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Biomedical subjects

E Skadhauge

Publications and source records attributed to E Skadhauge.

At least 19 recordsLinked to original sources
PubMed2000

Regional differences in neurogenic signal transduction pathway of cholera toxin-induced fluid, electrolyte and serotonin accumulation in the porcine jejunum.

Serotonin, acetylcholine and substance P are mediators involved in the secretory response to cholera toxin in the small intestine. The aim of this study was to investigate the regional difference in the effect of a serotonin receptor type 3 antagonist (ondansetron), a nicotinic receptor antagonist (hexamethonium), and a substance P antagonist (the neurokinin receptor type 1 antagonist, CP 99,994) on the cholera toxin-induced fluid accumulation in the porcine jejunum. A dose-range of cholera toxin (0.32-56.00 microg/loop) was instilled for 4 hr in ligated loops in two regions of the proximal jejunum in 6-8-week-old pigs. Ondansetron (200 microg/kg), hexamethonium (10 mg/kg), CP 99,994 (1 mg/kg), or saline alone (control) were given intravenously 10 min. before cholera toxin instillation. Cardiovascular parameters, blood gas data, net fluid accumulation, serotonin and electrolyte concentration in the accumulated fluid were measured. Cardiovascular and blood gas parameters were within the normal range in all treatments. The apparent maximal response in fluid accumulation was reduced 20% in case of ondansetron, and by 33% using CP 99,994 in the aboral region compared to control, whereas no effect was observed in the oral region. Hexamethonium reduced the apparent maximal secretory response in both the oral and aboral regions by 45%. None of the treatments with antagonists changed the luminal content of serotonin or the electrolyte concentrations in the accumulated fluid. The results demonstrate that the involvement of serotonin receptor type 3 and neurokinin type 1 receptors in the transductional pathway of cholera toxin-induced fluid accumulation vary significantly within the jejunum, while the cholinergic (nicotinic) transmission plays an even role.

Animals↗
PubMed1999

Differences in epithelial morphology correlate to Na(+)-transport: a study of the proximal, mid, and distal regions of the coprodeum from hens on high and low NaCl diet.

A study was performed to correlate regional morphology and amiloride inhibitable Na(+)-transport in the coprodeal epithelium in hens, Gallus domesticus, on low-NaCl diet and in controls. Proximal (close to colon), mid and distal (close to urodeum) regions were examined using light microscopy, transmission- and scanning electron microscopy. Na(+)-transport was measured electrophysiologically in Ussing-chambers in the proximal and distal regions. The epithelium, simple and columnar, is composed of absorptive intestinal epithelial cells, goblet cells, brush cells, migrating lymphoid cells, and enteroendocrine cells. Brush cells, identified in avians for the first time, occur in highest number in the proximal part of the coprodeum in low-NaCl hens. Na(+)-transport is high in the low-NaCl hens, ranging from 347 microA/cm2 (proximal) to 187 microA/cm2 (distal). In control hens, which correspond to hens on high-NaCl diet, it is low in all regions (0-4 microA/cm2). Absorptive intestinal epithelial cells as well as brush cells adapt to variations in transepithelial Na(+)-transport by regulating height and packing density of their microvilli, number, size, and localization of apical vesicles, and the width of the intercellular space. Regional differences in the epithelial cell composition and ultrastructure are closely correlated to transepithelial Na(+)-transport but only in low-NaCl hens, as controls do not show these variations.

Animals↗
PubMed1999

Ruminal transport and metabolism of short-chain fatty acids (SCFA) in vitro: effect of SCFA chain length and pH.

