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Biomedical subjects

H Bender

Publications and source records attributed to H Bender.

At least 91 records · Page 5Linked to original sources
PubMed1987

Effect of indomethacin on bombesin-like immunoreactivity, somatostatin and gastrin secretion from rat stomach.

In the present study the effect of indomethacin-induced prostaglandin deficiency was examined on the release of bombesin-like immunoreactivity (BLI), a putative peptidergic neurotransmitter, from the isolated perfused rat stomach. In addition, gastrin and somatostatin (SLI) secretion was determined. Pretreatment of rats with indomethacin (2 mg/kg X h) resulted in a 3-fold increase of basal BLI secretion. In response to acetylcholine (2 X 10(-6) M) BLI rose from 2,000 to 4,000 pg/min, whereas in controls BLI increased from 400 to 1,400 pg/min. While absolute values for BLI secretion were higher in indomethacin-treated stomachs the relative increase above baseline was lower (100 vs. 250%). In control rats the increase in BLI secretion in response to acetylcholine was abolished when the acidity in the gastric lumen was increased from pH 7 to pH 2. After indomethacin, however, the stimulatory effect of acetylcholine during luminal pH 7 and pH 2 was identical. The decrease of SLI by acetylcholine at luminal pH 7 was abolished in indomethacin-treated stomachs in response to 10(-6) M acetylcholine, and 2 X 10(-6) M had even a stimulatory effect on SLI secretion. Indomethacin pretreatment reduced gastrin secretion at luminal pH 7. These data demonstrate that endogenous prostaglandins exert an inhibitory tone on basal and stimulated BLI and stimulated SLI secretion in the rat stomach. It is suggested that endogenous prostaglandins also inhibit the release of a peptidergic neurotransmitter, similar to their effect on the classical neurotransmitters acetylcholine and norepinephrine.

Acetylcholine↗
PubMed1985

Studies of the inhibition by malto-oligosaccharides of the cyclisation reaction catalysed by the cyclodextrin glycosyltransferase from Klebsiella pneumoniae M 5 al with glycogen.

The substrate qualities of malto-oligosaccharides for the disproportionation reaction catalysed by the cyclodextrin glycosyltransferase [(1----4)-alpha-D-glucan:[(1----4)-alpha-D-glucopyranosyl]transferase (cyclising) EC 2.4.1.19] from Klebsiella pneumoniae M 5 al have been re-investigated. Maltose failed to be homologised with measurable velocity. The initial rates of disproportionation and the affinities of the enzyme increased with the chain lengths of the substrates. Maltopentaose was the smallest saccharide which, by disproportionation, yielded longer chains being cyclised initially. D-Glucose did not affect the initial cyclisation from glycogen, but served as acceptor for the "chain-shortening" reaction. Maltose inhibited the initial cyclisation reaction in a linearly competitive manner. Maltotriose and maltotetraose inhibited the cyclisation reaction competitively, the inhibition kinetics pointing to the binding of two effector-molecules to the enzyme. Competitive inhibition was also found with malto-pentaose, -hexaose, and -heptaose. The degrees of inhibition increased from maltose to maltotetraose, and decreased with the larger saccharides; maltotriose and maltotetraose were the most effective inhibitors of the initial cyclisation. Some possibilities for the subsite-mechanisms are discussed.

Chromatography, High Pressure Liquid↗
PubMed1985

[New cardiovascular acting 2-aryl-2-imidazolinyl-acetic acids. Synthesis and pharmacologic effects].

