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A Tøttrup

Publications and source records attributed to A Tøttrup.

36 records · Page 2Linked to original sources
PubMed1992

Action profiles of nitric oxide, S-nitroso-L-cysteine, SNP, and NANC responses in opossum lower esophageal sphincter.

Circular muscle strips from opossum lower esophageal sphincter were suspended in organ baths for measurement of isometric tension. Nonadrenergic noncholinergic (NANC) inhibitory nerves were stimulated by means of transmural field stimulation. This induced frequency-dependent relaxations of the muscle strips. Methylene blue (3 x 10(-6) M; inhibits guanylate cyclase) and pyrogallol (10(-4) M; generates superoxide anions) had no influence on relaxations, whereas oxyhemoglobin [10(-5) M; binds nitric oxide (NO) and other nitroso compounds extracellularly] inhibited relaxations at all frequencies. NO concentration dependently relaxed the muscle strips. Pyrogallol (10(-4) M) and methylene blue (3 x 10(-6) M) inhibited and oxyhemoglobin (10(-5) M) nearly abolished relaxation induced by NO. S-nitroso-L-cysteine caused concentration-dependent relaxations of the muscle strips, which were inhibited by pyrogallol (10(-4) M), whereas methylene blue (3 x 10(-6) M) augmented the action of S-nitroso-L-cysteine. Methylene blue (3 x 10(-6) M) had no influence on the concentration-dependent relaxations caused by sodium nitroprusside (SNP). Oxyhemoglobin (10(-5) M), and to a lesser extent pyrogallol (10(-4) M), both inhibited the effects of SNP. The action profiles for S-nitroso-L-cysteine, NO, and SNP differed from the action profile for NANC nerve-mediated response. Although pyrogallol inhibited the effects of SNP, the action profile generally resembled the action profile for NANC responses more closely than did the profiles for S-nitroso-L-cysteine or NO. In conclusion, of the nitroso compounds studied, SNP most closely resembled the response to NANC nerve stimulation. Neither NO nor S-nitroso-L-cysteine individually mimicked the NANC response.

Animals↗
PubMed1991

Motility regulating effects of galanin on smooth muscle of porcine ileum.

We studied the effect of synthetic porcine galanin on circular and longitudinal oriented strips of pig ileal muscle. Galanin 10(-11)-10(-6) M had no effect on resting tension in the two layers. In circular muscle precontracted with carbachol 10(-6) M, galanin dose-dependently inhibited the amplitude of contractions to a maximum of 33 +/- 8% at 10(-6) M. In longitudinal muscle the amplitude of contractions induced by carbachol 10(-7) M or transmural field stimulation increased after addition of galanin 10(-9)-10(-7) M to a maximum of 21 +/- 6%, while at higher concentrations inhibition occurred. Maximal inhibition was 36 +/- 14% at galanin 10(-6) M. Tetrodotoxin did not influence the effects of galanin in the preparations. The results indicate that in the homologous species galanin inhibits the circular muscle layer, possibly by a direct action on the smooth muscle. In the longitudinal muscle the effect of galanin is apparently excitatory. The inhibition observed with high concentration of galanin could be due to tachyphylaxis and desensitization. Alternatively, an additional population of low affinity, inhibitory receptors may exist.

Animals↗
PubMed1991

The role of the L-arginine-nitric oxide pathway in relaxation of the opossum lower oesophageal sphincter.

