PubMed Health⌕ Search

Biomedical subjects

U Beuers

Publications and source records attributed to U Beuers.

At least 73 records · Page 4Linked to original sources
PubMed1990

Tauroursodeoxycholic acid inhibits the cytosolic Ca++ increase in human neutrophils stimulated by formyl-methionyl-leucyl-phenylalanine.

The effect of the cytoprotective bile acid tauroursodeoxycholic acid (TUDCA) on basal cytosolic free Ca++ (Ca++)i and receptor-mediated (Ca++)i increase was studied in human polymorphonuclear neutrophils using the fluorescent dye quin2. Basal levels of (Ca++)i were 96 +/- 6 nmol/l (mean +/- SEM, n = 48). TUDCA and its cytotoxic epimer taurochenodeoxycholic acid (TCDCA) at 500 mumols/l increased (Ca++)i by 31 +/- 12 and 27 +/- 7 nmol/l, respectively (n = 6, p less than 0.05). Stimulation of neutrophils with the chemotactic tripeptide N-formyl-methionyl-leucyl-phenylalanine (FMLP; 10(-7) mol/l) induced a (Ca++)i increase of 200 +/- 32 nmol/l which was inhibited after preincubation with TUDCA (500 mumols/l) or TUDCA + TCDCA (500 mumols/l, each) by 60.1% and 59.5%, respectively, but not with TCDCA (500 mumols/l) alone. The inhibitory effect of TUDCA on FMLP-induced (Ca++)i increase was strongly concentration-dependent and was nearly complete at 1000 mumols/l. Since (Ca++)i is discussed as a mediator of cellular injury we hypothesize that TUDCA may exert its protective effects at least partly via inhibition of (Ca++)i-mediated cytotoxic processes.

Calcium↗
PubMed1990

Modulation by oxygen of the actions of noradrenaline, sympathetic nerve stimulation and prostaglandin F2 alpha on carbohydrate metabolism and hemodynamics in perfused rat liver.

Rat liver was perfused in situ via the portal vein without recirculation of the perfusate. The perfusion medium contained 5mM glucose, 2mM lactate and 0.2mM pyruvate, and it was equilibrated with different oxygen concentrations so as to vary the rate of oxygen delivery from 4 (normal) to either 12 or 0 mumol x min-1 x g-1 (U/g). 1) Basal glucose and lactate output were clearly increased, when oxygen delivery and therefore uptake were decreased from 4 to 2 and 0 U/g. 2) Noradrenaline caused a marked increase in the output of glucose and lactate and a slight increase in oxygen uptake; it also decreased the rate of flow of the perfusate. Decrease of the oxygen supply did not affect this alteration in the glucose and lactate balance, but it abolished the increase in oxygen uptake and decreased the magnitude of the effect on the perfusion rate. 3) Sympathetic nerve stimulation strongly increased glucose and lactate output and clearly reduced oxygen uptake and perfusate flow. Decreased oxygen delivery caused a decrease in the magnitude of all these changes. 4) Prostaglandin F2 alpha increased glucose and lactate release and decreased perfusate flow. Decrease of the oxygen supply did not affect the increased glucose and lactate release, but it decreased the magnitude of the effect on the perfusion rate. These results lead to the following major conclusions. Oxygen strongly regulates basal carbohydrate metabolism, while it does not affect the metabolic actions of noradrenaline and prostaglandin F2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[The prognostic value of liver function tests--clinical aspects, laboratory chemical parameters and quantitative function tests].

In view of increasing therapeutic possibilities interest focuses on prognosis of liver cirrhosis. Until nowadays studies on prognosis revealed significant importance only for some parameters: Ascites, encephalopathy and portal hypertension as signs of decompensation, bilirubin, albumin and prothrombin time as laboratory indices of decreasing liver function. The commonly used Child-Pugh-score is based on these parameters and allows a reasonable classification of diseased patients. Cholestasis and inflammation seem to be of minor prognostic importance. Assessment of liver function by quantitative tests is desirable (e.g. aminopyrine breath test, bile acids). The prognostic value, however, has not yet been proven in large studies. Use of these tests should therefore be restricted to studies (prognosis, therapy, indication to liver transplantation).

Hepatic Encephalopathy↗
PubMed1990

Relative contribution of glycogenolysis and gluconeogenesis to basal, glucagon- and nerve stimulation-dependent glucose output in the perfused liver from fed and fasted rats.

