Ruth Exner

University of Vienna, Vienna, Vienna, Austria

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Publications (6)17.86 Total impact

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    ABSTRACT: Catecholamines play a central role in the treatment of sepsis-associated hypotension. However, these hormones have also been shown to modulate the lipopolysaccharide (LPS)-induced induction of cytokines such as tumor necrosis factor alpha, interleukin (IL)-10, and IL-6 in vitro and in human endotoxemia. We hypothesized that catecholamines applied therapeutically in septic shock also influence cytokine patterns. We studied the cytokine response in tissues of the splanchnic compartment in a porcine endotoxin shock model up to 4 h. Shock was induced by a short infusion of LPS, and animals were treated either with fluid resuscitation alone or in combination with continuous epinephrine or norepinephrine. Animals, receiving epinephrine therapy, showed a significantly prolonged upregulation of IL-6 mRNA expression at 4 h after LPS application in liver (P = 0.0014), spleen (P < 0.0001), and mesenteric lymph nodes (P = 0.0078) as compared with animals treated with norepinephrine or fluid resuscitation. Serum IL-6 increased over time in all groups. The total concentration of the cytokine (area under the curve) was significantly higher in the epinephrine group as compared with the norepinephrine and fluid resuscitation groups (P = 0.017). The peak of serum tumor necrosis factor alpha at 1 h after LPS application was already significantly reduced by epinephrine, which was only administered at a mean of less than 0.05 microg/kg/min at this time point (P < 0.01). None of the catecholamines had a significant effect on IL-10 serum levels when compared with animals receiving fluid resuscitation alone. Our data suggest that the therapeutic application of epinephrine but not of norepinephrine is associated with a profound effect on the IL-6 response of splanchnic reticuloendothelial tissues.
    Shock 01/2004; 20(6):575-81. · 2.61 Impact Factor
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    ABSTRACT: To investigate whether the administration of different glutamine-containing dipeptides, glycyl-l-glutamine (GLY-GLN) and l-alanyl-l-glutamine, has a differing impact on perioperative immunomodulation. Surgery leads to transitory immunosuppression, which is associated with decreased plasma glutamine (GLN) levels and increased susceptibility to infection and sepsis. A useful tool to detect immunocompetence is the ex vivo lipopolysaccharide (LPS)-stimulated tumor necrosis factor alpha (TNF-alpha) secretion in whole blood. Forty-five patients undergoing major abdominal surgery were randomized prospectively to receive 0.5 g/kg/24 h GLN dipeptides administered as GLY-GLN or as ALA-GLN or isonitrogenous Vamin (a GLN-free amino acid solution; control group) as a continuous infusion over 72 hours, starting 24 hours before surgery. Blood samples were collected before infusion, at the end of surgery, and 48 hours postoperatively to determine the TNF-alpha release into whole blood stimulated with LPS. Groups were compared by analysis of variance. The groups were comparable in age, gender distribution, and length of operative time. At the end of surgery a significant reduction in ex vivo LPS-stimulated TNF-alpha production was observed in all groups. In patients who received GLY-GLN, the induced TNF-alpha production was restored after 48 hours. In this study perioperative infusion of GLY-GLN reduced immunosuppression. The effect of GLN-containing dipeptides seems to be different when administered in glycine or alanine form.
    Annals of Surgery 02/2003; 237(1):110-5. · 6.33 Impact Factor
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    ABSTRACT: In patients operated on for severe acute pancreatitis (SAP) the impact of the timing of operation on outcome is controversial. In a retrospective analysis of a prospectively documented database, we studied 250 patients suffering from SAP, who were in need for surgical treatment during their course of disease. From 1982 to 1998, 250 patients with the diagnosis of SAP who required operative treatment were admitted to the intensive care unit (ICU) of a university hospital. The mean APACHE II score on the day of admission was 16.1 (8-35). One hundred eighty-five patients (74%) required reoperation, of whom 111 patients (60%) underwent reoperation on demand and 74 (40%) patients a pre-planned reoperation. Overall mortality was 38.8% (97 patients). In patients who were operated during the first three weeks after onset of disease, mortality was significantly higher than in patients who were operated after three weeks (46% vs. 25%, p < 0.01). Besides patient age (p < 0.05), APACHE II score at admission (p < 0.01), multiple organ dysfunction (p < 0.01), infection of pancreatic necrosis (p < 0.05), surgical control of pancreatic necrosis (p < 0.0001), and the time of surgical intervention (p < 0.05) determined survival significantly. Patients who were operated later than three weeks after onset of disease had a significantly better outcome. In patients suffering from SAP who required surgical treatment, the timing of operation is crucial for survival.
