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E Holm

Publications and source records attributed to E Holm.

At least 55 records · Page 3Linked to original sources

Hyperammonemia-induced depletion of glutamate and branched-chain amino acids in muscle and plasma.

BACKGROUND/AIMS: Exogenous hyperammonemia is known to decrease the plasma levels of branched-chain amino acids (BCAA). To investigate whether changes in intracellular amino acid concentrations of muscle are associated with and may, at least in part, mediate this effect, experiments were carried out on a total of 60 male Wistar rats. METHODS: Five groups were formed in a randomized manner. Group A: no treatment; groups B1 and B2: 2-hour and 6-hour continuous central-venous infusions, respectively, of sodium salts; groups C1 and C2: 2-hour and 6-hour infusions of ammonium salts. We obtained venous blood samples and muscle biopsies. Plasma ammonia, whole blood glucose, serum insulin, blood pH, and amino acids in plasma as well as in the intracellular water of muscle were measured. RESULTS: As compared with control group A, groups C1 and C2 displayed a 3.3- and a 4-fold increase, respectively, in the plasma ammonium concentration. Regarding insulin, the ammonium-infused rats were similar to group A but not to the sodium-infused B groups, which had significantly lower insulin concentrations. Administering ammonium brought about a decline in BCAA concentrations in plasma after 2 hours and in muscle after 6 hours. The ammonium-induced fall in intracellular BCAA values was preceded by an increase of glutamine as well as by a decrease of glutamate and alanine in both plasma and muscle. CONCLUSIONS: It is pointed out that the inter-group differences in serum insulin, although possibly accounting for some of the findings, can by no means explain the entire pattern of amino acid concentrations seen after the ammonium infusions. Instead, our results agree with the hypothesis that hyperammonemia indirectly lowers the plasma levels of BCAA by stimulating glutamine synthesis, thus reducing the intracellular glutamate pool, which is likely to be restored, at least in part, by an intensified BCAA transamination. Clarification is needed as to whether carbon skeletons derived from valine and isoleucine additionally contribute to replenishing the glutamate pool.

Alanine↗

The effect of dialysis on radiocaesium in man.

Dialysis is used for cleaning the blood in patients with end-stage renal disease. The most common methods are hemodialysis (HD) and peritoneal dialysis (PD). Dialysis patients might constitute a critical group because of poor elimination of radioactive elements ingested. On the other hand dialysis may be a useful decontamination method for radioactivity. The effect of dialysis on the turnover of radiocaesium was studied in 10 HD patients and 4 PD patients. The dialysis fluid, which contains electrolytes and the metabolic waste products, was analyzed for radiocaesium. In this connection the patients were whole-body counted for radiocaesium and 40K. The results show that HD patients generally have a lower body burden of radiocaesium than normal subjects, while PD patients show normal levels. At steady state both dialysis methods eliminate slightly less radiocaesium than normal kidneys do, but in the case of HD during a much shorter time. The calculated effective half-life for radiocaesium was normal in the HD patients, and somewhat longer in the PD patients. Considering that HD is performed only for 12-15 h weekly, the elimination rate of radiocaesium by HD is much higher compared with that by normal kidneys. Thus, HD might constitute an important method for decontamination of radiocaesium after accidental internal contamination.

Body Burden↗

Substrate balances across colonic carcinomas in humans.

To investigate the utilization of nutrients by malignant tumors in humans, the balances of energy-yielding substrates and amino acids across colonic carcinomas were assessed in 17 patients during surgery. Blood samples were taken from an artery and the main tumor-draining vein, which was also used for determining tumor blood flow (direct venous outflow technique). Additionally, the substrate exchange by peripheral tissues was studied (femoral arteriovenous differences, venous occlusion plethysmography). Mean blood flow was greater in the carcinomas than in the leg tissues (43.2 versus 2.5 ml/100 ml/min; P < 0.001). There was a negative correlation between tumor blood flow and tumor weight (r = -0.87; P < 0.001). Glucose net uptake and lactate release by the malignancies exceeded the peripheral exchange rates 30- and 43-fold, respectively (mean values different at P < 0.001). The molar ratio of lactate output to glucose consumption was 0.78 in the tumors and 0.48 in the leg tissues (P < 0.05). Regarding free fatty acid and ketone body balances, no significant tumor-periphery differences were noted. The carcinomas utilized branched chain amino acids and serine, while alanine and, in particular, ammonia were released in large amounts. Net glutamine retention was not consistently observed. It is concluded that the energy metabolism of human colonic carcinomas relies predominantly on glucose, with fat-derived calories making no appreciable contribution. The impaired nutritive perfusion of malignant tumors appears to favor glycolysis and to limit both glucose oxidation and glutaminolysis. The present study has shown that the procedure chosen for the assessment of trans-tumor substrate flux rates is a workable and valid model for analyzing metabolic balances across human colonic cancers in vivo.

