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K Bukhave

Publications and source records attributed to K Bukhave.

At least 73 records · Page 4Linked to original sources
PubMed1984

Effects of sulphasalazine and disodium azodisalicylate on colonic PGE2 concentrations determined by equilibrium in vivo dialysis of faeces in patients with ulcerative colitis and healthy controls.

The role of arachidonic acid metabolites and the mode of action of 5-aminosalicylic acid, the active moiety of sulphasalazine and disodium azodisalicylate, in ulcerative colitis remain obscure. Therefore, experiments were performed in which the effects of medication on immunoreactive prostaglandin (PG) E2 concentrations in free faecal water were assessed using the equilibrium in vivo dialysis of faeces. Colonic PGE2 concentrations in patients with active ulcerative colitis (n = 11) ranged from 2035-18,000 pg/ml to be compared with a range of 103-188 pg/ml in healthy volunteers (n = 10; p less than 0.001). In all healthy volunteers PGE2 concentrations decreased slightly (p less than 0.05) after disodium azodisalicylate intake 2 g/day, whereas low dose disodium azodisalicylate (0.25 g/day) caused no change. In patients with ulcerative colitis in complete clinical, sigmoidoscopic, and histologic remission withdrawal of sulphasalazine (2 g/day; n = 6) increased PGE2 concentrations to values above normal levels (p less than 0.05) which returned to pretrial values (p less than 0.05) on disodium azodisalicylate (2 g/day; n = 7). In conclusion, increased PGE2 in free faecal water indicates an abnormality in the colonic mucosa, even in the absence of conventional signs of inflammation. We could not confirm the hypothesis that sulphasalazine and 5-aminosalicylic acid exert their therapeutic effect through promotion of endogenous cytoprotective prostaglandins. In contrast, the observation that raised PGE2 concentrations were normalised by disodium azodisalicylate in patients with inactive ulcerative colitis suggests that subclinical disease activity was decreased by 5-aminosalicylic acid.

Adult↗
PubMed1984

Colonic secretion mediated by prostaglandin E2 and 5-hydroxytryptamine may contribute to diarrhea due to morphine withdrawal in the rat.

Prostaglandins and cyclic adenosine monophosphate have been claimed to play a major role in the morphine withdrawal syndrome, but intestinal secretion has not been ruled out as being responsible, at least in part, for the accompanying diarrhea. Therefore, experiments were performed in which the effect of naloxone-induced morphine withdrawal on jejunal and on colonic fluid transport was assessed in tied-off loops of rat intestine in vivo simultaneously with mucosal cyclic adenosine monophosphate levels or colonic luminal release of prostaglandin E2 or 5-hydroxytryptamine. Naloxone-induced withdrawal reversed fluid absorption to secretion without changing cyclic adenosine monophosphate levels, but markedly enhanced local prostaglandin E2 and 5-hydroxytryptamine release (p less than 0.01). Indomethacin and the 5-hydroxytryptamine receptor antagonist ketanserin prevented withdrawal-induced fluid secretion and the increase in prostaglandin E2 release without influencing the release of 5-hydroxytryptamine. In addition, the alpha 2-adrenergic receptor agonist clonidine promoted absorption during withdrawal, whereas atropine failed to influence fluid transport. These data suggest that naloxone-precipitated intestinal fluid secretion may contribute to diarrhea due to morphine withdrawal and that 5-hydroxytryptamine may play an important role in mediating this secretion through stimulation of local prostaglandin formation.

Animals↗
PubMed1983

Comparison of radioimmunological determinations with gas chromatography mass spectrometry dosage. A study of PGE2 and PGF2alpha in gastrointestinal fluids.

