D Delbro

Sahlgrenska University Hospital, Goeteborg, Västra Götaland, Sweden

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Publications (52)123.59 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The effect of cholera toxin on small intestinal capillary function, utilizing the Evans blue dye method, was analyzed. The modulatory influence of plasma-derived or recombinant human antisecretory factor on this variable was also investigated. Male Sprague-Dawley rats were briefly anesthetized with ether, and a jejunal loop was constructed that was challenged for 90 min with phosphate-buffered saline or cholera toxin. Five minutes prior to death, the rats received an intravenous injection of Evans blue. The tissue content of dye in the loop was quantitated spectrophotometrically or demonstrated histochemically. Cholera toxin increased the recovery of Evans blue; extravasation of the dye was prominent in the top of the villi, while the crypts were spared. It is suggested that the toxin caused increased transcapillary permeation of albumin in a heterogenous fashion in the gut wall. This effect of the toxin was prevented by pretreatment with the antisecretory factor.
    Digestive Diseases and Sciences 10/1998; 43(9):2061-70. · 2.26 Impact Factor
  • D S Delbro, S Lange
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    ABSTRACT: It is well-known that enteric, secreto-motor nerves mediate cholera toxin-induced fluid secretion in the rat small intestine. This notion is, in part, derived from experiments on anaesthetized animals in which the response to cholera toxin was antagonized by the ganglionic nicotinic receptor antagonist, hexamethonium. In the current study, such anti-secretory action of ganglionic blocking compounds was analysed in an experiment designed to minimize any possible negative effect of general anaesthesia on intestinal secretion. Rats were anaesthetized with ether for 5-10 min, during which time a jejunal loop (10-12 cm) was constructed. The loop was challenged with one of the secretagogues, cholera toxin, prostaglandin E1 (PGE1) or okadaic acid. Saline (control) or either of the ganglionic blockers, hexamethonium and chlorisondamine, was administered intravenously. The rats were killed 5 h (cholera toxin) or 1.5 h (PGE1 and okadaic acid) after challenge, and the amount of fluid accumulated in the loops was determined. Cholera toxin-induced secretion was unchanged by hexamethonium but reduced by approximately 80% by chlorisondamine. The difference in effect between the two blockers might relate to the duration of ganglionic blockade. Chlorisondamine blocked secretion induced by either PGE1 or okadaic acid by approximately 60%. It is suggested that the anti-secretory effect of ganglionic blocking compounds might be a result of blockade of secreto-motor nerves but other mechanisms, for example interference with haemodynamic factors, cannot be ruled out.
    Journal of Pharmacy and Pharmacology 12/1997; 49(11):1109-13. · 2.03 Impact Factor
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    ABSTRACT: The relaxatory effect of acetylcholine was investigated on the feline internal anal sphincter (IAS), in vitro. Acetylcholine (10, 30, 100, and 1000 microM) caused a concentration-dependent relaxation of the same magnitude in strips from the proximal and distal IAS. The antagonist of nitric oxide synthase, N omega-nitro-L-arginine (L-NNA; 1, 10, and 100 microM), in a concentration-dependent and stereospecific manner, blocked the acetylcholine-induced relaxation, leaving a residual response of 10-30%. The blocking effect of L-NNA (100 microM) could not be shown in tissues that had been incubated with the substrate for nitric oxide synthase, L-arginine (1 mM). The present results suggest that the acetylcholine-induced relaxation of the IAS to a major extent is due to an activation of nitrergic, inhibitory motor neurons to the IAS.