1. The role of the L-arginine-nitric oxide pathway in lower oesophageal sphincter (LOS) relaxation and oesophageal peristalsis was investigated. 2. Twenty four adult opossums were anaesthetized and the right vagus nerve was isolated in the neck and sectioned. Electrical stimulation, applied to the peripheral end of the nerve, resulted in a frequency-dependent relaxation of the LOS, and peristaltic and non-peristaltic contractions in the oesophageal body. 3. N omega-nitro-L-arginine (L-NNA, 10(-8)-10(-5) mol kg-1), an inhibitor of the L-arginine-nitric oxide pathway, inhibited LOS relaxation in a dose-dependent manner, but did not affect resting LOS pressure. At the highest dose of L-NNA no relaxation of the LOS was elicited in response to vagal stimulation. The effect of L-NNA, (10(-5) mol kg-1) was fully reversed by infusion of 10(-4) mol kg-1 L-arginine. Peristaltic velocity and amplitude of contractions in the oesophageal body were unaffected by L-NNA. 4. Infusion of sodium nitroprusside reduced LOS pressure to zero, and the drug was equally potent in control animals (-log ED50:8.1 +/- 0.2 mol kg-1) and in animals pretreated with L-NNA (-log ED50:8.2 +/- 0.3 mol kg-1). This suggests that the effect of L-NNA was not directly on guanylate cyclase. 5. A significant elevation of blood pressure was recorded after administration of L-NNA (10(-5) mol kg-1). 6. It is suggested that the L-arginine-nitric oxide pathway plays an important functional role for relaxation of the LOS, but not for oesophageal peristalsis. Whether the active substance is nitric oxide or a related nitroso-compound remains to be settled.

Animals↗
PubMed1991

Mechanical properties of isolated human oesophageal submucosal veins.

The mechanical properties of isolated human oesophageal submucosal veins were investigated. The veins were without tone or spontaneous activity and possessed a high compliance, tolerating a stretch of several hundred per cent of the length at which the vessels were first able to contract with only minor increases in passive tension. The veins were capable of producing active tension when the length exceeded 30% of L0 (the length at which maximum wall tension (T0) was developed when activated by 124 mM K(+)-solution). The veins from the oesophageal body (OB) had a higher L0 than the veins from the gastrooesophageal junction (GOJ) (1180 microns vs 820 microns) and T0 was correspondingly higher (1.1 mN/mm vs. 0.6 mN/mm). However, there was no significant difference in the calculated effective transmural pressure (P) at the two locations. Noradrenaline induced contractions in all preparations tested with a maximum response equivalent to the tension achieved after stimulation with 124 mM K(+)-solution, pD2 values for noradrenaline in vessels from the oesophageal body and the gastroesophageal junction were 7.03 +/- 0.28 (mean +/- SEM) and 7.15 +/- 0.20, respectively. The present model seems suitable for future studies of human oesophageal submucosal veins from the oesophageal body and the gastrooesophageal junction.

Adult↗
PubMed1991

Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter.

Strips from opossum lower esophageal sphincter were prepared and mounted in organ baths for recording of isometric tension. Nonadrenergic, non-cholinergic (NANC) inhibitory responses were evoked by transmural field stimulation. The relaxant responses to field stimulation were inhibited in a concentration-dependent manner by N omega-nitro-L-arginine (L-NNA), a substance known to inhibit the formation of nitric oxide (NO). At a concentration at 10(-4) M of L-NNA, most preparations contracted during field stimulation, and this response was abolished by atropine (10(-6) M). L-Arginine (10(-5) M) shifted the concentration-response curve for L-NNA to the right. Relaxant responses to VIP (10(-9) to 10(-6)M) and sodium nitroprusside (10(-9) to 10(-5) M) were unaffected by preincubation with L-NNA (10(-5) to 10(-4) M) or L-arginine (10(-5) M). The inhibition of NANC-relaxation was apparently not due to an influence on release of a NANC transmitter different from NO, since L-NNA had no preserving effects on responses to field stimulation in preparations treated with scorpion venom. We conclude that involvement of a NO-generating process from L-arginine seems mandatory for NANC responses in the isolated lower esophageal sphincter.

Animals↗
PubMed1991

Importance of the L-arginine-nitric oxide pathway in NANC nerve function of the opossum esophageal body.