The unidirectional transport and metabolism of 14C-labeled acetate, propionate and butyrate across the isolated bovine rumen epithelium was measured in vitro by the Ussing chamber technique. There was a significant, but relatively small, net secretion of acetate and propionate, and a large and significant net absorption of butyrate. The results demonstrate that the mucosal-serosal (MS) pathway for short-chain fatty acids (SCFA) is different from the serosal-mucosal (SM) pathway, and that butyrate is treated differently from acetate and propionate by the epithelium. The results support that the main route for epithelial SCFA transport is transcellular. The correlation between SCFA lipophility and the flux rate was positive but weak at both pH 7.3 and 6.0. Decreasing pH increased all SCFA fluxes significantly, but not proportionally to the increase of protonized SCFA in the bathing solution. There was a significant and apparently non-competitive interaction between the transport of acetate, propionate and butyrate. It seems that mediated transport mechanisms must be involved in epithelial SCFA transport in the bovine rumen, but the data do not exclude that passive diffusion could account for a significant part of the flux. The metabolism of SCFA in the Ussing chamber system was considerable, and there was a clear preference for excretion of CO2 from this metabolism to the mucosal side, while side preference for non-CO2 metabolite excretion was not studied. Of the propionate and butyrate transported in the MS direction, 78 and 95% was metabolised, while only 37 and 38% was metabolised in the SM direction (acetate metabolism could not be measured). There was, however, no simple relation between the degree of metabolism and the transport rate or the transport asymmetry of the SCFA.

Animals↗
PubMed1999

Effect of age on vasoactive intestinal polypeptide-induced short-circuit current in porcine jejunum.

Vasoactive intestinal polypeptide is a transmitter at the neuroepithelial junction of the small intestine in cholera toxin-induced secretion. We investigated whether the secretory effect in vitro of vasoactive intestinal polypeptide in porcine jejunum was changed with age. Stripped tissue preparations from three age groups, neonatal (7-11 days), young (6-8 weeks) and adult (13-15 weeks) pigs, were mounted in Ussing chambers and short-circuited. Vasoactive intestinal polypeptide produced concentration dependent increases in short-circuit current in all three age groups with EC50 values (in nM) of 14.5 +/- 1.9, 16.2 +/- 2.0 and 147 +/- 0 in neonatal, young and adult pigs, respectively. The peak increases in short-circuit current in adult pigs were significantly decreased compared with the other two age groups. To evaluate the secretory capacity, theophylline was added to tissue preparations in which baseline short-circuit current again was established. Theophylline caused a significantly lesser increase in short-circuit current in adult pigs (25.4 +/- 2.0 microA.cm-2) than neonatal (57.1 +/- 3.6 microA.cm-2) and young pigs (63.1 +/- 2.9 microA.cm-2). In conclusion, vasoactive intestinal polypeptide showed a marked decrease in the secretory response with age in porcine jejunum, at least partly caused by a reduced secretory capacity of the enterocytes.

Aging↗
PubMed1999

Transport of butyrate across the isolated bovine rumen epithelium--interaction with sodium, chloride and bicarbonate.

The Ussing chamber technique was used for studying unidirectional fluxes of 14C-butyrate across the bovine rumen epithelium in vitro. Significant amounts of butyrate were absorbed across the bovine rumen epithelium in vitro, without any external driving force. The paracellular pathway was quantitatively insignificant. The transcellular pathway was predominately voltage-insensitive. The serosal to mucosal (SM) pathway was regulated by mass action, whereas the mucosal to serosal (MS) pathway further includes a saturable process, which accounted for 30 to 55% of the MS flux. The studied transport process for 14C-butyrate across the epithelium could include metabolic processes and transport of 14C-labelled butyrate metabolites. The transport of butyrate interacted with Na+, Cl- and HCO3-, and there was a linear relationship between butyrate and sodium net transport. Lowering the sodium concentration from 140 to 10 mmol l-1 decreased the butyrate MS flux significantly. Amiloride (1 mmol l-1) did, however, not reduce the butyrate flux significantly. Chloride concentration in itself did not seem to influence the transport of butyrate, but chloride-free conditions tended to increase the MS and SM flux of butyrate by a DIDS-sensitive pathway. DIDS (bilateral 0.5 mmol l-1) did further decrease the butyrate SM flux significantly at all chloride concentrations. Removing bicarbonate from the experimental solutions decreased the MS and increased the SM flux of butyrate significantly, and abolished net butyrate flux. There were no significant effects of the carbonic anhydrase inhibitor Acetazolamide (bilateral 1.0 mmol l-1). The results can be explained by a model where butyrate and butyrate metabolites are transported both by passive diffusion and by an electroneutral anion-exchange with bicarbonate. The model couples sodium and butyrate via CO2 from metabolism of butyrate, and intracellular pH.

