Biomedical subjects

P A Pelckmans

Publications and source records attributed to P A Pelckmans.

At least 19 recordsLinked to original sources

PubMed2006

Study on the cyclic GMP-dependency of relaxations to endogenous and exogenous nitric oxide in the mouse gastrointestinal tract.

BACKGROUND AND PURPOSE: cGMP mediates nitrergic relaxations of intestinal smooth muscle, but several studies have indicated that cGMP-independent mechanisms may also be involved. We addressed this contention by studying the effect of ODQ and ns2028, specific inhibitors of soluble guanylate cyclase, on nitrergic relaxations of the mouse gut. EXPERIMENTAL APPROACH: Mouse gastric fundus and small intestinal muscle preparations were mounted in organ baths to study relaxations to exogenous NO, NO donors and electrical field stimulation (EFS) of enteric nerves. KEY RESULTS: In gastric fundus longitudinal muscle strips, ODQ and NS2028 abolished the L-nitroarginine-sensitive relaxations to EFS and the relaxations to NO and NO donors, glyceryl trinitrate (GTN), SIN-1 and sodium nitroprusside (SNP). EFS of intestinal segments and muscle strips showed L-nitroarginine-resistant relaxations, which were abolished by the purinoceptor blocker suramin. In the presence of suramin, ODQ and NS2028 abolished all relaxations to EFS in intestinal segments and strips. ODQ and NS2028 abolished the relaxations to exogenous NO and to the NO donors GTN, SIN-1 and SNP in circular and longitudinal intestinal muscle strips. Intestinal segments showed residual relaxations to NO and GTN. CONCLUSIONS AND IMPLICATIONS: Our results indicate that relaxations to endogenous NO in the mouse gastric fundus and small intestine are completely dependent on cGMP. ODQ and NS2028 incompletely blocked nitrergic relaxations to exogenous NO in intact intestinal segments. However, it is unlikely that this is due to the involvement of cGMP-independent pathways because ODQ and NS2028 abolished all relaxations to endogenous and exogenous NO in intestinal muscle strips.

Animals↗

PubMed2006

Acute distal colitis impairs gastric emptying in rats via an extrinsic neuronal reflex pathway involving the pelvic nerve.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease often present with abnormal gut motility away from the inflammatory site. We studied remote motility disturbances and their pathophysiology in a rat model of colitis. METHODS: Colitis was induced 72 h prior to experiments using trinitrobenzene sulphate (TNBS) instillation. Inflammation was verified using histology and myeloperoxidase (MPO) measurements. To assess gut motility, we determined gastric emptying, distal front and geometric centre (GC) of intestinal transit 30 min after intragastric administration of a semiliquid Evans blue solution. The effects of hexamethonium (20 mg/kg), capsaicin (125 mg/kg) and pelvic nerve section on colitis induced motility changes were evaluated. c-Fos expression was studied in the pelvic nerve dorsal root ganglion (DRG) S1. RESULTS: Colitis reduced gastric emptying from 38.4 (3.6)% in controls to 22.7 (4.4)% in TNBS treated rats in the absence of local gastric inflammation. Colitis had no effect on the distal front or on the geometric centre of small intestinal transit. Hexamethonium reduced gastric emptying in controls to 26.3 (4.1)% but restored it to 35.8 (4.4)% in TNBS treated rats. Capsaicin significantly impaired gastric emptying in controls from 33.1 (5.2)% to 9.5 (3.3)% while this effect was less pronounced in TNBS treated rats (from 19.2 (2.3)% to 11.5 (3.8)%; NS). In TNBS treated rats, pelvic nerve section completely restored gastric emptying from 19.8 (5.3)% to 52.5 (6.3)% without any effect on gastric emptying in control rats. TNBS colitis induced de novo c-Fos expression in the DRG S1. CONCLUSIONS: Experimental colitis in rats delays gastric emptying via a neuronal pathway involving pelvic afferent nerve hyperactivity.

Acute Disease↗

PubMed2005

Spatiotemporal electrical and motility mapping of distension-induced propagating oscillations in the murine small intestine.

