Maximilian Ledochowski

IST Austria, Klosterneuberg, Lower Austria, Austria

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Publications (65)285.8 Total impact

  • Maximilian Ledochowski · Dietmar Fuchs
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    ABSTRACT: Es wurde öfters spekuliert, dass Christus durch die Kreuzigung nicht gestorben ist. Aus der Schilderung “einer der Soldaten stieß mit dem Speer in seine Seite, und sogleich floß Blut und Wasser heraus”, geht ziemlich eindeutig hervor, dass Jesus einen Pleuraerguss gehabt haben muss, als er gekreuzigt wurde. Es ist heute allgemein anerkannt, dass ein ausgedehnter Pleuraerguss zu Hypoxie und schließlich zum Erstickungstod führen kann, wenn nicht rechtzeitig eine Entlastungspunktion durchgeführt wird. Man kann spekulieren, dass mit dem Lanzenstich des Longinus nicht der sichere Tod, sondern ein lebensrettender “therapeutischer” Eingriff durchgeführt wurde, der Jesus Christus das Überleben ermöglichte. Did Jesus Christ die on the cross? It has been repeatedly speculated that Jesus of Nazareth did not really die on the cross when he was crucified. The spear thrust into his side and the flow of blood and water when pierced with a spear suggests that Jesus must have had some sort of hydrothorax and/or haemothorax at the time he was crucified. Management of hydrothorax and/or haemothorax in modern medicine is the establishment of chest drains. Further one might speculate that the thrust of the spear on the side, carried out to ensure the death of Jesus, may have had, in fact, an opposite effect, namely relief of hypoxemia, which might have been followed by recovery of consciousness after he was taken down from the cross.
    No preview · Article · Apr 2014 · Biologie in unserer Zeit
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    ABSTRACT: Inflammation is crucially involved in a variety of diseases like autoimmune syndromes, cardiovascular and neurodegenerative disorders, cancer, sepsis and allograft rejection. Freshly isolated human peripheral blood mononuclear cells (PBMCs) are used as a screening assay for anti-inflammatory properties of compounds. Determinations of neopterin production by ELISA and of tryptophan degradation by HPLC are used as read-outs. Results are compared with further markers of immune response and oxidative stress. Phytohaemagglutinin induced significant tryptophan degradation and neopterin formation in PBMC, which correlated with IFN-γ, TNF-α, soluble cytokine receptors and isoprostane-8. Addition of vitamin C and E suppressed the responses dose-dependently. The determination of tryptophan degradation and neopterin production in PBMC reflects various pro- and anti-inflammatory cascades that are of relevance also in patients. It constitutes a robust and reliable approach to screen anti-inflammatory or immunosuppressive drugs and may improve throughput, speed and cost-effectiveness in drug discovery.
    Full-text · Article · Feb 2011 · Agents and Actions
  • M Ledochowski · S Schroecksnadel · D Fuchs