The syntheses of new 2-aryl-2-imidazolinyl-acetic acids and esters are reported together with pharmacological results concerning structure-activity relationship. In contrast to the already known but inactive N(1)-alkylated derivatives of 2-arylamino-2-imidazolines the new compounds with an aryl acetic acid substitution in N(1) position of the imidazoline nucleus show the bradykardic activity of the exocyclic alkylated clonidine derivatives such as alinidine. The majority of these new substances reduce blood pressure and heart rate in anesthetized rats significantly with a long duration of action. 2-[2-(2,6-Dichloro-phenylamine)-2-imidazoline-1-yl]-2-(2-thienyl)- acetic acid 8a is the most potent compound. Blood pressure is lowered by 30-40 mmHg and heart rate by 175 beats/min with a duration of action greater than 60 min. The effect is weakened if the thienyl radical is replaced by other heterocycles or if the 2,6-dichlorphenyl group is replaced by a hydrogen atom. The variation of the substituents in the phenyl nucleus shows that the 2,6-dichlorphenyl structure is the optimum substitution pattern, as in the case of clonidine. In the series comprising the 2-[2-(2,6-dichlorphenylamino)-2-imidazoline-1-yl]-2-phenyl acetic acids (8j-8n) the incorporation of different substituents into the phenyl nucleus in the 2-position results in derivates of different activity. The esters 9a-9c show a faster onset of action as compared to the corresponding carboxylic acid 8a. The most interesting effect of compound 8a in normotensive conscious dogs is a strong and long-lasting decrease in heart rate accompanied by a moderate LVP dp/dtmax decrease, weak lowering of blood pressure and slight increase in LVEDP. After blocking beta-receptors by atenolol the compound 8a still reduces heart rate. Results in ganglion-blocked and pithed rats indicate a presynaptic and postsynaptic alpha 2-agonistic effect. A decrease in sympathetic tone as well as an increase in vagal activity in conscious dogs are considered as possible causes for bradycardic activity. Unlike alinidine, however, compound 8a does not affect directly sinus node function. The bradycardic effect of compound 8a which results in a decrease in oxygen consumption is supposed to be the cause of the reduction of infarct size in anesthetized dogs by 28%.

Acetates↗
PubMed1985

Increased sensitivity to somatostatin in obese Zucker rats.

The release of somatostatin from the pancreas and stomach following the ingestion of a meal and its increase in the peripheral circulation elicits an attenuation of postprandial hormone secretion such as insulin, pancreatic polypeptide and gastrin and retards the rate at which nutrients enter the circulation. Reduced tissue somatostatin content and/or an attenuated somatostatin release is associated with hyperinsulinism and obesity in certain animal models. In the obese Zucker rat, however, tissue somatostatin levels are increased and therefore the present study was designed to determine the effect of synthetic somatostatin on basal and postprandial arterial insulin levels in obese and lean Zucker rats. Synthetic somatostatin was infused at doses of 0.25, 0.5, 1 and 5 ng/kg X min before and after the intragastric instillation of a liver extract/sucrose test meal. In the obese rats somatostatin at a dose of 5 ng/kg X min reduced basal plasma insulin levels significantly, whereas no effect of somatostatin was observed on basal insulin levels in the lean animals at all doses employed. The integrated postprandial insulin response was reduced during 0.25, 0.5, 1 and 5 ng/kg X min somatostatin in the obese animals, whereas only 0.5 ng/kg X min and higher doses had an inhibitory effect in the lean rats. The degree of inhibition in relation to the postprandial insulin response during saline infusions was 35-230% in the obese and 30-100% in the lean Zucker rats within the range of somatostatin infusions employed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Cardiac sarcomas presenting as metastatic disease.

We describe two patients with primary sarcoma of the heart in whom metastatic lesions were the first evidence of disease. One patient had a fibrosarcoma of the tricuspid valve with only pulmonary metastases. The second had a pleomorphic sarcoma of the mitral valve with renal and bony metastases. The possibility of a primary cardiac tumor should be considered in patients with occult metastatic sarcoma.

Adolescent↗
PubMed1984

Effect of continuous and oscillatory portal vein insulin infusion upon glucose-induced insulin release in rats.

The present study was designed to determine the effect of low dose continuous and oscillatory intraportal insulin infusions upon subsequent glucose-induced insulin release. In overnight-fasted and anesthetized rats with indwelling catheters in the jugular vein, carotid artery, and mesenteric vein insulin was infused intraportally for 3 h via the mesenteric vein catheter at a continuous rate of 45 microU/kg X min, or the same amount of insulin was administered at alternating high (72 microU/kg X min) and low infusion rates (18 microU/kg X min), respectively, in 2-, 4-, 8-, and 16-min cycles (oscillatory infusions). Another group received a continuous infusion of saline. Glucose (0.4 g/kg) was given i.v. 30 min after the end of the insulin or saline infusion. During the 3-h infusion of insulin or saline the peripheral glucose level remained unchanged in all groups. In response to the i.v. glucose load peripheral arterial plasma insulin levels were significantly elevated after preceding oscillatory infusions compared to the continuous insulin infusion. As compared to the group receiving saline the glucose-induced insulin response after continuous insulin infusion was significantly reduced. The plasma glucose responses were not different except for inexplicably elevated glucose levels in the 4-min cycle group. No difference was observed for plasma glucagon levels in all groups. The present data demonstrate an augmented responsiveness of the beta-cell to glucose after a preceding oscillatory infusion of insulin and an impaired responsiveness to glucose after continuous insulin infusion. This indicates that an oscillatory insulin release might be of importance for an adequate regulation of beta-cell function.