Since the development of knockout animals, the mouse has become an important model to study gastrointestinal motility. However, little information is available on the electrical and contractile activities induced by distension in the murine small intestine. Spatiotemporal electrical mapping and mechanical recordings were made from isolated intestinal segments from different regions of the murine small intestine during distension. The electrical activity was recorded with 16 extracellular electrodes while motility was assessed simultaneously by tracking the border movements with a digital camera. Distension induced propagating oscillatory contractions in isolated intestinal segments. These propagating contractions were dictated by the underlying propagating slow wave with superimposed spikes. The frequencies, velocities, and direction of the propagating oscillations strongly correlated with the frequencies (r = 0.86), velocities (r = 0.84), and direction (r = 1) of the electrical slow waves. N(omega)-nitro-L-arginine methyl ester decreased the maximal diameter of the segment and reduced the peak contraction amplitude of the propagating oscillatory contractions, whereas atropine and verapamil blocked the propagating oscillations. Tetrodotoxin had little effect on the maximal diameter and peak contraction amplitude. In conclusion, distension in the murine small intestine does not initiate peristaltic reflexes but induces a propagating oscillatory motor pattern that is determined by propagating slow waves with superimposed spikes. These spikes are cholinergic and calcium dependent.

Animals↗

PubMed2005

Role of oxidative stress in the pathogenesis of septic ileus in mice.

We investigated the role of oxidative stress in the pathogenesis of septic ileus. Sepsis was induced by intraperitoneal (i.p.) injection of lipopolysaccharides (LPS, 20 mg kg(-1)) in mice. The effect of two i.p. injections of superoxide dismutase [polyethylene glycol (PEG)-SOD, 4000 U kg(-1)] and catalase (PEG-CAT, 15,000 U kg(-1)) was investigated on gastric emptying, intestinal transit and total nitrite plasma concentrations. We also performed immunohistochemical experiments on gastric and ileal tissue. LPS significantly delayed gastric emptying and intestinal transit while plasma nitrite levels increased. Polyethylene glycol (PEG)-SOD reversed the endotoxin-induced delay in gastric emptying and improved the delay in intestinal transit without effect on plasma nitrite levels. PEG-CAT slightly improved the delay in gastric emptying without effect on intestinal transit. Immunohistochemistry showed the presence of nitrotyrosine (NT) and 4-hydroxy-2-nonenal (HNE) in the gastric and ileal mucosa of LPS-treated mice. Treatment with PEG-SOD or PEG-CAT of LPS mice diminished the presence of NT or HNE in both tissues. In addition, LPS induced a significant increase in inducible nitric oxide synthase (iNOS)-positive residential macrophages in the external musculature of stomach and ileum, which significantly decreased after PEG-SOD or PEG-CAT treatment. The present results support a role for oxidative and nitrosative stress in the pathogenesis of septic ileus in mice.

Aldehydes↗

PubMed2005

Regional differences in gastrointestinal motility disturbances during acute necrotising pancreatitis.

Patients with acute pancreatitis often suffer from intestinal motility disturbances but the mechanism of this dysfunction is largely unknown. We studied the effect of acute necrotising pancreatitis (ANP) on in vivo gastrointestinal motility and in vitro intestinal contractility in mice. ANP was induced non-invasively by feeding young female mice a choline-deficient ethionine-supplemented (CDE) diet during 72 h. Gastric emptying and intestinal transit were measured in vivo 15 min after intragastric gavage of a semiliquid Evans blue bolus. Gastric and intestinal neuromuscular function was determined in vitro on isolated muscle strips. ANP significantly decreased gastric emptying from 61.2 +/- 9.8 to 34.9 +/- 7.1% and intestinal transit from 63.4 +/- 5.6 to 32.5 +/- 5.4%. ANP did not affect receptor-dependent and receptor-independent gastric muscle contractions except the contractions to substance P, which were slightly inhibited. In intestinal muscle strips, ANP significantly decreased contractions to EFS, carbachol, PGF(2alpha), substance P and KCl. Our results show that ANP delays gastric emptying in vivo, associated with a specific reduction in substance P contractility in vitro. ANP also impairs intestinal transit in vivo, associated with a non-specific reduction of intestinal contractility in vitro. We conclude that ANP impairs gastrointestinal motility in mice with underlying regional differences in the pathogenic mechanisms.

Acute Disease↗

PubMed2004

Effect of ghrelin and growth hormone-releasing peptide 6 on septic ileus in mice.

