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The vagal nerve as a link between the nervous and immune system in the instance of polymicrobial sepsis 总被引:5,自引:0,他引:5
Wolfram Kessler Tobias Traeger Alexandra Westerholt Friederike Neher Marlene Mikulcak Antje Müller Stefan Maier Claus-Dieter Heidecke 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》2006,391(2):83-87
Background The role of the vagal nerve in the autonomic nervous system is widely well known. Recently, an additional function was revealed
serving as a connector between the nervous and immune system. This connection is called the “cholinergic inflammatory pathway.”
Through stimulation of the acetylcholine receptors located upon the macrophages, the “unspecific” immune system can be directly
influenced.
Methods The vagal nerve was completely transected directly posterior to its passage through the diaphragm. The effect of complete
vagotomy was analyzed using a murine model of polymicrobial peritonitis (colon ascendens stent peritonitis, CASP). Survival
and clinical course of vagotomized or sham-operated mice were analyzed in the CASP model.
Results After CASP surgery, vagotomy led to a significantly increased mortality (64.7%) in comparison to sham-vagotomized animals
(34%). No difference in the bacterial load of various tissues (lung, liver, spleen, blood, lavage fluid, and kidney) from
septic animals with or without vagotomy was observed. Vagotomized animals reveal elevated serum cytokine levels (TNF, IL-6,
IL-10, and MCP-1) 20 h after the induction of polymicrobial peritonitis.
Conclusion The vagal nerve is therefore an important modulator of the immune system.
W. Kessler and T. Traeger contributed equally to this work
Best of Forum Papers presented at the Annual Meeting of the German Society of Surgery, 2–5 May 2006, Berlin, Germany 相似文献
4.
Prevalence of H pylori associated 'high risk gastritis' for development of gastric cancer in patients with normal endoscopic findings 总被引:1,自引:0,他引:1
Andreas Leodolter Matthias P Ebert Ulrich Peitz Kathlen Wolle Stefan Kahl Peter Malfertheiner 《World journal of gastroenterology : WJG》2006,(34)
INTRODUCTION H pylori infection is an established risk factor for development of gastric cancer[1,2]. According to the model of carcinogenesis of the intestinal type adenocarcinoma proposed by Correa, the multi-step development starts from the condition o… 相似文献
5.
Chronic hepatitis C in patients with persistently normal alanine transaminase levels. 总被引:2,自引:0,他引:2
Mitchell L Shiffman Moisés Diago Albert Tran Paul Pockros Robert Reindollar Daniele Prati Maribel Rodríguez-Torres Pilar Lardelli Steven Blotner Stefan Zeuzem 《Clinical gastroenterology and hepatology》2006,4(5):645-652
BACKGROUND & AIMS: Many patients with chronic hepatitis C virus (HCV) have persistently normal serum alanine transaminase (ALT) levels. We compared characteristics of chronic hepatitis C patients with patients with normal and elevated ALT levels using data from 3 randomized phase III trials of peginterferon alfa-2a (40 kDa). METHODS: The characteristics of 480 patients with normal ALT values (on >or=3 occasions without any increases in ALT level over a 6- to 18-month period) and 1993 patients with elevated ALT levels were compared. Sixty-eight of the 480 patients with normal ALT levels were randomized to no treatment and monitored for 72 weeks. RESULTS: More patients with normal ALT levels than patients with elevated ALT levels were women (59% vs 32%; P<.01). The serum HCV RNA titer was significantly lower in patients with normal ALT levels (P<.01 vs in patients with elevated ALT levels). Patients with normal ALT levels had significantly lower inflammation and fibrosis scores on liver biopsy examination than patients with elevated ALT levels, but almost two-thirds had portal fibrosis and 10% had bridging fibrosis. No correlation between baseline ALT activity, HCV RNA level, and liver histology was observed in patients with normal ALT levels. During the 72-week follow-up period, ALT activity elevated above the upper limit of normal in 53% of the untreated patients with normal levels of ALT. None became HCV RNA undetectable. CONCLUSIONS: Chronic hepatitis C patients with normal ALT levels should be evaluated in a similar manner as patients with elevated ALT levels because they are at risk for developing significant liver disease. The decision to treat with peginterferon alfa and ribavirin should be based on multiple factors, rather than on ALT levels alone. 相似文献
6.