The relative contribution to basal, glucagon- and nerve stimulation-enhanced glucose output of glycogenolysis (glucose output in the presence of the gluconeogenic inhibitor mercaptopicolinate) and gluconeogenesis (difference in glucose output in the absence and presence of the inhibitor) was investigated in perfused livers from fed rats with high and from fasted animals with low levels of glycogen. 1) Basal glucose output in both states was due only to gluconeogenesis. 2) Glucagon-enhanced glucose output was due about equally to glycogenolysis and gluconeogenesis in the fed state, but predominantly to gluconeogenesis (80%) in the fasted state. 3) Nerve stimulation-increased glucose output was due mainly to glycogenolysis (65%) in the fed state and about equally to both processes in the fasted state. The results suggest that under basal conditions of normal demands the liver supplies glucose only via gluconeogenesis and thus spares its glycogen stores, and that in situations of enhanced demands signalled by an increase in glucagon or sympathetic tone the liver liberates glucose mainly via glycogenolysis.

Animals↗
PubMed1989

Modulation of the sympathetic nerve action on carbohydrate and ketone body metabolism by fatty acids, glucagon und insulin in perfused rat liver.

Rat liver was perfused in situ via the portal vein without recirculation: 1) Nerve stimulation (20 Hz, 2 ms, 20 V) increased glucose output and shifted lactate uptake to output; the alterations were diminished by oleate but not octanoate. 2) Glucagon (1nM) stimulated glucose output maximally also in the presence of the fatty acids, so that nerve stimulation could not increase it further. The hormone also enhanced lactate uptake and nerve stimulation counteracted this effect. The counteraction was diminished by oleate but not octanoate. 3) Insulin (100nM) slightly lowered glucose output and had no effect on lactate balance. It antagonized the increase of glucose output by nerve stimulation, but left the shift of lactate uptake to release unaffected. These events were not influenced by the fatty acids. 4) Nerve stimulation decreased ketone body production from oleate and octanoate. 5) Glucagon increased ketogenesis from oleate, but not octanoate. In the presence of glucagon nerve stimulation also lowered ketogenesis. This decrease was diminished in the presence of oleate. 6) Insulin lowered ketogenesis from oleate but not octanoate. In the presence of insulin nerve stimulation decreased ketogenesis; the relative change was independent of the fatty acids. The complex interactions between fatty acids, glucagon and insulin in the modulation of sympathetic nerve actions can be summarized as follows: Oleate, which enters the mitochondria via the carnitine system, but not octanoate, which enters independently from this system, as well as insulin but not glucagon effectively modulated the nerve actions on carbohydrate metabolism. Glucagon but not insulin modulated the nerve effects on ketogenesis from oleate but not octanoate. The regulatory interactions between substrates, hormones and nerves can best be explained on the basis of the model of metabolic zonation.

Animals↗
PubMed1987

Intracellular mechanism of action of sympathetic hepatic nerves on glucose and lactate balance in perfused rat liver.

In rat liver perfused in situ stimulation of the nerve plexus around the hepatic artery and the portal vein caused an increase in glucose output and a shift from lactate uptake to output. The effects of nerve stimulation on some key enzymes, metabolites and effectors of carbohydrate metabolism were determined and compared to the actions of glucagon, which led to an increase not only of glucose output but also of lactate uptake. 1. Nerve stimulation caused an enhancement of the activity of glycogen phosphorylase a to 300% and a decrease of the activity of glycogen synthase I to 40%, while it left the activity of pyruvate kinase unaltered. Glucagon, similarly to nerve action, led to a strong increase of glycogen phosphorylase and to a decrease of glycogen synthase; yet in contrast to the nerve effect it lowered pyruvate kinase activity clearly. 2. Nerve stimulation increased the levels of glucose 6-phosphate and of fructose 6-phosphate to 200% and 170%, respectively; glucagon enhanced the levels to about 400% and 230%, respectively. The levels of ATP and ADP were not altered, those of AMP were increased slightly by nerve stimulation. 3. Nerve stimulation enhanced the levels of the effectors fructose 2,6-bisphosphate and cyclic AMP only slightly to 140% and 125%, respectively; glucagon lowered the level of fructose 2,6-bisphosphate to 15% and increased the level of cyclic AMP to 300%. 4. In calcium-free perfusions the metabolic responses to nerve stimulation showed normal kinetics, if calcium was re-added 3 min before, but delayed kinetics, if it was re-added 2 min after the onset of the stimulus. The delay may be due to the time required to refill intracellular calcium stores. The hemodynamic alterations dependent on extracellular calcium were normal in both cases. The activation of glycogen phosphorylase, the inhibition of glycogen synthase and the increase of glucose 6-phosphate can well explain the enhancement of glucose output following nerve stimulation. The unaltered activity of pyruvate kinase and the marginal increase of fructose 2,6-bisphosphate cannot be the cause of the nerve-stimulation-dependent shift from lactate uptake to output. The very slight increase of the level of cyclic AMP after nerve stimulation cannot elicit the observed activation of glycogen phosphorylase.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine Nucleotides↗
PubMed1987

