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Dive into the research topics where Joris G. De Man is active.

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Featured researches published by Joris G. De Man.


British Journal of Pharmacology | 1997

Effect of adrenergic and nitrergic blockade on experimental ileus in rats

Benedicte Y. De Winter; Guy E. Boeckxstaens; Joris G. De Man; Tom G. Moreels; Arnold G. Herman; Paul A. Pelckmans

1 In a rat model of experimental ileus, the effect of blockade of adrenergic and nitrergic neurotransmission was studied on the intestinal transit of Evans blue. 2 Ether anaesthesia and skin incision had no influence on the transit. Laparotomy significantly inhibited the transit of Evans blue. This inhibition was even more pronounced when the small intestine was manipulated. 3 Reserpine (5 mg kg−1), a drug that blocks adrenergic neurotransmission, completely reversed the inhibition of the transit induced by laparotomy but only partially reversed that induced by laparotomy with manipulation of the small intestine. 4 Nω‐nitro‐L‐arginine (L‐NOARG, 5 mg kg−1), a nitric oxide synthase inhibitor, completely reversed the reserpine‐resistant inhibition induced by laparotomy with manipulation of the small intestine. The effect of L‐NOARG was prevented by concomitant administration of L‐arginine. L‐Arginine itself slightly, but significantly enhanced the inhibition. S‐methylisothiourea and aminoguanidine, selective inhibitors of the inducible NO synthase, had no effect on the transit after the three operations. 5 Treatment of the rats with reserpine plus L‐NOARG had no additional effect on the transit after laparotomy as compared to reserpine alone. However, reserpine plus L‐NNA completely reversed the inhibition of the transit induced by laparotomy with manipulation of the small intestine. 6 These findings support the involvement of adrenergic pathways in the pathogenesis of ileus and suggest that the additional inhibitory effect of mechanical stimulation results from an enhanced release of NO by the constitutive NO synthase.


Inflammatory Bowel Diseases | 2009

Therapeutic potential of helminth soluble proteins in TNBS‐induced colitis in mice

Nathalie E. Ruyssers; Benedicte Y. De Winter; Joris G. De Man; Alex Loukas; Mark S. Pearson; Joel V. Weinstock; Rita M. Van den Bossche; Wim Martinet; Paul A. Pelckmans; Tom G. Moreels

Background: The hygiene hypothesis suggests an inverse relationship between the incidence of parasitic infections and chronic inflammatory bowel diseases (IBD). We investigated the therapeutic potential of Schistosoma mansoni and Ancylostoma caninum soluble proteins on experimental colitis in mice. Methods: Colitis was induced by intrarectal administration of 10 mg trinitrobenzene sulfonic acid (TNBS) in 30% ethanol. Six hours after TNBS injection, mice were treated intraperitoneally with helminth proteins. Three days later, colonic inflammation was scored based on 5 inflammatory parameters: clinical disease activity, macroscopic and microscopic inflammation score, extent of inflammation, and myeloperoxidase (MPO) activity. To determine immunological pathways induced by S. mansoni proteins we measured cytokine profiles of T‐lymphocytes from colon, mesenteric lymph nodes (MLN), and spleen by real‐time reverse‐transcriptase polymerase chain reaction (RT‐PCR). Results: Control mice showed no signs of inflammation, whereas all inflammatory parameters were significantly increased in mice with colitis. Treatment of mice with colitis with S. mansoni or A. caninum proteins decreased the macroscopic inflammation score, extent of inflammation, and MPO activity. Immunologically, induction of colitis significantly increased expression of IFN‐γ mRNA in the inflamed colon. Treatment with S. mansoni proteins caused a decrease of proinflammatory cytokines (IFN‐γ, IL‐17) in colon and MLN, whereas the production of regulatory cytokines (IL‐10, TGF‐β) increased significantly in colon tissue. Conclusions: Treatment with proteins of S. mansoni and A. caninum ameliorated TNBS‐induced colitis in mice. S. mansoni proteins increased mRNA expression of regulatory cytokines while suppressing expression of proinflammatory cytokines. Therefore, we suggest a therapeutic potential for helminth proteins in the treatment of IBD. (Inflamm Bowel Dis 2009)


British Journal of Pharmacology | 1991

Evidence for nitric oxide as mediator of non-adrenergic non-cholinergic relaxations induced by ATP and GABA in the canine gut.