Animals↗
PubMed1999

Effects of dietary substitution with raw and heat-treated cowpea (Vigna unguiculata) on intestinal transport and pancreatic enzymes in the pig.

Tropical grain legumes represent potentially important feed for farm animals. However, diarrhoea and poor growth performance have been reported, due to the various anti-nutritional factors they contain. This study addressed in particular whether dietary cowpea impaired the growth of pigs, whether the small intestinal Na+/D-glucose coabsorptive transport capacity was decreased, whether the Cl- secretory capacity was increased, and, finally, whether these parameters were affected by heat treatment of cowpea. Pigs, 4 weeks old, were fed for 3 weeks with one of three diets: (i) standard soy, (ii) 75% of soy substituted with raw cowpea, or (iii) 75% of soy substituted with heat-treated cowpea. The absorptive and secretory capacities of the jejunum and ileum were measured with the Ussing chamber technique. Weight gain, feed intake, pancreatic protein and enzyme concentrations and levels of the blood hormones glucagon and cholecystokinin were also measured. The Na+ transport capacity was measured as the increase in short-circuit current (Isc) when D-glucose was added to the luminal side in the Ussing chambers. Isc was significantly higher in the jejunum from raw cowpea-fed pigs than in the jejunum from standard soy-fed pigs, with no difference between the two cowpea-fed groups. The phosphodiesterase inhibitor theophylline was subsequently added bilaterally, and the increase in Isc indicated the cAMP-depedent Cl- secretory capacity. In the jejunum this was significantly higher in raw and heat-treated cowpea-fed pigs than in standard soy-fed pigs. In contrast, there were no differences in the ileal transport capacities. There were no differences in the pancreatic protein and trypsin concentrations or the blood hormones, but the raw cowpea-fed pigs had significantly lower pancreatic amylase than standard soy-fed pigs. Weight gain and feed intake were lowest in the cowpea-fed groups, with no significant difference between the two groups. In conclusion, the hypothesis of impaired small intestinal absorption of D-glucose and Na+ as causing malabsorption, and therefore impaired growth, during cowpea substitution in the feed may be firmly rejected. The increased Cl- secretory capacity, although moderate, may contribute to the higher incidence of post-weaning diarrhoea in cowpea-fed pigs, as observed in other studies. Additionally, the decreased food intake, feed conversion and weight gain were unaffected by heat treatment, further suggesting involvement of heat-stable anti-nutritional factors.

Animal Feed↗
PubMed1998

Functional characterisation of tachykinin receptors mediating ion transport in porcine jejunum.

In the present study, tachykinin receptors (designated NK 1, NK2 and NK3) involved in regulation of ion transport in porcine jejunum were characterised. Stripped tissue preparations were mounted in Ussing chambers and short-circuited. Substance P produced a concentration dependent increase in short-circuit current, the relationship showing a double sigmoidal form. The non-peptide NK1 receptor antagonist, CP 99,994 ((2S,3S)-3-(2-methoxybenzyl)amino-2-phenylpiperidine), caused a dextral shift of the first sigmoidal response, indicating the involvement of an NK1 receptor. This was further supported by a concentration-dependent response of the NK1 receptor agonist [Sar9Met(O2)11]substance P with an EC50 value of 235.0+/-53.9 nM. Increasing concentrations of CP 99,994 (0.1, 0.3 and 1 microM) produced a parallel dextral shift of the [Sar9Met(O2)11]substance P curve with a slope of the Schild regression significantly different from unity (1.59). The neurokinin A concentration-response curve, with an EC50 value of 68.87+/-16.23 nM, was not significantly changed by the non-peptide NK2 receptor antagonist SR 48,968 ((S)-N-methyl-N-(4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichlorophe nyl)butyl)bezamide). In additional studies, the peptide NK2 receptor antagonists, GR 94,800 (PhCO-Ala-Ala-DTrp-Phe-DPro-Pro-NleNH2) and PD 147,714 ((2,3-diOMeZ)-(S)Trp(S)alphaMePheGlyNH2), did not change the response to neurokinin A. However, CP 99,994 totally inhibited neurokinin A responses at 0.5 microM and above. The NK2 receptor agonist, [beta-Ala8]neurokinin A-(4-10), caused only an increase in short-circuit current in microM concentrations, whereas the NK3 receptor agonist, senktide, did not elicit a response. These results indicate, that substance P and neurokinin A mediate ion transport in porcine jejunum through NK1 receptors. However, tachykinins seem to activate another receptor. Two active conformers of the NK1 receptor might be present.

