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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 55 (1982), S. 309-315 
    ISSN: 1435-1463
    Keywords: Hepatic coma ; L-valine binding ; branched chain amino acids
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serotonin (5-HT) receptors are modulated by L-valine (VAL). For further characterization of this effect a binding assay of [14C]-L-VAL has been developed. A brief description of the experimental conditions is given. Moreover, measurement of VAL-binding has been applied to human brain tissue either from controls or hepatic failure. A marked increase of VAL-binding sites with no change in affinity was noted in hepatic coma, while in patients treated with parenteral nutrition plus VAL no such change could be measured. It is concluded that the beneficial therapeutic effects of VAL in hepatic encephalopathy are, at least in part, due to its modulating action on post-synaptic receptor membranes.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 64 (1986), S. 615-618 
    ISSN: 1432-1440
    Keywords: Fructose ; Hyperlactemia ; Hyperosmolar syndromes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Severe hyperlactemia of 8.7, 8.6 and 7.9 mmol/l, respectively, developed in three patients with hyperosmolar syndromes (two hypernatremic, 417 and 415 mosmol/kg H2O; one hyperglycemic 437 mosmol/kg H2O) during rehydration treatment with 5% fructose in water (fructose dosage 0.5 g/kg body wt. per hour). After resolution of the electrolyte disturbances, the infusion of fructose at the same dosage increased the plasma lactate concentration in two of the patients to 4.9 and 4.0 mmol/l, indicating near normalization of hepatic lactate utilization. Thus, in addition to peripheral insulin resistance and decreased muscular glucose utilization, the hyperosmolar state is associated with a reduced tolerance to fructose. This is most likely due to an osmolality-dependent impairment of hepatic gluconeogenesis. In rehydration therapy for hyperosmolar syndromes, fructose-containing infusion solutions should no longer be used.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Catecholamines ; Octopamine ; Hepatic coma ; Sympathetic nervous system ; Katecholamine ; Octopamin ; Coma hepaticum ; Sympathisches Nervensystem
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Plasmaspiegel von Adrenalin, Noradrenalin und Octopamin wurden mit Hilfe radioenzymatischer Methoden bei neun ambulanten Zirrhose-Patienten mit Enzephalopathie und bei zehn Patienten im Coma hepaticum (Comagrad III–IV) bestimmt. Bei den Zirrhose-Patienten wurden sowohl normale als auch erhöhte Plasmaspiegel von Noradrenalin gemessen. Octopamin war im Plasma dieser Patienten sowie bei zehn gesunden Kontrollpersonen nicht nachweisbar. Erhöhte Noradrenalinspiegel im Plasma waren bei allen Patienten im Coma hepaticum vorhanden. Die Noradrenalinkonzentration im Plasma blieb auch während des Comaverlaufes erhöht oder stieg weiter an. Der Adrenalinplasmaspiegel war hingegen nicht regelmäßig erhöht. In acht der zehn Patienten war Octopamin wiederum nicht nachweisbar. Nur bei zwei Coma-Patienten konnten Octopaminspiegel bis zu 59,5 ng/ml bei gleichzeitiger Erhöhung der Noradrenalinkonzentration gefunden werden. Die Infusion der verzweigtkettigen Aminosäure L-Valin beeinflußte weder den Noradrenalin- noch den Octopaminspiegel. Die Ergebnisse sprechen dafür, daß die Aktivität des sympathischen Nervensystems im Coma hepaticum erhöht ist. Eine Akkumulierung von Octopamin ist kein charakteristischer Befund bei chronischer Lebererkrankung und hepatischem Coma. Nachdem bei zwei Coma-Patienten die Akkumulierung von Octopamin bei einer gleichzeitigen Erhöhung des Noradrenalinspiegels auftrat, erscheint eine Verdrängung von Noradrenalin durch den falschen Neurotransmitter Octopamin im noradrenergen Neuron des peripheren Sympathikus unwahrscheinlich. Die Resultate sprechen dafür, daß die Entwicklung einer Hypotension im Rahmen der Leberzirrhose und des Coma hepaticum nicht auf einen Mangel an Noradrenalin zurückzuführen ist.
