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Biomedical subjects

E Roth

Publications and source records attributed to E Roth.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1989

Influence of alanylglutamine infusion on gastrointestinal glutamine and alanine metabolism in anesthetized dogs.

In this study we administered an infusion of alanylglutamine (10 mumol/kg.min) for 60 minutes to postoperative anaesthetized dogs with catheters placed in the portal and hepatic veins. Arterial plasma levels of alanylglutamine were 83 +/- 27 mumol/L 20 minutes after the onset of the infusion and remained constant throughout the infusion period. Plasma levels of glutamine and alanine approximately doubled compared with preinfusion levels, indicating a release of these amino acids from the dipeptide. The halflife of alanylglutamine, calculated after bolus injection of 2 g, was 1.7 +/- 0.5 minutes. Alanylglutamine was extracted from the liver and the gut (0.9 +/- 0.3 and 0.5 +/- 0.1 mumol/kg.min, respectively). In the basal period (without infusion of alanylglutamine), a glutamine uptake by the liver and the intestine was found. Alanine was taken up by the liver and released from the gut. The infusion of alanylglutamine significantly increased the hepatic uptake of glutamine and alanine (from 0.8 +/- 0.2 to 3.8 +/- 0.6 and from 3.0 +/- 0.4 to 7.5 +/- 0.7 mumol/kg.min respectively; P less than .01) and did not significantly change the intestinal uptake of glutamine and the release of alanine. We conclude that the infusion of alanylglutamine markedly influences the hepatic metabolism of glutamine and alanine, probably via the increased arterial and portal levels of glutamine and alanine.

Alanine↗
PubMed1989

Infusion of dipeptides as nutritional substrates for glutamine, tyrosine, and branched-chain amino acids in patients with acute pancreatitis.

In this study we investigated the effect of a total parenteral nutrition supplemented with synthetic dipeptides on plasma and muscle amino acid metabolism in four patients with acute pancreatitis. We infused an amino acid solution containing alanylglutamine, glycylglutamine, glycylvaline, glycylisoleucine, glylcylleucine, and glycyltyrosine for a period of five days in daily dosages of 10.3, 22.1, 68.8, 37.2, 42.5, and 15.7 mmol, respectively. The plasma levels remained below 100 mumol/L for all infused dipeptides. The plasma concentrations of alanylglutamine were not measurable. Mean peptide urine excretion remained below 5%, with the exception of glycylglutamine (8.5% +/- 5.1%). Arteriovenous concentration differences of the dipeptides across the leg were not significantly different from zero, indicating that the infused dipeptides have no important role in the nitrogen exchange of skeletal muscle. A marked intracellular glutamine deficiency in skeletal muscle was found in all four patients (5.1 +/- 0.6 mmol/L v 19.5 +/- 0.8 in healthy subjects) before infusion. Intracellular glutamine concentration was significantly higher after the infusion period (5.1 +/- 0.7 v 9.5 +/- 1.8 mmol/L, P greater than .05), but no normalization of the intracellular glutamine levels was achieved by the infusion of the two glutamine-containing peptides. We conclude that peptides are well metabolized as substrates for parenteral nutrition in catabolic patients. Furthermore, the infusion of glutamine peptides caused a significant increase in intracellular glutamine levels; however, the dosage of glutamine peptides was too low to normalize the muscular glutamine concentrations.

Acute Disease↗
PubMed1989

A controlled study of neuropsychological deficits in acute spinal cord injury patients.