    No preview · Article · Dec 2010 · Acta Paediatrica
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    ABSTRACT: Neopterin production is induced in human monocyte-derived macrophages and dendritic cells upon stimulation with Th1-type cytokine interferon-gamma (IFN-gamma). In parallel, IFN-gamma induces the tryptophan-(trp)-degrading enzyme indoleamine 2,3-dioxygenase (IDO) and triggers the formation of reactive oxygen species (ROS). Translocation of the signal transduction element nuclear factor-kappaB (NF-kappaB) is induced by ROS and accelerates the pro-inflammatory response by activation of other pro-inflammatory pathways. Therefore, a close relationship between NF-kappaB expression, the production of neopterin and the degradation of trp can be assumed, although this has not been demonstrated so far. In the present in vitro study we compared the influence of lipopolysaccharide (LPS) on NF-kappaB activation, neopterin formation and the degradation of trp in THP-1Blue cells, which represent the human myelomonocytic cell line THP-1 stably transfected with an NF-kappaB inducible reporter system. In cells stimulated with LPS, a significant induction of NF-kappaB was observed, and this was paralleled by an increase of kynureunine (kyn) and neopterin concentrations and a decline of trp. The increase of the kyn to trp quotient indicates accelerated IDO activity. Higher LPS concentrations and longer incubation of cells were associated with higher activities of all three biochemical pathways and significant correlations existed between NF-kappaB activation, neopterin release and trp degradation (all p<0.001). We conclude that there is a parallel induction of NF-kappaB, neopterin formation and trp degradation in monocytic THP-1 cells, which is elicited by pro-inflammatory triggers like LPS during innate immune responses.
    No preview · Article · Sep 2010 · Biochemical and Biophysical Research Communications
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    ABSTRACT: Patients suffering from autoimmune disease, cancer or chronic inflammatory diseases mostly suffer from severe “complications” of their underlying illness, like weight loss, physical inefficiency, immunodeficiency, anemia, chronic fatigue, mood disorders or even depression. All these symptoms can severely impair the quality of life of patients. The percentage of patients with chronic diseases complaining about poor quality of life is high, irrespective of their underlying disease. Interestingly, most patients suffering from chronic inflammatory disease have a strongly disturbed tryptophan metabolism. Within cellular immune response the essential amino acid tryptophan is degraded by the enzyme indoleamine-2,3-dioxygenase (IDO), leading to lowered tryptophan serum/plasma concentrations and increased levels of tryptophan catabolites like kynurenine. Tryptophan is not only necessary for the growth and proliferation of various cells as well as pathogens, it is also the precursor of the important neurotransmitters serotonin (5-hydroxytryptamin) and nicotinamide adenine dinucleotide (NAD). Increased tryptophan degradation within chronic inflammatory cascades thus leads to a diminished tryptophan availability, which might not only decrease the immunoresponsiveness of patients, but may also influence their mood, physical strength and haematopoiesis. In fact, immune-mediated tryptophan degradation is supposed to contribute importantly to the development of fatigue, weight loss, and neuropsychiatric disorders. This review provides an overview, how enhanced IDO-activation might contribute to the development of various symptoms impairing the quality of life of patients with chronic disease.
    No preview · Chapter · Jan 2010
  • H. Jarz · M. Ledochowski
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    ABSTRACT: Der menschliche Gastrointestinaltrakt (GI) ist nicht nur Ort der Verdauung und Resorption von Nährstoffen, sondern vielmehr ein komplexes Organ, welches einer nervalen und hormonalen Steuerung unterliegt. Als Antwort auf Reize wie Magendehnung, pH-Wert-Änderung oder das Erscheinen von Nährstoffen werden Botenstoffe sezerniert. Durch diese Sekretion, welche entweder auf endokrinem oder parakrinem Weg erfolgt, kann der GI die eigene Peristaltik und die Ausschüttung der Verdauungssekrete den momentanen Verdauungsprozessen adäquat anpassen. Verantwortlich hierfür sind neuroendokrine Zellen, welche zwischen den Enterozyten eingestreut sind und deren Gesamtmasse insgesamt größer ist als die Masse aller anderen endokrinen Zellen im Körper. Im Folgenden sollen einige Neurotransmitter bzw. Botenstoffe und deren Wirkung auf den GI näher vorgestellt werden. Die Tabellen 2–5 geben zudem einen Überblick über die bisher bekannten Botenstoffe.
    No preview · Chapter · Dec 2009
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    ABSTRACT: Die essenzielle Aminosure Tryptophan ist für den Aufbau von Proteinen von zentraler Bedeutung. Daneben ist Tryptophan aber auch Substrat für zwei wichtige biochemische Stoffwechselwege: (1) die Bildung des Neurotransmitters Serotonin (5-Hydroxytryptamin) durch das Enzym Tryptophan-5-Hydroxylase und (2) die Biosynthese von Kynureninderivaten und Nicotinamid-Adenin-Dinukleotiden, die durch die Enzyme Tryptophan-2,3-Dioxygenase (TDO, Tryptophanpyrrolase) und Indolamin-2,3-Dioxygenase (IDO) (EC eingeleitet wird (Abb. 1) Abb. 1.Neben seiner Bedeutung als Proteinbaustein ist Tryptophan auch Substrat für die Biosynthese des Neurotransmitters Serotonin (5-Hydroxytryptamin) durch das Enzym Tryptophan-5-Hydroxylase (T5H) und von Kynureninderivaten und Nicotinamid-Adenin-Dinukleotiden (NAD, NADH), die durch die Enzyme Tryptophan 2,3-Dioxygenase (TDO) und Indolamin 2,3-Dioxygenase (IDO) eingeleitet wird.
    No preview · Chapter · Dec 2009
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    M Jenny · E Santer · A Klein · M Ledochowski · H Schennach · F Ueberall · D Fuchs
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    ABSTRACT: The fruits of Theobroma cacao L. (Sterculiaceae) have been used as food and a remedy for more than 4000 years. Today, about 100 therapeutic applications of cacao are described involving the gastrointestinal, nervous, cardiovascular and immune systems. Pro-inflammatory cytokine interferon-gamma and related biochemical pathways like tryptophan degradation by indoleamine 2,3-dioxygenase and neopterin formation are closely associated with the pathogenesis of such disorders. To determine the anti-inflammatory effect of cacao extracts on interferon-gamma and biochemical consequences in immunocompetent cells. Effects of aqueous or ethanolic extracts of cacao were examined on mitogen-induced human peripheral blood mononuclear cells (PBMC) of healthy donors and on lipopolysaccharide-stimulated myelomonocytic THP-1 cells. Antioxidant activity of extracts was determined by oxygen radical absorption capacity (ORAC) assay. In mitogen-stimulated PBMC, enhanced degradation of tryptophan, formation of neopterin and interferon-gamma were almost completely suppressed by the cacao extracts at doses of > or = 5 microg/mL. Cacao extracts had no effect on tryptophan degradation in lipopolysaccharide-stimulated THP-1 cells. There is a significant suppressive effect of cacao extracts on pro-inflammatory pathways in activated T-cells. Particularly the influence on indoleamine 2,3-dioxygenase could relate to some of the beneficial health effects ascribed to cacao.
    Full-text · Article · Apr 2009 · Journal of ethnopharmacology
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    Alexander Eisenmann · Maximilian Ledochowski

