Prophylactic Glycine Administration Attenuates Pancreatic Damage and Inflammation in Experimental Acute Pancreatitis

Background/Aims: Acute pancreatitis (AP) is characterized by premature zymogen activation, systemic inflammatory response resulting in inflammatory infiltrates, sustained intracellular calcium, neurogenic inflammation and pain. The inhibitory neurotransmitter and cytoprotective amino acid glycine exerts a direct inhibitory effect on inflammatory cells, inhibits calcium influx and neuronal activation and therefore represents a putative therapeutic agent in AP. Methods: To explore the impact of glycine, mild AP was induced in rats by supramaximal cerulein stimulation (10 µg/kg BW/h) and severe AP by retrograde injection of sodium taurocholate solution (3%) into the common biliopancreatic duct. 100/300 mmol glycine was administered intravenously before induction of AP. To elucidate the effect of glycine on AP, we determined pathomorphology, pancreatic cytokines as well as proteases, serum lipase and amylase, pancreatic and lung MPO activity and pain sensation. Results: Glycine administration resulted in a noticeable improvement of pathomorphological alterations in AP, such as a reduction of necrosis, inflammatory infiltrates and cytoplasmic vacuoles in cerulein pancreatitis. In taurocholate pancreatitis, glycine additionally diminished pancreatic cytokines and MPO activity, as well as serum lipase and amylase levels. Conclusions: Glycine reduced the severity of mild and much more of severe AP by attenuating the intrapancreatic and systemic inflammatory response. Therefore, glycine seems to be a promising tool for prophylactic treatment of AP

Magnesium reduziert den Schweregrad der experimentellen Caerulein-Pankreatitis und die Proteasenaktivierung an isolierten Azinuszellen

Eine kausale Therapie der akuten Pankreatitis konnte bis zum heutigen Tage nicht etabliert werden. Holtmeier et al zeigten erstmals., dass eine Magnesium-Applikation, im Rahmen der akuten Pankreatitis, den Krankheitsverlauf positiv beeinflusste. Das Ziel war die Untersuchung, ob Magnesium, bei intravenöser Gabe, eine therapeutische Wirkung auf eine experimentell induzierte Pankreatitis hat und deren Verlauf beeinflussen kann. Eine prophylaktische, als auch eine therapeutische Behandlung der Caerulein-Pankreatitis mit Magnesium reduzierte die Amylase- und Lipaseaktivität im Serum, das Pankreasödem und den Azinusschaden. Die Aktivierung der Proteasen konnte bei der Caerulein-Pankreatitis und an stimulierten Pankreas-Azinuszellen durch eine Behandlung mit Magnesium reduziert werden. Somit könnte eine prophylaktische Gabe von Magnesium bei Risikopatienten die Inzidenz einer Pankreatitis senken und die Behandlung mit Magnesium eventuell auch nach Beginn der Pankreatitis einen ther apeutischen Effekt zeigen

Insulin/IGF-driven cancer cell-stroma crosstalk as a novel therapeutic target in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is unrivalled the deadliest gastrointestinal cancer in the western world. There is substantial evidence implying that insulin and insulin-like growth factor (IGF) signaling axis prompt PDAC into an advanced stage by enhancing tumor growth, metastasis and by driving therapy resistance. Numerous efforts have been made to block Insulin/IGF signaling pathway in cancer therapy. However, therapies that target the IGF1 receptor (IGF-1R) and IGF subtypes (IGF-1 and IGF-2) have been repeatedly unsuccessful. This failure may not only be due to the complexity and homology that is shared by Insulin and IGF receptors, but also due to the complex stroma-cancer interactions in the pancreas. Shedding light on the interactions between the endocrine/exocrine pancreas and the stroma in PDAC is likely to steer us toward the development of novel treatments. In this review, we highlight the stroma-derived IGF signaling and IGF-binding proteins as potential novel therapeutic targets in PDAC