Guy E. Boeckxstaens; Paul A. Pelckmans; Hidde Bult; Joris G. De Man; Arnold G. Herman; Yvan M. Van Maercke

1 The effects of haemoglobin, and the nitric oxide (NO) biosynthesis‐inhibitors NG‐monomethyl‐l‐arginine (l‐NMMA), its enantiomer d‐NMMA, and NG‐nitro‐l‐arginine (l‐NNA) were investigated on non‐adrenergic non‐cholinergic (NANC)‐mediated relaxation of circular muscle strips of the canine terminal ileum and ileocolonic junction induced by electrical stimulation, adenosine 5′‐triphosphate (ATP), γ‐aminobutyric acid (GABA) and NO. 2 Tetrodotoxin, l‐NMMA and l‐NNA, but not d‐NMMA, inhibited the relaxations induced by electrical stimulation, ATP and GABA, but not those in response to NO. 3 The inhibitory effect of l‐NMMA and l‐NNA was prevented by l‐arginine, but not by d‐arginine. l‐Arginine did not potentiate any of the NANC relaxations. 4 Haemoglobin reduced the relaxation induced by electrical stimulation, ATP and GABA, and abolished those in response to NO. 5 Our results demonstrate that the ATP‐ and GABA‐induced relaxations resulting from stimulaton of intramural NANC neurones, in addition to those induced by electrical impulses, are mediated by NO or a NO releasing substance and thus provide further evidence in support of the proposal that NO is the final inhibitory NANC neurotransmitter in the canine terminal ileum and ileocolonic junction.


British Journal of Pharmacology | 1991

The role of nitric oxide in inhibitory non-adrenergic non-cholinergic neurotransmission in the canine lower oesophageal sphincter.

Joris G. De Man; Paul A. Pelckmans; Guy E. Boeckxstaens; Hidde Bult; Luc Oosterbosch; Arnold G. Herman; Yvan M. Van Maercke

1 The role of nitric oxide (NO) in non‐adrenergic non‐cholinergic (NANC) neurotransmission was studied on circular muscle strips of the canine lower oesophageal sphincter (LOS). Electrical field stimulation evoked frequency‐dependent relaxations, which were resistant to adrenergic and cholinergic blockade and abolished by tetrodotoxin. 2 Exogenous administration of NO induced concentration‐dependent and tetrodotoxin‐resistant relaxations which mimicked those in response to electrical stimulation. 3 NG‐nitro‐l‐arginine (l‐NNA), a stereospecific inhibitor of NO‐biosynthesis, inhibited the relaxations induced by electrical stimulation but not those by exogenous NO or vasoactive intestinal polypeptide (VIP). 4 The effect of l‐NNA was prevented by l‐arginine, the precursor of the NO biosynthesis but not by its enantiomer d‐arginine. 5 Haemoglobin abolished the NO‐induced responses and reduced those evoked by electrical stimulation. 6 Cumulative administration of VIP induced concentration‐dependent relaxations, which were slow in onset and sustained. A complete relaxation to VIP was not achieved and the relaxations were not affected by l‐NNA. 7 In conclusion, our results provide evidence that NANC relaxations are mediated by NO, suggesting NO or a NO releasing substance as the final inhibitory NANC neurotransmitter in the canine LOS.


British Journal of Pharmacology | 1991

Bioassay of nitric oxide released upon stimulation of non‐adrenergic non‐cholinergic nerves in the canine ileocolonic junction

Guy E. Boeckxstaens; Paul A. Pelckmans; Isabelle F. Ruytjens; Hidde Bult; Joris G. De Man; Arnold G. Herman; Yvan M. Van Maercke

