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Biomedical subjects

E Roth

Publications and source records attributed to E Roth.

At least 91 records · Page 5Linked to original sources
PubMed1991

Effect of alpha-ketoglutarate infusions on organ balances of glutamine and glutamate in anaesthetized dogs in the catabolic state.

1. The salt complex of L-(+)-ornithine and alpha-ketoglutarate (2-oxoglutarate) has recently been proposed for the treatment of patients in the catabolic state. As yet, it is unclear which of the two substrates (ornithine or alpha-ketoglutarate) is responsible for the anticatabolic effect. We infused alpha-ketoglutarate into anaesthetized post-operative dogs in order to investigate whether infusion of alpha-ketoglutarate affects the flux of glutamine and glutamate between skeletal muscle and the splanchnic bed. We used three infusion rates: 3, 10 and 20 mumol min-1 kg-1. A steady state of alpha-ketoglutarate concentration in arterial whole-blood was attained only when the infusion rate was 3 mumol min-1 kg-1. 2. Arterial whole-blood concentrations of alpha-ketoglutarate were 8.8 +/- 1.2 mumol/l in the basal period and rose to 208 +/- 41, 344 +/- 61 and 1418 +/- 315 mumol/l after 60 min infusions of alpha-ketoglutarate at 3, 10 and 20 mumol min-1 kg-1, respectively. 3. alpha-Ketoglutarate uptake was measured in skeletal muscle, liver, gut and kidneys in the basal period and during the infusion of alpha-ketoglutarate. The net uptake of infused alpha-ketoglutarate was highest in the skeletal muscle, followed by kidneys, liver and gut. 4. The alpha-ketoglutarate load increased the muscular tissue content of alpha-ketoglutarate from 49.5 +/- 5 to 142 +/- 15 nmol/g of dry substance (P less than 0.001), but did not alter the muscular glutamate or glutamine contents.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Utilization of tyrosine dipeptides and acetyltyrosine in normal and uremic humans.

The impact of renal failure on the elimination and hydrolysis of three sources of tyrosine for parenteral nutrition, the dipeptides alanyltyrosine (Ala-Tyr), glycyltyrosine (Gly-Tyr), and N-acetyltyrosine (NAc-Tyr) was investigated in eight patients on regular hemodialysis therapy (HD) and seven healthy controls (CON). In CON, whole body clearance (Ctot) of Ala-Tyr (3,169 +/- 198 ml/min) was higher than Gly-Tyr (1,781 +/- 184, P less than 0.001), and both exceeded NAc-Tyr (284 +/- 24, P less than 0.001). In HD, Ctot of Ala-Tyr was not different from CON, but Ctot of Gly-Tyr (858 +/- 73, P less than 0.001) and NAc-Tyr (129 +/- 30, P less than 0.02) was decreased. The rise in plasma levels of constituent amino acids was higher in Ala-Tyr vs. Gly-Tyr (P less than 0.01). In HD, the pattern was similar, although the increase in Tyr was less than in CON. Plasma Tyr did not increase with NAc-Tyr in either group. Urinary loss of peptides was neglible, but 60% of NAc-Tyr infused was excreted by CON. The half-life of peptides incubated in CON and HD plasma was unchanged for Ala-Tyr (12.3 +/- 0.9 vs. 14.6 +/- 1.9 min) and prolonged for Gly-Tyr in HD (101.7 +/- 4.9 vs. 131.3 +/- 12, P less than 0.05). Thus renal failure does not impair Ala-Tyr disposal and delays Gly-Tyr utilization. These differential effects on peptide assimilation underscore the importance of peptide structure on metabolism. Both peptides, but not NAc-Tyr, may serve as a nutritional substrate in renal failure patients.

Adult↗
PubMed1990

Increased serotoninergic and noradrenergic activity in hepatic encephalopathy in rats with thioacetamide-induced acute liver failure.