    Scandinavian Journal of Gastroenterology 01/1997; 31(12):1189-94. · 2.33 Impact Factor
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    ABSTRACT: The effects of the Lps gene on the development of experimental ulcerative colitis were studied in two genetically different mouse strains: C57B1 and C3H. Acute colitis was induced by adding 3% dextran sulfate sodium (DSS) to the drinking water for a 7-day (C57B1 and C3H) or a 10-day (C57B1) experimental period. Although the DSS treatment initiated the same type of morphological changes in the colon in all groups of mice, an earlier onset and persistent intestinal bleeding occurred in the Lpsn mice (sensitive to lipopolysaccharide, LPS) in comparison with the Lpsd mice (hyporesponsive to LPS). Rectal bleeding appeared on day 7 in 90% of the Lpsn compared to 13% of the Lpsd mice (p < 0.0001). In C57B1 mice, followed for three additional days, 50% of the Lpsn mice died and the surviving animals showed as well as rectal bleeding a large number of Gram-negative bacteria in the liver and spleen. In contrast, the Lpsd mice of the C57B1 strain appeared unaffected by the treatment, although a transient rectal bleeding occurred in 90% on day 8. Also, significantly fewer Gram-negative bacteria were found in the liver and spleen. Even though significantly increased serum endotoxin levels were seen in all DSS-treated groups compared to controls on day 7, the serum levels of TNF alpha were significantly increased only in the Lpsn mice. In DSS-induced colitis the Lpsn genotype conferred on the mice an increased LPS susceptibility, resulting in an augmentation of the inflammatory response to Gram-negative bacteria and their endotoxins. The results suggest that LPS-induced host effector mechanisms significantly enhanced the intestinal bleeding, systemic inflammatory response, and mortality in mice with DSS-induced colitis. In addition, the host defense against the invading and systemically spread bacteria most probably involved additional genes.
    Apmis 11/1996; 104(11):823-33. · 2.07 Impact Factor
  • S Lange, D S Delbro
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    ABSTRACT: In the present study, we addressed the problem whether sympathoadrenal mechanisms could influence the paracellular permeation of macromolecules from the lumen to the lamina propria of the small intestine. Experiments were conducted with rats that were anesthetized with ether for 10-20 min, during which time laparotomy was performed and six consecutive loops (each of 5 cm length) of the jejunum were prepared. A 3% solution of the azo dye, Evans blue (EB; MW 960.83) in phosphate-buffered saline, was instilled into each loop at a volume of 0.3 ml, this compound serving as a marker for tight junctional permeability. Thereafter, the abdomen was closed and the rats were allowed to wake up, but were killed after 60 min. The loops were dissected, opened, and rinsed with acetylcysteine in order to remove the adherent mucus layer. Each loop was weighed and incubated with formamide for 24 hr to elute the amount of EB absorbed, which was quantitated spectrophotometrically. In the control situation, the uptake was homogenous along the loops. beta-Adrenoceptor-blocking, or -stimulating agents could influence the uptake considerably. The data obtained could indicate that noradrenergic nerves, via an activation of beta 2-adrenoceptors, may cause an increase of tight junction permeability for macromolecules, but circulatory mechanisms also must be taken into account in order to explain the observed effects.
    Digestive Diseases and Sciences 01/1996; 40(12):2623-9. · 2.26 Impact Factor
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    ABSTRACT: Recto-anal motility response to bladder distension was studied under general anaesthesia in 12 patients undergoing intestinal resection for Crohn's disease of the small intestine or colonic cancer. The effect of epidural anaesthesia on anal tone and on the motility response to bladder distension was studied in six of these patients. An anal pressure increase on bladder distension was observed in all individuals. No motility response was noted in the rectum. The anal pressure response to bladder distension was abolished by epidural anaesthesia. It was concluded that anal pressure in man under general anaesthesia was tonically influenced by the thoracolumbar sympathetic outflow. An excitatory vesico-anal reflex was demonstrated. It appears as this reflex is mediated via the spinal cord.
