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Biomedical subjects

E Beubler

Publications and source records attributed to E Beubler.

At least 55 records · Page 3Linked to original sources
PubMed1985

Stimulation of PGE2 synthesis and water and electrolyte secretion by senna anthraquinones is inhibited by indomethacin.

The effect of dried senna pod extract, containing 10% sennoside B, on colonic electrolyte and fluid transport was examined in the anaesthetized rat in-situ. Oral administration of senna pod extract dose-dependently (17.5-30 mg kg-1, calculated as sennoside B) reversed net absorption of water, sodium and chloride to net secretion and increased potassium secretion. Senna pod extract stimulated the output of prostaglandin E2 into the colonic lumen. Inhibition of prostaglandin biosynthesis by pretreatment of the rats with indomethacin (10 mg kg-1) significantly inhibited the effects of senna pod extract (17.5-30 mg kg-1) both on net fluid transport and on prostaglandin E2 synthesis. The inhibitory effect of indomethacin on net fluid transport induced by senna pod extract (30 mg kg-1) was dose-dependent. It is concluded that anthraquinones exert their laxative action at least partially via stimulation of colonic fluid and electrolyte secretion, and that this secretion is mediated by stimulation of endogenous prostaglandin E2 formation.

Animals↗
PubMed1985

[HPLC determination of troxerutin in plasma and urine following oral administration in man].

A high-performance liquid chromatographic method (HPLC) is described for the analysis of 3',4',7-tri-O-(beta-hydroxy-ethyl)-rutoside (troxerutin) in human plasma and urine. After separation of interfering substances on XAD-2 trihydroxyethylrutoside is converted to tetrahydroxyethylrutoside by 2-chlorethanol in alkaline medium. After HPLC-separation tetrahydroxyethylrutoside is quantified by fluorescence detection. The pharmacokinetics of troxerutin were measured in plasma after oral administration to man. The relative bioavailability of the drug from Venelbin was 97.8 +/- 37.1% compared to an aqueous standard solution.

Anticoagulants↗
PubMed1984

Retention time and concentration in human skin of bifonazole and clotrimazole.

The retention time and the extent of penetration in human skin of [14C] labelled bifonazole in comparison to [14C] labelled clotrimazole were investigated in 8 healthy volunteers. In the course of the investigation the backs of the volunteers were treated half with bifonazole, half with clotrimazole which remained on the skin for 24 h. From 24 to 168 h after the administration the skin was stripped with the tear-off strip technique. Three dermal layers of different depth were examined. The results of the examinations revealed, that the quantity of bifonazole that penetrated into the skin was more than twice as high as the quantity of clotrimazole. However, the half-lives and the mean retention times of bifonazole and clotrimazole were nearly similar to each other.

Administration, Topical↗
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

Bioavailability and pharmacokinetics of D-penicillamine.

The absolute and the relative bioavailability of D-penicillamine, available from different dosage forms and products, was studied in 10 healthy volunteers. Plasma levels and urine excretion of D-penicillamine were determined up to 8 h after administration by high performance liquid chromatography after intravenous administration of 250 mg and after oral administration of 250 mg (2 products) and 150 mg (1 product) D-penicillamine. The absolute bioavailability on oral administration was 50-70%. No statistical difference was found between the relative bioavailabilities of the different dosage forms tested.

Administration, Oral↗
PubMed1982

Pharmacokinetics of the pivaloyloxyethyl (POE) ester of methyldopa, a new prodrug of methyldopa.

A prodrug of methyldopa, the pivaloyloxyethyl (POE) ester, was administered orally to healthy human volunteers at doses equivalent to 500 and 1000 mg of methyldopa and was compared to oral and intravenous doses of methyldopa. The time courses of availability of methyldopa to the general circulation were compared and contrasted with the model-independent estimates of total systemic availability. The POE ester of methyldopa is completely hydrolyzed on the first pass; delivery of methyldopa to the general circulation was faster, more uniform, and more extensive compared to orally administered methyldopa. The systemic availability of methyldopa averaged 64% of the dose with a coefficient of variation (CV) of 15% for the prodrug treatments compared to 27% of the dose with a CV of 63% for methyldopa. First-pass metabolism of drug to the mono-O-sulfate conjugate of methyldopa was lower for the POE ester than for methyldopa.

Absorption↗
PubMed1982

Single dose pharmacokinetics of fendiline in humans.

Fendiline was administered intravenously (3 mg) and orally (50 mg and 75 mg) in a cross-over study to six healthy volunteers. The plasma levels of unchanged fendiline and of total radioactivity were measured. Fendiline was absorbed well and its concentration declined biexponentially with mean terminal half-lives of 20-35 h. Since the drug is extensively metabolized, only 12% of total radioactivity in plasma corresponded to fendiline in the case of intravenous administration as compared to less than 2% after oral administration. 56-65% of the administered dose are excreted via the urine and 18-25% with the feces within five days.

Adult↗
PubMed1982

Studies on the possible function of beta 2-glycoprotein-I: influence in the triglyceride metabolism in the rat.