Ghrelin is an orexigenic peptide with prokinetic effects in the rat. We investigated the effect of ghrelin and growth hormone-releasing hormone 6 (GHRP-6) on gastric emptying and transit in control and septic mice. Mice were injected i.p. with lipopolysaccharides (LPS) or saline (control). After 16-17 h mice were pretreated with saline, ghrelin or GHRP-6 1 h before intragastric administration of Evans blue. Fifteen minutes later, after assessment of the behaviour scale, mice were killed and gastric emptying, transit and rectal temperature were measured. In control mice, ghrelin (100 microg kg(-1)) and GHRP-6 (20-100 microg kg(-1)) accelerated gastric emptying, whereas ghrelin and GHRP-6 failed to increase transit significantly. Septic mice developed a delay in gastric emptying and transit, hypothermia and a deterioration of the behaviour scale. In septic mice, ghrelin (20 microg kg(-1)) accelerated gastric emptying without effect on transit while GHRP-6 significantly accelerated gastric emptying dose-dependently and failed to increase transit significantly. Ghrelin and GHRP-6 had no effect on the endotoxin-induced hypothermia or deterioration of behaviour scale. Therefore, the beneficial prokinetic effect of ghrelin but mainly of GHRP-6 offers potential therapeutic options in the treatment of septic gastric ileus.

Animals↗

PubMed2004

Concurrent infection with Schistosoma mansoni attenuates inflammation induced changes in colonic morphology, cytokine levels, and smooth muscle contractility of trinitrobenzene sulphonic acid induced colitis in rats.

BACKGROUND AND AIMS: Crohn's disease, characterised by chronic T helper 1 (Th1) inflammation and dysmotility of the gut, is most prevalent in developed countries. Parasitic infections are most prevalent in developing countries and induce a T helper 2 (Th2) immune response. We hypothesised that this Th2 immune response protects against Th1 gut inflammation. METHODS: The parasite Schistosoma mansoni induces a transient Th2 immune response in the semipermissive rat host. 2,4,6-Trinitrobenzene sulphonic acid (TNBS) induced colitis is an experimental model of Th1-like gut inflammation. The effect of concurrent infection with S mansoni on the course of TNBS induced colitis was assessed using macroscopic and microscopic damage scores, histology, myeloperoxidase (MPO) activity assay, cytokine production assay, and by studying in vitro contractility of longitudinal and circular colonic muscle strips. RESULTS: TNBS induced colitis that spontaneously healed after four weeks. Concurrent infection with S mansoni significantly reduced the duration of TNBS induced colitis to two weeks, as shown by macroscopic and microscopic damage scores and by a faster decrease in colonic MPO activity. TNBS increased colonic interleukin 2 (IL-2) production whereas S mansoni increased splenic IL-4 and IL-2 levels. Contractility of longitudinal and circular muscle strips was maximally inhibited one week after TNBS and normalised after three weeks. After four weeks, longitudinal muscle strip contractility was significantly increased. Concurrent infection with S mansoni normalised longitudinal muscle contractility after one week whereas circular muscle contractility remained inhibited. CONCLUSIONS: Concurrent infection with S mansoni significantly attenuates TNBS induced colitis in the rat. Inflammation induced disturbances in contractility of longitudinal and circular colonic muscle strips may outlast the inflammatory reaction.

Animals↗

PubMed2003

Effects of Schistosoma mansoni infection on somatostatin and somatostatin receptor 2A expression in mouse ileum.

Intestinal schistosomiasis is accompanied by motility-related dysfunctions but the underlying mechanisms are not well-known. Therefore, the presence and effects on intestinal contractility of somatostatin (SOM) and its receptor, SSTR2A, were investigated in the ileum of normal and infected mice. The distribution of SOM and SSTR2A was visualized using immunocytochemistry. Radioimmunoassay combined with oogram studies was performed to determine SOM levels and contractility measurements were determined in organ bath experiments. Schistosomiasis resulted in a significant decrease in somatostatin-positive endocrine cells, whereas the number of somatostatin-immunoreactive (IR) neuronal cell bodies did not change. From 8 weeks postinfection onwards, an increase was noted in somatostatin-IR nerve fibres in both villi and granulomas. The staining intensity for SSTR2A, expressed in somatostatin-negative myenteric cholinergic neurones, increased during infection suggesting an upregulation of this receptor. SOM levels were negatively correlated with the number of eggs during the acute phase, and were elevated during the chronic phase. Pharmacological experiments revealed that schistosomiasis diminished the inhibitory effect of SOM on neurogenic contractions. We can conclude that schistosomiasis influences the distribution and expression levels of SOM and SSTR2A in the murine ileum, which might explain the changed motility pattern.

