Maximilian Ledochowski

Medizinische Universität Innsbruck, Innsbruck, Tyrol, Austria

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Publications (56)256.41 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.
    Biologie in unserer Zeit 04/2014; 44(2).
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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.
    Agents and Actions 02/2011; 60(2):127-35. · 1.59 Impact Factor
  • M Ledochowski, S Schroecksnadel, D Fuchs
    Acta Paediatrica 12/2010; 99(12):1756-7. · 1.97 Impact Factor
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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.
    Biochemical and Biophysical Research Communications 09/2010; 399(4):642-6. · 2.41 Impact Factor
  • 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.
    12/2009: pages 47-62;
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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 1.13.11.17) 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.
    12/2009: pages 323-417;
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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.
    Journal of ethnopharmacology 04/2009; 122(2):261-7. · 2.32 Impact Factor
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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.
    Immunobiology 02/2009; 214(2):129-34. · 2.81 Impact Factor
  • Alexander Eisenmann, Bettina Datta, Maximilian Ledochowski
    Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie - ANASTHESIOL INTENS N. 01/2009; 24(01):16-20.
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    Alexander Eisenmann, Maximilian Ledochowski
    Anasthesiologie Intensivmedizin Notfallmedizin Schmerztherapie - ANASTHESIOL INTENS N. 01/2009; 24(01):10-14.
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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.
    Current Drug Metabolism 10/2008; 9(7):622-7. · 4.41 Impact Factor
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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.
    Scandinavian Journal of Gastroenterology 10/2008; 44(2):168-71. · 2.33 Impact Factor
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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).
    Cancer letters 09/2008; 272(1):141-7. · 4.86 Impact Factor
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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.
    Journal of Breath Research 07/2008; 2(4):046002. · 2.57 Impact Factor
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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.
    Clinica Chimica Acta 07/2008; 392(1-2):58-62. · 2.85 Impact Factor
  • Toxicology Letters - TOXICOL LETT. 01/2008; 180.
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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.
    Clinica Chimica Acta 09/2007; 383(1-2):91-6. · 2.85 Impact Factor
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    ABSTRACT: This study examined the direct interaction of serotonin (5-hydroxytryptamine (5-HT)) with Aspergillus species. Accumulation of 5-HT in aspergilli was investigated by immunofluorescence staining and laser confocal scanning microscopy. The influence of 5-HT on fungal ergosterol content, cell membrane integrity, fungal growth and hyphal elongation was determined. 5-HT was localised in the cytoplasm of Aspergillus spp., as 5-HT fluorescent signals appeared after 30min at 4 degrees C and in the presence of inhibitors of oxidative phosphorylation. 5-HT treatment of Aspergillus spp. significantly affected ergosterol synthesis, fungal cell membrane integrity and hyphal elongation (P<0.05). 5-HT treatment for 4h resulted in a lag of re-growth (post-antifungal effect). In conclusion, our findings suggest that 5-HT affects hyphal growth and diminishes fungal cell membrane integrity.
    International Journal of Antimicrobial Agents 04/2007; 29(4):424-9. · 4.42 Impact Factor
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    ABSTRACT: BackgroundDetermination of the diagnostic usefulness of proton transfer reaction mass spectrometry (PTR-MS) for detecting primary lung cancer through analysis of volatile organic compounds (VOCs) in exhaled human breath was demonstrated in this investigation. Unlike, for example, gas-chromatographic analyses, PTR-MS can be used without time-consuming preconcentration of the gas samples.MethodsBy means of PTR-MS, exhaled breath samples from primary lung cancer patients (n = 17) were analyzed and compared with both an overall control collective (controls total, n = 170) and three sub-collectives: hospital personnel (controls hospital, n = 35), age-matched persons (controls age, n = 25), and smokers (controls s, n = 60), respectively.ResultsAmong the VOCs present at reasonably high concentrations, the ones leading to the product ion at m/z = 31 (VOC-31, tentatively protonated formaldehyde) and m/z = 43 (VOC-43, tentatively a fragment of protonated iso-propanol), were found at significantly higher concentrations in the breath gas of the primary lung cancer patients as compared to the healthy controls at the following median concentrations (with interquartile distance, iqr): For VOC-31 the median concentrations were 7.0 ppb (iqr, 15.5 ppb) versus 3.0 ppb (iqr, 1.9 ppb) with P < 10−4. For VOC-43 the median concentrations were 244.1 ppb (iqr, 236.2 ppb) versus 94.1 ppb (iqr, 55.2 ppb) with P < 10−6. The discriminative power between the two collectives was further assessed by ROC-curves obtained upon variation of the chosen threshold concentration and by Fisher's Quadratic Discriminant Method.ConclusionsWithin the limits of pilot study, VOC-31 and -43 were found to best discriminate between exhaled breath of primary lung cancer cases and healthy controls. Simple and time-saving breath gas analysis by PTR-MS makes this method attractive for a larger clinical evaluation. It may become a new valuable tool for diagnosing primary lung cancer.
    International Journal of Mass Spectrometry. 01/2007;
  • European Neuropsychopharmacology - EUR NEUROPSYCHOPHARMACOL. 01/2007; 17.

Publication Stats

1k Citations
256.41 Total Impact Points

Institutions

  • 2005–2011
    • Medizinische Universität Innsbruck
      • • Sektion für Biologische Chemie
      • • Sektion für Molekularbiologie
      Innsbruck, Tyrol, Austria
  • 1998–2011
    • University of Innsbruck
      • Institute of Biochemistry
      Innsbruck, Tyrol, Austria
  • 2009
    • Landeskrankenhaus - Universitätskliniken Innsbruck
      Innsbruck, Tyrol, Austria