Seven rats were infused with 14C-labeled Intralipid at a constant rate of 0.38 ml per hour over a time period of 4 hours. Four rats served as controls and received an infusion of 0.15 M NaCl or of serum albumin two hours after the start of the experiment. In these animals the plasma triglyceride concentration rose linearly from 30 to 240 min and paralleled the total blood radioactivity. The triglyceride concentrations at the end of the experiments were about 25 times as high as at the beginning. Three rats receiving 2 hr after the start an additional infusion of beta 2-glycoprotein-I at a rate of 10 mg per hr showed a markedly enhanced triglyceride removal from the plasma, reaching a steady state which lasted for more than 30 min. It is concluded that beta 2-glycoprotein-I affects the triglyceride clearance under these experimental conditions.

Animals↗
PubMed1981

VIP and PGE1 activate adenylate cyclase in rat intestinal epithelial cell membranes via different mechanisms.

The effect of vasoactive intestinal polypeptide (VIP) and of prostaglandin E1 (PGE1) alone and in combination was tested in an adenylate cyclase (AC) preparation from rat intestinal epithelial cell membranes. AC activity increased linearly with time up to 15 min in the absence or presence of VIP or PGE1, respectively. NaF, VIP and PGE1 concentration-dependently stimulated AC activity. The dose-response curve of VIP in the presence of PGE1 was shifted to the left and the maximal effect of VIP was significantly enhanced. The dose-response curve obtained experimentally was significantly different from theoretical additive dose-response curve, indicating that PGE1 potentiates the effect of VIP on AC activity. The possible mechanisms of potentiation are discussed. The results suggest that VIP and PGE1 activate AC via two different but not entirely independent mechanisms.

Adenylyl Cyclases↗
PubMed1980

Influence of vasoactive intestinal polypeptide on net water flux and cyclic adenosine 3',5'-monophosphate formation in the rat jejunum.

1. The effects were studied of vasoactive intestinal polypeptide (VIP), theophylline, and morphine on net water flux and cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels in the jejunum of anaesthetized rats in vivo and of VIP and morphine on adenylate cyclase activity in rat epithelial cell membranes in vitro. 2. Infusion of VIP (0.1-2 x 10(-9) mol/min/kg) dose dependently caused a reversal from net water absorption to net secretion; 2 x 10(-9) mol/min/kg enhanced the mucosal cyclic AMP content by 67%. 3. Theophylline (5 mg/ml, intraluminally) enhanced the effect of intra-arterial infusion of VIP (2 x 10(-9) mol/min/kg) as to net water secretion and increase in mucosal cyclic AMP content. 4. Pretreatment with morphine (5 mg/kg, s.c.) did not influence the effects of VIP on net water flux and on mucosal cyclic AMP content. 5. Atropine (2 mg/kg, s.c.) also failed to reduced the effect of VIP (0.4 x 10(-9) mol/min/kg) on net water flux. 6. Stimulation of adenylate cyclase activity was a function of VIP concentration over a range of 1 x 10(-10)-1 x 10(-7) M. Morphine (up to 1 x 10(-3) M) failed to influence stimulation of adenylate cyclase by VIP. 7. The finding that low doses of VIP, which already have an effect on net water flux, fail to increase cyclic AMP levels makes it likely that other mediators besides cyclic AMP are involved in the effect of VIP on net water flux. Some of the present results, however, support the assumption that VIP stimulates intestinal fluid secretion by increasing mucosal cyclic AMP levels.

Adenylyl Cyclases↗
PubMed1980

Naloxone increases carbon dioxide stimulated respiration in the rabbit.

1. The effects were studied of morphine and naloxone on the respiratory minute volume and the minute volume stimulated by carbon dioxide in the anaesthetized rabbit. 2. The respiratory minute volume is reduced by morphine (2 mg/kg) to about 60% of control. The effect of morphine is abolished by naloxone (5 mg/kg); the minute volume depressed by morphine transiently becomes larger after naloxone than prior to morphine. Also the minute volume stimulated by carbon dioxide becomes larger after naloxone than that prior to the period of depression produced by morphine. 3. Naloxone (0.5 mg and 5 mg/kg i.v.) enhances the sensitivity of respiration to carbon dioxide by about 21% and 28%, respectively. 0.5 mg/kg naloxone itself had no influence, 5 mg/kg for about 5 min increases basal respiratory minute volume. 4. It is assumed that endogenous opiates modulate respiration and, like exogenously administered opiates, reduce the sensitivity of respiration to carbon dioxide. 5. The hypothesis is discussed that endogenous opiates are involved in regulation of biological functions which are known to be inhibited by opiates and which belong to the "protective system" postulated by O. Schaumann.

Animals↗
PubMed1980

Inhibition by morphine of prostaglandin E1-stimulated secretion and cyclic adenosine 3',5'-monophosphate formation in the rat jejunum in vivo.