Adrenergic Fibers↗

PubMed2002

Helicobacter pylori, parietal cell antibodies and autoimmune gastropathy in type 1 diabetes mellitus.

BACKGROUND: Fifteen to 20% of type 1 diabetic patients exhibit parietal cell antibodies (PCA), which are associated with autoimmune gastritis, hypochlorhydria, iron deficiency and pernicious anaemia. AIM: To examine whether Helicobacter pylori infection could explain the high prevalence of PCA and autoimmune gastropathy in diabetes. If so, H. pylori eradication could prevent autoimmune gastritis. METHODS: In 229 type 1 diabetics (M/F: 135/94; age: 41 +/- 12 years) PCA were measured. H. pylori infection was assessed by serology, urea breath test in all and by histology (updated Sydney system) in 88 subjects. Pentagastrin tests were performed in 42 patients. RESULTS: Sixty-nine patients were PCA-positive. H. pylori infection was present in 72 patients and was negatively associated with HLA-DQA1*0103-B1*0603 (OR=0.12, P=0.015) and positively with DQA1*0501-B1*0201 (OR=1.9, P=0.032). PCA-positivity was linked to HLA-DQA1*0501-B1*0301 (OR=3.9, P=0.017). A link between H. pylori and PCA was observed when PCA-positivity was defined as a titre > or = 1/20 (OR=2.0, P=0.03), but not if > or =1/40 was the cut-off point. PCA-positivity, but not H. pylori infection, was associated with iron deficiency anaemia (OR=2.7, P=0.008), pernicious anaemia (OR= 33.5, P < 0.0001), hypochlorhydria (OR=12.1, P=0.0008) and autoimmune gastritis (OR=12.5, P < 0.0001). CONCLUSIONS: The HLA-bound susceptibility of H. pylori and PCA differed. PCA-positivity but not ongoing H. pylori infection is associated with autoimmune gastritis. Low titres of PCA might reflect H. pylori infection rather than autoimmune gastropathy.

Adult↗

PubMed2002

Is anorectal endosonography valuable in dyschesia?

AIMS: Dyschesia can be provoked by inappropriate defecation movements. The aim of this prospective study was to demonstrate dysfunction of the anal sphincter and/or the musculus (m.) puborectalis in patients with dyschesia using anorectal endosonography. METHODS: Twenty consecutive patients with a medical history of dyschesia and a control group of 20 healthy subjects underwent linear anorectal endosonography (Toshiba models IUV 5060 and PVL-625 RT). In both groups, the dimensions of the anal sphincter and the m. puborectalis were measured at rest, and during voluntary squeezing and straining. Statistical analysis was performed within and between the two groups. RESULTS: The anal sphincter became paradoxically shorter and/or thicker during straining (versus the resting state) in 85% of patients but in only 35% of control subjects. Changes in sphincter length were statistically significantly different (p<0.01, chi(2) test) in patients compared with control subjects. The m. puborectalis became paradoxically shorter and/or thicker during straining in 80% of patients but in only 30% of controls. Both the changes in length and thickness of the m. puborectalis were significantly different (p<0.01, chi(2) test) in patients versus control subjects. CONCLUSIONS: Linear anorectal endosonography demonstrated incomplete or even absent relaxation of the anal sphincter and the m. puborectalis during a defecation movement in the majority of our patients with dyschesia. This study highlights the value of this elegant ultrasonographic technique in the diagnosis of "pelvic floor dyssynergia" or "anismus".

Adolescent↗

PubMed2001

Effect of TNBS-induced morphological changes on pharmacological contractility of the rat ileum.