    Notes: Summary Plasma levels of adrenaline, noradrenaline and octopamine were estimated by a radioenzymatic method in nine cirrhotic outpatients with encephalopathy and in ten patients with hepatic coma (coma grade III–IV). In the cirrhotic outpatients normal as well as elevated plasma levels of noradrenaline were found. Octopamine could not be detected in the plasma of these patients as well as of ten healthy volunteers. Elevated noradrenaline levels were present in all patients with hepatic coma. Plasma noradrenaline remained elevated or even further increased during the course of hepatic coma, whereas adrenaline was elevated less frequently. In eight of the ten patients with hepatic coma octopamine was again not detectable in plasma. Only in two patients high levels of octopamine up to 59.5 ng/ml could be found in addition to increased noradrenaline concentrations. The infusion of the branched chain amino acid L-valine had no influence on the plasma level of either noradrenaline or octopamine. The data indicate that the sympathetic nervous system is activated during the course of hepatic coma. An accumulation of octopamine is not a common finding in chronic liver disease and hepatic coma. Since in the two patients with elevated octopamine levels the rise in octopamine occured concomitantly with a rise in noradrenaline, a displacement of noradrenaline by the false neurotransmitter octopamine in the noradrenergic neuron of the peripheral sympathetic nervous system seems unlikely. The results indicate that the development of hypotension in the course of liver cirrhosis and hepatic coma cannot be related to a deficiency of noradrenaline.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    World journal of surgery 10 (1986), S. 20-32 
    ISSN: 1432-2323
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Un apport nutritif adéquat est essentiel pour assurer la guérison d'un traumatisme, une relation étroite existant entre le traumatisme et le catabolisme au cours de la phase catabolique. Lors des dernières années de nombreuses contre-indications envers la perfusion intraveineuse d'emulsions de graisse ont été soulevées mais elles se sont avérées peu fondées. La création récente d'émulsions graisseuses et de solutions complexes (all-in-one solution) perfusables par voie intraveineuse pour assurer l'alimentation parentérale chez les blessés présentant ou non des complications majeures a été couronnée de succès. Les examens précis de la stabilité des graisses en émulsion dans les solutions complexes: modifications visibles à l'oeil nu, anomalies à l'exploration microscopique classique ou électronique, étude des liposomes montrent que les émulsions de graisse ne présentent pas de dangers pour assurer l'alimentation parentérale. La réponse métabolique au traumatisme et à l'opération est caractérisée par deux phases: la phase de choc suivie de la phase catabolique. Alors que dans la première phase l'alimentation n'est pas indiquée, dans la deuxième phase l'alimentation parentérale avec un produit complexe est indispensable en raison de la diminution de l'apport énergétique et de l'augmentation des besoins nutritifs dus à la blessure ou à des complications telles que l'infection ou la défaillance organique. Il est plus que probable que l'apport énergétique pour obtenir un état nutritif suffisant sans provoquer de troubles métaboliques consiste en l'emploi d'une part d'hydrates de carbone, d'autre part de graisses contenues dans une même préparation et administrées par voie intraveineuse. Les diverses expériences qui ont été rassemblées montrent que la part des graisses employées comme source énergétique chez les blessés ou les opérés présentant ou non des complications majeures (diabète, pancréatite aiguë, défaillance rénale aiguë, insuffisance hépatique grave, infection) diminue les désordres métaboliques et améliore l'état nutritif. Après plusieurs années d'une étude mondiale, à la fois expérimentale et clinique l'emploi des graisses est contre-indiqué seulement dans la phase de choc ou lorsque des troubles primitifs ou secondaires du métabolisme graisseux se traduisent par un taux sérique de triglycéride supérieur à 4.5 mmol/l au cours de l'alimentation parentérale continue.