    Full-text · Article · Mar 2009 · Zeitschrift für Komplementärmedizin
  • Alexander Eisenmann · Bettina Datta · Maximilian Ledochowski

    No preview · Article · Mar 2009 · Ernährung & Medizin
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    ABSTRACT: In most of the diseases which are considered to benefit from propolis, cellular immune reaction is activated, neopterin levels in body fluids are increased and enhanced tryptophan degradation is observed. In this study, the immunomodulatory effects of six Turkish propolis samples were evaluated by using the in vitro model of peripheral blood mononuclear cells (PBMC). Concentrations of neopterin, tryptophan, kynurenine and pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were determined and also the viability of the cells was checked with trypan blue and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test. In PBMC treated with mitogen phytohaemagglutinin, neopterin production and tryptophan degradation by enzyme indoleamine 2,3-dioxygenase (IDO) as well as release of cytokines was significantly enhanced and upon treatment with propolis extracts all these effects were dose-dependently suppressed. Results show an immunomodulatory effect of propolis extracts which includes down-regulation of IDO activity. IDO enzyme is considered to play an important role in the development of immunodeficiency and neuropsychiatric symptoms in patient with chronic inflammation. The suppression of tryptophan degradation by propolis extracts may therefore be related with some of its beneficial health properties in humans.
    No preview · Article · Feb 2009 · Immunobiology
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    ABSTRACT: Nigella sativa, commonly known as black cumin seed, belongs to the botanical family of Ranunculaceae. The active antioxidant components of Nigella sativa display a remarkable array of biochemical, immunological and pharmacological actions, including bronchodilatory, anti-inflammatory, antibacterial, hypoglycaemic, antitumoural and immunopotentiating effects. Effects of Nigella sativa seeds extracts were investigated in freshly isolated human peripheral blood mononuclear cells stimulated with the mitogens phytohaemagglutinin and concanavalin A in vitro. Tryptophan degradation and neopterin production were monitored in culture supernatants, both these immunobiochemical pathways are induced by pro-inflammatory cytokine interferon-γ. Compared to unstimulated cells, the mitogens enhanced degradation of tryptophan and production of neopterin. Nigella sativa seeds extracts significantly suppressed both pathways in a dose-dependent way. Suppression of tryptophan degradation and neopterin formation by Nigella sativa seeds extracts demonstrates an inhibitory influence on activated T-cells and macrophages. Data are in line with an anti-inflammatory activity of the extracts.
    Full-text · Article · Dec 2008