1 The release and the nature of the inhibitory non‐adrenergic non‐cholinergic (NANC) neurotransmitter was studied in the canine ileocolonic junction. A circular muscle strip of the canine ileocolonic junction served as donor tissue in a superfusion bioassay in which rings of rabbit aorta with the endothelium removed served as detector tissue. 2 The ileocolonic junction released a labile factor with vasodilator activity upon stimulation of non‐adrenergic non‐cholinergic (NANC) nerves in response to electrical impulses and the nicotinic receptor agonist 1,1‐dimethyl‐4‐phenylpiperazinium (DMPP). This release was respectively frequency‐ and concentration‐dependent. 3 The release was reduced by the blocker of neuronal conductance, tetrodotoxin, and by the inhibitor of the nitric oxide (NO) biosynthesis NG‐nitro‐l‐arginine. The biological activity was enhanced by superoxide dismutase and eliminated by haemoglobin. Hexamethonium abolished only the release in response to DMPP. 4 Injection of adenosine 5′‐triphosphate (ATP) or vasoactive intestinal polypeptide (VIP) onto the cascade induced relaxations of the rabbit aorta but they were different from those induced by NO or the transferable factor. 5 Based on organ bath experiments in which the reactivity of different parts of the circular smooth muscle layer of the ileocolonic junction was investigated, a muscle strip of superficial circular muscle with submucosa was chosen as the detector strip in the bioassay cascade. 6 The ileocolonic junction dose‐dependently relaxed in response to nitroglycerin and NO. NO was much more potent in the rabbit aorta than in the canine ileocolonic junction. Equivalent amounts of the transferable factor, endothelium‐derived relaxing factor and NO, as assessed by the relaxation of the rabbit aorta, failed to affect the ileocolonic junction. 7 In conclusion, our results demonstrate the release of a transferable vasorelaxant factor in response to NANC nerve stimulation which behaves pharmacologically like NO but not like ATP or VIP. Therefore, we suggest that NO or a NO releasing substance is the inhibitory NANC neurotransmitter in the canine ileocolonic junction.


Shock | 2002

Effect of inhibition of inducible nitric oxide synthase and guanylyl cyclase on endotoxin-induced delay in gastric emptying and intestinal transit in mice

Benedicte Y. De Winter; Albert J. Bredenoord; Joris G. De Man; Tom G. Moreels; Arnold G. Herman; Paul A. Pelckmans

Nitric oxide (NO) is postulated to play a role in endotoxin-induced ileus. We investigated the effect of selective blockade of inducible NO synthase (iNOS) and guanylyl cyclase on endotoxin-induced ileus in mice. Thirty minutes before injection of lipopolysaccharides (LPS), mice were pretreated with L-NAME (Nω-nitro-L-arginine methyl ester, non-selective NOS inhibitor), 1400W (N-(3-(aminomethyl)benzyl)acetamide, selective iNOS inhibitor), ODQ (1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one, guanylyl cyclase inhibitor), dimethyl sulfoxide (DMSO, vehicle), or dexamethasone. After 18 h, general well being deteriorated and the mice developed hypothermia and a significant delay in gastric emptying and intestinal transit as measured by Evans blue. 1400W completely reversed the endotoxin-induced delay in gastric emptying, while L-NAME did not have these beneficial effects. On the contrary, even in control mice, L-NAME delayed gastric emptying. Dexamethasone, DMSO, and ODQ mimicked the effect of 1400W on endotoxin-induced delay in gastric emptying. The endotoxin-induced delay in transit was significantly improved only by 1400W. None of the drugs reversed the hypothermia. In LPS mice treated with L-NAME, the behavior scale increased even further, while it decreased after treatment with 1400W. In conclusion, selective inhibition of iNOS reverses the endotoxin-induced delay in gastric emptying and transit and improves general well being. The pathway used by NO, derived from iNOS, may involve inhibition of guanylyl cyclase or radical scavenging.