Animals↗
PubMed1998

Tachykinins mediate changes in ion transport in porcine jejunum through release of prostaglandins and neurotransmitters.

In the present study, we investigated the mediators involved in substance P (SP) and neurokinin A (NKA) induced ion transport. Stripped preparations of porcine jejunal tissue were mounted in Ussing-chambers and short-circuited. The cyclo-oxygenase inhibitor, piroxicam (10 microM) and the neuronal conduction blocker, tetrodotoxin (TTX) (0.1 microM) both significantly decreased the SP (0.1 microM) (66% and 36%, respectively) and NKA (1 microM) (64% and 31%, respectively) induced increase in short-circuit current (SCC). Pretreatment with both piroxicam and TTX totally abolished the SP and NKA response. SP (0.1 microM) caused a significant release of prostaglandin E2 (PGE2), whereas the release of PGE2 induced by NKA was not significant. Experiments were performed to clarify if vasoactive intestinal polypeptide (VIP) was mediating SP or NKA responses. VIP caused a TTX-insensitive and a concentration-dependent increase in SCC. Two VIP antagonists did not change the response to VIP (10 nM and 0.1 microM). Thus, these antagonists could not be used to further elucidate the role of VIP. We were unable to measure a significant release of VIP after SP or NKA treatment. These results indicate, that SP and NKA regulate ion transport in porcine jejunum, entirely through the release of prostaglandins and enteric neurotransmitters.

Animals↗
PubMed1998

Morphological adaptations to induced changes in transepithelial sodium transport in chicken lower intestine (coprodeum): a study of resalination, aldosterone stimulation, and epithelial turnover.

Transepithelial sodium transport and epithelial morphology during short-term adaptation to resalination or aldosterone stimulation were studied in the chicken coprodeum. Coprodeum was sampled for light and electron microscopy after 0-3 days of resalination in hens on a low-NaCl diet and after 0-6 days of aldosterone stimulation in hens on a high-NaCl diet. Sodium transport was measured in vitro with Ussing chambers. Plasma osmolality and electrolyte concentrations were measured in aldosterone-stimulated hens. Epithelial proliferation and migration between 1 h and 16 days were investigated in chickens on high-NaCl and low-NaCl diets using a bromodeoxyuridine technique. Resalination abolished the otherwise high sodium transport within 1 day, while the height and number of microvilli, as well as the number of brush cells, decreased over 3 days. Aldosterone stimulation increased sodium transport, the height and number of microvilli, and the brush-cell number. Bromodeoxyuridine studies indicated an epithelial cell turnover of more than 16 days. The results thus demonstrate that epithelial cells have an unusual capacity to adjust rap- idly to variations in sodium intake. A strong correlation between structure and function was apparent.

Aldosterone↗
PubMed1998

The organisation of the enteric nervous system in the submucous and mucous layers of the small intestine of the pig studied by VIP and neurofilament protein immunohistochemistry.

The arrangement of the enteric ganglia and nerve fibre plexuses was examined in the submucous and mucous layers and around Peyer's patches of the porcine small intestine to clarify their organisation. Immunohistochemistry of vasoactive intestinal peptide (VIP) and neurofilament proteins in wholemounts, chopped or paraffin sections was used to locate the neural elements. The ganglia of the internal and external submucous plexuses were situated at 2 different topographic locations, being clearly demarcated by the submucosal vascular arcades and differing in neuronal composition. The internal submucous plexus was the only contributor to the plexus surrounding the follicles of Peyer's patches as a continuous mesh of 3 ganglionated nerve subplexuses. VIP-immunoreactive fibres from this mesh innervated the dome. The mucosal plexus, which was subdivided into 4 subunits--the outer proprial, inner proprial, pericryptal and villous plexuses--contained a few solitary neuronal perikarya. Labelling for neurofilament proteins revealed Dogiel types II, IV and VI neurons. The observations reveal several new features in the enteric nervous system of the pig and clarify its nomenclature.