Animals↗
PubMed1984

Modulation of acetylcholine-induced secretion of gastric bombesin-like immunoreactivity by cholinergic and histamine H2-receptors, somatostatin and intragastric pH.

Recently we have shown the release of bombesin-like immunoreactivity (BLI) from the isolated perfused rat stomach. In these experiments we have shown that BLI secretion is stimulated by acetylcholine. Gastric inhibitory peptide (GIP) exerts an inhibitory effect which is dependent on the intraluminal pH. The present study was designed to examine further the exact cholinergic mechanisms and to study the interaction between cholinergic and histaminergic mechanisms as well as the effect of the intraluminal pH. Acetylcholine elicited a dose-dependent increase in BLI and gastrin secretion (10(-6) M and 2 X 10(-6)M), whereas somatostatin release was suppressed at luminal pH 7. Blockade of muscarinic cholinergic receptors by atropine (10(-5)M) and nicotinic cholinergic receptors by hexamethonium (10(-5) M) abolished the effect of acetylcholine on all three peptides. Reduction of the intraluminal pH to 2 also abolished acetylcholine-induced stimulation of BLI and gastrin secretion and the inhibition of somatostatin secretion. Changes of intraluminal pH per se had no effect on the secretion of either peptide. Somatostatin (10(-7) M) reduced both BLI and gastrin secretion during stimulation with acetylcholine. The addition of the H2-receptor antagonist cimetidine (10(-5) M) abolished the effect of both doses of acetylcholine on BLI and somatostatin secretion and also the effect of the lower dose of acetylcholine (10(-6) M) on gastrin secretion during luminal pH 7. At luminal pH 2 cimetidine did not alter BLI and somatostatin secretion in response to acetylcholine, however, gastrin release was augmented in the presence of cimetidine. These data demonstrate that the effect of acetylcholine on BLI, gastrin, and somatostatin secretion is mediated by muscarinic and nicotinic cholinergic receptors and also by histamine H2-receptors. Somatostatin inhibits cholinergically induced BLI secretion. The cholinergic effects on BLI, somatostatin and gastrin secretion are abolished during an acidic intragastric pH. In this isolated perfused rat stomach model the inhibitory effect of intraluminal acid on gastrin secretion is, at least in part, mediated by H2-receptors. This suggests that the secretion of bombesin, a potential peptidergic neurotransmitter is modulated by neural, endocrine and local tissue factors and also by alterations of intragastric pH.

Acetylcholine↗
PubMed1983

Cyclodextrin glycosyltransferases from Klebsiella pneumoniae M 5 al and Bacillus macerans: quantitative analysis by high-performance liquid chromatography of the (1 leads to 4)-alpha-D-glucopyranosyl transfer-products from some linear and cyclic substrates.

The analysis of the (1 leads to 4)-alpha-D-glucopyranosyl transfer-products from some linear and cyclic substrates by quantitative h.p.l.c. illuminated the mode of action of the cyclodextrin glycosyltransferases [1 leads to 4)-alpha-D-glucan:[(1 leads to 4)-alpha-D-glucopyranosyl]transferase (cyclising), EC 2.4.1.19) from Klebsiella pneumoniae M 5 al and Bacillus macerans. D-Glucopyranosyl transfer, obligatory for maltose (poor substrate), was preferred for maltotriose (good substrate). The lengths of linear disproportionation-products increased with the lengths of the linear substrates. Cyclodextrins were produced from maltotriose and maltopentaose, but not from maltose. The cyclodextrins were substrates in the absence of acceptors. The cyclodextrin transformation started without the formation of detectable amounts of linear transfer-products. The cyclodextrin composition of long-term digests was nearly the same with all the cyclic substrates, cycloheptaamylose being the main cyclic compound. The linear carbohydrate was uniformly distributed from maltose up to at least maltononaose. The enzyme from Bacillus macerans was the least active, but long-term digests yielded results comparable to those obtained with the enzyme from Klebsiella pneumoniae M 5 al.