  • No preview · Article · Oct 2008 · Toxicology Letters
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    ABSTRACT: Neuropsychiatric symptoms like mood changes and depression are common in patients with chronic inflammatory disorders such as infections, autoimmune diseases or cancer. The pathogenesis of these symptoms is still unclear. Pro-inflammatory stimuli interfere not only with the neural circuits and neurotransmitters of the serotonergic, but also with those of the adrenergic system. The pro-inflammatory cytokine interferon-gamma stimulates the biosynthesis of 5,6,7,8-tetrahydrobiopterin (BH4), which is cofactor for several aromatic amino acid monooxygenases and thus is strongly involved in the biosynthesis of the neurotransmitter serotonin and the catecholamines dopamine, epinephrine (adrenaline) and norepinephrine (noradrenaline). In macrophages, interferon-gamma also triggers the high output of reactive oxygen species, which can destroy the oxidation-labile BH4. Recent data suggest that oxidative loss of BH4 in chronic inflammatory conditions can reduce the biosynthesis of catecholamines, which may relate to disturbed adrenergic neurotransmitter pathways in patients.
    No preview · Article · Oct 2008 · Current Drug Metabolism
  • Alexander Eisenmann · Christian Murr · Dietmar Fuchs · Maximilian Ledochowski
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    ABSTRACT: Circulating immune complexes (CICs) in blood are associated with autoimmune-diseases such as systemic lupus erythematosus, immune complex glomerulonephritis, rheumatoid arthritis and vasculitis. However, slightly increased serum concentrations of such CICs are sometimes also found in healthy individuals. The objective of the current study was to assess whether food antigens could play a role in the formation of CICs. A total of 352 (265 F, 87 M), so far, healthy individuals were tested for CICs containing C1q and immunoglobulin G (IgG) as well as for gliadin IgG antibodies using the ELISA technique. Additionally, fructose and lactose malabsorption was assessed using hydrogen breath tests. In our study, 15.3% (54/352) of the patients presented with elevated CIC concentrations (above 50 microg/ml) and 6.5% (23/352) of the study population were positive for gliadin IgG antibodies (above 20 U/ml). CIC concentration levels were significantly higher in the group with elevated gliadin IgG antibodies (CIC median: 49.0 microg/ml) compared with the group with normal levels of gliadin IgG antibodies (CIC median: 30.0 microg/ml; Mann-Whitney U-test, U=1992; p <0.001). As expected, there was no difference in CIC concentrations (Mann-Whitney U-test, U=6106; p=0.783) and gliadin IgG (Mann-Whitney U-test, U=3761; p=0.411) between patients in the fructose or lactose malabsorber groups and the subjects without malabsorption. The results of this study indicate that certain food antigens (e.g. gluten) could play a role in the formation of CICs. An association between CICs and fructose or lactose malabsorption seems to be improbable.
    No preview · Article · Oct 2008 · Scandinavian Journal of Gastroenterology
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    ABSTRACT: Increased blood concentrations of essential amino acid phenylalanine are common in patients with HIV infection, in trauma and sepsis and in patients with cancer. The reason for this phenomenon is still unclear. However, all these clinical conditions are known to be linked with inflammation and immune activation. Oxidative stress resulting from chronic immune activation and inflammation could impair activity of phenylalanine (4)-hydroxylase (PAH) and thus give rise to increased phenylalanine concentrations. We therefore examined in 20 patients with ovarian cancer a possible association of serum concentrations of phenylalanine and tyrosine with immune activation markers 75 kDa soluble tumor necrosis factor-alpha receptor (sTNF-R75) and neopterin, and of oxidative stress marker isoprostane-8. Phenylalanine concentrations were higher in patients with higher FIGO stage and correlated with concentrations of sTNF-R75 (rs=0.441) and neopterin (rs=0.346; both p<0.05). No such correlations existed for tyrosine levels. The phenylalanine to tyrosine ratio (phe/tyr), an estimate of PAH activity, correlated somewhat stronger with sTNF-R75 (rs=0.549; p<0.01) and neopterin (rs=0.497; p=0.01). Finally, phenylalanine concentrations correlated with isoprostane-8 concentrations (rs=0.450, p=0.02). Correlations of phenylalanine and phe/tyr with immune activation markers point to a potential role of inflammation and immune activation in the accumulation of phenylalanine. The relationship between oxidative stress marker isoprostane-8 and phenylalanine as well as sTNF-R75 concentrations suggests a link between reactive oxygen species formed during chronic immune activation and inflammation and the decline of PAH activity, which might underlie the increase of phe/tyr (248 words).
    Full-text · Article · Sep 2008 · Cancer letters
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    Alexander Eisenmann · Anton Amann · Michael Said · Bettina Datta · Maximilian Ledochowski
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    ABSTRACT: Hydrogen breath tests are non-invasive and safe diagnostic tools used to investigate functional intestinal disorders. For the diagnosis of fructose or lactose malabsorption as well as for the detection of small intestinal bacterial overgrowth syndrome, hydrogen breath tests are even regarded as gold standard. However, standardization of the testing procedure and the interpretation of the test results are still lacking. In this paper, reliable information on the implementation of the most common hydrogen breath tests and precise guidelines for the interpretation of the test results are presented.
    Full-text · Article · Jul 2008 · Journal of Breath Research
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    ABSTRACT: Adult-type hypolactasia is a genetically determined inability to digest lactose after weaning. Two single-nucleotide polymorphisms (C-13910T, G-22018A) located upstream of the lactase gene (LCT) within the gene MCM6 are associated with the lactase persistence/non-persistence trait in patients of European descent. Therefore, the genotyping of these SNPs has been established as a diagnostic tool for adult-type hypolactasia. We have recently shown that several novel allelic variants located in close proximity to the C-13910T SNP interfere with the diagnostic accuracy of real-time PCR-based genotyping methods. We describe here the validation of a comprehensive reverse-hybridization teststrip-based assay for the detection of common and novel LCT SNPs (C-13907G, C-13910T, T-13913C, G-13914A, T-13915G, and G-22018A). This assay is based on multiplex DNA amplification and ready-to-use membrane teststrips containing variant-specific oligonucleotide probes immobilized as an array of parallel lines. We evaluated the novel reverse-hybridization StripAssay on 125 DNA samples in comparison to LightCycler analysis and sequencing. The outcome of StripAssay genotyping was found to be completely concordant with that obtained by sequencing. The StripAssay represents an accurate and robust screening tool to identify multiple LCT/MCM6 variants in a rapid manner. It overcomes diagnostic pitfalls that were reported and allows the simultaneous genotyping of closely spaced LCT variant sites in a single-step diagnostic approach.
    Full-text · Article · Jul 2008 · Clinica Chimica Acta