    Abstract: Resumen Una adecuada nutrición es factor esencial para la recuperación después de trauma y de enfermedad grave; existe una relación bastante precisa entre la severidad de la lesión y el catabolismo en la fase “flow” (la fase hipermetabólica e hipercatabólica descrita por Cuthbertson). En el curso de los últimos años se han discutido muchas de las contraindicaciones para la infusión intravenosa de emulsiones de grasa y se ha encontrado que en general no son válidas. El desarrollo de emulsiones intravenosas de grasa para aplicación clínica y la introducción de las soluciones “Todas-en-Una” (TEU) para la nutrición intravenosa continua han significado un notable éxito en el cuidado de pacientes traumatizados con y sin complicaciones mayores. Investigaciones cuidadosas sobre la estabilidad de las emulsiones de grasa en soluciones TEU mediante el examen de alteraciones visibles, anormalidades bajo microscopía de luz y electrónica, determinación de potencial zeta y conteo de coulter del tamaño y distribución de los liposomas, han revelado que las emulsiones de grasa son seguras en programas de nutrición parenteral a largo plazo. La respuesta metabólica al trauma y a la operación se caracteriza por una fase “ebb” (o de shock) y una fase “flow” (hipermetabólica y catabólica). En tanto que no hay indicación para nutrición parenteral en pacientes en la fase “flow” o de shock, los pacientes en la fase “flow” o catabólica, la cual resulta de la combinación de provisión nutricional disminuida con requerimientos nutricional aumentados por efecto de la lesión y sus complicaciones de sepsis y falla orgánica, presentan clara indicación para nutrición intravenosa sofisticada. La mejor posibilidad de lograr una nutrición suficiente y evitar trastornos metabólicos, es mediante la partición de la provisión energética entre carbohidratos y grasa, y la administración intravenosa continua en soluciones TEU. Las experiencias adquiridas con la administración de soluciones TEU revelan que la utilización de grasa como fuente energética en los pacientes traumatizados con y sin complicaciones mayores (diabetes mellitus, pancreatitis aguda, falla renal aguda, insuficiencia hepática y sepsis) atenúa la alteración metabólica y eleva el estándar del soporte nutricional. Después de muchos años de amplia investigación experimental y clínica se ha establecido que la grasa sólo está contraindicada en la fase de shock y en casos de alteraciones primarias o secundarias del metabolismo graso que puedan dar lugar a niveles séricos de triglicéridos superiores a 4.5 mmol/l en el curso de la nutrición intravenosa continua.
    Notes: Abstract Adequate nutrition is essential to recover from injury. There is a close correlation between the severity of injury and the catabolism in the flow phase. During the last few years, many contraindications against the intravenous infusion of fat emulsions have been discussed and determined to be invalid. The development of clinical applicable intravenous fat emulsions and the introduction of all-in-one (AIO) solutions for continuous intravenous nutrition have been a great success in the care of injured patients with and without major complications. Careful investigations of the stability of fat emulsions in AIO solutions by examination of visible changes, light and electron microscopic abnormalities, zeta potential, and coulter counting of the size distribution of liposomes revealed that fat emulsions are now safe for long-term complete parenteral nutrition. The metabolic response to trauma and operation is characterized by the ebb and flow phase. While the patients in the ebb or shock phase should not receive nutrition, patients in the flow or catabolic phase resulting from the combination of decreased nutritional intake and increased nutritional requirement due to injury and its complication as sepsis and organ failure should receive sophisticated intravenous nutrition. The most probable means of achieving sufficient nutrition without metabolic derangement is the partitioning of the energy supply on carbohydrates and fat and the continuous intravenous administration of an AIO solution. Data that have been gathered reveal that the partial use of fat as energy source in injured patients with and without major complications (diabetes mellitus, acute pancreatitis, acute renal failure, liver insufficiency, and sepsis) diminishes the metabolic derangements and improves the standard of nutritional care. After many years of worldwide experimental and clinical investigations, fat is contraindicated only in the shock phase and in primary or secondary disturbances of fat metabolism that lead to a triglyceride level in serum above 4.5 mmol/l during continuous intravenous nutrition.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 43 (1978), S. 63-68 