Circular muscle strips from the opossum esophageal body obtained 3-5 cm above the esophagogastric junction were suspended in organ baths for measurement of isometric tension. Stimulation of nonadrenergic, noncholinergic (NANC) inhibitory nerves was performed using transmural field stimulation (TMS). During TMS, no mechanical response was elicited. After cessation of the stimulus a short period, also without mechanical response, intervened, and this period is called latency. The latency was followed by the 'off'-contraction. In control preparations, the latency and the amplitude of the 'off'-contraction were 1.47 +/- 0.17 s, and 3.8 +/- 0.9 mN, respectively. The inhibitor of the L-arginine-nitric oxide (NO) pathway, NG-nitro-L-arginine (L-NNA) concentration-dependently reduced the latency at concentrations greater than 10(-6) M (n = 6-7). At the highest concentration of L-NNA (10(-4) M), 'off' contractions were no longer seen. In 5 out of 7 preparations exposed to L-NNA (10(-4) M), a small contraction was seen during stimulation, and this contraction was abolished by atropine (10(-6) M) in all strips. L-NNA concentration-dependently reduced the amplitude of contractions at concentrations greater than 10(-6) M (n = 6-7). At 10(-4) M, the amplitude was reduced to 3 +/- 2% of that of the initial contraction. Preincubation with L-arginine (10(-5) M) had no influence on the latency. The effects of L-NNA on both latency and the amplitude of contraction were antagonized by preincubation with L-arginine (10(-5) M). Atropine (10(-6) M had no effect on the amplitude of the 'off'-contraction in control preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1991

Mechanical properties of isolated smooth muscle from rabbit sphincter of Oddi and duodenum.

Isolated smooth muscle from rabbit sphincter of Oddi (SO) and duodenum were mounted in organ baths. The SO strips were obtained as transversal strips from the midsection of the SO. The duodenal strips were prepared as longitudinal (Dl) or circumferential (Dc) strips. Resting length was defined. Carbachol was used for activation of the contractile apparatus. By repeatedly increasing the length of the strips by 20% of the resting length and recording values of resting and active tension, length-tension relations for each muscle type were constructed. None of the strips developed active resting tension. Twelve of the Dl strips (75%) developed spontaneous contractions versus four of the Dc strips (10%) and one of the SO strips. The strips eventually reached a length (Lo) at which further elongation gave no additional increase in active tension development. The Lo from the Dc strips differed significantly from SO Lo (p greater than 0.02) and Dl Lo (p less than 0.02), indicating structural differences. SO Lo and Dl Lo did not differ significantly. Differential extension of these tissues should be applied in future experiments on smooth muscles from this area.

Animals↗
PubMed1990

[Treatment of esophageal achalasia].

Achalasia is a motor disease of the oesophagus which can be treated surgically (myotomy), medically or by dilatation. After myotomy satisfactory results are obtained in 84%-95% of the patients. Unacceptable results are due primarily to gastro-oesophageal reflux, inadequate or healed myotomy. Dilatation provide good results in about 70% but generally repeated dilatation is required. The remaining 30% can usually be treated surgically. Dilatation is complicated by perforation in about 3% of the patients, but reflux is not as frequent as after myotomy. At present medical treatment is only indicated temporarily prior to dilatation or surgery. Surgical treatment is recommended for patients with contemporary delayed gastric emptying, hiatal hernia, vigorous achalasia, epiphrenic diverticula and for children with achalasia. For the remaining patients both methods can be used but after 2-3 dilatations myotomy is recommended.

Dilatation↗
PubMed1990

The actions of some beta-receptor agonists and xanthines on isolated muscle strips from the human oesophago-gastric junction.