Adult↗

Protein metabolism in human colon carcinomas: in vivo investigations using a modified tracer technique with L-[1-13C]leucine.

To quantify the protein anabolism of tumors it is not sufficient simply to determine the level of protein synthesis. The decisive factor is the net balance. This is the first attempt to establish this parameter in human tumors in vivo. Intraoperative tumor leucine/protein metabolism was studied in 15 patients with resectable malignant colon tumors using a balance model and L[1-13C]leucine as the tracer substance. Comparative measurements were also carried out simultaneously for peripheral tissue (forearm); in addition, protein kinetics parameters were established for the whole body using a proven two-pool model (with the same tracer as above). In view of the frequently conflicting data on amino acid metabolism in tumors, the tumoral and peripheral exchange rates of 20 amino acids were also determined. In tumors, essential and branched-chain amino acid uptakes were found to be 1.68 +/- 0.59 (SE) and 1.52 +/- 0.23 mumol/100 g tissue/min, respectively; in peripheral tissue there was overall an amino acid release [-0.11 +/- 0.06 and -0.05 +/- 0.04 mumol/100 g/min; in either case P < 0.01 (tumor versus periphery)]. Tracer analyses yielded a net retention for the tumors but a protein loss for peripheral tissue (8.941 +/- 3.113 versus -0.557 +/- 0.53 g/kg/24 h; P < 0.01) and for the whole body (-0.363 +/- 0.04 g/kg/24 h). The tumors were divided into two prognostic groups on the basis of their histology. Significant differences were found between the two groups in terms of the net retention rate for 10 amino acids, including leucine; retention was elevated in tumors with an unfavorable prognosis, possibly due to a higher amino acid requirement because of more rapid growth or for export processes (mucus production). The protein balance model used here has proved satisfactory for our purposes and could also be used to directly evaluate dietary measures (e.g., adjuvant parenteral nutrition in connection with chemotherapy).

Aged↗

Distribution and coassociations of selected metals in seals of the Antarctic.

Zinc, Cu, Cd, Pb, Ag, Ni, Co, Cr, Fe and Mn concentrations in some tissues of crabeater seal (Lobodon carcinophagus), leopard seal (Hydrurga leptonyx) and Weddell seal (Leptonychotes weddelli) from the Antarctic were determined. Distinct inter-tissue differences in metal concentrations in seals were observed; liver contained maximum levels of Zn, Cu, Ag and Mn, whilst kidney showed the highest levels of Cd, Ni and Co. Muscle was characterized by low concentrations of all the elements analyzed. The metal concentrations in the vertebrates analyzed were compared with those for organisms originating from various aquatic areas. Significant correlations were found between the levels of several of the metals analyzed, e.g. between renal and hepatic concentrations of Zn and Cd. Strong relationships between the hepatic concentrations of some metals were found, e.g. Cd-Zn. These two metals also showed a significant coassociation in their renal concentrations. The slope of the regression line for renal Cd/Zn was about three times higher than the hepatic one and this may reflect a relatively high Cd exposure, probably from specific food (squid and krill) provenance, of the seals analyzed.

Journal Article↗

Nickel-63 in Baltic fish and sediments.

The determination of 63Ni was carried out on fish samples of cod (Gadus morhua), herring (Clupea harengus), sprat (Sprattus Sprattus) and samples of sediment core from the Gdańsk Bay. In contrast to stable nickel, 63Ni is non-uniformly distributed within the fish. More than 95% of total 63Ni content in cod and herring is located in fillet with skin and scale. Our data suggesting, that mechanism for uptake of 63Ni in cod and herring is by passive adsorption onto the surface of skin and scale mucus. The concentration of 63Ni in analysed sediment lies within the range from 0.5 to 3.8 mBq.g-1 dry wt, while values of its specific activity ranged between 10 and 70 Bq.g-1.

Animals↗

Concentration of selected metals in penguins and other representative fauna of the Antarctica.

