Motility responses of the human small intestine to prostaglandins E2 and F2 alpha.
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Dinoprost↗
Biomedical subjects
C Johansson
Publications and source records attributed to C Johansson.
Integration of screw implants in the rabbit: a 1-year follow-up of removal torque of titanium implants.
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Animals↗
Topical prostaglandin E2 for chronic leg ulcers.
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Administration, Topical↗
Temporary bone tissue ischemia in the hind limb of the rabbit. A vital microscopic study.
With in situ bone vital microscopy it was demonstrated that a cuff pressure of 300 mm Hg applied over the rabbit thigh is sufficient to cause a complete vascular standstill in the tibial cortex. Cuff-induced tissue ischemia applied for 30 min did not result in any adverse bone tissue reactions over a follow-up period of 30 days. Locally applied isolated bone ischemia for 3 or 6h resulted in an inflammatory response, and 4-6 weeks after the 6-h ischemia bone resorption was evident.
Animals↗
Stimulation of duodenal bicarbonate secretion by misoprostol.
Graded doses of topical misoprostol were examined for effects on duodenal bicarbonate output in fasted conscious rats and compared with perfusions of the H2-receptor blocker cimetidine. Chronic loops (2 cm) of the proximal duodenum were prepared in male Sprague-Dawley rats weighing 250 g. A thin perfusion tube was placed in the duodenal bulb, and a permanent cannula drained the distal end to the exterior. The stomach and remaining duodenum with biliary and pancreatic ducts were then reanastomosed. During tests, the loops were perfused with isotonic saline at 0.5 ml/min and samples of 15-min effluents analyzed for HCO3- using a modified back-titration method. Drugs and stimulants were added to the perfusion fluid. Misoprostol at 10(-10) M significantly (P less than 0.02) elevated the duodenal HCO3- from basal value (N = 10), and concentrations of 10(-10) to 4 X 10(-4) M produced dose-dependent increases of bicarbonate secretion, with a peak output of 49 +/- 7 mumol/cm/hr. A peak response of the same magnitude, 42 +/- 4 mumol/cm/hr, is observed after 5-min exposure of the loops to 150 mm HCl. The response to a single dose of 10(-4) M misoprostol was sustained, similar to the prolonged stimulatory effects of 5-min acid exposure. Perfusions of the loop with graded natural PGE2 result in similar increases of duodenal HCO3-, but the peak may be lower and the response to a single dose is less sustained. The H2-receptor blocker cimetidine, perfused at concentrations of 10(-7) to 10(-4) M failed to affect duodenal HCO3- output.(ABSTRACT TRUNCATED AT 250 WORDS)
Alprostadil↗
Ulcerations of the colon associated with naproxen and acetylsalicylic acid treatment.
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Aspirin↗
In vivo induction of Ia antigens on rat keratinocytes by gamma-interferon.
Recombinant rat IFN-gamma was found to induce Ia antigen expression on rat keratinocytes in vivo. Strong expression of Ia antigen on keratinocytes of rat ears was produced after intradermal injections of 10,000 U IFN-gamma once daily on 3 successive days. The expression was still pronounced 2 days after the last injection, but had disappeared 4 days later.
Animals↗
Effect of oral prostaglandin E2 on DNA turnover in gastric and intestinal epithelia of the rat.
The mucosal incorporation and clearance of a DNA precursor was examined in the rat stomach and intestine following oral treatment with natural prostaglandin E2 (PGE2) or 15(R) 15 methyl prostaglandin E2 (Me PGE2). Control groups received vehicle or pentagastrin. After five days of treatment animals were labelled with methyl-3H-thymidine. Groups of rats were killed at 0.75, 24, 72, 96 and 120 h after labelling. Treatments continued until killed. Mucosal scrapings were analysed for radioactivity and DNA. Morphometric measurements were performed and plasma levels of gastrin and somatostatin determined. PGE2 and its stable analogue produced hyperplasia within one week of treatment, in particular of the gastric antrum and changed the incorporation and clearance of radioactive thymidine from gastric and intestinal epithelia. The most consistent finding was a delayed elimination of thymidine from the mucosa, indicating a slowing of the DNA turnover. The DNA synthesis was differently affected along the gastrointestinal tract, being unchanged or reduced in the stomach and moderately increased in the intestine. Prostaglandin treatment was associated with a three- to ten-fold increase of the gastric acid contents and with elevated plasma levels of gastrin and somatostatin. It is concluded that E2 prostaglandins produce hyperplasia of gastric and intestinal epithelia in the rat by prolonging the cell survival time rather than by increasing new cell production. Hypergastrinemia is not a likely mediator of trophic actions of E2 prostaglandins, which develop despite elevated plasma levels of somatostatin.
