J C Kalff

University of Bonn, Bonn, North Rhine-Westphalia, Germany

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Publications (81)233.79 Total impact

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    ABSTRACT: Postoperative ileus (POI) is defined as a transient episode of impaired gastrointestinal motility after abdominal surgery, which prevents effective transit of intestinal contents or tolerance of oral intake. This frequent postoperative complication is accompanied by a considerable increase in morbidity and hospitalisation costs. The aetiology of POI is multifactorial. Besides a suppression of peristalsis by inhibitory neuronal signalling and administration of opioids, particularly in the prolonged form, immunological processes play an important role. After surgical trauma, resident macrophages of the muscularis externa (ME) are activated leading to the liberation of proinflammatory mediators and a spreading of the inflammation along the entire gastrointestinal tract. To date, no prophylaxis or evidence-based single approach exists to treat POI. Since none of the current treatment approaches (i.e., prokinetic drug treatment) has provided a benefit in randomised trials, immunoregulatory interventions appear to be more promising in POI prevention or treatment. The present contribution gives an overview of immunological mechanisms leading to POI focusing on current and future therapeutic and prophylactic approaches.
    Zentralblatt für Chirurgie 12/2013; · 0.69 Impact Factor
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    ABSTRACT: As data about prevalence and standard of care in short bowel syndrome (SBS) are not available for Germany, this study estimated the prevalence and assessed the medical infrastructure to potentially improve care of SBS patients. In a validated approach for prevalence estimation in rare diseases, a randomized census of 478 size-stratified hospitals with surgical, internal medicine and pediatric departments was conducted to estimate SBS prevalence. The number of SBS patients, specialized outpatient clinics and caregiver expertise were assessed. The response rate was 85 % of randomized hospitals (405/478). Strata-derived estimation yielded a total of 2,808 SBS patients in Germany for 2011/2012 (95 % CI: 1750.3865), translating into a prevalence estimation for 34/million inhabitants (95 % CI: 21.47). Overall expertise in SBS treatment was only rated "satisfactory" by most caregivers. While 86 specialized outpatient clinics were identified, there was no central registry to access these resources. Short bowel syndrome, with a newly estimated prevalence of 34/million inhabitants is not a very rare medical condition in Germany. The interdisciplinary approach needed for optimal care for SBS patients would be greatly facilitated by a central registry.
    Der Chirurg 11/2013; · 0.52 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: Regulatory CD4(+) T cells (Tregs) are considered to affect outcomes of HCV infection, because they increase in numbers during chronic hepatitis C and can suppress T cell functions. METHODS: Using microarray analysis, in situ immunofluorescence, ELISA, and flowcytometry we characterised functional differentiation and localisation of adaptive Tregs in patients with chronic hepatitis C. RESULTS: We found substantial up-regulation of IL-8 in Foxp3(+)CD4(+) Tregs from chronic hepatitis C. Activated GARP-positive IL-8(+) Tregs were particularly enriched in livers of patients with chronic hepatitis C in close proximity to areas of fibrosis and their numbers were correlated to the stage of fibrosis. Moreover, Tregs induced up-regulation of profibrogenic markers TIMP1, MMP2, TGF-beta1, alpha-SMA, collagen and CCL2 in primary human hepatic stellate cells (HSC). HSC activation but not Treg suppressor function was blocked by adding a neutralizing IL-8 antibody. CONCLUSION: Our studies identified Foxp3(+)CD4(+) Tregs as an additional intrahepatic source of IL-8 in chronic hepatitis C acting on HSC. Thus, Foxp3(+)CD4(+) Tregs in chronic hepatitis C have acquired differentiation as regulators of fibrogenesis in addition to suppressing local immune responses.
    Journal of Hepatology 04/2013; · 9.86 Impact Factor
  • Transplant International 03/2013; · 3.16 Impact Factor
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    ABSTRACT: It remains unclear which liver graft reperfusion technique leads to the best outcome following transplantation. An online survey was sent to all transplant centres (n = 37) within Eurotransplant (ET) to collect information on their technique used for reperfusion of liver grafts. Furthermore, a systematic review of all literature was performed and a meta-analysis was conducted based on patients' mortality, number of retransplantations and incidence of biliary complications, depending on the technique used. Of the 28 evaluated centres, 11 (39%) reported performing simultaneous reperfusion (SIMR), 13 (46%) perform initial portal vein reperfusion (IPR), 1 (4%) performs an initial hepatic artery reperfusion (IAR) and 3 (11%) perform retrograde reperfusion (RETR). In 21 centres (75%), one reperfusion technique is used as a standard, but in only one centre is this decision based on available literature. Twenty centres (71%) said they would agree to participate in randomized controlled trials (RCT) if required. For meta-analysis, IAR vs. IPR, SIMR vs. IPR and RETR vs. IPR were compared. There was no difference between any of the techniques compared. There is no consensus on a preferable reperfusion technique. Available evidence does not help in the decision-making process. There is thus an urgent need for multicentric RCTs.
