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54. Cardiac metabolism as a driver and therapeutic target of myocardial infarction

Author

Zuurbier, C.J. Bertrand, L. Beauloye, C.R. Andreadou, I. Ruiz-Meana, M. Jespersen, N.R. Kula-Alwar, D. Prag, H.A. Eric Botker, H. Dambrova, M. Montessuit, C. Kaambre, T. Liepinsh, E. Brookes, P.S. Krieg, T.

Abstract

Reducing infarct size during a cardiac ischaemic-reperfusion episode is still of paramount importance, because the extension of myocardial necrosis is an important risk factor for developing heart failure. Cardiac ischaemia-reperfusion injury (IRI) is in principle a metabolic pathology as it is caused by abruptly halted metabolism during the ischaemic episode and exacerbated by sudden restart of specific metabolic pathways at reperfusion. It should therefore not come as a surprise that therapy directed at metabolic pathways can modulate IRI. Here, we summarize the current knowledge of important metabolic pathways as therapeutic targets to combat cardiac IRI. Activating metabolic pathways such as glycolysis (eg AMPK activators), glucose oxidation (activating pyruvate dehydrogenase complex), ketone oxidation (increasing ketone plasma levels), hexosamine biosynthesis pathway (O-GlcNAcylation; administration of glucosamine/glutamine) and deacetylation (activating sirtuins 1 or 3; administration of NAD+-boosting compounds) all seem to hold promise to reduce acute IRI. In contrast, some metabolic pathways may offer protection through diminished activity. These pathways comprise the malate-aspartate shuttle (in need of novel specific reversible inhibitors), mitochondrial oxygen consumption, fatty acid oxidation (CD36 inhibitors, malonyl-CoA decarboxylase inhibitors) and mitochondrial succinate metabolism (malonate). Additionally, protecting the cristae structure of the mitochondria during IR, by maintaining the association of hexokinase II or creatine kinase with mitochondria, or inhibiting destabilization of FOF1-ATPase dimers, prevents mitochondrial damage and thereby reduces cardiac IRI. Currently, the most promising and druggable metabolic therapy against cardiac IRI seems to be the singular or combined targeting of glycolysis, O-GlcNAcylation and metabolism of ketones, fatty acids and succinate. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd

Published
2020

59. TRAIL-β und TRAIL-γ: Zwei neue alternative Spleißvarianten des humanen TNF-related apoptosis inducing ligand und erste Hinweise für deren Bedeutung in der Tumorbiologie des Magenkarzinoms

Author

Krieg, A., Mahotka, C., Krieg, T., Schulte am Esch, J., 2nd, Peiper, M., Ramp, U., Gabbert, H. E., Knoefel, W. T., Bruch, H. P., editor, Büchler, M. W., editor, Buhr, H. J., editor, Hohenberger, W., editor, Klar, E., editor, Kremer, B., editor, Post, S., editor, Schilling, M., editor, Schumpelick, V., editor, Siewert, J. R., editor, Thiede, A., editor, Becker, H., editor, Bittner, R., editor, Függer, R., editor, Köckerling, F., editor, Saeger, H. D., editor, Zornig, C., editor, Hölscher, A., editor, Izbicki, J. R., editor, Junginger, T., editor, Senninger, N., editor, Allgayer, H., editor, Broll, R., editor, Bruns, C. J., editor, Fries, H., editor, Kalthoff, H., editor, Schackert, H. K., editor, Ertel, W., editor, Faist, E., editor, Holzheimer, R. G., editor, Holzmann, B., editor, Schade, U. F., editor, Vollmar, B., editor, Brückner, U. B., editor, Heidecke, C. D., editor, Menger, M. D., editor, Neugebauer, E., editor, Spiegel, H. U., editor, Biemer, E., editor, Germann, G., editor, Haas, N., editor, Machens, H. G., editor, Stark, G. B., editor, Steinau, H. U., editor, Haverich, A., editor, Heberer, M., editor, Rogiers, X., editor, Jauch, K. W., editor, Roth, H., editor, von Schweinitz, D., editor, Waag, K. L., editor, Altendorf-Hofmann, A., editor, Celik, I., editor, Lehnert, T., editor, Lorenz, W., editor, Ohmann, C., editor, Bechstein, W. O., editor, Broelsch, C., editor, Hopt, U., editor, Klempnauer, J., editor, Neuhaus, P., editor, Fändrich, F., editor, Markus, B., editor, Minor, T., editor, Wonigeit, K., editor, Dralle, H., editor, Goretzki, P. E., editor, Rothmund, M., editor, Bühren, V., editor, Josten, C., editor, Muhr, G., editor, Nast-Kolb, D., editor, Stürmer, K. M., editor, Trentz, O., editor, Brunkwall, J., editor, Sandmann, W., editor, Schmitz-Rixen, T., editor, Storck, M., editor, Branscheid, D., editor, Dienemann, H., editor, Hirner, A., editor, Passlick, B., editor, Toomes, H., editor, Beyersdorf, F., editor, Hetzer, R., editor, Schäfers, H. J., editor, Zerkowski, H. R., editor, Becker, H. D., editor, Saeger, H. -D., editor, Jauch, K. -W., editor, and Bauer, H., editor