The reliability of radioimmunoassays for determination of PGE2 and PGF2alpha in gastrointestinal fluids was checked by two gas chromatographic mass spectrometric methods. Analyses were performed on samples of gastric juice from dogs and man (healthy volunteers), jejunal fluids from patients with celiac disease, mucous discharge from a villous adenoma of rectum, and bathing solutions from the Ussing chamber containing human jejunal mucosa. The radioimmunoassays included extraction and Sephadex LH-20 chromatography as a preliminary purification before quantification was carried out. Gas chromatographic mass spectrometric analysis of PGE2 was performed by monitoring the molecular ion of the trimethylsilyl ether of PGB2 methyl ester, m/z 420 and m/z 424 for the protium and the deuterium form, respectively, while PGF2alpha was quantified as the triacetyl derivative of the methyl ester, using the ion pair (M-3x60) i.e. m/z 314 and m/z 318. Recovery of immunoreactive PGE2 relative to gas chromatographic mass spectrometric dosage was 85.5% + / - 6.5 (mean + / - SEM; n=13), while the amount of PGF2alpha in the same sample volume was at the borderline of sensitivity for the gas chromatographic mass spectrometric method used, with a recovery of 114% + / - 19 (mean + / - SEM; n=4).

Animals↗
PubMed1983

Colonic transport of water and electrolytes in a patient with secretory diarrhea due to collagenous colitis.

Whole colon perfusion studies and measurements of luminal prostaglandin E2 were carried out in a 41-year-old female with collagenous colitis to investigate pathophysiological mechanisms for the diarrhea. Biopsies of the colorectal mucosa had revealed a continuous 25- to 60-micron subepithelial collagenous layer, but normal junctional complexes and capillaries. When the patient fasted, the diarrhea persisted and fecal electrolytes, as estimated from the concentration of sodium, potassium, and their anions, accounted for all the osmolality (284 mosm/kg) of stool water, the pH of which was above 8.0. The lumen-negative electrical potential difference in the rectum was -64 mV vs -45 +/- 2 mV (mean +/- SEM) in healthy controls. Profuse secretion of fluid and electrolytes occurred during colonic perfusion with saline. Transport of sodium appeared to be passive with flux ratios equal to those predicted for passive sodium movements, while chloride transport against a steep electrical gradient indicated active secretion. Perfusion with an "ileal output"-like solution decreased fluid and electrolyte secretion, suggesting that bicarbonate, in addition to chloride, may be a major determinant of secretion rates. Since immunoreactive prostaglandin E2 levels following in vivo equilibrium dialysis of feces ranged from 555 to 650 pg/ml vs 55 to 235 pg/ml (99% confidence limits) in healthy controls, it is speculated that prostaglandins synthesized locally in response to mucosal hypoxia might be the mediators of anion secretion.

Adult↗
PubMed1983

Effect of carbenoxolone on gastric prostaglandin E2 levels in patients with peptic ulcer disease following vagal and pentagastrin stimulation.

The influence of oral carbenoxolone sodium (50 mg X 3 daily) on prostaglandin E2 release into gastric juice has been examined in nine peptic ulcer patients (duodenal ulcer, n = 6; prepyloric ulcer, n = 1; gastric ulcer, n = 2) during modified sham feeding and following bolus stimulation of acid secretion by pentagastrin (6 micrograms/kg). Carbenoxolone increased the overall mean of prostaglandin E2 concentrations in gastric juice following modified sham feeding by 32 +/- 9% (mean +/- SEM; P less than 0.02) and decreased the acidity slightly but significantly (P less than 0.05). A marked rise in prostaglandin E2 levels (46 +/- 11%; n = 5; P less than 0.02) was observed in for duodenal ulcer patients and the patient with a prepyloric ulcer responding to therapy (i.e., pain relief and ulcer healing within 4 weeks of treatment). A significant peak (P less than 0.05) related to modified sham feeding was observed only during medication, while a late gradual increase in prostaglandin E2 levels--not associated with vagal stimulation--occurred both in control and carbenoxolone experiments. No significant differences were observed following pentagastrin stimulation. The initial peak in prostaglandin E2 levels observed during medication favours the notion that the mechanism of drug action relies on inhibition of enzymatic degradation while the late increase in prostaglandin E2 levels may be explained by artificial prostaglandin formation during the aspiration procedure.

Adult↗
PubMed1981

Release of prostaglandin E2 into gastric juice during stimulation of muscarinic- and gastrin receptors in dogs and in humans.