Intraluminal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in ethanol is a classical model of colitis in the rat. Little is known about the time-related effect of TNBS on the contractility and morphology of the rat ileum. After 36 h, TNBS induced acute ileitis. Spontaneous activity of longitudinal muscle strips was decreased, as were receptor- and nonreceptor-mediated contractions and contractions induced by electrical stimulation. After 1 week, mucosal integrity was restored, although the thickness of both mucosal and muscle layers was increased. Spontaneous activity, receptor- and nonreceptor-mediated contractions and electrically induced contractions of longitudinal muscle strips were increased due to hypertrophy and hyperplasia of smooth muscle cells. This was confirmed in the contractility study of individual muscle cells. Functional alterations after 1 week were restricted to a decreased response to substance P. TNBS-ileitis in the rat lacks a chronic phase and is accompanied by functional hypocontractility of longitudinal smooth muscle cells during the acute inflammation, whereas the contractility of the longitudinal muscle layer is increased in the postinflammation phase due to structural alterations. There is a selective inhibition of the response to substance P in the postinflammation phase.

Acetylcholine↗

PubMed2001

How to express pharmacological contractions of the inflamed rat intestine.

Inflammation leads to intestinal dysmotility which can be due to both functional and trophic alterations of the neuromuscular apparatus. To discriminate between trophic and functional changes, several normalization procedures are used in contractility studies. It is important to know how normalization procedures may influence the obtained results. In a rat model of TNBS-induced ileitis, we compared seven known normalization procedures for pharmacological contractions of longitudinal muscle strips. During acute ileitis, contractility was significantly decreased, irrespective of the normalization procedure used. During the post-inflammation phase, hypertrophy and hyperplasia of smooth muscle cells led to increased contractility on raw strip chart recordings. However, when contractions were corrected for the increase in muscle mass, the contractility was either normal or decreased, depending on the normalization procedure used. Normalization of contractions to the cross-sectional area (CSA) of the longitudinal muscle is the gold standard. Comparison of three methods to determine the CSA, showed that the commonly used equation to calculate the CSA, based on the tissue weight, length and density, might overestimate the CSA. We conclude that this equation should be adapted by a muscle thickness ratio, or alternatively the CSA can be determined on histological sections.

Acetylcholine↗

PubMed2001

Pre- and postjunctional protective effect of neocuproine on the nitrergic neurotransmitter in the mouse gastric fundus.

1. Electrical field stimulation (EFS) of non-adrenergic non-cholinergic nerves of the mouse gastric fundus induced frequency-dependent transient relaxations which were mimicked by nitric oxide (NO), added as acidified NaNO(2). The NO donors S-nitrosocysteine, S-nitrosoglutathione, SIN-1 and hydroxylamine induced sustained concentration-dependent relaxations. The NO synthase blocker L-nitro arginine (L-NOARG; 300 microM) abolished the relaxations to EFS without affecting the relaxations to NO. 2. The copper(I) chelator neocuproine (10 microM) enhanced the relaxations to EFS and NO but inhibited those to S-nitrosocysteine and S-nitrosoglutathione. Neocuproine potentiated the relaxations to SIN-1, which releases NO extracellularly, without affecting the relaxations to hydroxylamine, which releases NO intracellularly. 3. The potentiating effect of neocuproine on the relaxations to EFS was more pronounced after inhibition of catalase with 3-amino-1,2,4-triazole (1 mM) but not after inhibition of Cu/Zn superoxide dismutase (SOD) with diethyl dithiocarbamic acid (DETCA, 1 mM). The potentiating effect of neocuproine on relaxations to NO was not altered by 3-amino-1,2,4-triazole or DETCA treatment. 4. The relaxations to EFS were significantly inhibited by the oxidants hydrogen peroxide (70 microM) and duroquinone (10 microM) but only after inhibition of catalase with 3-amino-1,2,4-triazole or after inhibition of Cu/ZnSOD with DETCA respectively. 5. Our results suggest that neocuproine can act as an antioxidant in the mouse gastric fundus and that both catalase and Cu/ZnSOD protect the nitrergic neurotransmitter from oxidative breakdown. Since inhibition of catalase but not inhibition of Cu/ZnSOD potentiated the effect of neocuproine on relaxations to EFS without affecting the relaxations to NO, catalase may protect the nitrergic neurotransmitter mainly at a prejunctional site whereas Cu/ZnSOD protects at a postjunctional site.

Animals↗

PubMed2001

Disturbance of the prejunctional modulation of cholinergic neurotransmission during chronic granulomatous inflammation of the mouse ileum.