    ISSN: 1432-0533
    Keywords: Monoamines ; Indoleamines ; Serotonin ; Hepatic encephalopathy ; Metabolic coma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Dopamine (DA) serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA), and tryptophan (Trp) were assayed spectrofluorometrically in various brain regions of 10 patients with acute hepatic coma, in 3 cases of uremic coma, 4 cases of diabetic coma, in three patients with liver cirrhosis without coma, and in 5 cases of hepatic coma treated by parenteral nutrition withi-valine a branched-chain amino acid. The results were as follows: 1. In all types of coma, brain DA showed a mild general decrease, the average reduction being 20 to 30% of the controls. 2. In hepatic and other metabolic comata, brain 5-HT and 5-HIAA were generally increased, most significantly in the brainstem tegmentum and parts of the limbic system. 3. Brain Trp was significantly increased in hepatic coma, with the highest elevation in the brainstem tegmentum. 4. In liver cirrhosis without coma, brain 5-HT was within normal range, while Trp and 5-HIAA were elevated in the brainstem, their increase being much less than in untreated hepatic coma. 5. In hepatic coma treated by parenterali-valine, brain Trp showed slight elevation similar to non-comatose cirrhosis, while 5-HIAA showed almost normal values, and 5-HT was even decreased in most brain areas. These preliminary results in human postmortem brains confirm previous CSF and brain findings in experimental and human hepatic and uremic encephalopathies, indicating considerable derangement in central monoamine neurotransmitters which are attributed, at least in part, to amino acid imbalance in plasma and brain. Increased 5-HT synthesis or turn-over in the ascending serotonergic brainstem systems might represent one biochemical substrate of clinical disorders of consciousness in hepatic failure and other metabolic catastrophes. Manipulation of plasma and hence brain amino acids may influence neurological symptoms of hepatic encephalopathy by changing the brain neurotransmitter profile.
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  • 6
    ISSN: 1432-1238
    Keywords: Diabetic ketoacidosis ; Fluid replacement ; Extravascular lung water ; Colloid-osmotic pressure ; Pulmonary hemodynamics ; Pulmonary gas exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fluid replacement is a major issue in the treatment of patients with diabetic ketoacidosis. During this therapy, development of pulmonary edema has been reported and attributed to an increase in pulmonary microvascular pressure and a decrease in colloid-osmotic pressure (COP). Because clinically apparent pulmonary edema is associated with an increase in extravascular lung water (EVLW) and impairment of pulmonary gas exchange, we studied the effect of fluid replacement on EVLW, COP, pulmonary hemodynamics and gas exchange parameters in 8 patients with diabetic ketoacidosis (blood glucose〉300 mg/dl, pH〈7.1). EVLW was estimated by the thermal-dye technique. All variables were successively determined upon adminssion (A), after initial fluid replacement (IFR), when glucose had fallen below 180 mg/dl, after 8 h of intravenous glucose treatment (G), and after 24 h of total parenteral nutrition (TPN). Despite a total net fluid intake of 6.0±1.61, a significant decrease (p〈0.001) in COP from 29.6±5.5 at A to 18.8±2.2 mmHg after TPE and a significant increase (p〈0.001) in PCWP from 4±2 at A to 10±3 mmHg after TPE, EVLW remained almost unchanged. EVLW was 5.1±2.8 at A, 5.3±2.1 after IFR, 4.8±1.4 after G, and 5.3±1.7 ml/kg after TPN. However, PaO2 decreased from 137±17 at A to 87±10 mmHg after TPE (p〈0.001), while Qs/Qt increased significantly (p〈0.05). The alterations in gas exchange may be indicative of pulmonary dysfunction but as they were not associated with accumulation of EVLW, they may as well reflect the compensation of metabolic derangements in diabetic ketoacidosis.