Functional changes of various neurotransmitter systems have been implicated in the pathogenesis of hepatic encephalopathy. In this study the role of brain monoaminergic neurotransmitter systems in hepatic encephalopathy was investigated in rats with thioacetamide-induced acute liver failure. Concentrations of serotonin, dopamine, noradrenaline and of their metabolites 5-hydroxyindoleacetic acid, dihydroxyphenylalanine (following inhibition of dihydroxyphenylalanine-decarboxylase), dihydroxyphenylacetic acid, homovanillic acid and 3-methoxy-4-hydroxyphenyl-glycol, were measured in the cerebral cortex, striatum and hippocampus by high performance liquid chromatography with electrochemical detection. In hepatic encephalopathy concentrations of 5-hydroxyindoleacetic acid were increased in all three brain areas (196%, 204% and 264% of saline-treated controls, p less than 0.01), and concentrations of serotonin were increased in the frontal cortex (121%, p less than 0.01). In the frontal cortex and hippocampus of encephalopathic rats dopamine levels were increased (157% and 289%, p less than 0.05), and levels of noradrenaline (53% and 46%, p less than 0.05) were decreased associated with increased 3-methoxy-4-hydroxyphenylglycol levels (173% and 206%, p less than 0.05). The extent of these changes correlated with the stage of hepatic encephalopathy. In hepatic encephalopathy dihydroxyphenylalanine accumulation was increased in the hippocampus and unchanged in the cerebral cortex. Dopamine, noradrenaline, dihydroxyphenylacetic acid and homovanillic acid concentrations were unchanged in the striatum. The results of this study indicate that hepatic encephalopathy in thioacetamide-induced acute liver failure in rats is associated with neurochemical changes, suggesting an increased activity of the noradrenergic and serotoninergic neurotransmitter systems.

Amino Acids↗
PubMed1990

Splanchnic, renal, and muscle clearance of alanylglutamine in man and organ fluxes of alanine and glutamine when infused in free and peptide forms.

The present study was designed to investigate organ metabolism of intravenously (IV) infused (100 mumol.h-1.kg-1) alanylglutamine and its amino acid constituents in a group of healthy subjects. The dipeptide clearance (mumol/min) by kidney (51 +/- 3) was significantly (P less than .01) greater than the clearance by either splanchnic organs (19 +/- 6) or skeletal muscle (21 +/- 8). Infusion of alanylglutamine significantly (P less than .01) increased arterial plasma concentrations of free alanine (260 +/- 31 v 330 +/- 38 mumol/L) and free glutamine (620 +/- 66 v 764 +/- 65 mumol/L) when compared with the baseline period. Concurrently, splanchnic uptake of alanine and glutamine increased and muscle release of alanine ceased. However, muscle release of glutamine remained unaffected. Renal balances of alanine and glutamine changed from neutral to negative (net release) and from positive (net uptake) to neutral, respectively. Infusion of a corresponding mixture of alanine and glutamine had similar effects on arterial plasma concentrations and splanchnic and muscle balances of alanine and glutamine, but had no effect on renal balances of these amino acids. From these studies in man, we conclude that kidney predominates over other organs in clearance of alanylglutamine from plasma and that this may account for the different effect of infusion of alanine and glutamine in free and peptide forms on renal fluxes of these amino acids.

Adult↗
PubMed1990

Coronary reperfusion studies with pro-urokinase in acute myocardial infarction: evidence for synergism of low dose urokinase.

Pro-urokinase is a single chain precursor of two chain urokinase, which has been shown to induce fibrin-selective plasminogen activation. In the present study, thrombolytic efficacy of 9 million U of glycosylated pro-urokinase administered intravenously was compared with that of a combined regimen utilizing 4.5 million U of pro-urokinase and 0.2 million U of urokinase. Seventy-five patients with a first myocardial infarction were randomized to receive high dose pro-urokinase (n = 40, group A) or the combination therapy (n = 35, group B). Reperfusion of the infarct-related artery was assessed by repeat coronary angiography. Thrombolysis in Myocardial Infarction trial (TIMI) grade II or III reperfusion was achieved in 73% of group A patients compared with 66% of group B patients (p = NS). A trend toward faster reopening of the infarct-related artery was observed in patients in group B. Coronary artery reocclusion occurred in 5 (10%) of 49 patients in whom angiography was repeated within 36 h after the start of therapy. Clot-selective thrombolysis was indicated by a minimal fibrinogen decline (15% and 13%, respectively, in groups A and B). Alpha 2-antiplasmin levels, however, decreased more rapidly in patients in group B (p less than 0.05). This finding and the equivalent reperfusion rate in the combined treatment group strongly suggest synergistic interaction between these two thrombolytic agents. In summary, the high incidence of reperfusion, the low rate of early reocclusion and the paucity of side effects, particularly with regard to bleeding complications, indicate that pro-urokinase possesses the characteristics of an ideal thrombolytic agent.