Administration, Oral↗
Gastrin, gastric acid secretion, and gastric microflora in patients with rheumatoid arthritis.
The relation between the basal and stimulated gastric acid secretion, plasma gastrin, and the gastric microflora was examined in 45 patients with rheumatoid arthritis. Sixteen patients (36%) had basal achlorhydria, and of these, 10 (22%) had achlorhydria or hypochlorhydria after stimulation with pentagastrin. The peak acid output and acidity showed inverse correlation with the disease duration but were not associated with age or with the degree of physical disability. Hypergastrinaemia was found in nine patients (20%), of whom 6 (13%) had significant titres of parietal cell antibody. The acidity of the peak acid output showed negative correlation with plasma gastrin. It was confirmed that the gastric secretory state is a determinant of plasma gastrin levels and in addition influences the growth of micro-organisms in the gastric lumen. The type of microflora in the non-acid stomach was similar to that found in the saliva. A subgroup of eight females was identified who showed low gastric acid secretion rates, positive bacterial cultures, and atlantoaxial subluxation. Gastrin- and insulin-like immunoreactivities were found in joint fluid. The concentrations reflected their plasma levels, suggesting that the peptides are not released at the inflammatory site, but rather that they reach synovial fluid from circulating blood.
Adult↗
Cholinergic influence on duodenal bicarbonate response to hydrochloric acid perfusion in the conscious rat.
Present information suggests that endogenous prostaglandins, hormonal factors, and neuropeptides participate in the regulation of duodenal bicarbonate secretion in response to luminal hydrochloric acid. The purpose of this study was to examine the effects of cholinergic antagonists and agonists on basal and acid-stimulated bicarbonate secretion in the proximal duodenum of the conscious rat. The basal bicarbonate secretion, 9 mumol X cm-1 X h-1, increased to 21 +/- 3 mumol X cm-1 X h-1 after 5 min of exposure to 150 mM HCl and remained significantly elevated for more than 3.5 h. The muscarinic blocker atropine, 0.5 mg X kg-1, reduced the acid-stimulated bicarbonate response by a third, and higher doses did not increase the inhibition. The ganglionic blocker hexamethonium, 10-20 mg X kg-1, suppressed in a dose-related manner the alkaline response by maximally one half. The opioid inhibitor naloxone was also an effective inhibitor. Hexamethonium, but not atropine, inhibited the basal duodenal bicarbonate secretion, which was unaffected by graded doses of the cholinergic agonists bethanechol and carbachol. We conclude that cholinergic nicotinic activity participates in maintaining basal duodenal bicarbonate secretion in the conscious rat. The bicarbonate response to luminal 150 mM HCl is partially dependent on cholinergic sites, but activation of such sites is not a single final step, since cholinergic agonists failed to elevate bicarbonate secretion from basal.
Animals↗
Cell kinetics of rat gastrointestinal mucosa. Autoradiographic study after treatment with 15(R)15-methyl-prostaglandin E2.
Forty Sprague Dawley rats (120 g) were divided in groups of five rats each, and 2 mg , kg-1 15(R)15-methyl-prostaglandin E2 or vehicle was administered orally, twice daily for 5 days. On the 6th day, 1 mCi . kg-1 methyl-3H-thymidine was given intraperitoneally to all rats. Groups of rats were killed at 45 min and 24 h, 72, and 120 h after the labelling. Treatments were continued until death. Samples were taken from the corpus, antrum, and jejunum and processed for autoradiography. Microscopic evaluation of the proliferative and functional compartments included cell counts and determination of the labelling index (LI) and mitotic index (MI). Prostaglandin treatment increased the number of cells in the jejunal and gastric epithelia. The DNA synthesis, evaluated from the LI and 45 min after thymidine injection, was unaffected by treatment. The clearance of label from jejunal crypts and villi was significantly slower in the prostaglandin groups. Similar observations were made in the proliferative zone of the corporal and antral epithelia. The MI was unchanged or reduced by prostaglandin treatment, the reduction being significant after 8 to 10 days' treatment. It is suggested that the trophic action of prostaglandin E2 is produced by reduction of epithelial cell losses, thereby prolonging the cell survival time. The reduced MI may be secondary to negative feedback from the hyperplastic epithelium. Trophic actions are produced by short-term treatments.
Animals↗
Differential induction of cytochrome P-450-dependent monooxygenase, epoxide hydrolase, glutathione transferase and UDP glucuronosyl transferase activities in the liver of the rainbow trout by beta-naphthoflavone or Clophen A50.