To investigate the causal relationship, if any, between gastric PG formation and gastric acid output, the release of PGE2 into gastric juice has been studied in eight beagle dogs with a gastric fistula, using sustained half-maximal stimulation by bethanechol and pentagastrin, and in eight duodenal ulcer patients, using the combined sham feeding/pentagastrin test. Immunoreactive PGE2 was determined by a method validated by gas chromatography-mass spectrometry and PGE2 values were normalized by expressing them as ng PGE2 released per meq H+ secreted. In the dogs "steady state" PGE2 output (0.4-10 ng/meq H+) was interrupted during continuous i.v. pentagastrin infusion by symmetrical peaks (50-60 minutes of duration) with a maximum of 24 +/- 3.1 ng/meq H+ (mean +/- SEM). During bethanechol stimulation the rhythmic variations were smaller, but the median values for the periods 30 to 180 or 240 minutes significantly (p less than 0.01) higher (3.9-46 ng/meq H+) than in pentagastrin experiments (0.8-20 ng/meq H+). In humans the peak PGE2 output during sham feeding (3.4-41 ng/meq H+) was significantly (p less than 0.02) larger than following bolus stimulation (6/micrograms/kg) by pentagastrin (2.2-18 ng/Meq H+). The findings are consistent with the hypothesis that activation of muscarinic receptors represents the physiologic mechanism by which gastric release of PGs is regulated. Cyclic variations in gastric PG formation appear to occur in response to vagal stimulation since the peaks in PGE2 output were preceded by increased myoelectrical activity (i.e. mean contractile index).

Adult↗
PubMed1981

Prostaglandin E2 in jejunal fluids and its potential diagnostic value for selecting patients with indomethacin-sensitive diarrhoea.

Since prostaglandins (PGs) appear to be important in the pathogenesis of secretory diarrhoea, a radioimmunoassay for determination of PGE2 was applied to purified samples of jejunal fluids aspirated at the ligament of Treitz. Studies on validation of the assay system included quantification of PGE2 following alkali-treatment of the samples, variation of the sample volume, and fractionation of immunoreactive- and tracer PGE2. In addition, the specificity of the assay system was confirmed by gas chromatography--mass spectrometry. In healthy volunteers (n = 22) the PGE2 concentration range was 5--205 pg/ml (99% confidence limits). Alcohol addicts (n = 27) with diarrhoea or steatorrhoea had PGE2 levels within the normal range. Values beyond the 99% upper confidence limit were observed in ten out of seventeen patients with chronic diarrhoea (205--340 pg/ml) and two out of fifteen patients with intermittent diarrhoea (265 and 275 pg/ml) classified as irritable bowel syndrome. In six patients with high PGE2 concentrations indomethacin treatment (25 mg x 4 daily) halved the associated diarrhoea and reduced PGE2 concentrations to normal levels. Subsequently, a double-blind multiple randomized clinical trial was carried out in two single patients. Indomethacin proved to be effective in preventing diarrhoea only in the patient with a raised PGE2 level (P less than 0.005).

Alcoholism↗
PubMed1981

Prostaglandin E2-mediated secretory diarrhea in villous adenoma of rectum: effect of treatment with indomethacin.

Biochemical and clinical evidence is presented to indicate that prostaglandin (PG)E2 is the mediator of fluid and electrolyte secretion by villous adenomas of the rectum. A 64-yr-old man with a 2-mo history of mucous diarrhea had, on admission, prerenal uremia, severe hyponatremia, and hypokalemia. At sigmoidoscopy an 11 X 11-cm villous adenoma of the rectum was revealed. The rectal fluid discharge was 1800-1825 ml/day, with sodium and potassium concentrations of 150 and 12 mEq/L, respectively. Immunoreactive PGE2 levels in the rectal effluents were high (viz. 1160-1250 pg/ml vs. 200-395 pg/ml) compared with those in stool water from patients with infectious diarrhea. The concentration of vasoactive intestinal polypeptide (VIP) in the tumor was lower (viz. 10.5 pmol/g vs. 100-700 pmol/g) than in normal colonic mucosa. Indomethacin treatment (24 mg X 4 daily) reduced the rectal PGE2 excretion from 2.2 to 0.3 microgram/day and caused a decrease in the rectal fluid loss of 850 ml/day associated with a similar reduction in rectal sodium excretion. Discontinuing medication, a rise in the rectal excretions of PGE2, fluid, and sodium was observed. In conclusion, PGE2 formation in the villous adenoma appears to be the cause of fluid secretion by the abnormal tumor epithelium. The use of PG synthetase inhibitors may facilitate the preoperative correction of severe fluid-electrolyte deficits in patients with large villous adenomas of the rectum.

