409 research outputs found

    Antimicrobial Peptide Human Neutrophil Peptide 1 as a Potential Link Between Chronic Inflammation and Ductal Adenocarcinoma of the Pancreas

    Get PDF
    Objectives Defensins are antimicrobial peptides playing a role in innate immunity, in epithelial cell regeneration, and in carcinogenesis of inflammation-triggered malignancies. We analyzed this role in pancreatic ductal adenocarcinoma (PDAC) in the context of its association with chronic pancreatitis (CP). Methods Human tissue of healthy pancreas, CP, and PDAC was screened for defensins by immunohistochemistry. Defensin 1 (human neutrophil peptide 1 [HNP-1]) expression was validated using mass spectrometry and microarray analysis. Human neutrophil peptide 1 expression and influences of proinflammatory cytokines (tumor necrosis factor , interleukin 1, and interferon ) were studied in human pancreatic cancer cells (Colo 357, T3M4, PANC-1) and normal human pancreatic duct epithelial cells (HPDE). Results Accumulation of HNP-1 in malignant pancreatic ductal epithelia was seen. Spectrometry showed increased expression of HNP-1 in CP and even more in PDAC. At RNA level, no significant regulation was found. In cancer cells, HNP-1 expression was significantly higher than in HPDE. Proinflammatory cytokines significantly led to increased HNP-1 levels in culture supernatants and decreased levels in lysates of cancer cells. In HPDE cytokines significantly decreased HNP-1 levels. Conclusions Inflammatory regulation of HNP-1 in PDAC tissue and cells indicates that HNP-1 may be a link between chronic inflammation and malignant transformation in the pancreas

    PCB 47, 51, 68 – Bestimmung von PCB 47, 51, 68 in der Luft am Arbeitsplatz mittels Gaschromatographie (GC-ECD)

    Get PDF
    This analytical method is a validated measurement procedure for the determination of the three tetrachlorinated biphenyls PCB 47 [2437-79-8], PCB 51 [68194-04-7] and PCB 68 [73575-52-7] in workplace air in a concentration range of 0.16 to 0.62 ÎŒg/m3. It was developed to detect PCB that only may be generated during the manufacture of silicone products with peroxidic crosslinking with bis(2,4-dichlorobenzoyl) peroxide. By measurement in manufacturing plants it could be proven that the PCB to be investigated are present exclusively in vapour form. For this reason, the method was only validated for vaporous samples. There are currently no valid evaluation criteria for these PCB. Therefore, the German Occupational Exposure Limit Value for the sum of all PCB (5 × sum of the 6 indicator PCB [28, 52, 101, 138, 152, 180]) of 3 ÎŒg/m3 was used as the assessment standard for each congener. For sampling, a defined volume of air is drawn through a sorbent tube filled with Florisil. The flow rate is set to 1 l/min and sampling duration is 4 hours (which correspond to a sampling volume of 240 l). The PCB are extracted with n-hexane at 40 °C in an ultrasonic bath and subsequently analysed using gas chromatography with electron capture detection. The quantitative determination is based on a calibration function. The limit of quantification is 0.11 ÎŒg/m3 based on an air sample volume of 240 l. The mean recovery is 96% and the expanded uncertainty for the validation range of 0.16 to 0.62 ÎŒg/m3 is 22 to 24%

    The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation

    Get PDF
    Background. Chronic pancreatitis is one of the main risk factors for pancreatic cancer. In acute and chronic pancreatitis, oxidative stress is thought to play a key role. In this respect, the recently described mitochondria-targeted antioxidant SkQ1 effectively scavenges reactive oxygen species at nanomolar concentrations. Therefore, we aimed to characterize the influence of SkQ1 on tissue injury and pain in acute and chronic pancreatitis. Methods. Both acute and chronic pancreatitis were induced in C57BL/6 mice by intraperitoneal cerulein injections and treatment with SkQ1 was carried out by peroral applications. Hyperalgesia was assessed by behavioral observation and measurement of abdominal mechanical sensitivity. Blood serum and pancreatic tissue were harvested for analysis of lipase and histology. Results. SkQ1 did not influence pain, serological, or histological parameters of tissue injury in acute pancreatitis. In chronic pancreatitis, a highly significant reduction of pain-related behavior (p < 0.0001) was evident, but histological grading revealed increased tissue injury in SkQ1-treated animals (p = 0.03). Conclusion. After SkQ1 treatment, tissue injury is not ameliorated in acute pancreatitis and increased in chronic pancreatitis. However, we show an analgesic effect in chronic pancreatitis. Further studies will need to elucidate the risks and benefits of mitochondria-targeted antioxidants as an analgesic