    Transplant International 03/2013; · 3.16 Impact Factor
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    ABSTRACT: Chirurgisch implantierte, zentralvenöse Portsysteme sind ein fester Bestandteil in der Versorgung vieler chronisch kranker und onkologischer Patienten, und deren Implantation gehört zu den am häufigsten durchgeführten Operationen. Trotz der hohen Implantationsfrequenz gibt es keine einheitliche Meinung über den optimalen Zugangsweg.Retrospektiv erfolgte bei 154 Patienten die Erhebung der Reoperations- und Komplikationsrate sowie der aktuarischen Funktionsdauer über eine mittlere Nachbeobachtungszeit von 541 Tagen (,,as-treated“ Analyse). Verglichen wurden die drei häufigsten Zugangswege: Venae sectio der V. cephalica (n = 51) sowie Punktion und Seldinger-Technik von Vv. jugularis interna (n = 71) und subclavia (n = 32).Revisionsoperationen erfolgten bei einem Zugang über die V. cephalica in 15,7 % vs. V. jugularis interna in 15,5 % vs. V. subclavia in 9,4 % der Fälle. Frühkomplikationen innerhalb der ersten 24 h waren durch die Nachblutung bestimmt. Im Verlauf kam es am häufigsten zu Infektionen des Portsystems. Patienten mit mindestens einer Komplikation fanden sich nach einem Zugang über die V. cephalica in 17,7 % vs. V. jugularis int. in 15,5 % vs. V. subclavia in 9,4 % der Fälle. Die 3-Jahres-Funktionsdauer der Portsysteme betrug für die V. subclavia 82,1 % vs. 76,9 % für die V. cephalica vs. 69,5 % für die V. jugularis. Statistisch signifikante Unterschiede in Abhängigkeit des gewählten Zugangswegs fanden sich nicht.Die statistische Interpretation der absoluten Komplikationsraten ist aufgrund des retrospektiven Studiendesigns limitiert. Die Wahl des Zugangswegs hat aber weder einen (signifikanten) Einfluss auf die Komplikationsrate noch die Funktionsdauer des venösen Portsystems im direkten Vergleich. Unabhängig vom Zugangsweg stellt die Katheterinfektion die häufigste Komplikation mit der Notwendigkeit zur Explantation dar. Wir favorisieren den chirurgischen Zugang über die V. cephalica, da bei jedem Portsystem ein Hautschnitt notwendig ist und dieser Zugangsweg sowohl zur Venae sectio als auch zur Kammerimplantation verwendet werden kann. Weiterhin kann bei technischen Problemen die V. subclavia direkt über den gleichen Zugangsweg punktiert werden.
    Gefässchirurgie 01/2013; 18(8). · 0.24 Impact Factor
  • Zentralblatt für Chirurgie 12/2012; · 0.69 Impact Factor
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    ABSTRACT: Clinical evidence suggests that recurrent acute cellular rejection (ACR) may trigger chronic rejection and impair outcome after intestinal transplantation. To test this hypothesis and clarify underlying molecular mechanisms, orthotopic/allogenic intestinal transplantation was performed in rats. ACR was allowed to occur in a MHC-disparate combination (BN-LEW) and two rescue strategies (FK506monotherapy vs. FK506+infliximab) were tested against continuous immunosuppression without ACR, with observation for 7/14 and 21 days after transplantation. Both, FK506 and FK506+infliximab rescue therapy reversed ACR and resulted in improved histology and less cellular infiltration. Proinflammatory cytokines and chemotactic mediators in the muscle layer were significantly reduced in FK506 treated groups. Increased levels of CD4, FOXP3 and IL-17 (mRNA) were observed with infliximab. Contractile function improved significantly after FK506 rescue therapy, with a slight benefit from additional infliximab, but did not reach nontransplanted controls. Fibrosis onset was detected in both rescue groups by Sirius-Red staining with concomitant increase of the fibrogenic mediator VEGF. Recovery from ACR could be attained by both rescue therapy regimens, progressing steadily after initiation of immunosuppression. Reversal of ACR, however, resulted in early stage graft fibrosis. Additional infliximab treatment may enhance physiological recovery of the muscle layer and enteric nervous system independent of inflammatory reactions.
