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1,105 results on '"Paschke R"'

1. Neurohumoral stimulation in type-2-diabetes as an emerging disease concept

Author

Blüher M, Fasshauer M, Pliquett RU, and Paschke R

Subjects
diabetes mellitus, sympathetic nervous system, hormones, oxidative stress, inflammation, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Neurohumoral stimulation comprising both autonomic-nervous-system dysfunction and activation of hormonal systems including the renin-angiotensin-aldosterone system (RAAS) was found to be associated with Type-2-diabetes (T2D). Therapeutic strategies such as RAAS interference proved to be beneficial in both T2D treatment and prevention. In addition to an activated RAAS, hyperleptinemia in obesity, hyperinsulinemia in conditions of peripheral insulin resistance and overall oxidative stress in T2D represent known activators of the sympathetic component of the autonomic nervous system. Here, we hypothesize that sympathetic activation may cause peripheral insulin resistance defined as partial blocking of insulin effects on glucose uptake. Resulting hyperinsulinemia or hyperglycemia-related oxidative stress may further aggravate sympatho-excitation. This notion leads to a secondary hypothesis: sympathetic activation worsens from obesity towards insulin resistance, and further towards T2D. In this review, existing evidence relating to neurohumoral stimulation in T2D and consequences thereof, such as oxidative stress and inflammation, are discussed. The aim of this review is to provide a rationale for therapies, which are able to intercept neuroendocrine pathways in T2D and precursor states such as obesity.

Published
2004
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2. Evaluation of Betulinic Acid Derivatives as PET Tracers for Hypoxia-Induced Carbonic Anhydrase IX (CA IX) Expression

Author

Haupt, V., Gündel, D., Prell, E., Kahnt, M., Sommerwerk, S., Riemann, A., Paschke, R., Csuk, R., Odparlik, A., Thews, O., Crusio, Wim E., Series Editor, Dong, Haidong, Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Steinlein, Ortrud, Series Editor, Xiao, Junjie, Series Editor, Scholkmann, Felix, editor, LaManna, Joseph, editor, and Wolf, Ursula, editor

Published
2022
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6. Integrative model of the FSH receptor reveals the structural role of the flexible hinge region

Author

Nagel, Marcus, Moretti, R., Paschke, R., von Bergen, Martin, Meiler, J., Kalkhof, Stefan, Nagel, Marcus, Moretti, R., Paschke, R., von Bergen, Martin, Meiler, J., and Kalkhof, Stefan

Abstract

The follicle-stimulating hormone receptor (FSHR) belongs to the glycoprotein hormone receptors, a subfamily of G-protein-coupled receptors (GPCRs). FSHR is involved in reproductive processes such as gonadal development and maturation. Structurally, the extensive extracellular domain, which contains the hormone-binding site and is linked to the transmembrane domain by the hinge region (HR), is characteristic for these receptors. How this HR is involved in hormone binding and signal transduction is still an open question. We combined in vitro and in situ chemical crosslinking, disulfide pattern analysis, and mutation data with molecular modeling to generate experimentally driven full-length models. These models provide insights into the interface, important side-chain interactions, and activation mechanism. The interface indicates a strong involvement of the connecting loop. A major rearrangement of the HR seems implausible due to the tight arrangement and fixation by disulfide bonds. The models are expected to allow for testable hypotheses about signal transduction and drug development for GPHRs.

Published
2022

32. Myocardial Infarction after Long-Term Treatment with a Tyrosine Kinase Inhibitor (TKI) with Anti-VEGF Receptor Activity

Author

Paschke, L., Lincke, T., Mühlberg, K., Lindner, Tom H., and Paschke, R.

Subjects
Article Subject
Abstract

TKIs including anti-VEGF receptor activity have been approved for the treatment of patients with radioiodine resistant thyroid carcinomas. For lenvatinib arterial thromboembolic events are listed as adverse events of special interest with lenvatinib. In the phase III study, arterial thromboembolic events were reported in 3% of lenvatinib-treated patients and 1% in the placebo group. Most of the patients had predisposing factors. Only one myocardial infarct was reported in the lenvatinib phase III study. We report a 73-year-old female patient with metastatic thyroid papillary carcinoma who was treated with total thyroidectomy. The operation was followed by four radioiodine therapies over a period of 6 years. At 6 years she developed lung metastasis without radioiodine uptake, one solitary liver metastasis and one solitary right renal metastasis. One year after the first diagnosis of radioiodine resistant lung metastasis the lung metastasis showed progression according to RECIST criteria. This treatment was resulting in prolonged partial response with disappearance of a hepatic and renal metastasis. A myocardial infarction occurred after 39 months of lenvatinib treatment resulting in implantation of 3 stents and a two chamber pacemaker. The treatment was discontinued. Except for well controlled hypertension there were neither predisposing diseases like diabetes nor symptoms of cardiac ischemia on exertion. However, the family history for cardiovascular diseases was positive for cardiac infarction reported for one brother. Another brother was treated for hypertension and the patient’s mother suffered from a cerebral infarction at the age of 60. While only one myocardial infarct was reported in the lenvatinib phase III study with 392 patients this case suggests that long-term treatment with lenvatinib may be associated with an increased risk for myocardial infarct also in patients with no predisposing diseases except well controlled hypertension and positive family history for cardiovascular diseases.

Published
2019
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50. Follicular thyroid carcinoma

Author

Livolsi V, Abdulkader I, Baloch Zw, Bartolazzi A, Chan Jkc, De Lellis Ra, El-naggar Ak, Eloy C, Eng C, Fagin Ja, Ghossein Ra, Giordano Tj, Kondo T, Lloyd Rv, Mete O, Nikiforov Ye Nonaka D, Paschke R, Perren A, Rosai J, Sadow P, Schneider Ab, Sobrinho-simoes M, Tallini G, Williams Md, Livolsi, V, Abdulkader, I, Baloch, Zw, Bartolazzi, A, Chan, Jkc, De Lellis Ra, El-naggar, Ak, Eloy, C, Eng, C, Fagin, Ja, Ghossein, Ra, Giordano, Tj, Kondo, T, Lloyd, Rv, Mete, O, Nikiforov Ye Nonaka, D, Paschke, R, Perren, A, Rosai, J, Sadow, P, Schneider, Ab, Sobrinho-simoes, M, Tallini, Giovanni, and Williams, Md

Subjects
endocrine system, endocrine system diseases, thyroid, tumour, carcinoma, follicular
Abstract

Follicular thyroid carcinoma (FTC) is a thyroid malignancy arising from follicular cells in which the diagnostic nuclear features of papillary thyroid carcinoma (PTC) are lacking. The lesions are usually encapsulated and show invasive growth

Published
2017

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