After administration of beta-naphthoflavone and Clophen A50 to juvenile rainbow trout, activities of hepatic cytochrome P-450-dependent deethylation of 7-ethoxyresorufin was increased 172- and 49-fold, respectively. Glutathione transferase activity towards 1-chloro 2,4 dinitrobenzene and UDP glucuronosyltransferase activities towards p-nitrophenol, 1-naphthol and testosterone were increased 1.4 to 3.0-fold by beta-naphthoflavone or Clophen A50. However, significant increases of the rate of glucuronidation of 1-naphthol by Clophen A50 and of testosterone by both Clophen A50 and beta-naphthoflavone were only determined when the activities were measured in digitonin activated microsomes. Epoxide hydrolase activity was not affected by beta-naphthoflavone or Clophen A50. The time course of induction of the various xenobiotic metabolizing enzymes exhibited different patterns. 7-Ethoxyresorufin-O-deethylase activity reached peak values 3 and 7 days after the administration of beta-naphthoflavone and Clophen A50, respectively. The rate of induction of glutathione transferase activity and UDP glucuronosyltransferase activities towards p-nitrophenol and 1-naphthol were relatively slow and did not reach distinct peak levels. These activities were still on maximum levels 4-6 weeks after the treatment. Glucuronidation of testosterone reached peak values 1 week after treatment with both beta-naphthoflavone and Clophen A50. The dissimilar patterns of induction of the cytochrome P-450-dependent activities and the various conjugation activities may indicate that these xenobiotic metabolizing enzymes are differently regulated in the rainbow trout liver.
Animals↗
Forebrain serotonergic involvement in avoidance learning.
The one-way active avoidance deficit caused by the serotonergic (5-HT) releasing compound p-chloroamphetamine (PCA) was examined in rats after degeneration of 5-HT neurons in the forebrain. Injection of 5,7-dihydroxytryptamine (5,7-DHT) into the forebrain in desipramine (20 mg/kg)-pretreated rats resulted in a 65-70% decrease in 5-HT concentrations in the prefrontal cortex and hippocampus without any significant effect on striatal 5-HT. Slight reductions in noradrenaline (NA) (25%) and dopamine (DA) (34%) concentrations were observed in the prefrontal cortex only. The 5,7-DHT lesions markedly attenuated the impaired avoidance performance induced by PCA (2.5 mg/kg), suggesting that the avoidance deficit depends on intact 5-HT terminals in cortex and/or hippocampus. The 5,7-DHT lesion alone caused a slight but significant impairment of acquisition. The results suggest that 5-HT terminal systems in the forebrain play an important role in avoidance learning.
5,7-Dihydroxytryptamine↗
Separation of the associative and non-associative effects of brain serotonin released by p-chloroamphetamine: dissociable serotoninergic involvement in avoidance learning, pain and motor function.
p-Chloramphetamine (PCA, 0.63-5 mg/kg IP) injected 30-60 min before testing produced a dose-related impairment of avoidance acquisition, prolonged reaction time in the hot-plate test and increased locomotor activity. Pretreatment with the selective serotonin (5-HT) uptake inhibitor zimeldine (10 mg/kg IP) blocked these behavioral effects. Degeneration of brain 5-HT neurons by a high neurotoxic dose of PCA (2 X 10 mg/kg IP) or inhibition of tryptophan hydroxylase by p-chlorophenylalanine (300 mg/kg IP) also blocked the behavioral effects of PCA. There was a complete blockade of the PCA-induced avoidance deficit following pretreatment with metergoline, a central 5-HT receptor blocking agent. On the other hand, metergoline failed to block the hot-plate analgesia and the increased locomotion caused by PCA. Depletion of brain NA and DA by the tyrosine hydroxylase inhibitor H44/68 did not counteract the PCA effect on avoidance or hot-plate performance, but reduced the locomotor stimulating effect. The selective NA neurotoxin DSP4 (50 mg/kg IP) or the opiate antagonist naloxone (1 mg/kg) failed to affect the PCA-induced modulations of the behaviours studied. In addition, PCA administration in doses that caused avoidance deficits, did not result in motor impairment as assessed by the tread mill test. The above results support the hypothesis that the PCA-induced impairment of active avoidance acquisition does not involve changes in nociception or altered locomotor activity. It is concluded that behavioural processes related to serotonergic neurotransmission can be independently modified, suggesting differences in the underlying 5-HT mechanisms.
Amphetamines↗
Involvement of spinal serotonergic pathways in nociception but not in avoidance learning.