    American Journal of Transplantation 09/2012; · 6.19 Impact Factor
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    ABSTRACT: PURPOSE: Postoperative ileus (POI) is an iatrogenic complication of abdominal surgery, mediated by a severe inflammation of the muscularis externa (ME). Previously, we demonstrated that intravenous application of the tetravalent guanylhydrazone semapimod (CNI-1493) prevents POI, but the underlying mode of action could not definitively be confirmed. Herein, we investigated the effect of a novel orally active salt of semapimod (CPSI-2364) on POI in rodents and distinguished between its inhibitory peripheral and stimulatory central nervous effects on anti-inflammatory vagus nerve signaling. METHODS: Distribution of radiolabeled orally administered CPSI-2364 was analyzed by whole body autoradiography and liquid scintillation counting. POI was induced by intestinal manipulation with or without preoperative vagotomy. CPSI-2364 was administered preoperatively via gavage in a dose- and time-dependent manner. ME specimens were assessed for p38-MAP kinase activity by immunoblotting, neutrophil extravasation, and nitric oxide production. Furthermore, in vivo gastrointestinal (GIT) and colonic transit were measured. RESULTS: Autoradiography demonstrated a near-exclusive detection of CPSI-2364 within the gastrointestinal wall and contents. Preoperative CPSI-2364 application significantly reduced postoperative neutrophil counts, nitric oxide release, GIT deceleration, and delay of colonic transit time, while intraoperatively administered CPSI-2364 failed to improve POI. CPSI-2364 also prevents postoperative neutrophil increase and GIT deceleration in vagotomized mice. CONCLUSIONS: Orally administered CPSI-2364 shows a near-exclusive dispersal in the gastrointestinal tract and effectively reduces POI independently of central vagus nerve stimulation. Its efficacy after single oral dosage affirms CPSI-2364 treatment as a promising strategy for prophylaxis of POI.
    Langenbeck s Archives of Surgery 08/2012; · 1.89 Impact Factor
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    ABSTRACT: Objectives. This summary evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-positive patients in Germany. Methods. Retrospective chart analysis of HIV-positive patients, who had been liver-transplanted in Germany between July 1997 and July 2011. Results. 38 transplantations were performed in 32 patients at 9 German transplant centres. The reasons for OLT were end-stage liver disease (ESLD) and/or liver failure due to hepatitis C (HCV) (n = 19), hepatitis B (HBV) (n = 10), multiple viral infections of the liver (n = 2) and Budd-Chiari-Syndrome. In July 2011 19/32 (60%) of the transplanted patients were still alive with a median survival of 61 months (IQR (interquartile range): 41-86 months). 6 patients had died in the early post-transplantation period from septicaemia (n = 4), primary graft dysfunction (n = 1), and intrathoracal hemorrhage (n = 1). Later on 7 patients had died from septicaemia (n = 2), delayed graft failure (n = 2), recurrent HCC (n = 2), and renal failure (n = 1). Recurrent HBV infection was efficiently prevented in 11/12 patients; HCV reinfection occurred in all patients and contributed considerably to the overall mortality. Conclusions. Overall OLT is a feasible approach in HIV-infected patients with acceptable survival rates in Germany. Reinfection with HCV still remains a major clinical challenge in HIV/HCV coinfection after OLT.
    AIDS research and treatment 01/2012; 2012:197501.
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    ABSTRACT: Ischemia-reperfusion injury leads to impaired smooth muscle function and inflammatory reactions after intestinal transplantation. In previous studies, infliximab has been shown to effectively protect allogenic intestinal grafts in the early phase after transplantation with resulting improved contractility. This study was designed to reveal protective effects of infliximab on ischemia-reperfusion injury in isogenic transplantation. Isogenic, orthotopic small bowel transplantation was performed in Lewis rats (3 h cold ischemia). Five groups were defined: non-transplanted animals with no treatment (group 1), isogenic transplanted animals with vehicle treatment (groups 2/3) or with infliximab treatment (5 mg/kg body weight intravenously, directly after reperfusion; groups 4/5). The treated animals were sacrificed after 3 (group 2/4) or 24 h (group 3/5). Histological and immunohistochemical analysis, TUNEL staining, real-time RT-PCR, and contractility measurements in a standard organ bath were used for determination of ischemia-reperfusion injury. All transplanted animals showed reduced smooth muscle function, while no significant advantage of infliximab treatment was observed. Reduced infiltration of neutrophils was noted in the early phase in animals treated with infliximab. The structural integrity of the bowel and infiltration of ED1-positive monocytes and macrophages did not improve with infliximab treatment. At 3 h after reperfusion, mRNA expression of interleukin (IL)-6, TNF-α, IL-10, and iNOS and MCP-1 displayed increased activation in the infliximab group. The protective effects of infliximab in the early phase after experimental small bowel transplantation seem to be unrelated to ischemia-reperfusion injury. The promising effects in allogenic transplantation indicate the need for further experiments with infliximab as complementary treatment under standard immunosuppressive therapy. Further experiments should focus on additional infliximab treatment in the setting of acute rejection.