Isolated preparations from the circular muscle layer of the human oesophago-gastric junction were mounted in organ baths and isometric tension recorded. During an equilibration period, active resting tension developed suggesting that the preparations were representing the lower oesophageal sphincter. Active tension was abolished by exposing the preparations to Ca(++)-free medium. The two xanthines theophylline and enprofylline almost equipotently relaxed the preparations in a concentration-dependent manner (10(-7)-10(-3) M). Within therapeutic concentrations, theophylline inhibited active resting tension by 30-60%, while enprofylline lowered tension by less than 20%. Inhibitory actions of adenosine were demonstrated, and this suggests that adenosine antagonism is not the mechanism of action for xanthines in the oesophagus. Non-selective beta-receptor stimulation with isoprenaline inhibited active tension by 70% (10(-7) M), while beta 2-receptor stimulation with terbutaline inhibited tension by 47% (10(-5) M). Dobutamine, believed to preferentially stimulate beta 1-receptors, inhibited active tension in a concentration-dependent manner (10(-7)-10(-4) M). Metoprolol (10(-6) M), a selective beta 1-receptor antagonist, shifted the concentration-response curve for isoprenaline to the right, but left the maximal response unchanged. It is concluded that xanthines and beta-receptor agonists have inhibitory actions on circular muscle from the human oesophagogastric junction. The experimental data suggest the presence of beta 1- as well as beta 2-receptors, both mediating inhibition of active resting tension.

Adenosine↗
PubMed1990

Mechanical properties of isolated human esophageal smooth muscle.

Isolated smooth muscle strips from the human esophagus representing both the longitudinal and circular layers of the esophagogastric junction and the esophageal body were prepared. The strips were mounted in organ baths, and resting length was defined. By repeatedly increasing the length of the strips with 20% of resting length and recording values of resting and active tensions, length-tension relations for each muscle type were constructed. Only circular strips from the esophagogastric junction developed active, resting tension, disclosed by replacing the normal Ca2(+)-containing Krebs solution with Ca2(+)-free medium. Carbachol (10(-6) M) was used for submaximal activation of the contractile apparatus. At lengths between 180 and 260% of resting length, all strips reached optimum length (LO) where further elongation gave no further increase in active tension development. Repeated stimulations with carbachol was possible at a length of 200% of LO without affecting reproducibility. Determination of different collagen components revealed no differences between muscle types.

Calcium↗
PubMed1990

Effects of transmural field stimulation in isolated muscle strips from human esophagus.

Smooth muscle strips representing longitudinal and circular muscle layers of the esophagogastric junction (EGJ) and esophageal body (EB) of the human esophagus were prepared. The strips were mounted in organ baths and isometric tension was recorded. Square wave stimulation was applied through platinum electrodes. Only responses abolished by tetrodotoxin (TTX) were considered neurogenic. Strips taken from longitudinal muscle layers of the EB and EGJ contracted during field stimulation. The responses evoked were abolished by atropine, and optimal frequency of stimulation was 40 Hz. In strips taken from the circular muscle layer of the EB, a contraction occurred after cessation of the stimulus. Atropine inhibited 90% of this response; the optimal stimulation frequency was 40 Hz. When a tone was induced in strips from this layer, a TTX-sensitive relaxation was seen during field stimulation. During stimulation of strips from the EGJ circular muscle layer, which was the only preparation developing spontaneous active tone, a relaxation was seen. A small contraction followed after termination of the stimulus. The relaxation, which was nonadrenergic, noncholinergic, reached maximum at 10 Hz. Atropine inhibited 40% of the contraction. The results suggest that in the longitudinal muscle layer of the human lower esophagus field stimulation causes postganglionic nerves to release transmitter(s) acting on muscarinic receptors. The responses of circular muscle layers seem to be mediated through release of at least two transmitters.

Atropine↗
PubMed1989

Severe destruction of esophageal nerves in a patient with achalasia secondary to gastric cancer. A possible role of eosinophil neurotoxic proteins.

We present a case of secondary achalasia due to an adenocarcinoma of the stomach with no tumor infiltration of the esophagus. Immunohistochemical staining revealed a massive infiltration of activated eosinophils in the muscularis of the esophagus with secretion of the highly cytotoxic and neurotoxic eosinophil cationic protein (ECP). Immunohistochemical staining for the neuropeptides VIP and substance P, as well as the histochemical demonstration of AChE, revealed a nearly total absence of all three neurotransmitters/modulators compared to control. The hypothesis is advanced that eosinophil neurotoxicity is the cause of secondary achalasia.