  • No preview · Article · Oct 2007 · European Neuropsychopharmacology
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    ABSTRACT: Two single nucleotide polymorphisms (-13910 C/T and -22018 G/A) upstream of the lactase gene (LCT) have been found to be associated with lactose tolerance in Europeans. In one hundred and twenty Austrian outpatients, who visited the physician's office for symptoms of irritable bowel syndrome (IBS), hydrogen breath testing (HBT) and LCT genotyping by polymerase chain reaction and reverse-hybridisation were performed in parallel. The coincidence between a genotype suggesting lactase non-persistence (lactose intolerance) and a positive HBT result was almost perfect (97.4% for LCT-13910 C/T and 100% for LCT-22018 G/A). Between a genotype indicating lactase persistence (lactose tolerance) and a negative HBT result the coincidence was lower (72% and 71.4%, respectively). Among heterozygotes, there was a statistically significant increase in the proportion of positive HBT results with age. Both SNPs were in accordance in 117/120 (97.5%) patients. Genetic analysis of LCT-13910 C/T and LCT-22018 G/A is a good indicator for the presence of lactose intolerance. Because age, as well as a number of secondary causes (e.g. celiac disease), can influence HBT results, it is useful to combine HBT and genetic analysis in the diagnostic assessment of IBS.
    No preview · Article · Sep 2007 · Clinica Chimica Acta

Publication Stats

2k Citations
285.80 Total Impact Points


  • 2014
    • IST Austria
      Klosterneuberg, Lower Austria, Austria
  • 1998-2011
    • University of Innsbruck
      • Institute of Biochemistry
      Innsbruck, Tyrol, Austria
  • 2009
    • Landeskrankenhaus - Universitätskliniken Innsbruck
      Innsbruck, Tyrol, Austria
  • 2007
    • Austrian Academy of Sciences
      Wien, Vienna, Austria