    Langenbeck s Archives of Surgery 09/2011; 397(1):131-40. · 1.89 Impact Factor
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    ABSTRACT: The repair of complicated abdominal hernias remains a challenging problem. The components separation technique introduced by Ramirez et al. is an increasingly popular method for autogenous reconstruction of the abdominal wall, especially in combination with epifascial mesh reinforcement. In a retrospective study carried out at a university hospital, 40 consecutive patients between 2002 and 2010 were analyzed. Indications for abdominal reconstruction were fascial defects after secondary healed laparostoma in 22 patients (55%) and fascial defects combined with colostomy reversal after a Hartmann procedure in 10 patients (25%). A total of 9 wound infections (22.5%) occurred and 10 hernia recurrences (10/36 patients) were identified in the follow-up (mean 3.8 years, range 1-9 years). Reconstructions with mesh reinforcement resulted in a lower rate of recurrences (19% with mesh vs 40% without mesh). The components separation technique, in combination with epifascial mesh reinforcement as appropriate, is the procedure of choice for most complicated abdominal wall hernias. Therefore, each visceral surgeon should be able to perform this method. Recurrence rates depend on the underlying disease of the patient and the complexity of the hernia.
    Der Chirurg 09/2011; 83(6):555-60. · 0.52 Impact Factor
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    ABSTRACT: Chronic organ donor shortage has led to the consideration to expand the donor pool with livers from non-heart-beating donors (NHBD), although a higher risk of graft dys- or nonfunction is associated with these livers. We examined the effects of selective cyclooxygenase-2 (COX-2) inhibition on hepatic warm ischemia (WI) reperfusion (I/R) injury of NHBD. Male Wistar rats were used as donors and meloxicam (5 mg/kg body weight) was administered into the preservation solution. Livers were excised after 60 min of WI in situ, flushed and preserved for 24 h at 4°C. Reperfusion was carried out in vitro at a constant flow for 45 min. During reperfusion (5, 15, 30 and 45 min), enzyme release of alanine aminotransferase and glutamate lactate dehydrogenase were measured as well as portal venous pressure, bile production and oxygen consumption. The production of malondialdehyde was quantified and TUNEL staining was performed. Quantitative PCR analyzed COX-2 mRNA. COX-2 immunohistochemistry and TxB(2) detection completed the measurements. Meloxicam treatment led to better functional recovery concerning liver enzyme release, vascular resistance and metabolic activity over time in all animals. Oxidative stress and apoptosis were considerably reduced. Cold storage using meloxicam resulted in significantly better integrity and function of livers retrieved from NHBD. Selective COX-2 inhibition is a new therapeutic approach achieving improved preservation of grafts from NHBD.
    European Surgical Research 07/2011; 47(3):109-17. · 0.75 Impact Factor
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    ABSTRACT: In comparison to the conventional technique of incisional or umbilical hernia repair with sublay mesh augmentation, incisional hernias in obese patients can be surgically treated with minor surgical trauma by laparoscopic intraperitoneal onlay mesh (IPOM) repair. However, although shortened operation time, hospital stay and faster postoperative reconvalescence might be possible with IPOM repair, the economic calculation including mesh costs is significantly higher. In this study the two operation techniques were compared and the perioperative advantages and disadvantages of both methods were analyzed based on the German diagnosis-related groups (DRG) system.