The effect of chronic granulomatous inflammation of the intestine was studied on the prejunctional modulation of cholinergic nerve activity in the mouse ileum. Contractions to carbachol (0.01 - 0.3 microM) and to electrical field stimulation (EFS, 0.25 - 8 Hz) of enteric neurons were higher in inflamed ileum as compared to control ileum. However, when the neurally-mediated contractions to EFS were expressed as percentage of the direct smooth muscle contraction to carbachol, the responses to EFS were similar in control and inflamed ileum. Atropine (1 microM) abolished all contractions to EFS and carbachol in control and inflamed ileum. DMPP (3 - 30 microM), a nicotinic receptor agonist, induced concentration-dependent contractions that were more pronounced in inflamed ileum as compared to control ileum. Hexamethonium (100 microM), a nicotinic receptor blocker, significantly inhibited the contractions to EFS in inflamed ileum but not in control ileum. In control ileum, histamine (10 - 100 microM) and the histamine H(1) receptor agonist HTMT (3 - 10 microM) inhibited the contractions to EFS concentration-dependently without affecting the contractions to carbachol. The inhibitory effect of histamine and HTMT was prevented by the histamine H(1) antagonist mepyramine (5 - 10 microM) but not by the H(2)- and H(3)-receptor antagonists cimetidine and thioperamide (both 10 microM). In chronically inflamed ileum however, histamine (10 - 100 microM) and HTMT (3 - 10 microM) failed to inhibit the contractions to EFS. The histamine H(2) and H(3) receptor agonists dimaprit and R(-)-alpha-methylhistamine did not affect the contractions to EFS in control and inflamed ileum. The alpha(2)-receptor agonist UK 14.304 (0.01 - 0.1 microM) inhibited the contractions to EFS in control and inflamed ileum without affecting the contractions to carbachol. The effect of UK 14.304 was reversed by the alpha(2)-receptor antagonist yohimbine (1 microM). The inhibitory effect of UK 14.304 on contractions to EFS was of similar potency in control and inflamed ileum. Our results suggest that the prejunctional modulation of cholinergic nerve activity by nicotinic and histaminic H(1) receptors is disturbed during chronic intestinal inflammation whereas the modulation by alpha(2)-receptors is preserved. Such a disturbance of cholinergic nerve activity may contribute to the motility disturbances that are often observed during chronic intestinal diseases in humans.

Adrenergic Agonists↗

PubMed2001

Effect of 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced ileitis on the motor function of non-inflamed rat gastric fundus.

During intestinal inflammation, motility disturbances are not restricted to inflamed regions, but may also occur in remote non-inflamed sites of the gastrointestinal tract. Our aim was to investigate the motor function of the gastric fundus after the induction of terminal ileitis in the rat. Ileal inflammation was induced by intraluminal installation of 2,4,6-trinitrobenzenesulphonic acid (TNBS) into the ileum. Inflammation was assessed both histologically and biochemically. Contractions and relaxations of longitudinal muscle strips from the gastric fundus were studied 36 h and 1 week later. During the acute phase of ileal inflammation (36 h), the non-inflamed stomach was distended. The contractility of longitudinal muscle strips of the gastric fundus was decreased due to a post-receptor defect. In addition, nonadrenergic noncholinergic (NANC) relaxations were inhibited due to neuronal dysfunction. Aortic contractility remained normal and the mere presence of food in the stomach did not account for the disturbed neuromuscular function in the gastric fundus. Ablation of extrinsic primary afferent neurones by capsaicin further impaired gastric fundus contractility. Transection and re-anastomosis of the jejunum reversed the effect of TNBS-induced ileitis on the neuromuscular function of the gastric fundus. One week after TNBS, cholinergic neurotransmission was increased in the gastric fundus. During acute ileitis, smooth muscle cell contractility and inhibitory NANC neurotransmission are inhibited in the non-inflamed gastric fundus. This phenomenon may be mediated by intrinsic connections within the enteric nervous system.

Animals↗

PubMed2001

Effect of Schistosoma mansoni-induced granulomatous inflammation on murine gastrointestinal motility.