Regulation of liver metabolism by the hepatic nerves.

In the isolated rat liver perfused as usual via the portal vein, joint electrical stimulation of the nerve fibers around the artery and the portal vein in the liver hilus increased glucose output, shifted lactate uptake to output, decreased urea and glutamine formation as well as ammonia uptake, reduced ketone body production, lowered oxygen uptake and reduced perfusion flow simultaneously changing the intrahepatic flow distribution; it was accompanied by an overflow of noradrenaline into the hepatic vein. All effects were mediated predominantly via alpha-receptors; they were dependent on extracellular calcium. In livers perfused both via the artery and the portal vein, separate stimulation of the plexus at the common hepatic artery or at the portal vein caused similar effects on glucose and lactate balance and on perfusion flow. Arterial stimulation caused the higher metabolic responses and alterations not only in arterial but also 'transhepaticly' in portal flow, and conversely, portal flow elicited the smaller metabolic responses and alterations in both portal and 'transhepaticly' arterial flow. If sympathetic nerve actions were blocked using alpha- and beta-antagonists, the resulting parasympathetic stimulation increased glucose uptake in the presence of insulin and antagonized the glucagon stimulated glucose release, both alone and more strongly in the presence of insulin. The sympathetic nerves may act directly at the parenchymal cells or indirectly via an overflow of neurotransmitter from the vasculature into the sinusoids or via hemodynamic changes. Experiments with the smooth muscle relaxant sodium nitroprusside and with retrograde flow indicate that neither hemodynamic changes nor noradrenaline overflow from the vasculature can play a major role in the mechanism of action of sympathetic liver nerves on glucose and lactate metabolism. Comparative studies with perfused livers of rats, guinea pigs and tupaias are in line with the view that in the rat the sympathetic nerves act via contacts with only a few periportal hepatocytes, from where the signal is propagated through gap junctions, while in guinea pig and tupaia the nerves act via contacts with almost all parenchymal cells. Sympathetic nerve stimulation of the perfused rat liver caused an increase in the activity of glycogen phosphorylase and a decrease of glycogen synthase, but left the activity of pyruvate kinase unaltered; fructose 2,6-bisphosphate and cAMP were only slightly enhanced.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Mechanism of action of sympathetic hepatic nerves on carbohydrate metabolism in perfused rat liver.

In the perfused rat liver stimulation of the hepatic nerves around the portal vein and the hepatic artery was previously shown to increase glucose output, to shift lactate uptake to output, to decrease and re-distribute intrahepatic perfusion flow and to cause an overflow of noradrenaline into the hepatic vein. The metabolic effects could be caused directly via nerve hepatocyte contacts or indirectly by the hemodynamic changes and/or by noradrenaline overflow from the afferent vasculature into the sinusoids. Evidence against the indirect modes of nerve action is presented. Reduction of perfusion flow by lowering the perfusion pressure from 2 to 1 ml X min-1 X g-1--as after nerve stimulation--or to 0.35 ml X min-1 X g-1--far beyond the nerve stimulation-dependent effect--did not change glucose output and lowered lactate uptake only slightly. Only re-increase of flow to 2 ml X min-1 X g-1 enhanced glucose and lactate release transiently due to washout of glucose and lactate accumulated in parenchymal areas not perfused during low perfusion flow. In chemically sympathectomized livers nerve stimulation decreased perfusion flow almost normally but without changing the intrahepatic microcirculation; yet it enhanced glucose and lactate output only insignificantly and caused noradrenaline overflow of less than 10% of normal. Conversely, in the presence of nitroprussiate (III) nerve stimulation reduced overall flow only slightly without intrahepatic redistribution but still increased glucose and lactate output strongly and caused normal noradrenaline overflow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Control of ketogenesis in the perfused rat liver by the sympathetic innervation.