    Der Chirurg 03/2011; 82(9):813-9. · 0.52 Impact Factor
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    ABSTRACT: Standardized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we demonstrated that this so-called gastrointestinal field effect (FE) is immune mediated. This study aimed to investigate the role of CCR7 in IM-induced FE. Since CCR7 is expressed on activated dendritic cells and T cells and is well known to control their migration, we hypothesized that lack of CCR7 reduces or abolishes FE. Small bowel muscularis and colonic muscularis from CCR7(-/-) and wild-type (WT) mice were obtained after IM of the jejunum or sham operation. FE was analyzed by measuring gastrointestinal transit time of orally given fluorescent dextran (geometric center), colonic transit time, infiltration of MPO-positive cells, and circular smooth muscle contractility. Furthermore, mRNA levels of the inflammatory cytokine IL-6 were determined by RT-PCR. The number of dendritic cells and CD3+CD25+ T cells separately isolated from jejunum and colon was determined in mice after IM and sham operation. There was no significant difference in IL-6 mRNA upregulation in colonic muscularis between sham-operated WT and CCR7(-/-) mice after IM. Contractility of circular muscularis strips of the colon was significantly improved in CCR7(-/-) animals following IM and did not vary significantly from sham-operated animals. Additionally, inflammation of the colon determined by the number of MPO-positive cells and colonic transit time was significantly reduced in CCR7(-/-) mice. In contrast, jejunal contractility and jejunal inflammation of transgenic mice did not differ significantly from WT mice after IM. These data are supported by a significant increase of CD3+CD25+ T cells in the colonic muscularis of WT mice after IM, which could not be observed in CCR7(-/-) mice. These data demonstrate that CCR7 is required for FE and postoperative ileus. CCR7 indirectly affects FE by inhibiting migration of activated dendritic cells and of T cells from the jejunum to the colon. These findings support the critical role of the adaptive immune system in FE.
    AJP Gastrointestinal and Liver Physiology 02/2011; 300(4):G665-75. · 3.65 Impact Factor
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    ABSTRACT: Zusammenfassung Im Vergleich zur konventionellen Technik mittels offener Netzimplantation (Sublay-Technik) können mit der laparoskopischen intraperitonealen Onlay-Mesh (IPOM)-Technik Narbenhernien und Nabelhernien, insbesondere bei adipösen Patienten, mit einem geringeren Operationstrauma erfolgreich versorgt werden. Der kürzeren Operationsdauer und der schnelleren postoperativen Rekonvaleszenz der Patienten und dementsprechend kürzeren Krankenhausverweildauer stehen höhere (Material-)Kosten entgegen. Diese Studie soll anhand einer vergleichenden Analyse beider Operationstechniken unter Berücksichtigung des DRG-Systems die perioperativen Vor- und Nachteile beider Methoden aufzeigen.
    Der Chirurg 01/2011; · 0.52 Impact Factor
  • J C Kalff, N Schäfer
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    ABSTRACT: The tremendous increase in medical knowledge over the last decades and technical progress in medicine have caused further professional specialization. Numerous medical fields have evolved through the process of separation from the parent specialization and the traditional distinction between surgical and medical disciplines has been blurred. As a result of this development organ-specific interdisciplinary units have been formed and new partners have united, such as surgeons and gastroenterologists in the field of interventional endoscopy. The fading boundaries brought with them resistance and even resentment and called for a mutual regulation by the professional associations which took place 10 years ago. Nowadays, surgeons and gastroenterologists in Germany are trained in interventional endoscopy and are the foundation of endoscopic interdisciplinary teamwork in emergency care, diagnostics, therapy, complication management and palliative treatment. Technical innovations striving for a minimization of operative trauma like NOTES depend on the cooperation of both fields of expertise. The driving force behind these efforts should be the shared interest in further improvement of patient care at the highest level of individual expertise, patient-oriented process optimization and adequate use of resources.
    Der Chirurg 12/2010; 81(12):1073-6. · 0.52 Impact Factor
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    ABSTRACT: As we have shown in the past, acute rejection-related TNF-α upregulation in resident macrophages in the tunica muscularis after small bowel transplantation (SBTx) results in local amplification of inflammation, decisively contributing to graft dysmotility. Therefore, the aim of this study is to investigate the effectiveness of the chimeric-monoclonal-anti-TNF-α antibody infliximab as perioperative single shot treatment addressing inflammatory processes during acute rejection early after transplantation. Orthotopic, isogenic and allogenic SBTx was performed in rats (BN-Lewis/BN-BN) with infliximab treatment. Vehicle and IV-immunoglobulin-treated animals served as controls. Animals were sacrificed after 24 and 168 h. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry, mediator mRNA expression by Real-Time-RT-PCR, apoptosis by TUNEL and smooth muscle contractility in a standard organ bath. Both, infliximab and Sandoglobulin® revealed antiinflammatory effects. Infliximab resulted in significantly less leukocyte infiltration compared to allogenic controls and IV-immunoglobulin, which was accompanied by lower gene expression of MCP-1 (24 h), IFN-γ (168 h) and infiltration of CD8-positive cells. Smooth muscle contractility improved significantly after 24 h compared to all controls in infliximab treated animals accompanied by lower iNOS expression. Perioperative treatment with infliximab is a possible pharmaceutical approach to overcome graft dysmotility early after SBTx.