    International Journal of Colorectal Disease 02/1995; 10(3):148-51. · 2.24 Impact Factor
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    B I Gustafsson, D S Delbro
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    ABSTRACT: 1. The effects of electrical stimulation of the peripheral end of the cervical vagal nerve on jejunal motility were investigated in anaesthetized cats, pretreated with guanethidine, with sectioned splanchnic nerves and ligated adrenal vessels. Motility was monitored as volume changes of an intraluminal balloon. 2. Vagal stimulation elicited frequency-dependent hypermotility with a short latency. Relaxatory events were also observed, which could indicate the presence of a non-adrenergic inhibitory pathway. 3. After atropine treatment, contractions and relaxations could still be elicited. The former were compared to cholinergic contractions and showed a lower maximal amplitude and a longer latency to onset. Moreover, they were antagonized by 80-100% by the opioid receptor antagonist, naloxone. 4. Vagal stimulation after hemicholinium, given in order to deplete the preganglionic acetylcholine content, elicited naloxone-sensitive contractions. This suggests that a subpopulation of the vagal preganglionic fibres is non-cholinergic. 5. Isolation of the balloon-containing segment did not qualitatively alter the responses, indicating that the vagal fibres reach the small intestine via the paravascular mesenteric nerves. 6. It is concluded that cholinergic and non-adrenergic, non-cholinergic (NANC) contractions, as well as relaxations, could be elicited by efferent vagal stimulation. The NANC contractions seem to result from the activation of opioid receptors causing disinhibition of a tonic neurogenic restraint on the gut muscle.
    The Journal of Physiology 12/1994; 480 ( Pt 3):587-95. · 4.38 Impact Factor
  • B I Gustafsson, D S Delbro
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    ABSTRACT: Duodenal or jejunal motility (monitored as pressure changes in a saline-perfused intraluminal catheter) was studied in anaesthetized rats, vagotomized and pretreated with adrenergic blocking agents. In the duodenum (but not the jejunum), atropine or the selective muscarinic M1 and M3 receptor antagonists, pirenzepine and 4-diphenyl-acetoxy-N-methylpiperidine (4-DAMP), respectively, augmented the spontaneous contractile activity. This effect could be abolished either by nicotinic ganglionic receptor antagonism with hexamethonium, or with morphine. Moreover, blockade of the synthesis of nitric oxide by N omega-nitro-L-arginine elicited hypermotility both in the duodenum and the jejunum, and also this response was abolished by hexamethonium. It is proposed from the present results that the rat small is controlled by non-adrenergic, non-cholinergic inhibitory as well as excitatory motor neurons. The latter motor neurons seem to be modulated by muscarinic, nitroxergic or opioidergic mechanisms.
    European Journal of Pharmacology 06/1994; 257(3):227-33. · 2.59 Impact Factor
  • S Lange, D S Delbro, E Jennische
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    ABSTRACT: The azo dye Evans blue (EB; molecular weight, 960.83) is widely used as an indicator of increased capillary permeability. In the present study, however, rat gut absorption of EB was investigated after dye instillation in either the small or large intestine. During a brief period of ether anaesthesia, EB was injected either into jejunal loops with a challenge period of 30 or 60 min or into a proximal and a distal colon loop with a challenge period of 30, 60, or 120 min. After the rats had been killed the intestinal specimens were washed with 6 mM acetylcysteine dissolved in phosphate-buffered saline, which efficiently cleared the tissues of mucus, and thus of EB trapped in mucus. Only EB absorbed by the gut wall remained to be estimated, and this absorption was found to be both dose- and time-dependent in the jejunum and the colon. After instillation in the colon, but not in jejunum, EB could be detected in the blood. EB absorption from the jejunum remained unaffected by the addition of either ouabain (1 mM) or lidocaine (0.38 mM). Either of these compounds inhibited EB uptake in the proximal part of the colon, while enhancing it in the distal part. Fluorescence microscopy showed penetration into the intestinal wall to be a prerequisite for EB to become fluorescent, and EB fluorescence increased with time. It is proposed that EB is transported over the mucosa by the paracellular route and that the amount of absorbed EB reflects epithelial permeability differently in different parts of the gastrointestinal tract.(ABSTRACT TRUNCATED AT 250 WORDS)
    Scandinavian Journal of Gastroenterology 02/1994; 29(1):38-46. · 2.33 Impact Factor
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    ABSTRACT: Peroperative manometry was performed in 12 patients operated on with endoanal proctectomy and a hand-sewn pouch-anal anastomosis and in 12 in whom proctectomy was performed entirely from above, with the ileal pouch stapled to the top of the anal canal. Results from both groups showed that division of the superior rectal artery reduced the median (95 per cent confidence interval (c.i.)) resting anal pressure from 77.5 (69.9-83.3) mmHg to 64.5 (55.2-70.0) mmHg (P < 0.01). Complete rectal mobilization to the pelvic floor decreased resting pressure by an additional 22 per cent, to a median of 50.0 (95 per cent c.i. 40.1-53.5) mmHg (P < 0.01). After completion of anastomosis, irrespective of the operative technique used, a further decline in median pressure to 35.0 (95 per cent c.i. 26.0-47.7) mmHg could be demonstrated (P < 0.05). This study indicates that anal sphincter pressure is reduced to a similar extent after hand-sewn and stapled anastomoses. Injury to the autonomic nervous supply to the anal sphincter mechanism might be the major cause for this reduction.