According to a number of studies, between 40% and 60% of acute traumatic spinal cord injury (SCI) patients demonstrate cognitive dysfunction resulting from various forms of cerebral damage, including concurrent or premorbid closed head injury, chronic alcohol or substance abuse, and other causes. However, applicability of findings from these reports has been limited due to the use of inadequate neuropsychological testing techniques and the lack of control data. In a collaborative investigation, 81 acute SCI patients and 61 non-injured control subjects between 18 and 55 years of age completed a comprehensive motor-free neuropsychological test battery, including: Halstead Category Test (HCT), Vocabulary Subtest (VOCAB) of the Wechsler Adult Intelligence Scale - Revised; Mental Control (MC) Subtest, and Initial and Recall trials of Logical Memory (LM) and Paired Associates (PA) Subtests of the Wechsler Memory Scale; and the 8 trials of the Rey Auditory Verbal Learning Test (RAVLT). Percentages of retained information on the LM and PA were also calculated. Impairment levels for each test were defined as values which exceeded two standard deviations (one-tailed) from the control mean. Based on this definition, the prevalence of neuropsychological abnormality on each test ranged between 10% and 40%. Mean performance levels of patients were significantly more impaired than those of control subjects for all tests except for the Interference trial of the RAVLT and for the percentages of retained information on the LM and PA subtests. Comparison of test results of SCI patients with those of control subjects demonstrates that poor attention span and limited initial learning ability are frequent problems among SCI patients. Other common neuropsychological deficits among these patients include poor concentration ability, impaired memory function, and altered problem solving ability. These deficits may interfere with rehabilitation following SCI.

Adolescent↗
PubMed1989

Plasma glutamate--a prognostic marker of cancer and of other immunodeficiency syndromes?

Elevated plasma levels of glutamate (GLU) have been reported to occur in patients with malignancies and other immunodeficiency syndromes (IDS). To evaluate, whether GLU is useful as prognostic indicator, the plasma concentrations were determined in patients with colorectal carcinoma (CRC), with breast cancer (BRC), and with HIV-infection (HIV). The results were correlated with the disease-stages, and compared with data obtained from patients with benign diseases of the same organ, as well as from sex-matched healthy volunteers. GLU concentrations (volunteers: 27.4 +/- 17.6 mumol/l) were elevated in all BRC patients (range of mean values: 53.5-83.2 mumol/l), in CRC patients with T2-T4-tumours (means: 46.8-85.9), and in HIV+ patients of stage WR 5, 6 (means: 53.9-69.7 mumol/l). All CRC- and BRC-patients with metastases showed highly significant elevations of GLU concentrations (p less than 0.001), but there were no direct correlations between disease stages and GLU levels. Pre-operative patients with benign diseases (diverticulitis, adenoma = GID; and mastopathy = MTP) showed increased GLU levels, which were comparable to those of the tumour patients. The glutamine/GLU ratios (volunteers: 19.3 +/- 15.0) were decreased only in HIV-WR 6 (7.6 +/- 2.1), and BRC-stage 4 (8.0 +/- 1.7). From these results we deduce that the plasma GLU concentrations do not allow a discrimination either between patients with malignancies and without, and between persons of different disease stages.

Aged↗
PubMed1989

Glutamine-containing dipeptides as infusion substrates in the septic state.