Adenoma↗
PubMed1979

Prostaglandins and chronic diarrhoea: methodological problems.

In order to determine the arterio-venous difference in circulating prostaglandin levels the isotope derivative technique was applied to rat plasma for measurements of prostaglandin E2 (PGE2). No arterio-venous difference was observed if the blood was collected without precautions to avoid in vitro prostaglandin production in the sampling tube. In contrast, inhibition of the in vitro prostaglandin release by the infusion of indomethacin into the catheter from which the blood was drawn, showed PGE2 levels in the right atrium of 60 +/- 20 pg/ml (mean +/-SD; N = 8), and peripheral levels insignificantly different from zero. A significant difference in PGE2 levels of right atrial plasma from fed and fasted rats was observed without the use of in vitro indomethacin in blockade (210 +/- 70 pg/ml; N=4, and 330 +/- 35 pg/ml; N = 4, respectively). This difference could not be reproduced if indomethacin was infused into the catheter (60 +/- 20 pg/ml; N = 8 and 90 +/- 35 pg/ml; N = 5, for fed and fasted rats, respectively). Measurements by radio-gas-liquid-chromatography of the arachidonic acid plasma level showed values of 6.8 +/- 1.6 micrometers (N = 7) and 12.0 +/- 3.4 micrometers (N = 7) for fed and fasted rats, respectively. It is suggested that the higher level of PGE2 (without indomethacin) in fasted rats reflects that of arachidonic acid. The present available methods for the determination of primary prostaglandins and prostaglandin metabolites are discussed with respect to their value not only in physiological studies on fluid and electrolyte transport in the gut, but also for clinical use.

Animals↗
PubMed1978

Separation of prostaglandin metabolites on sephadex LH 20 columns.

Sephadex LH 20 columns have been investigated for the separation of initial prostaglandin metabolites. Solvent systems are described for the separation of the free acids of 15-keto-dihydro-PGE1, 15-keto-PGE1, PGE1, and PGF1alpha. Further, one of the solvent systems is described for the separation of pulmonary metabolites of PGE1 and PGF1alpha, and another one for separation of dihydro-PGE1 and PGE1.

Chromatography, Gel↗
PubMed1977

Elimination of low steady-state concentrations of [5,6-3H2]prostaglandin E1 in the pulmonary and the systemic circulations of anaesthetized rats.

The elimination of [3H]prostaglandin E1 in anaesthetized rats was studied by continuous intravenous or intraarterial infusions, producing steady-state concentrations at the level of endogenous prostaglandin E2 in mixed venous blood. Blood samples (0.5 ml) were collected from the carotid artery or the right atrium, respectively. The levels of [3H]prostaglandin E1 were measured at different infusion time intervals and the 3H-labeled hydrophobic metabolites characterized. Cardiac output was estimated by a modification of the dye injection method, using 125I-labelled albumin as the marker. From the cardiac output and the rate of infusion, the fractional clearance of the lung and the systemic beds in the steady-state situation were estimated to 88.3 +/- 3.2% and 54.1 +/- 15.2% (mean +/- S.D.), RESPECTIVELY. The hydrophobic metabolites were characterized chromatographically on Sephadez LH-20 columns, using synthetically prepared [14C]prostaglandin metabolites as internal standards and markers. The identities of some metabolites were further established by derivative formation to a constant [3H]/[14C] ratio. The major metabolite was 15-keto-13,14-dihydro-[3H]prostaglandin E1, while 15-keto-[3H]prostaglandin E1 and 13,14-dihydro-[3H]prostaglandin E1 could not be demonstrated.

Animals↗