Published
2006
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60. Long term outcomes of immunmodulatory drugs in SSc-ILD - data rom the German SSc network

Author

Kreuter, M., Bonella, F., Blank, N., Siegert, E., Henes, J., Worm, M., Sunderkoetter, C., Schmalzing, M., Kreuter, A., Guenther, C., Susok, L., Zeidler, G., Koetter, I, Mueller-Ladner, U., Krieg, T., Juche, A., Schmeiser, T., Riemekasten, G., Aberer, E., Gaebelein-Wissing, N., Distler, J. H. W., Sardy, M., Pfeiffer, C., Kuhr, K., Lorenz, H. M., Moinzadeh, P., Hunzelmann, N., Kreuter, M., Bonella, F., Blank, N., Siegert, E., Henes, J., Worm, M., Sunderkoetter, C., Schmalzing, M., Kreuter, A., Guenther, C., Susok, L., Zeidler, G., Koetter, I, Mueller-Ladner, U., Krieg, T., Juche, A., Schmeiser, T., Riemekasten, G., Aberer, E., Gaebelein-Wissing, N., Distler, J. H. W., Sardy, M., Pfeiffer, C., Kuhr, K., Lorenz, H. M., Moinzadeh, P., and Hunzelmann, N.

Published
2020

61. Whole blood gene expression profiling distinguishes systemic sclerosis-overlap syndromes from other subsets

Author

Moinzadeh, P., Frommolt, P., Franitza, M., Toliat, M. R., Becker, K., Nuernberg, P., Nihtyanova, S. I., Ahrazoglu, M., Belz, D., Hunzelmann, N., Abraham, D., Ong, V. H., Mouthon, L., Hesselstrand, R., Denton, C. P., Krieg, T., Moinzadeh, P., Frommolt, P., Franitza, M., Toliat, M. R., Becker, K., Nuernberg, P., Nihtyanova, S. I., Ahrazoglu, M., Belz, D., Hunzelmann, N., Abraham, D., Ong, V. H., Mouthon, L., Hesselstrand, R., Denton, C. P., and Krieg, T.

Published
2020

62. Does anti-acid treatment influence disease progression in SSc-ILD? Data form the German SSc-network

Author

Kreuter, M., Bonella, F., Blank, N., Siegert, E., Henes, J., Worm, M., Sunderkoetter, C., Schmalzing, M., Kreuter, A., Guenther, C., Susok, L., Zeidler, G., Koetter, I, Mueller-Ladner, U., Krieg, T., Juche, A., Schmeiser, T., Riemekasten, G., Aberer, E., Gaebelein-Wissing, N., Distler, J. H. W., Sardy, M., Pfeiffer, C., Kuhr, K., Lorenz, H. M., Moinzadeh, P., Hunzelmann, N., Kreuter, M., Bonella, F., Blank, N., Siegert, E., Henes, J., Worm, M., Sunderkoetter, C., Schmalzing, M., Kreuter, A., Guenther, C., Susok, L., Zeidler, G., Koetter, I, Mueller-Ladner, U., Krieg, T., Juche, A., Schmeiser, T., Riemekasten, G., Aberer, E., Gaebelein-Wissing, N., Distler, J. H. W., Sardy, M., Pfeiffer, C., Kuhr, K., Lorenz, H. M., Moinzadeh, P., and Hunzelmann, N.

Published
2020

80. Does anti-acid treatment influence disease progression in SSc-ILD? Data form the German SSc-network

Author

Kreuter, M, additional, Bonella, F, additional, Blank, N, additional, Siegert, E, additional, Henes, J, additional, Worm, M, additional, Sunderkoetter, C, additional, Schmalzing, M, additional, Kreuter, A, additional, Guenther, C, additional, Susok, L, additional, Zeidler, G, additional, Koetter, I, additional, Mueller-Ladner, U, additional, Krieg, T, additional, Juche, A, additional, Schmeiser, T, additional, Riemekasten, G, additional, Aberer, E, additional, Gaebelein-Wissing, N, additional, Distler, JHW, additional, Sárdy, M, additional, Pfeiffer, C, additional, Kuhr, K, additional, Lorenz, HM, additional, Moinzadeh, P, additional, and Hunzelmann, N, additional

Published
2020
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81. Long term outcomes of immunmodulatory drugs in SSc-ILD – data rom the German SSc network

Author

Kreuter, M, additional, Bonella, F, additional, Blank, N, additional, Siegert, E, additional, Henes, J, additional, Worm, M, additional, Sunderkoetter, C, additional, Schmalzing, M, additional, Kreuter, A, additional, Guenther, C, additional, Susok, L, additional, Zeidler, G, additional, Koetter, I, additional, Mueller-Ladner, U, additional, Krieg, T, additional, Juche, A, additional, Schmeiser, T, additional, Riemekasten, G, additional, Aberer, E, additional, Gaebelein-Wissing, N, additional, Distler, JHW, additional, Sárdy, M, additional, Pfeiffer, C, additional, Kuhr, K, additional, Lorenz, HM, additional, Moinzadeh, P, additional, and Hunzelmann, N, additional