Recently a relationship has been postulated between lowered intracellular glutamine concentrations in the skeletal muscle and the rate of protein synthesis. We investigated the effect of 48 hours of parenteral nutrition supplemented with a solution containing glutamine in free or dipeptide form (alanylglutamine or glycylglutamine) on the intracellular glutamine pool in skeletal muscle and on the hind limb exchange of glutamine in dogs with sepsis after surgery. Before surgery, dogs were fasted for 48 hours. We used glutamine dipeptides as sources because they remain stable in an aqueous solution. Nutrition solutions were isocaloric (17.8 kcal/kg body weight/day on day 1 and 35.6 kcal/kg on day 2) and isonitrogenous (0.33 gm nitrogen/kg body weight/day), providing 2.6 mmol/kg body weight/day as glutamine source. During starvation, muscular free glutamine levels decreased by 41% to 10.4 mmol/L (p less than 0.001). On the second postoperative day the dogs had lowered plasma protein levels, a sharp drop in platelet count, an increase in the leukocyte count, and positive blood cultures. None of the solutions investigated in this study was effective in repleting the glutamine pool during 2 days of postoperative nutrition (11 +/- 2.0 mmol/L without glutamine, 10.3 +/- 2.2 mmol/L with glutamine plus alanine, 9.9 +/- 1.6 mmol/L with alanylglutamine, 7.5 +/- 1.1 mmol/L with glutamine plus glycine, and 7.2 +/- 1.2 mmol/L with glycylglutamine, respectively). The release of glutamine from the hindquarter was 631 +/- 38 nmol/kg body weight/min in the control group and decreased significantly in dogs receiving alanylglutamine (13.5 +/- 45 nmol/kg body weight/min; p less than 0.001) or the constituent amino acids (265 +/- 66 nmol/kg body weight/min; p less than 0.01) but was unchanged in dogs receiving glycylglutamine or glutamine plus glycine. We conclude that the duration and dosage of glutamine administration (equivalent to 26 gm glutamine per day in a patient weighing 70 kg) used in this study are not sufficient to restore glutamine deficiency of the skeletal muscle in the depleted state.

Alanine↗
PubMed1989

Phenylalanine and tyrosine metabolism in renal failure: dipeptides as tyrosine source.

Several lines of evidence suggest that tyrosine formation is impaired in renal failure. The concentration of tyrosine is decreased and the phenylalanine/tyrosine ratio is increased in plasma and in skeletal muscle cells. After an oral or intravenous load, the rise of plasma phenylalanine is augmented, the clearance is decreased, oxidation is diminished and the corresponding rise of plasma tyrosine level is blunted. Tyrosine elimination and oxidation are not altered in uremia. The defect in tyrosine formation may be especially important in uremic patients on a low protein diet supplemented with tyrosine-free essential amino acid preparations and in subjects on artificial nutritional support. Thus, tyrosine should be regarded as a conditionally essential amino acid in renal failure and should be supplied exogenously, at least in these patient groups. Oral tyrosine supplementation was shown to replete plasma and intracellular pools and improve nitrogen balance in chronic renal failure patients on a low protein diet. However, because of poor solubility in aqueous solutions, tyrosine cannot be included in the free form in amino acid solutions for parenteral nutrition. To circumvent stability or solubility problems, tyrosine containing dipeptides and/or N-acetyl-tyrosine may serve as tyrosine sources for parenteral supply. Renal failure does not affect alanyl-tyrosine hydrolysis, and there is an immediate increase of plasma tyrosine concentration after peptide infusion. Elimination and hydrolysis of glycine-tyrosine is retarded in renal failure, but the clearance exceeds clinically relevant infusion rates. After infusion of N-acetyl-tyrosine, no increase in plasma tyrosine is seen, and the half-life N-acetyl-tyrosine is grossly prolonged in uremia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Selective effect of personality markers and psychosocial stress on T lymphocyte subpopulations].

Measurements were made of cellular immune system parameters in a group of healthy medical students. On the basis of psychosocial stress encountered during a five-day topic-centered self-awareness course, we investigated modulation in immunity in relation to personality characteristics. 6 days before the beginning of the seminar personality profiles were drawn and blood samples taken. Further immunological measurements were made on day four of the seminar and three weeks after its conclusion. On the fourth day of the seminar we observed throughout the group higher lymphocyte and suppressor/cytotoxic T lymphocyte counts in comparison with counts one week earlier, and likewise a heightened responsiveness to PHA- and IL-2 stimulation. The T lymphocyte counts had dropped. In subjects with a higher need for succorance/nurturance, the depression of the immune system was manifested in a drop in the helper/inducer T lymphocyte counts, and in the more achievement- and order-oriented subjects in a downregulation as observed by higher suppressor/cytotoxic T lymphocyte counts. Our results show that under psychosocial stress, healthy people experience on the one hand an activation of the immune system, and on the other hand an immunodepression bearing a specific relation to personality characteristics.

Adult↗