Olle Zetterström Christer Andersson Leif Eriksson ers Fredriksson Johan Friskopp Gunnar Heden Bernt Jansson Tord Lundgren Rolf Nilveus ers Olsson Stefan Renvert Lars Salonen Lars Sjöström ers Winell ers Östgren Stina Gestrelius 《Journal of clinical periodontology》1997,24(9):697-704
Abstract The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN® in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN® in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN® at I comparable site. In total 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery. 56 other samples were taken after one treatment with EMDOGAIN®, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN® is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of post-surgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months post surgery. and this difference had increased further at the 3 year follow-up. The 2.5–3 mm increase in attachment and bone level after treatment with EMDOGAIN® was of the same magnitude as seen in the studies with split-mouth design aiming for lest of effectiveness of EMDOGAIN®. 相似文献
7.
Cytokines as therapeutic drugs. 总被引:1,自引:0,他引:1
Cytokines are a growing group of proteins that are responsible for the communication of cells of the immune system, hematopoietic cells, and other cell types. They play a dominant role in various diseases, particularly in promoting and perpetuating inflammation. Cytokine production is a reaction of the body to a pathologic state to restore homeostasis. In such cases, the therapeutic intervention should support the reaction of the body by giving the cytokine itself (agonistic therapeutics). In other cases, manifestation of a disease results from an overproduction of cytokines, making cytokine antagonists desirable therapeutic drugs. Furthermore, cytokines may be good candidates as cancer therapeutics, especially to support the restoration of blood cell populations after chemotherapy or radiation. 相似文献
8.
Galanin-like immunoreactivity has been visualized in nerve fibers in the islets of Langerhans, suggesting an involvement of
galanin in the neural regulation of islet function. In this study, we investigated the effects of galanin on basal and stimulated
insulin and glucagon secretion by infusing the peptide at three different dose rates in rats. We also studied the direct effect
of galanin on insulin secretion from freshly isolated rat islets. At 320 pmol/kg/min, but not at 20 or 80 pmol/kg/min, galanin
lowered basal plasma insulin levels. In contrast, basal plasma glucagon levels were lowered by galanin already at 20 and 80
pmol/kg/min. Furthermore, galanin inhibited both glucose- and arginine-induced insulin release at all three dose levels, whereas
arginine-induced glucagon release was not affected by galanin. Glucose-stimulated insulin secretion from isolated rat islets
was dose-dependently suppressed by galanin (10-6-10-8M). Therefore, it is concluded that galanin in rats inhibits insulin secretion, both in vivo and in vitro, and that at lower
dose levels, the peptide also inhibits basal glucagon release. 相似文献
9.
Andreas Lange Claudia Kistler Tanja B. Jutzi Alexandr V. Bazhin Claus Detlev Klemke Dirk Schadendorf Stefan B. Eichmüller 《Experimental dermatology》2009,18(6):527-535
Abstract: The identification of tumor-specific proteins located at the plasma membrane is hampered by numerous methodological pitfalls many of which are associated with the post-translational modification of such proteins. Here, we present a new combination of detergent fractionation of cells and of subtractive suppression hybridization (SSH) to gain overexpressed genes coding for membrane-associated or secreted proteins. Fractionation of subcellular components by digitonin allowed sequestering mRNA of the rough Endoplasmatic reticulum and thereby increasing the percentage of sequences coding for membrane-bound proteins. Fractionated mRNAs from the cutaneous T-cell lymphoma (CTCL) cell line HuT78 and from normal peripheral blood monocytes were used for SSH leading to the enrichment of sequences overexpressed in the tumor cells. We identified some 21 overexpressed genes, among them are GPR137B, FAM62A, NOMO1, HSP90, SLIT1, IBP2, CLIF, IRAK and ARC. mRNA expression was tested for selected genes in CTCL cell lines, skin specimens and peripheral blood samples from CTCL patients and healthy donors. Several of the detected sequences are clearly related to cancer, but have not yet been associated with CTCL. qPCR confirmed an enrichment of these mRNAs in the rough endoplasmic reticulum fraction. RT-PCR confirmed the expression of these genes in skin specimens and peripheral blood of CTCL patients. Western blotting verified protein expression of HSP90 and IBP2 in HuT78. GPR137B could be detected by immunohistology in HuT78 and in keratinocytes of dysplastic epidermis, but also in sweat glands of healthy skin. In summary, we developed a new technique, which allows identifying overexpressed genes coding preferentially for membrane-associated proteins. 相似文献
10.
Walter S Speidl Markus Exner Jasmin Amighi Wolfgang Mlekusch Schila Sabeti Stefan P Kastl Gerlinde Zorn Gerald Maurer Oswald Wagner Kurt Huber Erich Minar Johann Wojta Martin Schillinger 《Journal of endovascular therapy》2007,14(1):62-69
PURPOSE: To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS: C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS: Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION: Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The complement component C5a exerts strong chemotactic and proinflammatory effects. Enhanced complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of complement inhibition thus may be worth investigating with respect to improving patency rates. 相似文献