Bacillus↗
PubMed1983

Cholinergic mechanisms in intestinal phase insulin secretion in rats.

The present study was designed to examine the role of neural cholinergic mechanisms in intestinal phase insulin secretion during increasing intraduodenal instillation rates of the test meals. In groups of 12 anesthetized rats arterial insulin levels rose significantly in relation to the increase of the rate at which the liver extract/sucrose was instilled intraduodenally (0.15, 0.5 and 1.5 ml/min). The injection of atropine (10 micrograms/kg) 5 min prior to the intraduodenal infusion of the test meals abolished this rate-dependent augmentation of insulin levels completely. Similarly, no effect of increasing intraduodenal infusion rates of the meal was observed in islet-transplanted rats. These data demonstrate that neural - at least in part muscarinic cholinergic - mechanisms participate in intestinal phase insulin secretion of rats supporting previous observations about the importance of neural factors in the regulation of postprandial insulin release.

Acetylcholine↗
PubMed1983

Release of bombesin-like immunoreactivity from the isolated perfused rat stomach.

In the present study the release of bombesin-like immunoreactivity (BLI), somatostatin and gastrin was determined form the isolated perfused rat stomach. Gastric inhibitory polypeptide (GIP, 2 X 10(-9) M) had no effect on BLI while stimulating somatostatin and gastrin release. In these experiments the luminal pH of the stomach was kept at pH 7. Reduction of the luminal pH to 2 resulted in an inhibition of BLI secretion by GIP while gastrin release was abolished and somatostatin remained unaffected compared to luminal pH 7. Acetylcholine (10(-6) and 2 X 10(-6) M) elicited a dose-dependent stimulation of BLI secretion while gastrin was stimulated and somatostatin secretion suppressed independent of the administered dose. The present data demonstrate that release of bombesin-like immunoreactivity can be modulated by intestinal hormones and neurotransmitters and is integrated into the complex system of gastrointestinal neuroendocrine regulation.

Acetylcholine↗
PubMed1982

Effect of various acceptors on the rates of the cyclization and chain-shortening of amylose catalyzed by the cyclodextrin glycosyltransferase from Klebsiella pneumoniae M 5 al. Improvement of new photometric assay methods.

The effect of various acceptors on the cyclization and chain-shortening reaction of amylose catalyzed by cyclodextrin glycosyltransferase [(1 leads to 4)-alpha-D-glucan: [(1 leads to 4)-alpha-D-glycopyranosyl]transferase (cycling) EC 2.4.1.19] from Klebsiella pneumoniae M 5 al was studied by use of photometric-assay methods. The requirements for the acceptor were the same for both cyclization and chain-shortening, indicating the close relationship between both reactions. Maltose proved to be the most effective (2.48- and 5-fold acceleration of the cyclization and chain-shortening, respectively, in the presence of 584 micrometers maltose). The dependence of the chain-shortening reaction on the conformational state of the amylose molecules is discussed.

Amylose↗
PubMed1982

Dose-dependent inhibitory and non-inhibitory action of somatostatin on insulin release in rats.

The dose-dependent effect of intravenously infused synthetic somatostatin-14 on basal and postprandial insulin and gastrin release was assessed in anesthetized rats. Infusion of 1 ng . kg-1 . min-1 elicited a significant reduction of basal and postprandial insulin levels compared to the saline control groups. At 15 ng . kg-1 . min-1 basal insulin was not affected but postprandial insulin levels were still significantly reduced. At 30 ng . kg-1 . min-1 neither basal nor stimulated insulin levels were affected. At the highest concentration of 120 ng . kg-1 . min-1 basal and postprandial insulin levels were suppressed similar to lowest infusion rate of 1 ng . kg-1 . min-1. Basal gastrin levels were significantly reduced only at the highest rate of 120 ng . kg-1 . min-1. A significant reduction of postprandial gastrin levels was observed at 15 ng . kg-1 . min-1 and all higher infusion rates employed. Measurements of plasma somatostatin-like immunoreactivity (SLI) demonstrated that plasma SLI levels during the lowest infusion rate of 1 ng . kg-1 . min-1 were not different from the controls. No significant rise of plasma SLI levels was observed in response to the test meal. The higher infusion rates elicited a dose-dependent increase in plasma SLI levels. These data demonstrate that in rats somatostatin exerts a biological effects on insulin release at very low doses while certain greater infusion rates hae no suppressive effect. Gastrin secretion is inhibited in a more linear pattern.