1 The effects were studied of prostaglandin E1 (PGE1), theophylline and morphine on net water flux and mucosal cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels in the jejunum of anaesthetized rats in vivo. 2 Infusion of PGE1 (3.2 micrograms/min, i.a.) caused a reversal from net water absorption to net secretion and enhanced the mucosal cyclic AMP content by 54%. 3 Theophylline (5 mg/ml, intraluminal) similarly produced a reversal from net water absorption to net secretion and increased mucosal cyclic AMP content by 54%. Additional intra-arterial infusion of PGE1 resulted in a massive increase in net water secretion and an increase in mucosal cyclic AMP content by about 200%. 4 Pretreatment with morphine (10 mg/kg, s.c.) reduced the effect of PGE1 on net water flux and completely inhibited its effect on the mucosal cyclic AMP content. Naloxone (10 mg/kg, s.c.) abolished both effects of morphine. 5 A good correlation (r = 0.99) was demonstrated between mucosal cyclic AMP levels and net water flux. 6 The present results demonstrate that PGE1 stimulates intestinal fluid secretion by increasing mucosal cyclic AMP levels. The antidiarrhoeal effect of morphine can be explained by its inhibition of the PGE-mediated increase in cyclic AMP levels, which, in turn, leads to a reduction in intestinal secretion.

Alprostadil↗
PubMed1979

Inhibition of PGE1 induced intestinal secretion by the synthetic enkephalin analogue FK 33-824.

1. The effects of the enkephalin analogue, FK 33-824 were compared with those of morphine and naloxone on the prostaglandin E1-induced increase in intestinal fluid volume and unanaesthetized and pithed rats. 2. FK 33-824 inhibits the prostaglandin E1-induced increase in intestinal fluid volume both in unanaesthetized and pithed rats. 3. Naloxone abolished the inhibitory effect of FK 33-824 in both experimental models. 4. It can be concluded from the experiments in pithed rats that the inhibitory effect of FK 33-824, like that of morphine, on prostaglandin E1-induced secretion is caused by a peripheral action. 5. It is assumed that endogenous enkephalins protect against prostaglandin-mediated loss of fluid into the gut lumen. This protective effect can be mimicked by an enkephalin analogue and blocked by naloxone.

Animals↗
PubMed1979

Effect of ricinoleic acid and other laxatives on net water flux and prostaglandin E release by the rat colon.

Ricinoleic acid, oleic acid, dioctyl sodium sulphosuccinate, deoxycholic acid, sennoside A + B and mannitol reduced or reversed water flux from lumen to blood in rat colon in situ. Stearinic acid was without any effect. Ricinoleic acid, oleic acid, dioctyl sodium sulphosuccinate, deoxycholic acid and sennoside A + B stimulated release of PGE-like material into the colonic lumen whereas the osmotic laxative mannitol and stearinic acid did not. Inhibition of PGE biosynthesis by pretreatment of the rats with indomethacin significantly reduced (but did not abolish) the effect of ricinoleic, oleic and deoxycholic acids on net water flux and PGE release. Indomethacin reduced the effect of dioctyl sodium sulphosuccinate and of sennoside A + B on PGE release but not their effect on the net water flux. The effect of mannitol was not influenced by indomethacin. The amount of PGE release in experiments with ricinoleic acid, oleic acid, stearinic acid and dioctyl sodium sulphosuccinate (with and without indomethacin) showed a good correlation (r = 0.99) with the change in net water flux. Deoxycholic acid, sennoside A + B and mannitol did not show this correlation. It is assumed that the action of non-osmotic laxatives is partially mediated by PGE, although other mechanisms also seem to be involved in their mode of action.

Animals↗
PubMed1978

Is the effect of diphenolic laxatives mediated via release of prostaglandin E?

The diphenolic laxatives, bisacodyl and phenolphthalein, and the osmotic laxative mannitol increase intestinal fluid volume in the rat colon in situ. The diphenolic laxatives stimulate the biosynthesis of prostaglandin E (PGE) whereas mannitol does not. Inhibition of PG-biosynthesis by pretreatment with indomethacin only reduces the effect of the diphenolic laxatives. It is suggested that diphenolic laxatives increase intestinal fluid volume via stimulation of PGE biosynthesis in the colon.

Animals↗
PubMed1978

PGE-release, blood flow and transmucosal water movement after mechanical stimulation of the rat jejunal mucosa.

1. The influence of weak mechanical stimulation of the jejunal mucosa in vivo on PGE-release, on intestinal blood flow and transmucosal water movement was studied in rats. 2. Mechanical stimulation of the mucosa increased PGE-release into the venous outflow and into the gut lumen. This increase is followed by an increase in intestinal blood flow and transmucosal movement of tritiated water in both directions. 3. Pretreatment of the rat with indomethacin reduced the effect of mechanical stimulation on PGE-release. Indomethacin further reduced the increase in blood flow and in secretion of tritiated water. Absorption of tritiated water was not changed in these experiments. 4. Pretreatment of the rat with atropine (1 mg/kg, i.p.) or perfusion of the gut with methysergide (10 microgram/ml) did not influence the increase in intestinal blood flow after mechanical stimulation. 5. It is suggested that enhanced intestinal blood flow and transmucosal movement of tritiated water after mechanical stimulation are mainly provoked by a preceding release of PGE. 6. It is further supposed that such a mechanism may be physiologically involved in regulation of intestinal blood flow and transmucosal water movement during food intake.

Animals↗