The regulation of ketogenesis by the hepatic nerves was investigated in the rat liver perfused in situ. Electrical stimulation of the hepatic nerves around the portal vein and the hepatic artery caused a reduction of basal ketogenesis owing to a decrease in acetoacetate release to 30% with essentially no change in 3-hydroxybutyrate release. At the same time, as observed before [Hartmann et al. (1982) Eur. J. Biochem. 123, 521-526], nerve stimulation increased glucose output, shifted lactate uptake to output and decreased perfusion flow. Ketogenesis from oleate, which enters the mitochondria via the carnitine system, was also lowered after nerve stimulation owing to a decrease of acetoacetate release to 30% with no alteration in 3-hydroxybutyrate release. Ketogenesis from octanoate, which enters the mitochondria independently of the carnitine system, was decreased after nerve stimulation as a result of a drastic decrease of acetoacetate output to 15% and a less pronounced decrease of 3-hydroxybutyrate release to 65%. Noradrenaline mimicked the metabolic nerve effects on ketogenesis only at the highly unphysiological concentration of 0.1 microM under basal conditions and in the presence of oleate as well as partly in the presence of octanoate. It was essentially not effective at a concentration of 0.01 microM, which might be reached in the sinusoids owing to overflow from the hepatic vasculature. Sodium nitroprusside prevented the hemodynamic changes after nerve stimulation; it did not affect the nerve-dependent reduction of ketogenesis under basal conditions and in the presence of oleate, yet it diminished the nerve effect on octanoate-dependent ketogenesis. Phentolamine clearly reduced the metabolic and hemodynamic nerve effects, while propranolol was without effect. The present data suggest that hepatic ketogenesis was inhibited by stimulation of alpha-sympathetic liver nerves directly rather than indirectly via hemodynamic changes or noradrenaline overflow from the vessels and that the site of regulation should be mainly intramitochondrial.

Animals↗
PubMed1986

Inhibition of para-nitrophenol extraction by stimulation of the hepatic nerves in the perfused rat liver.

The influence of perivascular stimulation of the hepatic nerves on the extraction of para-nitrophenol (pNP) was studied in rat liver perfused in situ without recirculation. Electrical stimulation of the hepatic nerve plexus, which leads to a predominant activation of the sympathetic nerves, caused a decrease in pNP extraction, an increase in glucose output and a reduction in perfusion flow. Sodium nitroprusside (NPN) an inhibitor of vascular smooth muscle contraction, prevented the hemodynamic alterations without affecting the metabolic changes. These results suggest that sympathetic liver nerves regulate conjugation of pNP directly rather than indirectly via hemodynamic alterations.

Animals↗
PubMed1982

Release of beta-lipotropin- and beta-endorphin-like material induced by angiotensin in the conscious rat.

1 The influence of the renin-angiotensin system on plasma beta-endorphin-like immunoreactivity (beta-EI) was investigated in the conscious rat by use of a radioimmunoassay for beta-endorphin without prior extraction.2 Intravenous infusion of angiotensin I, II or (des-1-Asp)angiotensin II (angiotensin III) caused a dose-dependent increase in plasma beta-EI, angiotensin III infusion being less effective than angiotensin I or II. The plasma adrenocorticotrophin (ACTH) levels too were elevated by angiotensin II. The receptor antagonist, saralasin, prevented the angiotensin II-induced beta-EI release as did dexamethasone pretreatment.3 Both the release of beta-EI and the pressor response to angiotensin I were abolished by the converting enzyme inhibitor, captopril (SQ 14225). In contrast, captopril did not affect the action of angiotensin II.4 In view of the appreciable cross-reactivity of beta-lipotropin (beta-LPH) in our assay, plasma beta-EI was analysed by Sephadex G-50 chromatography. In plasma extracts of angiotensin II-infused rats, immunoreactivity corresponding to human beta-endorphin comprised about 49% of the total immunoreactivity, whereas 51% co-migrated with human beta-LPH.5 The increase in plasma levels of beta-EI elicited by angiotensin II was diminished by about 35% in rats with a hereditary absolute lack of vasopressin (Brattleboro rats), when compared to normal rats.6 These results suggest that the renin-angiotensin system can stimulate the secretion of beta-LPH and beta-endorphin with ACTH from rat anterior pituitary. One link in mediating the response appears to be vasopressin. The physiological function remains to be defined.

Angiotensin I↗