Animals↗
PubMed1998

Secretory pathways in Salmonella Typhimurium-induced fluid accumulation in the porcine small intestine.

The involvement of 5-hydroxytryptamine (5-HT) and 5-HT3 receptors and prostaglandin E2 (PGE2) in Salmonella Typhimurium-induced fluid accumulation in the porcine small intestine was investigated. Salmonella Typhimurium (10(8) and 10(10) cfu) and cholera toxin (CT; 20 microg) were instilled for 8 and 11 h in ligated loops in the porcine jejunum and ileum. Fluid accumulation and concentrations of Na+, K+, Cl-, 5-HT and PGE2 in the fluid accumulated in the loops were measured. The fluid accumulation was also measured when Salmonella Typhimurium (10(10) cfu) and CT (20 microg) were instilled for 8 h in ligated loops in jejunum and ileum in pigs given subcutaneous injections of saline or the 5-HT3 receptor antagonist ondansetron (200 microg/kg). Salmonella Typhimurium (10(10) cfu) and CT both induced fluid accumulation in jejunum and ileum after 8 and 11 h. Both treatments also induced an increase in luminal release of 5-HT and PGE2. The accumulated fluid was iso-osmotic and hyperosmotic in CT- and Salmonella Typhimurium-treated loops, respectively. Ondansetron reduced the Typhimurium-induced fluid accumulation in both jejunum and ileum by c. 40%, while it failed to reduce the response to CT. These results demonstrate that 5-HT and PGE2 are released and 5-HT3 receptors activated in the secretory pathway of Typhimurium in the porcine small intestine.

Analysis of Variance↗
PubMed1998

Regional differences in the effect of cholera toxin and enterotoxigenic Escherichia coli infection on electrolyte and fluid transport in the porcine small intestine.

The regional differences in secretory and absorptive responses to cholera toxin (CT) and to infection by enterotoxigenic Escherichia coli (ETEC), producing heat-stable enterotoxins, were studied in the porcine small intestine. Proximal, mid and distal small intestine from newly weaned piglets were used. Na+ and Cl- fluxes and electrical parameters in CT-stimulated and ETEC-infected intestine were measured by the Ussing chamber technique. In addition, CT-induced fluid accumulation in ligated loops was measured. CT induced fluid accumulation, which was highest in the proximal segment and decreased in the aboral direction of the small intestine. In addition, CT induced a net Cl- secretion in the proximal and mid segments, while net Na+ absorption was reduced only in the proximal segment. The ETEC-infected intestine showed a net increase in Cl- secretion in the proximal part and abolished the net Na+ absorption in the distal segment. These results demonstrate segmental differences in the epithelial transport responses to enterotoxin from Vibrio cholerae and to ETEC infection. This needs to be taken into consideration in relation to oral rehydration studies.

Animals↗
PubMed1998

Secretory response to cholera toxin in the porcine jejunum under different types of general anaesthesia.

Investigations of intestinal secretion are often performed under anaesthesia. This study evaluates the influence of anaesthetic agents on the intestinal secretion induced by cholera toxin (CT) in the pig. CT was instilled for 4 h in ligated jejunal loops under anaesthesia with halothane, saffan, alpha-chloralose, or propofol. Cardiovascular parameters, blood gas data, plasma cortisol levels, net fluid accumulation, intraluminal mediators (serotonin (5-HT), prostaglandin E2 (PGE2)) and electrolyte concentrations in the accumulated fluid were determined. The systolic blood pressure and heart rate was highest for saffan-anaesthetized pigs (blood pressure: saffan > alpha-chloralose > propofol = halothane; heart rate: saffan > alpha-chloralose = propofol = halothane), while blood gases and cortisol levels were within the same range. CT induced a dose-dependent fluid accumulation under all four anaesthetics. The fluid accumulation was significantly higher in pigs treated with saffan, alpha-chloralose and propofol than in halothane-treated pigs (saffan = alpha-chloralose > propofol > halothane). There was no significant difference in electrolyte concentrations in the accumulated fluid or in the luminal content of 5-HT and PGE2 between anaesthetics. The results demonstrate that anaesthetic agents profoundly influence the secretory response in the small intestine and indicate the importance of the choice of anaesthetic in this type of experiment.