    Symptoms and Surgical Management of a Distal Choledochal Cyst in a Patient with Pancreas Divisum: Case Report and Review of the Literature

    Get PDF
    We report the case of a 63-year-old woman who presented with the rare finding of a distal choledochocele in a pancreas divisum with recurrent abdominal pain and episodes of pancreatitis. She underwent successful resection with choledochectomy, papillectomy and reconstruction with a hepatico-jejunostomy and reinsertion of the uncinate pancreatic duct into the same jejunal loop. Comparable literature findings are discussed with regard to the presented case

    Astrocyte mediated modulation of blood-brain barrier permeability does not correlate with a loss of tight junction proteins from the cellular contacts

    Get PDF
    In the central nervous system (CNS) complex endothelial tight junctions (TJs) form a restrictive paracellular diffusion barrier, the blood-brain barrier (BBB). Pathogenic changes within the CNS are frequently accompanied by the loss of BBB properties, resulting in brain edema. In order to investigate whether BBB leakiness can be monitored by a loss of TJ proteins from cellular borders, we used an in vitro BBB model where brain endothelial cells in co-culture with astrocytes form a tight permeability barrier for 3H-inulin and 14C-sucrose. Removal of astrocytes from the co-culture resulted in an increased permeability to small tracers across the brain endothelial cell monolayer and an opening of the TJs to horseradish peroxidase as detected by electron microscopy. Strikingly, opening of the endothelial TJs was not accompanied by any visible change in the molecular composition of endothelial TJs as junctional localization of the TJ-associated proteins claudin-3, claudin-5, occludin, ZO-1 or ZO-2 or the adherens junction-associated proteins ÎČ-catenin or p120cas did not change. Thus, opening of BBB TJs is not readily accompanied by the complete loss of the junctional localization of TJ protein

    Einsatz des Modells “EROSION-3D” im FeldgemĂŒseanbau auf den Fildern/Lkrs. Esslingen

    Get PDF
    Kurzfassung Problem: Im Lössgebiet auf den Fildern haben seit der Ausweitung des GemĂŒseanbaus Bodenerosion und OberflĂ€chenabfluss deutlich zugenommen. Nachdem infolge von Gewitterregen extreme SchĂ€den (Äcker + Siedlung) auftraten, wandten sich die Gemeinde Neuhausen sowie die Bodenschutz- und die Landwirtschaftsverwaltung an das LTZ Augustenberg mit dem Anliegen Lösungswege zu entwickeln. Methodik: ZunĂ€chst wurde eine Ursachenanalyse im GelĂ€nde durchgefĂŒhrt und die Schadensdokumentationen der örtlichen Behörden ausgewertet. Dann wurden mit dem Prognosemodell “EROSION-3D“ fĂŒr ein im Einzugsgebiet der Gemeinde Neuhausen stattgefundenes Abtragsereignis neben der Null-Variante einige Maßnahmen-Szenarien durchgerechnet; beispielsweise die flĂ€chige konservierende Bodenbearbeitung oder der Einsatz von Mulchvlies. Ergebnisse - Bei Beibehaltung der Ackerbaunutzung kann nur eine flĂ€chige konservierende Bodenbearbeitung eine adĂ€quate ProblementschĂ€rfung beim Bodenabtrag bewirken. - Die modellierten Maßnahmen, die speziell auf Sonderkulturen zugeschnitten sind, reichen singulĂ€r nicht aus. Hier mĂŒssen Maßnahmenkombinationen ergriffen werden. Dabei besitzt das Abflussmanagement oberste PrioritĂ€t. Schlussfolgerungen: Durch die Ergebnisse der Modellierung konnten die Möglichkeiten und Grenzen von möglichen Lösungswegen, ĂŒber die im Vorfeld diskutiert wurde, aufgezeigt werden. FĂŒr etliche Sonderkulturen (etwa Salat) gibt es noch keine Produktionstechnik, die sowohl den Anforderungen des Erosionsschutzes, als auch den AnsprĂŒchen der Erzeuger gerecht wird. Hier besteht noch ein erheblicher Forschungsbedarf