British Journal of Pharmacology | 2003

Functional evidence that ATP or a related purine is an inhibitory NANC neurotransmitter in the mouse jejunum: study on the identity of P2X and P2Y purinoceptors involved

Joris G. De Man; Benedicte Y. De Winter; Tom C. Seerden; Heiko U. De Schepper; Arnold G. Herman; Paul A. Pelckmans

Conflicting views exist on whether ATP is a neurotransmitter in the enteric nervous system. We investigated the role of ATP in enteric transmission in circular muscle strips of the mouse jejunum. On PGF2α‐precontracted muscle strips and in the presence of atropine and guanethidine, electrical field stimulation (EFS, 1–8 Hz) of nonadrenergic noncholinergic (NANC) nerves induced transient relaxations that were abolished by the nerve‐conductance blocker tetrodotoxin. The NO synthase blocker L‐nitroarginine (L‐NOARG) partially inhibited the NANC relaxations to EFS, but fast‐twitch relaxations to EFS were still observed in the presence of L‐NOARG. In the presence of L‐NOARG, ATP, the P2X receptor agonist αβMeATP and the P2Y receptor agonist ADPβS relaxed jejunal muscle strips. Tetrodotoxin did not affect the relaxation to ATP and ADPβS, but inhibited that to αβMeATP. The L‐NOARG‐resistant NANC relaxations to EFS were almost abolished by apamin, a blocker of small‐conductance Ca2+ activated K+ channels, and by suramin and PPADS, blockers of P2 purinoceptors. Relaxations to ATP were almost abolished by apamin and suramin but not affected by PPADS. Desensitisation of αβMeATP‐sensitive P2X receptors, the P2X receptor blocker Evans blue and the P2X1,2,3 receptor blocker NF 279 inhibited the L‐NOARG‐resistant NANC relaxations to EFS and that to αβMeATP without affecting the relaxation to ADPβS. Brilliant blue G, a P2X2,5,7 receptor blocker, did not affect the relaxations to EFS. Desensitisation of P2Y receptors and MRS 2179, a P2Y1 receptor blocker, virtually abolished the L‐NOARG‐resistant NANC relaxations to EFS and the relaxation to ADPβS without affecting the relaxation to αβMeATP. Dipyridamole, an adenosine uptake inhibitor, or theophylline and 8‐phenyltheophylline, blockers of P1 and A1 purinoceptors, respectively, did not affect the purinergic NANC relaxations to EFS. Our results suggest that ATP or a related purine acts as an inhibitory NANC neurotransmitter in the mouse jejunum, activating P2 but not P1 purinoceptors. Relaxations to the purinergic NANC neurotransmitter mainly involve P2Y receptors of the P2Y1 subtype that are located postjunctionally. Purinergic NANC neurotransmission also involves P2X receptors, most likely of the P2X1 and P2X3 subtype, located pre‐ and/or postjunctionally.


British Journal of Pharmacology | 2003

Alteration of the purinergic modulation of enteric neurotransmission in the mouse ileum during chronic intestinal inflammation

Joris G. De Man; Tom C. Seerden; Benedicte Y. De Winter; Eric Van Marck; Arnold G. Herman; Paul A. Pelckmans

The effect of chronic intestinal inflammation on the purinergic modulation of cholinergic neurotransmission was studied in the mouse ileum. Chronic intestinal inflammation was induced by infection of mice with the parasite Schistosoma mansoni during 16 weeks. S. mansoni infection induced a chronic inflammatory response in the small intestine, which was characterised by intestinal granuloma formation, increased intestinal wall thickness, blunted mucosal villi and an enhanced activity of myeloperoxidase. In control ileum and in chronically inflamed ileum, electrical field stimulation (EFS) of longitudinal muscle strips induced frequency‐dependent contractions that were abolished by tetrodotoxin (TTX) and atropine. Carbachol induced dose‐dependent contractions that were not affected by TTX but abolished by atropine. In control ileum, adenosine and ATP dose‐dependently inhibited the contractions to EFS. Theophylline and 8‐phenyltheophylline, P1 and A1 receptor antagonists respectively, prevented this inhibitory effect of adenosine and ATP. PPADS, DMPX and MRS 1220, antagonists of P2, A2 and A3 receptors, respectively, did not prevent this inhibitory effect of adenosine and ATP. Adenosine and ATP did not affect the contractions to carbachol. The inhibitory effect of adenosine and ATP on contractions to EFS in control ileum was mimicked by the stable adenosine analogue methyladenosine and by the A1‐receptor agonist N(6)‐cyclohexyladenosine, but not by the A3 receptor agonist 2‐Cl IB‐MECA or by the ATP analogues αβ‐methylene‐ATP and ADPβS. The inhibitory effect of adenosine on contractions to EFS was lost after prolonged (90 min) treatment of control ileum with methyladenosine (100 μM). In chronically inflamed ileum, adenosine, methyladenosine, N(6)‐cyclohexyladenosine and ATP all failed to inhibit the cholinergic nerve‐mediated contractions to EFS. Also theophylline, 8‐phenyltheophylline, PPADS, DMPX and MRS 1220 had no effect on the contractions to EFS and carbachol. The loss of effect of adenosine and ATP was still evident after 52 weeks of infection. These results indicate that in physiological conditions neuronal adenosine A1 receptors modulate cholinergic nerve activity in the mouse ileum. However, during chronic intestinal inflammation, this purinergic modulation of cholinergic nerve activity is impaired. This suggests that chronic intestinal inflammation leads to a dysfunction of specific neuronal regulatory mechanisms in the enteric nervous system.