In Schistosoma mansoni-infected mice, gastrointestinal transit was measured in vivo and the neuromuscular function of longitudinal muscle strips of inflamed ileum and noninflamed gastric fundus was assessed in vitro. Eight weeks after infection, the ileal wall was acutely inflamed, as shown by a mucosal inflammatory infiltrate, leading to an increase in mucosal thickness, in myeloperoxidase (MPO) activity, and in interleukin (IL)-1beta production. At that time, both gastrointestinal transit and in vitro ileal contractility were normal. Twelve weeks after infection, chronic granulomatous inflammation led to proliferation of the muscle layer and to a further increase in MPO activity, whereas IL-1beta production normalized. Gastrointestinal transit was decreased, whereas in vitro ileal contractility was increased irrespective of the contractile stimulus. In vitro incubation with IL-1beta (10 ng/ml for 60 min) significantly increased ileal contractility only at 8 wk after infection. Indomethacin, tetrodotoxin, and atropine had no differential effect on ileal contractility in controls and infected mice. In vitro contractility of noninflamed gastric fundus was normal both 8 and 12 wk after infection. We conclude that intestinal schistosomiasis 8 wk after infection is associated only with structural changes of the ileum, whereas 12 wk after infection, both structural and functional changes are present. These changes are characterized by increased ileal wall thickness, decreased gastrointestinal transit, and increased smooth muscle contractility restricted to the inflamed gut segment.

Animals↗

PubMed1999

Neocuproine potentiates the activity of the nitrergic neurotransmitter but inhibits that of S-nitrosothiols.

In the present study, we investigated the cellular components that are involved in the release of nitric oxide (NO) from S-nitrosothiols and whether these components also modulate the activity of the nitrergic neurotransmitter in the rat gastric fundus. Electrical stimulation of nitrergic nerves induced frequency-dependent transient relaxations which were mimicked by exogenous NO. The S-nitrosothiols S-nitrosocysteine, S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine induced concentration-dependent relaxations which were generally more sustained as compared to those to nitrergic nerve stimulation or NO. The relaxations to nitrergic nerve stimulation and those to NO were significantly enhanced by the copper(I) chelator neocuproine but not affected by the copper(II) chelator cuprizone. The relaxations to the S-nitrosothiols were significantly inhibited by neocuproine but not by cuprizone. The antioxidant ascorbate did not affect the tension of the muscle strip. However, in the presence of an S-nitrosothiol, ascorbate induced an immediate, sharp and transient relaxation that was significantly inhibited by a low concentration of neocuproine but not by cuprizone. Ascorbate did not induce a relaxation during short-train or prolonged nerve stimulation of the muscle strip. These results suggest that ascorbate interacts with copper to modulate the biological activity of S-nitrosothiols but not that of the nitrergic neurotransmitter. The differential effect of neocuproine indicates that S-nitrosothiols do not mediate the nitrergic neurotransmission of the rat gastric fundus. As neocuproine is to date the only compound that exerts an opposite effect on the biological activity of the nitrergic neurotransmitter and on that of S-nitrosothiols, it may be useful to elucidate the nature of the nitrergic neurotransmitter in the peripheral nervous system.

Adenosine Triphosphate↗

PubMed1999

Effect of different prokinetic agents and a novel enterokinetic agent on postoperative ileus in rats.

BACKGROUND/AIM: The effects of different prokinetic agents, the motilide erythromycin and the substituted benzamides metoclopramide and cisapride, were investigated in a rat model of postoperative ileus. These effects were compared with that of granisetron, a 5-hydroxytryptamine (5-HT(3)) receptor antagonist, and a novel enterokinetic agent, prucalopride, a 5-HT(4) receptor agonist. METHODS: Different degrees of inhibition of gastrointestinal transit, measured by the migration of Evans blue, were achieved by skin incision, laparotomy, or laparotomy plus mechanical stimulation of the gut. RESULTS: Metoclopramide decreased the transit after laparotomy with or without mechanical stimulation, whereas cisapride increased it after all three operations. Granisetron had no effect on the transit after the three operations when given alone. Prucalopride tended to increase the transit after laparotomy with or without mechanical stimulation when given alone. However, statistical significance was only reached when prucalopride was combined with granisetron. Erythromycin, a motilin receptor agonist, did not improve postoperative ileus in the rat. CONCLUSIONS: Cisapride, but not metoclopramide or erythromycin, is able to improve postoperative ileus in the rat. The results suggest that a combination of 5-HT(3) receptor antagonist and 5-HT(4) receptor agonist properties may be required to obtain a beneficial effect on surgery induced ileus in the rat. Furthermore, they indirectly indicate that stimulation of the excitatory mechanisms is not able to overcome the inhibitory influence of the neural reflex pathways activated during abdominal surgery.

Animals↗