    British Journal of Surgery 06/1993; 80(5):631-5. · 4.84 Impact Factor
  • B I Gustafsson, D S Delbro
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    ABSTRACT: Some factors known to affect jejunal motility (recorded as volume changes of an intraluminal balloon) were investigated in anaesthetized cats (ether-chloralose) pretreated with guanethidine and atropine. Indomethacin, morphine (both compounds administered systemically) or vagal nerve stimulation elicited jejunal excitatory motor responses. The effect of indomethacin seemed to be independent of cyclooxygenase inhibition and probably did not involve opioid receptors. It is suggested that the spasmogenic stimuli caused jejunal hypermotility by inhibiting tonically active, inhibitory motor neurons that are intrinsic to the gut. Furthermore, when the jenunal tone had been raised by indomethacin or morphine spontaneous relaxations were observed, and these could be mimicked by vagal stimulation. Hexamethonium antagonized these relaxations but did not attenuate the drug-induced jejunal hypermotility.
    European Journal of Pharmacology 02/1993; 230(1):1-8. · 2.59 Impact Factor
  • B I Gustafsson, D S Delbro
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    ABSTRACT: The effects of blocking nitric oxide synthase with the arginine analog N omega-nitro-L-arginine (L-NNA) were investigated in anaesthetized cats, vagotomized and pretreated with guanethidine and atropine. Spontaneous NANC jejunal motility (recorded as the volume changes of an intraluminal balloon) was markedly increased in a dose-dependent and stereospecific manner. The effect of L-NNA was partly reversed by L-arginine, the substrate for nitric oxide (NO) synthesis. Thus, this study presents evidence for a tonic inhibitory influence, via the release of NO, on small intestinal motility in vivo. Furthermore, relaxations upon the L-NNA-induced hypermotility could be elicited by vagal nerve stimulation, which may suggest the existence of another NANC inhibitory transmitter. Hexamethonium abolished such relaxations but did not affect the tone or phasic activity after L-NNA.
    Journal of the Autonomic Nervous System 01/1993; 44(2-3):179-87.
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    ABSTRACT: Anticholinergic drugs are used on an empirical basis for treatment of functional disturbances after restorative proctocolectomy, but their mode of action on ileal pouch performance is mainly unknown. We studied the acute effects of atropine or benzilonium on pouch characteristics and anal sphincter function in 20 patients with a pelvic pouch. Pouch volume was increased by 27% by atropine at distension with 20 cm H2O (p less than 0.01). Benzilonium tended to have a similar effect, but the changes did not reach statistical significance (p = 0.06). Pouch contractility, as reflected by volume fluctuations and pressure changes during distension, was almost abolished by both drugs. Sensory thresholds for sense of filling and, particularly, urge were raised. Resting anal pressure was slightly lowered, whereas no significant effect was found on maximal squeeze pressure. In conclusion, anticholinergics appear to have specific properties of action on small-intestinal reservoirs, constituting possible explanations for the empirically observed beneficial effects of anticholinergic treatment of functional disturbances after restorative proctocolectomy.
    Scandinavian Journal of Gastroenterology 06/1991; 26(5):563-71. · 2.33 Impact Factor
  • B I Gustafsson, D S Delbro
    Pharmacology &amp Toxicology 03/1990; 66(2):155-6.