The effects of selective lesions of the descending serotonergic (5-HT) pathways on analgesia and avoidance deficit induced by the 5-HT releasing compound p-chloroamphetamine (PCA, 2.5 mg/kg) were investigated in male rats. Intrathecal injection of 5,6-DHT (20 micrograms/rat) reduced the uptake of labelled 5-HT into spinal synaptosomes by approximately 85% but did not significantly affect the uptake of noradrenaline. The lesions produced a significant hyperalgesia and strongly attenuated the analgesic effect of PCA in the hot-plate test. In the flinch-jump test 5,6-DHT lesioned rats receiving PCA did not differ from the saline control group. Spinal lesioning did not, however, affect one-way active avoidance performance and did not prevent the marked impairment of avoidance performance induced by PCA. Thus, the avoidance deficit caused by PCA is independent of the descending serotonergic pathways and of the analgesia induced by PCA. These results support the view of a differential involvement of the ascending and descending serotonergic projections in behavioural processes controlled by aversive stimuli.
5,6-Dihydroxytryptamine↗
Disturbances in the defecation mechanism with special reference to intussusception of the rectum (internal procidentia).
Anorectal disorders that disturb normal defecation are described, especially intussusception of the rectum (internal procidentia). A review of 190 patients, half of whom were treated operatively and the other half conservatively, is presented. Diagnostic procedures, symptoms, and indications for operations are evaluated. We believe that intussusception of the rectum is a relatively common cause of difficult emptying of the rectum and, when the correct diagnosis is established, operation presents a fair chance for improvement.
Adult↗
Trophic actions of E2 prostaglandins in the rat gastrointestinal mucosa. A quantitative morphologic study.
Adult, male Sprague-Dawley rats in groups of 10 received one of the following treatments orally twice daily for 3 wk: prostaglandin E2 (PGE2) 7.5 mg X kg-1, 15(R)-15-methyl prostaglandin E2 (MePGE2) at 0.2 or 2.0 mg X kg-1, or vehicle. After 18 h of fasting and 10-12 h after the last dose, the rats were anesthetized, and the gastrointestinal tract was fixed and processed for macroscopic and microscopic investigations. Trophic changes were more pronounced in the gastric antrum than in the gastric corpus or small intestine. The thickness of the antral mucosa was significantly increased by PGE2 and in a dose-related way by MePGE2. The mucosa of the gastric corpus became significantly thicker only with the higher dose of MePGE2. In all the prostaglandin-treated groups, the proportion of endocrine cells was reduced. Small--but sometimes significant--changes were registered in the proportions of the various exocrine cells. The parietal cells became significantly larger (+88%) in the rats treated with high doses of MePGE2. The secretory surface of the parietal cells was markedly increased by PGE2 and MePGE2. The enlargement of the secretory surface in animals treated with prostaglandins corresponded to a marked elevation of the basal gastric acid secretion and an increase in plasma gastrin levels. Hypergastrinemia can explain some, but not all, of the trophic changes observed in this study. Light microscopic examination of the duodenal and jejunal mucosa showed dose-related increases in villus heights and crypt lengths after treatment with MePGE2. Only the duodenal villus heights were increased by PGE2.
Animals↗
Oral PGE2 inhibits gastric acid secretion in man.
The effect of oral prostaglandin E2 (PGE2) on gastric acid secretion was examined in healthy subjects. The gastric secretion was stimulated by a modified shamfeeding procedure. Each subject underwent one control test and three tests with intragastrically administered graded doses of PGE2: 0.5, 1.0 and 2.0 mg. Oral PGE2 significantly suppressed the peak and total acid response to vagal stimulation. The total acid output in controls was 27.5 +/- 3.2 mmol/90 min and 20.8 +/- 2.8, 15.8 +/- 2.2 (p less than 0.01) and 15.9 +/- 3.8 (p less than 0.005) mmol/90 min in test series with 0.5, 1.0 and 2.0 mg PGE2 respectively. The two higher doses were equally inhibitory to an average 40%. Gastric outputs of sodium and potassium in response to modified shamfeeding were reduced by PGE2. In controls there was a significant release of plasma-gastrin in response to shamfeeding. Plasma-gastrin was apparently suppressed after the two lower doses of PGE2 but 2.0 mg PGE2 gave an elevation similar to controls. Thus the study demonstrates that oral natural PGE2 suppresses the gastric acid secretion in man. The absence of such an effect in prior studies has been one of the objections against an acid regulatory action of endogenously formed prostaglandins. The present results do not support this argument.
Administration, Oral↗