Published
2020
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82. Whole blood gene expression profiling distinguishes systemic sclerosis‐overlap syndromes from other subsets

Author

Moinzadeh, P., primary, Frommolt, P., additional, Franitza, M., additional, Toliat, M. R., additional, Becker, K., additional, Nürnberg, P., additional, Nihtyanova, S. I., additional, Ahrazoglu, M., additional, Belz, D., additional, Hunzelmann, N., additional, Abraham, D., additional, Ong, V. H., additional, Mouthon, L., additional, Hesselstrand, R., additional, Denton, C. P., additional, and Krieg, T., additional

Published
2020
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87. Idiopathic inflammatory myopathies: Narrative review of unmet needs in clinical practice guidelines

Author

Meyer A., Scire C. A., Talarico R., Alexander T., Amoura Z., Avcin T., Barsotti S., Beretta L., Blagojevic J., Burmester G., Cavazzana I., Cherrin P., Damian L., Doria A., Fonseca J. E., Furini F., Galetti I., Houssiau F., Krieg T., Maddalena L., Launay D., Campanilho-Marques R., Martin T., Matucci-Cerinic M., Moinzadeh P., Montecucco C., Moraes-Fontes M. F., Mouthon L., Neri R., Paolino S., Piette Y., Rednic S., Tamirou F., Tincani A., Toplak N., Bombardieri S., Hachulla E., Mueller-Ladner U., Schneider M., Smith V., Vieira A., Cutolo M., Mosca M., Cavagna L., Meyer, A, Scire, C, Talarico, R, Alexander, T, Amoura, Z, Avcin, T, Barsotti, S, Beretta, L, Blagojevic, J, Burmester, G, Cavazzana, I, Cherrin, P, Damian, L, Doria, A, Fonseca, J, Furini, F, Galetti, I, Houssiau, F, Krieg, T, Maddalena, L, Launay, D, Campanilho-Marques, R, Martin, T, Matucci-Cerinic, M, Moinzadeh, P, Montecucco, C, Moraes-Fontes, M, Mouthon, L, Neri, R, Paolino, S, Piette, Y, Rednic, S, Tamirou, F, Tincani, A, Toplak, N, Bombardieri, S, Hachulla, E, Mueller-Ladner, U, Schneider, M, Smith, V, Vieira, A, Cutolo, M, Mosca, M, and Cavagna, L

Subjects
myositi
Abstract

Idiopathic inflammatory myopathies (IIMs) encompass a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and inflammation, but in antisynthetase syndrome arthritis and interstitial lung disease are more frequent and often inaugurate the disease. Clinical practice guidelines (CPGs) have been proposed for IIMs, but they are sparse and heterogeneous. This work aimed at identifying: i) current available CPGs for IIMs, ii) patients ' and clinicians' unmet needs not covered by CPGs. It has been performed in the framework of the European Reference Network on rare and complex connective tissue and musculoskeletal diseases (ReCONNET), a network of centre of expertise and patients funded by the European Union's Health Programme. Fourteen original CPGs were identified, notably recommending that: i) extra-muscular involvements should be assessed; ii) corticosteroids and methotrexate or azathioprine are first-line therapies of IIMs. ii) IVIG is a treatment of resistant-DM that may be also used in other resistant-IIMs; iii) physical therapy and sun protection (in DM patients) are part of the treatment; v) tumour screening for patients with DM include imaging of chest, abdomen, pelvis and breast (in woman) along with colonoscopy (in patients over 50 years); vi) disease activity and damages should be monitor using standardised and validated tools. Yet, only half of these CPGs were evidence-based. Crucial unmet needs were identified both by patients and clinicians. In particular, there was a lack of large multidisciplinary working group and of patients ' preferences. The following fields were not or inappropriately targeted: diagnosis; management of extra-muscular involvements other than skin; co-morbidities and severe manifestations.

Published
2018

99. The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement

Author

Hunzelmann, N., Genth, E., Krieg, T., Lehmacher, W., Melchers, I., Meurer, M., Moinzadeh, P., Müller-Ladner, U., Pfeiffer, C., Riemekasten, G., Schulze-Lohoff, E., Sunderkoetter, C., Weber, M., Worm, M., Klaus, P., Rubbert, A., Steinbrink, K., Grundt, B., Hein, R., Scharffetter-Kochanek, K., Hinrichs, R., Walker, K., Szeimies, R.-M., Karrer, S., Müller, A., Seitz, C., Schmidt, E., Lehmann, P., Foeldvári, I., Reichenberger, F., Gross, W. L., Kuhn, A., Haust, M., Reich, K., Böhm, M., Saar, P., Fierlbeck, G., Kötter, I., Lorenz, H.-M., Blank, N., Gräfenstein, K., Juche, A., Aberer, E., Bali, G., Fiehn, C., Stadler, R., and Bartels, V.

Published
2008

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