PLOS ONE | 2011

Cannabidiol Reduces Intestinal Inflammation through the Control of Neuroimmune Axis

Daniele De Filippis; Giuseppe Esposito; Carla Cirillo; Mariateresa Cipriano; Benedicte Y. De Winter; Caterina Scuderi; Giovanni Sarnelli; Rosario Cuomo; Luca Steardo; Joris G. De Man; Teresa Iuvone

Enteric glial cells (EGC) actively mediate acute and chronic inflammation in the gut; EGC proliferate and release neurotrophins, growth factors, and pro-inflammatory cytokines which, in turn, may amplify the immune response, representing a very important link between the nervous and immune systems in the intestine. Cannabidiol (CBD) is an interesting compound because of its ability to control reactive gliosis in the CNS, without any unwanted psychotropic effects. Therefore the rationale of our study was to investigate the effect of CBD on intestinal biopsies from patients with ulcerative colitis (UC) and from intestinal segments of mice with LPS-induced intestinal inflammation. CBD markedly counteracted reactive enteric gliosis in LPS-mice trough the massive reduction of astroglial signalling neurotrophin S100B. Histological, biochemical and immunohistochemical data demonstrated that S100B decrease was associated with a considerable decrease in mast cell and macrophages in the intestine of LPS-treated mice after CBD treatment. Moreover the treatment of LPS-mice with CBD reduced TNF-α expression and the presence of cleaved caspase-3. Similar results were obtained in ex vivo cultured human derived colonic biopsies. In biopsies of UC patients, both during active inflammation and in remission stimulated with LPS+INF-γ, an increased glial cell activation and intestinal damage were evidenced. CBD reduced the expression of S100B and iNOS proteins in the human biopsies confirming its well documented effect in septic mice. The activity of CBD is, at least partly, mediated via the selective PPAR-gamma receptor pathway. CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients. These actions lead to a reduction of intestinal damage mediated by PPARgamma receptor pathway. Our results therefore indicate that CBD indeed unravels a new therapeutic strategy to treat inflammatory bowel diseases.


Clinical & Developmental Immunology | 2008

Worms and the treatment of inflammatory bowel disease: are molecules the answer?

Nathalie E. Ruyssers; Benedicte Y. De Winter; Joris G. De Man; Alex Loukas; Arnold G. Herman; Paul A. Pelckmans; Tom G. Moreels

The lack of exposure to helminth infections, as a result of improved living standards and medical conditions, may have contributed to the increased incidence of IBD in the developed world. Epidemiological, experimental, and clinical data sustain the idea that helminths could provide protection against IBD. Studies investigating the underlying mechanisms by which helminths might induce such protection have revealed the importance of regulatory pathways, for example, regulatory T-cells. Further investigation on how helminths influence both innate and adaptive immune reactions will shed more light on the complex pathways used by helminths to regulate the hosts immune system. Although therapy with living helminths appears to be effective in several immunological diseases, the disadvantages of a treatment based on living parasites are explicit. Therefore, the identification and characterization of helminth-derived immunomodulatory molecules that contribute to the protective effect could lead to new therapeutic approaches in IBD and other immune diseases.

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Guy E. Boeckxstaens

Katholieke Universiteit Leuven

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