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  • 7
    ISSN: 1432-1238
    Keywords: Pulmonary edema ; Chest X-ray ; Extravascular lung water ; Thermal-dye technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Extravascular lung water (EVLW) was estimated in 53 critically ill patients by the chest radiograph (CXR) and the thermal dye technique. The comparison between these two methods revealed a direct and positive correlation (r=0.83, p(0.001). However, EVLW-values obtained by the thermal dye technique showed considerable overlap between cases of radiographic low grade pulmonary edema and we were able to identify several reasons for radiographic over- or underestimation of EVLW. in these patients EVLW-measurement by the thermal dye technique provides additional information, thereby probably influencing further treatment.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 47 (1981), S. 241-243 
    ISSN: 1432-0738
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 9
    Publication Date: 2017-12-02
    Description: Contrary to findings in the human brain, 18 F-FDG PET shows cerebral hypermetabolism of aged wild-type (WT) mice relative to younger animals, supposedly due to microglial activation. Therefore, we used dual-tracer small-animal PET to examine directly the link between neuroinflammation and hypermetabolism in aged mice. Methods: WT mice (5–20 mo) were investigated in a cross-sectional design using 18 F-FDG ( n = 43) and translocator protein (TSPO) ( 18 F-GE180; n = 58) small-animal PET, with volume-of-interest and voxelwise analyses. Biochemical analysis of plasma cytokine levels and immunohistochemical confirmation of microglial activity were also performed. Results: Age-dependent cortical hypermetabolism in WT mice relative to young animals aged 5 mo peaked at 14.5 mo (+16%, P 〈 0.001) and declined to baseline at 20 mo. Similarly, cortical TSPO binding increased to a maximum at 14.5 mo (+15%, P 〈 0.001) and remained high to 20 mo, resulting in an overall correlation between 18 F-FDG uptake and TSPO binding (R = 0.69, P 〈 0.005). Biochemical and immunohistochemical analyses confirmed the TSPO small-animal PET findings. Conclusion: Age-dependent neuroinflammation is associated with the controversial observation of cerebral hypermetabolism in aging WT mice.
    Print ISSN: 0022-3123
    Topics: Medicine
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  • 10
    Publication Date: 2016-06-02
    Description: Amyloid imaging by small-animal PET in models of Alzheimer disease (AD) offers the possibility to track amyloidogenesis and brain energy metabolism. Because microglial activation is thought to contribute to AD pathology, we undertook a triple-tracer small-animal PET study to assess microglial activation and glucose metabolism in association with amyloid plaque load in a transgenic AD mouse model. Methods: Groups of PS2APP and C57BL/6 wild-type mice of various ages were examined by small-animal PET. We acquired 90-min dynamic emission data with 18 F-GE180 for imaging activated microglia (18-kD translocator protein ligand [TSPO]) and static 30- to 60-min recordings with 18 F-FDG for energy metabolism and 18 F-florbetaben for amyloidosis. Optimal fusion of PET data was obtained through automatic nonlinear spatial normalization, and SUVRs were calculated. For the novel TSPO tracer 18 F-GE180, we then calculated distribution volume ratios after establishing a suitable reference region. Immunohistochemical analyses with TSPO antisera, methoxy-X04 staining for fibrillary β-amyloid, and ex vivo autoradiography served as terminal gold standard assessments. Results: SUVR at 60–90 min after injection gave robust quantitation of 18 F-GE180, which correlated well with distribution volume ratios calculated from the entire recording and using a white matter reference region. Relative to age-matched wild-type, 18 F-GE180 SUVR was slightly elevated in PS2APP mice at 5 mo (+9%; P 〈 0.01) and distinctly increased at 16 mo (+25%; P 〈 0.001). Over this age range, there was a high positive correlation between small-animal PET findings of microglial activation with amyloid load ( R = 0.85; P 〈 0.001) and likewise with metabolism ( R = 0.61; P 〈 0.005). Immunohistochemical and autoradiographic findings confirmed the in vivo small-animal PET data. Conclusion: In this first triple-tracer small-animal PET in a well-established AD mouse model, we found evidence for age-dependent microglial activation. This activation, correlating positively with the amyloid load, implies a relationship between amyloidosis and inflammation in the PS2APP AD mouse model.
    Print ISSN: 0022-3123
    Topics: Medicine
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