Animals↗
PubMed1981

A bacterial glucoamylase degrading cyclodextrins. Partial purification and properties of the enzyme from a Flavobacterium species.

A Flavobacterium species has been isolated which produces a cyclodextrin-degrading glucoamylase. The inducible, cell-bound enzyme was purified about 10-fold to 75% purity in 57% yield. The action of the enzyme was studied with the main cyclodextrins (cyclohexaamylose, cycloheptaamylose and cyclooctaamylose) and with the typical glucoamylase substrates, respectively. The final degradation product with all the substrates was glucose. Small amounts of maltose, which could be detected in the course of cyclodextrin degradation, were hydrolyzed at a lower rate. V for cyclohexaamylase was found to be about 14-15 mumol glucose min-1 (mg pure protein)-1, the Km for cyclohexaamylose was 0.142 mM. Apparently the enzyme preferred shorter alpha-D-glucopyranosyl chains. Besides maltose, amylopectin and glycogen proved to be very poor substrates. Some properties of the enzyme have been described.

Cyclodextrins↗
PubMed1980

[Kinetic studies of the (1 linked to 4)-alpha-D-glucopyranosyltransferase reaction catalyzed by cyclodextrin glycosyltransferase, particularly the cyclization with (1 linked to 4)-alpha-D-glucopyranosyl chains (average polymerization of 16) as substrate].

The transfer reactions, particularly the cyclization reaction, catalyzed by the cyclodextrin glycosyltransferase ((1 leads to 4)-alpha-D-glucan:[(1 leads to 4)-alpha-D-glucopyranosyl]-transferase (cyclizing), EC 2.4.1.19; CGT) from Klebsiella pneumoniae M 5 al were studied with (1 leads to 4)-alpha-D-glucopyranosyl chains (d.p. 16). The initial rate of the cyclization reaction with substrate concentrations from 1 up to 16 mM indicated a V of 6.2 kat . kg-1 of protein and a molar catalytical activity of 421.6 kat . mol-1 of enzyme. Km was found to be 1.03 mM. In addition to the cyclization, CGT simultaneously catalyzed a disproportionation of the substrate, yielding shorter maltooligosaccharides and (1 leads to 4)-alpha-D-glucopyranosyl chains which were significantly longer than the substrate itself. Cyclohepta- and cycloocta-amylose were accumulated in the course of longer incubation. They arose mainly from coupling reactions with the initially formed cyclohexaamylose and corresponding disproportionation of these transfer products. The extremely low formation rates of the higher cyclodextrins point to a "mistake" of the enzyme, when cyclizing to cyclohepta- and cyclooctaamylose.

Cyclization↗
PubMed1980

[Kinetic studies of the (1 linked to 4)-alpha-D-glucopyranosyltransferase reaction catalyzed by cyclodextrin glycosyltransferase, particularly the cyclization with amylose, amylopectin and total starch as substrate].

The time course of the (1 leads to 4)-alpha-D-glucopyranosyltransfer reactions catalyzed by the cyclodextrin glycosyltransferase ((1 leads to 4)-alpha-D-glucan: [(1 leads to 4)-alpha-D-glucopyranosyl]transferase (cyclizing), EC 2.4.1.19, CGT) from Klebsiella pneumoniae was studied with several commercial amyloses, potato starch, and amylopectin, respectively. Amyloses were poor substrates for the cyclization reaction. In the initial phase of the transfer reactions, the CGT catalyzed a rapid shortening of the amylose chains. The rate of this shortening reaction was significantly accelerated by addition of maltooligosaccharides. Maximum rate of cyclohexaamylose formation was reached with amylose chains sufficiently short (less than Glc100) for the cyclization reaction. Cyclohexaamylose was formed with maximum rate from amyloses containing amylopectin impurities in the initial phase of the transfer reactions, suggesting that the non-reducing ends of the outer amylopectin chains serve as acceptors for the disproportionation of the amylose. Accordingly, water-soluble, high-molecular-weight products containing higher percentages of lengthened outer-chains were obtained from potato starch or amylopectin. In the course of the transfer reactions, only traces of smaller maltooligosaccharides were detected chromatographically.

Amylopectin↗