Drug Synergism↗
PubMed1990

Lesions of nonvisual inputs affect plasticity, norepinephrine content, and acetylcholine content of visual cortex.

1. The depletion of both norepinephrine (NE) and acetylcholine (ACh) in the visual cortex can decrease plasticity. This decrease in plasticity, although dramatic under some circumstances, fails to occur under others. 2. We depleted cortical NE and ACh in 35- to 42-day-old kittens by making a lesion of the white matter behind the cingulate gyrus. One eye was sutured on the day of the lesion. We recorded from the visual cortex 7 days or 2-3 mo later and used the influence of the deprived eye on the cortical cells as a measure of plasticity. 3. We measured NE content by high-pressure liquid chromatography (HPLC) and inferred ACh depletion from depletion of choline acetyltransferase (ChAT) activity. NE depletion averaged 60% in the successfully depleted animals. Depletion of ChAT activity was consistent with NE depletion. 4. When recording occurred 7 days after the lesion and the sutured eye was contralateral to the lesion, plasticity was decreased on the side with the lesion; 70% of the cells were driven by the deprived eye. On the control, uninjured side only 15% of the cells were driven by the deprived eye. 5. In two circumstances the lesion did not cause a decrease in plasticity. In animals with suture ipsilateral to the lesion, the cortex remained plastic. In these animals only 26% of the cells in the hemisphere with the lesion were driven by the deprived eye. The cortex also retained its plasticity if the contralateral eye remained sutured for several months after the lesion, even though there was no recovery from NE and ACh depletion. 6. We conclude that depletion of NE and ACh does decrease plasticity; that is, it protects the deprived eye from losing its ability to drive cortical cells, at least for a short period of time. Depletion protects only the normally dominant contralateral pathway; the ipsilateral visual pathway remains plastic. 7. Perhaps the importance of the side of the deprived eye can be explained by assuming that depletion of NE and ACh removes facilitatory input. This would decrease the ability of cortical cells on the side with lesion to potentiate the input from the nondeprived eye relative to the deprived eye; that is, it would decrease the molecular deprivation (MD) effect. A removal of facilitation would also increase the visual input required to drive cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1990

Torpedo acetylcholinesterase is inactivated by thiol reagents.

A number of sulphydryl reagents inhibit AChE of Torpedo california with pseudo-first-order kinetics, and inhibition can be retarded by quaternary ligands which bind at either the catalytic or peripheral anionic binding sites. Colorimetric determination with one of the inhibitory sulphydryl agents, 5,5'-dithiobis (2-nitrobenzoic acid), reveals the presence of a single thiol group per catalytic subunit; our data thus suggest that inhibition is achieved by reaction with the single free sulphydryl group of Cys231.

4-Chloromercuribenzenesulfonate↗
PubMed1990

Plasmodium falciparum carbohydrate metabolism: a connection between host cell and parasite.