Adenocarcinoma↗
PubMed1989

Eosinophil infiltration in primary esophageal achalasia. A possible pathogenic role.

Smooth-muscle specimens from the lower esophagus of nine patients operated on for esophageal achalasia were examined with routine hematoxylin-eosin staining. This procedure revealed only a few eosinophils in or between the external smooth-muscle layers. Using specific immunohistochemical methods for the detection of the eosinophil cationic protein (ECP), however, varying degrees of eosinophil infiltration and extracellular deposit of ECP were disclosed in the achalasia specimens. The ECP also reacted with the monoclonal antibody, EG2, indicating secretion of the cytotoxic ECP. Few or no eosinophils were seen in the muscularis externa in specimens from six control patients without esophageal disease. In two controls many eosinophils were observed in the muscularis externa. However, no extracellular ECP was detected and very few eosinophils reacted with the monoclonal antibody (EG2), suggesting that these eosinophils were not activated. Depletion or total absence of peptidergic innervation was seen in all achalasia specimens but not in controls. Since the eosinophil cationic protein (ECP), in its activated form, is cytotoxic, we propose a pathogenic role of the eosinophil infiltration in achalasia.

Adult↗
PubMed1989

Fetal weight estimation in twin pregnancies.

In this study the fetal weight was estimated by ultrasound measurements of the biparietal (BPD) and abdominal diameters (AD) in 154 consecutive twin pregnancies. In 80 twins an attempt to estimate fetal weight was made 0-4 days before delivery (26% of all twins examined). In 84% (67 infants) it was possible to estimate the fetal weight using the formula (0.0108 X AD1.72 X BPD0.99). 60% of the birth weights deviated less than 10% from the estimated fetal weight and 83% deviated less than 15%. The prediction error was nearly constant, expressed as percent of actual weight in the different weight groups (8.5-9.8%). In 19 LGA infants, 69% of the birth weights deviated less than 10% from the estimated fetal weight and 70% deviated less than 15%.

Body Weight↗
PubMed1989

The effect of a new selective alpha 2-adrenoreceptor antagonist, idazoxan, and the agonist, clonidine, on fasting antroduodenal motility in healthy volunteers.

Studies were carried out on 16 healthy male volunteers to investigate whether intravenous administration of the alpha 2-adrenoreceptor antagonist, idazoxan, could affect fasting antroduodenal motility with and without administration of the agonist, clonidine. Contractile activity was recorded using an oral tube with perfused side holes positioned in the stomach and duodenum. Clonidine decreased antral contractile activity, an effect that idazoxan did not restore. Idazoxan alone did not affect antral motility. In the duodenum, clonidine decreased the number of contractions significantly and idazoxan restored them. Idazoxan alone did not increase duodenal motility but clonidine induced phase-III activity within the first 15 min after administration. The observations indicate that regulation of antroduodenal motility is influenced by alpha 2-adrenoreceptor drugs. Idazoxan may have potential as a motility restoring drug, for example, in postoperative ileus.

Adolescent↗
PubMedDate not supplied

Detection of gastro-oesophageal reflux disease. The clinical value of a barium examination after food stimulation.

In a prospective study a barium examination combined with food stimulation was compared with the acid reflux test in 30 consecutive patients with symptoms of gastro-oesophageal reflux. Both methods were further compared with endoscopy and histology. Gastro-oesophageal reflux could be demonstrated by the radiologic examination in 22 patients and by the acid reflux test in 23 patients. By combining the two methods gastro-oesophageal reflux could be demonstrated in 27 patients. Comparing the two methods with symptoms, endoscopy, and histology they seemed to be of equal value. Accordingly, a food-stimulated barium examination is recommended as the first method for demonstrating gastro-oesophageal reflux because it is simple and well-tolerated by the patient.

Adult↗