the ganglia of the plexus. Seven of 8 specimens of esophagus from patients with neuronal storage diseases (infantile Niemann-Pick disease, Jansky-Bielschowsky disease, etc.) showed an increased fraction of neural tissue in the plane of the plexus, whereas 2 of 3 patients with Cockayne syndrome showed a reduced fraction, with abnormally slender interganglionic fibers. The fraction of neural tissue in the plane of the plexus was also abnormal at one or more levels in patients with adrenoleukodystrophy, ataxia telangiectasia, Krabbe disease, and juvenile metachromatic leukodystrophy. Abnormality of neuron size and cytology was seen in several neuronal lipidoses, including Jansky-Bielschowsky and Sandhoff diseases and juvenile GM2 gangliosidosis, with the most striking neuronal enlargement noted in infantile Niemann-Pick disease. Abnormalities of plexus mass or pattern, as well as those of neuronal cytoplasm and neuron number, offer improved insight into possible mechanisms producing gastrointestinal tract dysfunction (swallowing difficulty, gastroesophageal reflux, constipation, etc) in patients with genetic disorders.

Child↗

PubMed1995

Increased accuracy of the carbon-14 D-xylose breath test in detecting small-intestinal bacterial overgrowth by correction with the gastric emptying rate.

To date, there is no general agreement as to which test is to be preferred for the diagnosis of small-intestinal bacterial overgrowth. The 1-g carbon-14 D-xylose breath test has been proposed as a very sensitive and specific test for the diagnosis of bacterial overgrowth. However, in patients with severe gastrointestinal motor dysfunction, the lack of consistent delivery of 14C-D-xylose to the region of bacterial contamination may result in a "negative" result. The aim of this study was to determine whether the accuracy of 14C-D-xylose breath test for detecting bacterial overgrowth can be increased by correction with the gastric emptying rate of 14C-D-xylose. Ten culture-positive patients and ten culture-negative controls were included in the study. Small-intestinal aspirates for bacteriological culture were obtained endoscopically. A liquid-phase gastric emptying study was performed simultaneously to assess the amount of 14C-D-xylose that entered the small intestine. The results of the percentage of expired 14CO2 at 30 min were corrected with the amount of 14C-D-xylose that entered the small intestine. There were six patients in the culture-positive group with a 14CO2 concentration above the normal limit. Three out of four patients with initially negative results using the uncorrected method proved to be positive after correction. All these three patients had prolonged gastric emptying of 14C-D-xylose. When compared with cultures of small-intestine aspirates, the sensitivity and specificity of the uncorrected 14C-D-xylose breath test were 60% and 90%, respectively. In contrast, the sensitivity and specificity of the corrected 14C-D-xylose breath test improved to 90% and 100%, respectively. In conclusion, using the gastric emptying rate of 14C-D-xylose as a correcting factor, we found a higher sensitivity and specificity for the 14C-D-xylose breath test in the detection of small-intestinal bacterial overgrowth than were achieved with the conventional method.

Adult↗

PubMed1994

Reversal of megaduodenum and duodenal dysmotility associated with improvement in nutritional status in primary anorexia nervosa.

Anorexia nervosa is considered one type of eating disorder that may result in severe malnutrition. Patients with this disorder commonly complain of postprandial nausea, abdominal pain, and distension. We describe the radiologic and motility abnormalities associated with anorexia nervosa in a 21-year-old female. Barium gastrointestinal series demonstrated marked dilation of the duodenum, with prolongation of intestinal transit. A 4-hr fasting gastroduodenal motility study showed no propagating migrating motor complexes (MMC). Prolonged, but nonpropagating, bursts of high-amplitude phasic and tonic contractions were seen in the duodenum. In contrast, antral contractions were of low amplitude and esophageal motor function was normal. Metoclopramide and edrophonium caused an increase in gastroduodenal motor activity, but increased contractions were not associated with symptoms. Following a renutrition program that raised the patient's weight from 64 to 80% of her ideal body weight, the radiographic abnormalities and gastrointestinal dysmotility resolved completely. These observations suggest that anorexia-associated gastrointestinal motor dysfunctions are a consequence, not the cause of the generalized protein-calorie malnutrition associated with anorexia nervosa. The facts that motility in different parts of the gut is affected to different degrees and that gastric and duodenal muscle responds normally to exogenous stimulation argue against a generalized myogenic dysfunction and, rather, point to a reversible dysfunction of neural regulation.

Adult↗

PubMed2006

Ablation of connexin43 in smooth muscle cells of the mouse intestine: functional insights into physiology and morphology.

Connexin43 (Cx43) gap-junction channels are highly abundant in intestinal smooth muscle but their functional impact has not been studied so far. Here, we have aimed to elucidate the functional role of Cx43 in the tunica muscularis of the mouse intestine in vivo. Transgenic mice with conditional deletion of Cx43 in smooth muscle cells (SMC) were generated. Histological investigations by immunofluorescence analyses and organ-bath recordings to assess the contractility of intestinal tissue strips were carried out. Measurements of gastrointestinal transit and of the visceromotor response by utilizing a standardized colorectal distension model to quantify alterations of visceral sensory function were also performed in SMC-specific Cx43 null mice and control littermates. Histologically, we found thickening of the tunica muscularis and a 13-fold increase of neutrophil infiltration of the gastrointestinal wall of SMC-specific Cx43 null mice. These animals also exhibited a decrease of 29% in gastrointestinal transit time. In contrast, the visceromotor response to a standardized colorectal distension was elevated, as was the contractility in SMC-specific Cx43 null mice, compared with controls. Thus, SMC-specific ablation of Cx43 in mice leads to morphological and functional alterations of the intestinal tunica muscularis, to gastrointestinal motor dysfunction and to altered visceral sensory function.

Animals↗