Selected aspects of the metabolism of Plasmodium falciparum are reviewed, but conclusions based on the study of other species of plasmodia are intentionally not included since these may not be applicable. The parasites increase glucose consumption 50-100 fold as compared to uninfected red cells; most of the glucose is metabolized to lactic acid. The parasite contains a complete set of glycolytic enzymes. Some enzymes such a hexokinase, enolase and pyruvate kinase are vastly increased over corresponding levels in uninfected red cells. However, the pathway for synthesizing 2,3-diphosphoglycerate (2,3-DPG) is absent. Parasitized red cells show a decline in the concentration of 2,3-DPG which may function as an inhibitor for certain essential enzyme pathways. Pentose shunt activity is increased in absolute terms, but as a percent of total glucose consumption, there is a decrease during parasite infection of the red cell. The parasite contains a gene for G6PD and can produce a small quantity of parasite-encoded enzyme. It is not clear if the production of this enzyme can be up-regulated in G6PG deficient host red cells. The NADPH normally produced by the pentose shunt can be obtained from other parasite pathways (such as glutamate dehydrogenase). NADPH may subserve additional needs in the infected red cell such as driving diribonucleotide reductase activity--a rate limiting enzyme in DNA synthesis. The role of NADPH in protecting the parasite-red cell system against oxidative stress (via glutathione reduction) remains controversial. Parasitized red cells contain about 10 times more NAD(H) than uninfected red cells, but the NADP(H) content is unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1990

Intracellular free amino acid patterns in duodenal and colonic mucosa.

We report for the first time the concentrations of free amino acids in human intestinal biopsies obtained by routinely performed endoscopy. We studied 15 medical patients with no changes of the mucosa and six HIV-infected persons with duodenitis. The mean (and SD) sum of all amino acids, taurine excepted, was 61.9 (5.4) mmol/kg dry weight in duodenal biopsies of HIV-negative subjects (n = 11) and 82.9 (0.6) mmol/kg in colonic specimens: 50% (44%) of the total (minus taurine) consisted of aspartate and glutamate and 14% (12%), of the essential amino acids. The relative amino acid pattern in duodenum and colon differed completely from that for muscle: aspartate was fourfold higher; glutamate, phenylalanine, glycine, valine, leucine, and isoleucine were about twofold higher. In contrast, glutamine amounted only to 4% (duodenum) to 14% (colon) of muscle glutamine. In duodenal biopsies of the HIV-infected persons, we found significantly (P less than 0.01, except glutamine: P less than 0.025) increased concentrations of glutamate (24.1 vs 17 mmol/kg dry weight), ornithine (1.4 vs 0.4), valine (2.2 vs 1.7), and glutamine.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Functional neuromuscular stimulation for standing after spinal cord injury.

A study was undertaken to determine if functional neuromuscular stimulation could be used to obtain standing in patients with traumatic spinal cord injury. Twenty-five subjects were selected during the study, and standing was accomplished in 21 using bilateral quadriceps stimulation with the hips in hyperextension. Four subjects elected not to continue participation to the point of standing. Stimulation parameters were 0 to 120V pulse amplitude, frequency 13Hz or 20Hz, and pulse width of 0.4msec. Confirmation of standing with support of 95% of the body weight by the legs was verified by quantitative measurements with a dual-scale force platform or a biomechanics force platform. Subjects initially selected had injury levels between C7 and T11 and ranged in age from 22 to 47 years, with duration of injury from one to 13 years. The subjects had complete lesions, with no active motor function below the last normal level, and absent sensation or partial sparing of sensation with vague perception of pinprick, but no position sense. Six subjects stood at home and 15 stood only in the laboratory. This five-year experience indicates that paraplegic individuals may obtain standing with functional neuromuscular stimulation.

Adolescent↗
PubMed1989

The deamination of adenosine and adenosine monophosphate in Plasmodium falciparum-infected human erythrocytes: in vitro use of 2'deoxycoformycin and AMP deaminase-deficient red cells.

The role of enzymatic deamination of adenosine monophosphate (AMP) and adenosine in the in vitro growth of the malaria parasite Plasmodium falciparum was investigated by means of human red cells deficient in AMP deaminase to which the adenosine deaminase inhibitor 2'-deoxycoformycin was added. Malaria parasites grew normally in red cells lacking one or both of these enzyme activities. As a further probe of adenosine triphosphate (ATP) catabolism, both infected and uninfected RBCs were incubated with NaF (with and without 2'-deoxycoformycin) and the purine nucleotide/nucleoside content was analyzed by high-performance liquid chromatography (HPLC). Uninfected RBCs lacking either AMP or adenosine deaminase were able to bypass the enzyme block and degrade ATP to hypoxanthine. Uninfected RBCs with both deaminases blocked were unable to produce significant quantities of hypoxanthine. On the other hand, infected RBCs were able to bypass blockade of both deaminases and produce hypoxanthine and adenosine. These findings establish that deamination of adenosine and/or AMP are not essential for plasmodial growth. However, further work will be required to elucidate the pathways that permit the parasites to bypass these catabolic steps.