    Surgical Infections 01/2003; 4(2):205-11. · 1.87 Impact Factor
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    ABSTRACT: Glutamine (GLN) is the most abundant free amino acid (AA) in the human body. Under GLN-free conditions, which can be obtained when cells are cultivated in vitro, tissue cells cannot grow. Therefore, when classifying GLN as a "non-essential" AA, one must consider that in the human body GLN is synthesized from essential AAs and is continuously delivered from skeletal muscle to other organs. It is fascinating that a relatively simple AA like GLN can stimulate a large variety of cellular reactions. GLN stimulates not only the growth of cells but also the expression of surface antigens, the formation of cytokines, and the synthesis of heat shock proteins. Further, a GLN deficiency leads to a cell cycle arrest in G(0) to G(1) and reduces apoptosis. Interestingly, many of these biological activities also are associated with the cellular reduced oxygen potential, which depends mainly on the ratio of reduced to oxidized glutathione. Experimental animal studies have shown that the administration of GLN increases tissue concentrations of reduced glutathione. This review describes the relation of GLN to reduced glutathione metabolism and discusses the alteration of reduced glutathione metabolism under a variety of clinical conditions such as reperfusion injury, myocardial infarction, respiratory insufficiency, cancer, diabetes, liver disease, and clinical protein catabolism.
    Nutrition 04/2002; 18(3):217-21. · 2.86 Impact Factor
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    ABSTRACT: After major trauma and sepsis, patients frequently show a decreased blood glutamine (Gln) level. Gln deprivation has been shown to induce apoptosis in intestinal epithelial cells. In this study, we investigated whether the Gln level also affects the susceptibility of monocytic cells to apoptosis. Human monocytic U937 cells were suspended in a Gln-free medium, exposed for 20 minutes to either tumor necrosis factor alpha, Fas ligand, heat shock, or UV irradiation and allowed to recover for 4 hours or 24 hours. Apoptosis was measured by annexin-V assay and confirmed by nuclear condensation. The activation of caspase-3 was determined by Western blot. When induced by tumor necrosis factor alpha, Fas ligand, or heat shock, the apoptosis rate was significantly lower (50%-60%) in the presence of Gln than in the absence of Gln (P <.02). However, Gln had no effect on UV irradiation-induced apoptosis. Caspase-3 was activated by all inducers and was independent of Gln. This study shows that glutamine deprivation increases the susceptibility of monocytic cells to some but not all inducers of apoptosis. Because Gln has no effect on caspase-3 activation, we hypothesize that the selective anti-apoptotic effect of Gln occurs downstream of caspase-3. These results suggest that Gln serves as a selective immunomodulating factor.
    Surgery 02/2002; 131(1):75-80. · 3.37 Impact Factor
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    ABSTRACT: Reactive oxygen species, formed in various biochemical reactions, are normally scavenged by antioxidants. Glutathione in its reduced form (GSH) is the most powerful intracellular antioxidant, and the ratio of reduced to oxidised glutathione (GSH:GSSG) serves as a representative marker of the antioxidative capacity of the cell. Several clinical conditions are associated with reduced GSH levels which as a consequence can result in a lowered cellular redox potential. GSH and the redox potential of the cell are components of the cell signaling system influencing the translocation of the transcription factor NF kappa B which regulates the synthesis of cytokines and adhesion molecules. Therefore, one possibility to protect cells from damage caused by reactive oxygen species is to restore the intracellular glutathione levels. Cellular GSH concentration can be influenced by exogenous administration of GSH (as intravenous infusion or as aerosol), of glutathione esters or of GSH precursors such as glutamine or cysteine (in form of N-acetyl-L-cysteine, alpha-lipoic acid). The modulation of GSH metabolism might present a useful adjuvant therapy in many pathologies such as intoxication, diabetes, uremia, sepsis, inflammatory lung processes, coronary disease, cancer and immunodeficiency states.
    Wiener klinische Wochenschrift 08/2000; 112(14):610-6. · 0.81 Impact Factor