Anesthetics↗
PubMed1997

Electrophysiological properties of neurones in the internal and external submucous plexuses of newborn pig small intestine.

1. Intracellular microelectrodes were used to identify three major electrophysiological categories of neurone in both the internal and external submucous plexuses of the porcine small intestine. 2. Two classes of neurone with a long-lasting after-hyperpolarization following their action potential were differentiated by the presence or absence of fast excitatory synaptic inputs (EPSPs) and were termed AH neurones. S neurones received fast EPSPs but did not display after-hyperpolarizations. 3. The mean resting membrane potentials of the three groups of neurones showed a similar trend in both plexuses, with significantly higher values for the two populations of AH neurone than for S neurones. No significant variation of input resistance with cell type was detected. Neuronal input resistance was significantly greater in the internal submucous plexus than in the external submucous plexus. 4. Over 80% of AH neurones in the internal submucous plexus displayed fast EPSPs but a similar percentage of AH neurones in the external submucous plexus did not show fast EPSPs. S neurones constituted 60% of cells studied in the internal submucous plexus but less than 30% of the cell population in the external submucous plexus. 5. This study of porcine submucous neurones has revealed both similarities and differences to previous work in the guinea-pig small intestine. The most contrasting features are the relative abundance and subclassification of AH neurones in the pig in addition to the apparent paucity of slow synaptic potentials. The differences in the neuronal profiles of the internal and external submucous plexuses may reflect a differentiation of function between the two enteric nerve networks.

Animals↗
PubMed1997

The stress of not being able to perform dustbathing in laying hens.

The stress of not being able to perform dustbathing was studied in small groups of laying hens. The birds were reared and kept for 2.5 years in cages with either sand ("sand birds") or wire floors ("wire birds"), and subsequently deprived of sand (sand birds) or given access to sand (wire birds). Before this change, wire birds had a higher incidence of unilateral wing/leg stretching and stereotypic pecking compared to sand birds; however, there was no difference in corticosterone concentrations. Deprivation of sand in the sand birds resulted in a total absence of dustbathing and in a significant increase in corticosterone concentrations. Although the wire birds dustbathed on the wire before the change of floors, there was a significant increase in the incidence of dustbathing after sand was provided, but no changes in the concentrations of corticosterone. Threats and allopecks decreased in the wire birds after access to sand, whereas no changes were found in the sand birds. Stereotypic pecks on feathers were absent in the sand birds, but were frequent in most of the wire birds both before and after they were given sand. Also, in the wire birds, all feather pecking (stereotypic and nonstereotypic) was positively correlated with the concentration of corticosterone, and this kind of pecking may, thus, be an expression of stress in laying hens. We conclude that the nonperformance of dustbathing behavior is associated with the experience of stress.

Animals↗
PubMed1997

Effect of ondansetron on Salmonella typhimurium-induced net fluid accumulation in the pig jejunum in vivo.

Two major pathophysiological mechanisms explaining the diarrhoea induced by Salmonella typhimurium have been suggested to be: (a) invasion of the intestine by the bacteria, and (b) an enterotoxin resembling Vibrio cholerae toxin. Cholera toxin is a potent secretagogue in pig small intestine and induces secretion partly by activating 5-hydroxytryptamine receptors, following release of 5-hydroxytryptamine. Ondansetron is a selective 5-hydroxytryptamine-3 receptor antagonist, which reduces the cholera toxin-evoked fluid accumulation in pig jejunum. The aim of this study was to investigate the effect of ondansetron on Salmonella typhimurium-induced fluid accumulation in ligated loops of pig jejunum in vivo. 10(10) colony-forming units of the bacteria was injected into loops and incubated for 8 hr. 200 mg x kg-1 ondansetron given subcutaneously reduced the Salmonella typhimurium-induced fluid accumulation by about 40%. This results suggests the involvement of 5-hydroxytryptamine and 5-hydroxytryptamine-3 receptors in Salmonella typhimurium-induced diarrhoea.

Animals↗