AMP Deaminase↗
PubMed1989

Inhibition of noradrenaline release in the pig coronary artery via a novel serotonin receptor.

In pig coronary artery preincubated with [3H]noradrenaline, the effects of serotonin (5-HT) receptor agonists and antagonists on the electrically evoked (0.66 Hz) tritium overflow were determined. Tritium overflow was inhibited by 5-HT, 5-aminotryptamine, N,N-dimethyl-5-hydroxytryptamine, 5-hydroxytryptamine, 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969) and tryptamine. The maximum inhibition obtainable with 5-HT was by about 35%, its pIC20 value was 7.85. 8-Hydroxy-di(n-propylamino)tetralin, urapidil, ipsapirone, 5-carboxamidotryptamine, 4-hydroxytryptamine, 5-methoxytryptamine and alpha-methyl-5-hydroxytryptamine did not decrease 3H overflow. The inhibitory effect of 5-HT was not antagonized by ketanserin, mesulergine, metitepine, propranolol, (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205-930) and yohimbine. Additionally, it was not altered by indomethacin. We conclude from the present data that the sympathetic nerves of the pig coronary artery are endowed with inhibitory presynaptic 5-HT receptors which do not belong to the 5-HT1, 5-HT2 or 5-HT3 receptor type but seem to represent a so far unknown receptor class.

Animals↗
PubMed1989

Hepatic encephalopathy in thioacetamide-induced acute liver failure in rats: characterization of an improved model and study of amino acid-ergic neurotransmission.

An imbalance of excitatory and inhibitory amino acid-ergic neurotransmission has been suggested to play a role in the pathogenesis of hepatic encephalopathy. For further evaluation of this hypothesis, several parameters of amino acid-ergic neurotransmission were studied in rats with acute liver failure induced by the administration of 300 mg per kg thioacetamide by gavage on two consecutive days. By appropriate supportive care, hypoglycemia, renal failure and hypothermia were avoided. Rats were monitored clinically and neurologically. Hepatic encephalopathy evolved in four distinct, easily recognizable stages. Light and electron microscopic examination of brains of rats with hepatic encephalopathy revealed only a slight swelling of nuclei of neurons and astrocytes without signs of neuronal degeneration or brain edema. In rats with hepatic encephalopathy, the concentrations of GABA, glutamate and taurine were decreased in the cerebral cortex, the hippocampus and the striatum, whereas those of aspartate and glycine were unchanged or increased. GABAA and benzodiazepine receptors were studied as parameters for the postsynaptic GABAA-benzodiazepine receptor complex, glutamic acid decarboxylase as parameter for presynaptic GABA-ergic neurons and stimulation of benzodiazepine binding by GABA as a parameter for a GABA-mediated postsynaptic event. None of these parameters was different in hepatic encephalopathy as compared to controls. Similarly, Ca++/Cl(-)-dependent and -independent glutamate receptors as parameters for glutamatergic neurons were unchanged in rats with hepatic encephalopathy. Thus, in rats with thioacetamide-induced liver failure and hepatic encephalopathy, changes of the concentrations of neurotransmitter amino acids occur in the brain. Other neurochemical parameters, however, failed to identify alterations of GABA-ergic or glutamatergic neurotransmission in hepatic encephalopathy.

Acetamides↗
PubMed1989

Characterization of an endothelial 5-hydroxytryptamine (5-HT) receptor mediating relaxation of the porcine coronary artery.