Concentration of Zn, Cu, Cd, Pb, Ag, Co, Ni, Cr, Mn and Fe were determined in muscle and liver of three species of penguins and other animals of the antarctic region. Liver was characterized by maximum concentrations of all the metals analyzed. The element levels in the samples assayed are in keeping with those reported previously by other authors. It is assumed that specific food habits of penguins are mainly responsible for elevated Cd levels in livers of these birds.

Animals↗

Food.

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Animals↗

Mercury and major essential elements in seals, penguins, and other representative fauna of the Antarctic.

Concentrations of total Hg and major essential elements, Ca, Mg, Na, and K, were measured in the muscle, liver, and kidney of three species of seals, crabeater seal (Lobodon carcinophagus), leopard seal (Hydrurga leptonyx), and Weddell seal (Leptonychotes weddelli) collected in the Antarctic. The muscle and liver of three species of penguins, i.e., gentoo penguin (Pygoscelis papua), Adelie penguin (P. adeliae), chinstrap penguin (P. antarctica), and other representative fauna were also analyzed for the elements. Distinct inter-tissue differences in the metal concentration were observed; liver had the greatest concentrations of Hg, kidney showed maximum concentration of Ca and Na, while muscle was characterized by the greatest content of Mg and K. Inter-specimen differentiation of concentrations among the same species was distinctly visualized for Hg but not for the major essential elements. The Hg concentration in the seals analyzed are in keeping with those reported previously by other authors. Such comparison for Ca, Mg, Na, and K was impossible because of the lack of available literature data for their concentrations in marine seals. Numerous significant correlations were observed between concentrations of the several metals analyzed. There was no correlation between Hg, which is a non-essential element and both Zn and Cd which are essential and non-essential elements, respectively in the liver or kidney of seals. However, there were significant correlations between concentration of Zn and the sum of molar concentrations of Hg+Cd in kidney (r = 0.82) and liver (r = 0.76). The results suggest that several control mechanisms operate to maintain physiologically required levels that decreases any effect of heavy metal toxicants such as Hg and Cd.

Animals↗

Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design.

This paper documents dose-dependent effects of ornithine aspartate (OA) on postprandial hyperammonemia and plasma amino acids. Ten patients with cirrhosis were randomized to undergo 1 out of 4 infusion series. Each series consisted of four 8-h infusions (09:00 h-17:00 h), with placebo (NaCl), 5 g, 20 g or 40 g of OA being administered on separate days in varying sequences. This 4-fold crossover design was double-blind. On infusion days, patients received 2 oral protein loads (0.25 g/kg at 09:00 h and 0.5 g/kg at 13:00 h). Venous blood samples were drawn every 2 h and the 24-h urine was collected. In addition to measuring plasma ammonia and amino acids, the urea production rate, serum glucose and serum insulin were analyzed. A significant postprandial rise in the ammonia concentration was noted during the infusions of placebo and 5 g of OA but did not occur with the dosages of 20 g (after the second protein load) and 40 g (after both protein loads). Furthermore, the latter dose, compared with placebo, significantly reduced plasma ammonia after the minor protein load. Urea production rate increased when 20 g or 40 g of OA was administered. Of the amino acids involved in the metabolic pathways of ornithine and/or aspartate, glutamate showed a rise in its plasma level following infusion of 40 g of OA, whereas glutamine did not. Concentrations of methionine, phenylalanine, tyrosine, threonine, serine and glycine declined progressively with increasing doses of OA (5-40 g). The highest dose of the drug caused hyperglycemia and hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Haemodilution in acute ischaemic stroke comparison of two haemodilution regimen.

In a prospective study we randomly allocated 50 patients with acute ischaemic stroke in the area of the middle cerebral artery within 12 hours after onset to two moderate hypervolemic haemodilution regimen consisting of 500 ml of 10% hydroxyethyl starch per day for 10 days. In the high haematocrit group the target haematocrit of 41-42% was achieved by 0-3 phlebotomies and additional replacement of that volume with the colloid in 3 days. In the low haematocrit group with 1-4 phlebotomies a target haematocrit of 37-38% was reached in 4 days. The groups did not differ regarding age, risk factors, haematocrit and neurological score. The improvement of the disturbed blood rheology was more pronounced in the low haematocrit group. One death occurred in each group. The neurological score showed a significantly greater increase in the low haematocrit group with +59% at day 5 and +125% at day 11; the data for the high haematocrit group were +34% and +89% respectively. We calculated a correlation (r = 0.36, p less than 0.02) between the rise in neurological score and the reduction of haematocrit. Our data suggest but not do prove that an early start on moderate hypervolemic haemodilution is beneficial in patients with acute ischaemic stroke and disturbed blood rheology.