    American Journal of Transplantation 11/2010; 10(11):2431-41. · 6.19 Impact Factor
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    ABSTRACT: Inflammatory events within the intestinal muscularis, including macrophage activation and leukocyte recruitment, have been demonstrated to participate in causing postoperative ileus. Recently, glycine has gained attention due to its beneficial immunomodulatory effects in transplantation, shock and sepsis. Muscularis glycine receptors were investigated by immunohistochemistry. Gastrointestinal motility was assessed by in vivo transit distribution histograms with calculated geometric center analysis and jejunal circular smooth muscle contractility in a standard organ bath. The impact of glycine on the muscularis inflammatory responses to surgical manipulation of the intestine were measured by real-time PCR, nitric oxide Griess reaction, prostaglandin ELISA, Luminex and histochemistry. Glycine-gated chloride channels were immunohistochemically localized to muscularis macrophages and postoperative infiltrating leukocytes. Preoperative glycine treatment significantly improved postoperative gastrointestinal transit and jejunal circular muscle contractility. Preoperative glycine injection significantly reduced the induction of interleukin-6 (IL-6), tumor necrosis factor-α, inducible nitric oxide synthase and intercellular adhesion molecule-1 mRNAs, which was associated with the attenuation in postoperative leukocyte recruitment. Nitric oxide and prostanoid release from the postsurgical inflamed muscularis was diminished by glycine. The secretion of the inflammatory proteins IL-6, monocyte chemotactic protein-1/chemokine ligand 2 and macrophage inflammatory protein-1α/chemokine ligand 3 were also significantly decreased by glycine pretreatment. The data indicate that preoperative glycine reduces postoperative ileus via the early attenuation of primal inflammatory events within the surgically manipulated gut wall. Therapeutic modulation of resident macrophages by glycine is a potential novel pharmacological target for the prevention of postoperative ileus.
    Neurogastroenterology and Motility 10/2010; 23(1):76-87, e8. · 2.94 Impact Factor
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    ABSTRACT: In small bowel transplantation (SBTx), graft manipulation, ischemia/reperfusion injury and acute rejection initiate a severe cellular and molecular inflammatory response in the muscularis propria leading to impaired motility of the graft. This study examined and compared the effect of tacrolimus and sirolimus on inflammation in graft muscularis. After allogeneic orthotopic SBTx, recipient rats were treated with tacrolimus or sirolimus. Tacrolimus and sirolimus attenuated neutrophilic, macrophage and T-cell infiltration in graft muscularis, which was associated with reduced apoptotic cell death. Nonspecific inflammatory mediators (IL-6, MCP-1) and T-cell activation markers (IL-2, IFN-gamma) were highly upregulated in allogeneic control graft muscularis 24 h and 7 days after SBTx, and tacrolimus and sirolimus significantly suppressed upregulation of these mediators. In vitro organ bath method demonstrated a severe decrease in graft smooth muscle contractility in allogeneic control (22% of normal control). Correlating with attenuated upregulation of iNOS, tacrolimus and sirolimus treatment significantly improved contractility (64% and 72%, respectively). Although sirolimus reduced cellular and molecular inflammatory response more efficiently after 24 h, contrary tacrolimus prevented acute rejection more efficiently. In conclusion, tacrolimus and sirolimus attenuate cellular and molecular inflammatory response in graft muscularis and subsequent dysmotility of the graft after allogeneic SBTx.
    American Journal of Transplantation 07/2010; 10(7):1545-55. · 6.19 Impact Factor

Publication Stats

1k Citations
233.79 Total Impact Points

Institutions

  • 1998–2012
    • University of Bonn
      • • Faculty of Medicine
      • • Klinik und Poliklinik für Herzchirurgie
      Bonn, North Rhine-Westphalia, Germany
  • 2006–2011
    • University of Bonn - Medical Center
      Bonn, North Rhine-Westphalia, Germany
  • 1998–2010
    • University of Pittsburgh
      • • Division of Pediatric Gastroenterology
      • • Department of Surgery
      Pittsburgh, PA, United States