The pharmacological properties of the endothelial 5-hydroxytryptamine (5-HT) receptors involved in relaxation of vascular smooth muscle were determined in rings of pig coronary artery contracted with 10 nmol/l of the thromboxane A2 receptor agonist 9,11-dideoxy-11 alpha,9 alpha-epoxy-methano-prostaglandin F2 alpha (U 46619). (1) In the presence of 10 mumol/l ketanserin, relaxation was obtained with: 5-HT (apparent pD2 value 7.00), 5-carboxamidotryptamine (5-CONH2-T; 6.42), 5-aminotryptamine (5-NH2-T; 5.96), 5-methoxytryptamine (5-OCH3-T; 5.92), tryptamine, 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo(1,2-a)quinoxaline maleate (CGS 12066 A) and 5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU 24969). The maximum relaxation obtainable with the agonists was about 40-60% of the U 46619-induced contraction and the concentration-response curves for 5-HT, 5-NH2-T and 5-OCH3-T were bell-shaped. The endothelium-dependence of this effect (i.e. the failure to relax the artery in endothelium-denuded preparations) was demonstrated for 5-HT, 5-CONH2-T, RU 24969, CGS 12066A and tryptamine. (2) 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 4-hydroxytryptamine, quipazine and yohimbine were ineffective in decreasing the tension of arteries with or without endothelium. Ipsapirone elicited full relaxation of U 46619-induced contraction, but this effect was not endothelium-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Plasma concentrations of free amino acids during 3 weeks treatment of massively obese children with a very low calorie diet.

Eight grossly obese children (2 girls, 8 boys, age 12.6 +/- 2.1 mean +/- SD years, mean overweight 73.3 +/- 14%) were treated for 3 weeks with a very low calorie diet (VLCD), containing 1022 kJ/240 kcal, 33 g protein, 25.5 g carbohydrate and 0.7 g fat/day. Mean weight loss after 3 weeks was 9.47 +/- 2.8 kg and mean nitrogen loss was calculated to be 113.3 +/- 71.2 g. While serum electrolytes, enzymes, glucose, urea and creatinine remained almost unchanged, distinct alterations of 23 free amino acids in plasma could be observed. A transient increase of plasma valine, leucine, isoleucine and alpha-aminobutyrate during the 1st week was followed by a constant fall in the 2nd and 3rd week. Glycine, proline, serine and threonine showed a progressive increase, while cystine, histidine and, above all, alanine decreased, the diminution of alanine being most rapid during the 1st week. No significant changes were observed in plasma concentrations of arginine, asparagine, aspartic acid, citrulline, glutamic acid, glutamine, lysine, tyrosine, ornithine, phenylalanine and taurine. Total plasma amino acid content did not change during diet compared to the pre-diet period. The behavior of plasma amino acids shows a typical pattern within four groups, reflecting various interorgan substrate fluxes during hypocaloric dieting.

Adolescent↗
PubMed1989

Availability of glutamine from peptides and acetylglutamine for human tumor-cell cultures.

In a recent study we showed that the growth behavior of a hematopoietic cell line (K 562) in culture was the same when using glutamine-containing dipeptides or glutamine as substrate. In this article we study the growth behavior of different tumor cells, originating from the hematopoietic system (K 562), stomach (Kato III), pancreas (Panc 1), and breast (T 47 D), to test the biological activity as preclinical in vitro screening system. We compared L-glutamine (GLN), N-acetyl-L-glutamine (ACE-GLN), L-alanyl-L-glutamine (ALA-GLN), and glycyl-L-glutamine (GLY-GLN). Cell proliferation was measured with the incorporation of [3H] thymidine or the MTT assay (cleavage of 3-(4,5-dimethyldiazol-2-yl)-2-5-diphenyl tetrazolium bromide by mitochondria). In all investigated cell types cell growth was stimulated when using glutamine-containing dipeptides or ACE-GLN instead of a glutamine-free media (not significant for T 47 D). However, GLN or ALA-GLN was advantageous to GLY-GLN or ACE-GLN when measuring cell proliferation with the MTT-assay up to 72 hours. However, alanylglutamine does not enhance proliferation, compared with free glutamine.

Breast Neoplasms↗