  • D Delbro, B I Gustafsson
    Acta Physiologica Scandinavica 06/1989; 136(1):143-4. · 2.55 Impact Factor
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    ABSTRACT: A method to study electrically induced distal colonic motility in the rat in vivo is reported. The animals were anaesthetized with methohexital and chloralose and were artificially ventilated. Motility of a segment (2 cm) of the distal colon was monitored as volume changes of an intraluminal balloon, introduced via the anus. Local electrical stimulation of the wall of the segment was achieved by means of a bipolar electrode folded around the gut. Stimulations produced reproducible contractile responses in a frequency dependent fashion. Stimulation characteristics resembled those of other autonomic neuro-effector systems. The adrenergic neuron-blocker, guanethidine, significantly lowered colonic tone, but had no other effects on spontaneous or electrically induced motility. Atropine significantly lowered colonic tone. After the administration of this compound the electrically induced contractions were significantly smaller with a shorter duration and, furthermore, appeared upon the cessation of stimulation ('off' or 'rebound' contraction). Following the administration of tetrodotoxin (TTX, given close i.a. via a cannula with its tip in distal aorta) basal colonic tone and the number of spontaneously occurring contractions increased. The amplitude and duration of the electrically induced responses were significantly attenuated and, furthermore, appeared as 'rebound' contractions which were preceded by a relaxation. Such TTX-resistant responses may be myogenic, but a neurogenic origin cannot be excluded. The present study showed that local electrical stimulation of the distal colon elicits cholinergic contractions, but also atropine- and TTX-resistant motor responses.
    Acta Physiologica Scandinavica 01/1989; 134(4):549-56. · 2.55 Impact Factor
  • B I Gustafsson, D S Delbro
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    ABSTRACT: Stimulation of the sectioned cervical vagal nerve of anaesthetized cats (ether-chloralose), pretreated with guanethidine and atropine, in the peripheral direction produced gastric relaxation as well as jejunal and ileal contraction. The administration of indomethacin markedly enhanced intestinal tone and the amplitude of spontaneous phasic activity while the basal gastric motility was essentially unchanged. This suggests that endogenous prostaglandins exert an inhibitory influence on intestinal motility. The vagally induced gastric relaxation was significantly inhibited by indomethacin, with could suggest that prostaglandins modulate non-adrenergic, non-cholinergic inhibitory neurotransmission in the stomach.
    European Journal of Pharmacology 03/1988; 147(1):67-72. · 2.59 Impact Factor
  • Regulatory Peptides - REGUL PEPTIDES. 01/1988; 22(4):408-408.
  • Acta Physiologica Scandinavica 10/1987; 131(1):155-6. · 2.55 Impact Factor
  • B Gustafsson, D Delbro
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    ABSTRACT: Experiments were performed on chloralose-anaesthetized cats, pretreated with guanethidine and with ligated adrenals and sectioned splanchnic nerves. The animals were paralysed and artificially ventilated. Jejunal motility was recorded by an intraluminal balloon, as volume changes at a constant pressure. Cervical or abdominal vagal afferent stimulation was performed before and after the administration of atropine. In both circumstances jejunal contractions were elicited. The latency of onset and the duration of the responses were significantly shorter before than after atropine. Strength-duration and frequency-response relationships, respectively, did not differ significantly prior and subsequent to atropine. Naloxone (0.05-0.5 mg kg-1 i.v.) blocked these reflexly induced atropine-resistant jejunal contractions, as did section of the contralateral vagus. Possible mechanisms of action of these putative opioid receptor-mediated neurogenic effects are discussed. The present study demonstrates that non-adrenergic, non-cholinergic, naloxone-sensitive jejunal contractions can be elicited as a vago-vagal reflex, where the receptive field seems to be located within the abdominal cavity.
    Acta Physiologica Scandinavica 10/1987; 131(1):19-24. · 2.55 Impact Factor

Publication Stats

461 Citations
123.59 Total Impact Points

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Institutions

  • 1987–1997
    • Sahlgrenska University Hospital
      Goeteborg, Västra Götaland, Sweden
  • 1982–1991
    • University of Gothenburg
      • • Department of Surgery
      • • Department of Physiology
      Göteborg, Vaestra Goetaland, Sweden