Aged↗

Intra-neural electrical stimulation of cutaneous nociceptive fibres in humans: effects of different pulse patterns on magnitude of pain.

A study was performed to elucidate how different impulse frequencies and impulse patterns in cutaneous nociceptive fibres influence the subjective magnitude of pain. Groups of nociceptive A delta and C fibres were co-activated by electrical intraneural stimulation at constant intensity in cutaneous fascicles of the peroneal nerve in healthy human subjects. The resulting pain sensations were rated on a modified visual analogue scale. Five-second trains were administered randomly at irregular intervals of at least 30 s. Five of the stimulus patterns had regular interpulse intervals, corresponding to frequencies of 1, 2, 4, 10 and 15 Hz, and three other patterns were constructed to mimic to some extent the initially phasic and subsequently slowly adapting discharge patterns which may be encountered in recordings from human nociceptors. The results from these experiments using stimulation frequencies within physiological discharge ranges for human nociceptors indicate that the subjective magnitude of pain increases monotonously as a function of stimulus frequency, and that patterns mimicking nociceptor discharges in response to natural stimuli give rise to greater peak magnitudes of pain than artificial regular patterns with a corresponding number of impulses.

Adult↗

Comparison between Cytobrush and Papaplast in sampling vaginal smears.

The ability of Cytobrush and Papaplast to collect endocervical cells in vaginal smears was tested in a prospective randomized comparative study including 107 women. Endocervical cells were found more often and in greater numbers with Cytobrush, also in women over 50 years of age. Papaplast missed endocervical cells twice as often as did Cytobrush. The use of the latter instrument meant that the number of repeat smears necessitated due to the absence of endocervical cells could be considerably reduced, with consequent improvement in the cost/benefit ratio.

Adult↗

[The action profile of D,L-kavain. Cerebral sites and sleep-wakefulness-rhythm in animals].

To investigate neurophysiological effects of D,L-kavain, two studies were conducted on unrestrained cats with chronically implanted electrodes. In group A animals (n = 26) we recorded the blood pressure, the EEG of cortical and subcortical areas, the electromyogram, EEG arousal reactions, and subcortical evoked potentials elicited by central stimulation. This was done before and after injection of D,L-kavain (10-50 mg/kg i.p.) or--for comparison--of a kava extract in Ol. arachidis (50-100 mg pyrones/kg i.p.). Group B cats (n = 9) served for polygraphic, 10-h analyses of the sleep-wakefulness rhythm; they received--in a random sequence--0.9% NaCl (3 ml i.p.), D,L-kavain (28 mg/kg p.o.), pentobarbital (1 mg/kg i.m.), or the combination D,L-kavain plus pentobarbital. With both D,L-kavain and the extract, muscle tone was seen to be diminished in about 50% of the experiments. It was only the extract which exerted marked effects on the EEG; it induced high amplitude delta waves, spindle-like formations, and a continuous alpha- or beta-synchronization in the amygdalar recordings (p less than 0.001). Neither D,L-kavain nor the kava extract changed the threshold of the EEG arousal reaction. As to the evoked potentials, the hippocampal response following stimulation of the amygdalar nucleus showed an increase in amplitude in the animals given D,L-kavain (50 mg/kg; p less than 0.05) and in those given the extract (100 mg pyrones/kg; p less than 0.01). In addition, after injection of the extract, further projections arising from the amygdala as well as the connection from the caudate nucleus to the amygdala proved to be activated. The percentage duration of active wakefulness was significantly shortened by both D,L-kavain and pentobarbital, as compared to placebo. There was a likewise significant prolongation of synchronized sleep with D,L-kavain, pentobarbital, and the combination of both these agents. However, a potentiation of drug effects failed to occur. It is concluded from the findings that limbic structures and, in particular, the amygdalar complex represent the preferential site of action for both D,L-kavain and the kava extract. The participation of these structures in modulating emotional processes may explain the promotion of sleep, even in the absence of sedation. There is no congruity of D,L-kavain with either the tricyclic thymoleptics or the benzodiazepines regarding the profile of neurophysiological effects.

Animals↗