    Infected Necrosis in Severe Pancreatitis - Combined Nonsurgical Multi-Drainage with Directed Transabdominal High-Volume Lavage in Critically Ill Patients

    Get PDF
    Background: Infection of pancreatic necrosis is a life-threatening complication during the course of acute pancreatitis. In critically ill patients, surgical or extended endoscopic interventions are associated with high morbidity and mortality. Minimally invasive procedures on the other hand are often insufficient in patients suffering from large necrotic areas containing solid or purulent material. We present a strategy combining percutaneous and transgastric drainage with continuous high-volume lavage for treatment of extended necroses and liquid collections in a series of patients with severe acute pancreatitis. Patients and Methods: Seven consecutive patients with severe acute pancreatitis and large confluent infected pancreatic necrosis were enrolled. In all cases, the first therapeutic procedure was placement of a CT-guided drainage catheter into the fluid collection surrounding peripancreatic necrosis. Thereafter, a second endosonographically guided drainage was inserted via the gastric or the duodenal wall. After communication between the separate drains had been proven, an external to internal directed high-volume lavage with a daily volume of 500 ml up to 2,000 ml was started. Results: In all patients, pancreatic necrosis/liquid collections could be resolved completely by the presented regime. No patient died in the course of our study. After initiation of the directed high-volume lavage, there was a significant clinical improvement in all patients. Double drainage was performed for a median of 101 days, high-volume lavage for a median of 41 days. Several endoscopic interventions for stent replacement were required (median 8). Complications such as bleeding or perforation could be managed endoscopically, and no subsequent surgical therapy was necessary. All patients could be dismissed from the hospital after a median duration of 78 days. Conclusion: This approach of combined percutaneous/endoscopic drainage with high-volume lavage shows promising results in critically ill patients with extended infected pancreatic necrosis and high risk of surgical intervention. Neither surgical nor endoscopic necrosectomy was necessary in any of our patients. Copyright (C) 2009 S. Karger AG, Basel and IA

    Outcomes and risks in palliative pancreatic surgery: an analysis of the German StuDoQ|Pancreas registry

    Get PDF
    BACKGROUND: Non-resectability is common in patients with pancreatic ductal adenocarcinoma (PDAC) due to local invasion or distant metastases. Then, biliary or gastroenteric bypasses or both are often established despite associated morbidity and mortality. The current study explores outcomes after palliative bypass surgery in patients with non-resectable PDAC. METHODS: From the prospectively maintained German StuDoQ|Pancreas registry, all patients with histopathologically confirmed PDAC who underwent non-resective pancreatic surgery between 2013 and 2018 were retrospectively identified, and the influence of the surgical procedure on morbidity and mortality was analyzed. RESULTS: Of 389 included patients, 127 (32.6%) underwent explorative surgery only, and a biliary, gastroenteric or double bypass was established in 92 (23.7%), 65 (16.7%) and 105 (27.0%). After exploration only, patients had a significantly shorter stay in the intensive care unit (mean 0.5 days [SD 1.7] vs. 1.9 [3.6], 2.0 [2.8] or 2.1 [2.8]; P < 0.0001) and in the hospital (median 7 days [IQR 4–11] vs. 12 [10–18], 12 [8–19] or 12 [9–17]; P < 0.0001), and complications occurred less frequently (22/127 [17.3%] vs. 37/92 [40.2%], 29/65 [44.6%] or 48/105 [45.7%]; P < 0.0001). In multivariable logistic regression, biliary stents were associated with less major (Clavien–Dindo grade ≄ IIIa) complications (OR 0.49 [95% CI 0.25–0.96], P = 0.037), whereas—compared to exploration only—biliary, gastroenteric, and double bypass were associated with more major complications (OR 3.58 [1.48–8.64], P = 0.005; 3.50 [1.39–8.81], P = 0.008; 4.96 [2.15–11.43], P < 0.001). CONCLUSIONS: In patients with non-resectable PDAC, biliary, gastroenteric or double bypass surgery is associated with relevant morbidity and mortality. Although surgical palliation is indicated if interventional alternatives are inapplicable, or life expectancy is high, less invasive options should be considered. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12893-022-01833-3
    • 

    corecore