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Neuroscience Letters 375(3): 170-173. urn:nbn:de:hebis:04-z2013-04341 Sekretion The secretion of the gastrointestinal hormone ghrelin is dependent on an intact vagal nerve. The discovery of pathognomonic α-synuclein aggregation in parts of the vagal nerve in earlier stages of Parkinson’s disease (PD) has led to the assumption of a potential vagal function disorder. Hypothetically this dysfunction could affect the ghrelin secretion of patients with PD and idiopathic REM-sleep behavior disorder (iRBD), a potential preclinical stage of PD. A recent study revealed an impaired postprandial ghrelin secretion in these patients. However, analysis techniques used in these studies could not distinguish between acylated and desacylated ghrelin subtypes (AG and DAG). Further investigations revealed distinct differences in their physiological effects, strongly indicating that separate measurement is required. In order to exactly determine the pathophysiological context of disturbed ghrelin secretion, the current study analyzed pre- and postprandial concentrations of AG and DAG. Additionally, patients with multiple sclerosis who also showed a change in ghrelin secretion were included. Consequently, the design of the investigation included five groups: PD patients with (n=25) and without (n=15) treatment, patients with iRBD (n=15), patients with multiple sclerosis (n=16) and healthy controls (n=25). AG and DAG were determined at eight selected points of time using a commercial “enzyme linked immunosorbent assay” (ELISA). The area under the curve, fasting concentrations of the respective hormones and the DAG:AG ratio were defined as outcome parameters. For each group of patients, we demonstrated a reduction of both AG and DAG concentrations at every measuring point. However, none of these outcome parameters reached a significant level due to a high inter-individual variability. The present results can be interpreted in two ways. Either there is no altered ghrelin secretion in the above mentioned diseases or the missing detectability is a result of an insufficient control of factors affecting AG and DAG concentrations and thus may be responsible for the high inter-individual variability. In this context, an improved preanalytic phase, a more adapted research design and objectively measured comorbidities should be considered in further research on the topic. parkinson ppn:323295142 2013-06-26 German Ghrelin https://doi.org/10.17192/z2013.0434 ths Prof. Dr. med. Dr. h.c. Oertel Wolfgang Oertel, Wolfgang (Prof. Dr. med. Dr. h.c. ) Die Sekretion des gastrointestinalen Hormons Ghrelin ist von einem intakten Nervus vagus abhängig. Die Entdeckung von pathognomonischen α-Synukleinaggregaten in Teilen des Nervus vagus in bereits frühen Stadien des idiopathischen Parkinsonsyndroms (IPS) führte zur Annahme einer potentiellen vagalen Funktionsstörung. Hypothetisch könnte sich diese Störung auf die Ghrelinsekretion bei Patienten mit IPS und der idiopathischen REM-Schlaf- Verhaltensstörung (iRBD), einer potentiellen Vorstufe des IPS, auswirken. In einer Studie zeigte sich bei diesen Patienten eine gestörte postprandiale Ghrelinauschüttung. Allerdings konnte das dabei eingesetzte Auswertungsverfahren nicht zwischen der acetylierten bzw. desacetylierten Unterform von Ghrelin (AG und DAG) differenzieren. Eine separate Messung erscheint jedoch notwendig, da weitere Untersuchungen zeigten, dass sich beide Hormonunterformen in ihrer Wirkung deutlich unterscheiden. Um den pathophysiologischen Kontext der gestörten Ghrelinsekretion differenzierter erfassen und bewerten zu können, wurde in der vorliegenden Arbeit die prä- und postprandiale Sekretion beider Hormonformen analysiert. Zusätzlich wurden Patienten mit Multipler Sklerose eingeschlossen, welche ebenfalls eine veränderte Ghrelinsekretion aufweisen. Im Rahmen der Untersuchung wurden fünf Probandengruppen gebildet: Patienten mit IPS unter (n=25) und bislang ohne (n=15) Therapie, Patienten mit iRBD (n=15), Patienten mit Multipler Sklerose (n=16) sowie gesunde Kontrollpersonen (n=25). Mit Hilfe eines „enzyme linked immunosorbent assay“ (ELISA) wurde die Plasmakonzentration von AG und DAG vor und nach einer Testmahlzeit an acht definierten Zeitpunkten bestimmt. Als Zielgrößen wurden die „area under the curve“, die Nüchternkonzentrationen der Hormonunterformen sowie das DAG:AG-Verhältnis definiert. Alle Erkrankungsbilder zeigten gegenüber der Kontrollgruppe zu allen Messzeitpunkten rein deskriptiv niedrigere AG- und DAG-Konzentrationen, wobei durch eine hohe interindividuelle Variabilität kein Auswertungsparameter im Gruppenvergleich ein signifikantes Niveau erreichte. Die vorliegenden Ergebnisse lassen zwei mögliche Erklärungen zu: Entweder besteht bei den erwähnten Erkrankungen tatsächlich keine gestörte Ghrelinsekretion oder die fehlende Nachweisbarkeit beruht auf einer unzureichenden Kontrolle möglicher Faktoren, welche die zu messenden AG- und DAG-Konzentrationen beeinflussen und somit für die hohe interindividuelle Variabilität verantwortlich sein könnten. Neben einer verbesserten Präanalytik und angepasstem Untersuchungsdesign, sollten vor allem die Komorbiditäten der Probanden gezielter objektiviert werden. Erst auf dieser Basis können die vermuteten Kausalitäten zwischen Erkrankung und Ghrelinsekretion im Rahmen von zukünftigen Projekten verifiziert werden. ghrelin https://archiv.ub.uni-marburg.de/diss/z2013/0434/cover.png 2013 monograph Nervenheilkunde Publikationsserver der Universitätsbibliothek Marburg Universitätsbibliothek Marburg doctoralThesis Prä- und postprandiale Ghrelinsekretion bei Patienten mit Parkinson Erkrankung,REM-Schlaf-Verhaltensstörung und Multipler Sklerose Multiple Sklerose application/pdf 2013-07-04 Pre- and postprandial ghrelin secretion in patients with parkinson disease, REM-sleep-behaviour-disorder and multiple sclerosis Thomi, Daniel Thomi Daniel secretion opus:4970 Philipps-Universität Marburg