Publications by authors named "Patrik Efferz"

Article Synopsis
  • Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer that spreads and invades surrounding nerves, but the role of glial cells associated with these nerves in PDAC progression is not well understood.
  • Researchers cultured PDAC cell lines with media from glial and Schwann cells to assess changes in cancer cell behavior, including their invasiveness and sensitivity to treatment.
  • The study found that glial cells enhance PDAC cell migration and resistance to chemotherapy by promoting epithelial-to-mesenchymal transition, suggesting that targeting glial signaling could be a potential therapeutic strategy for PDAC.
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  • Intestinal mucosal cells, such as macrophages and epithelial cells, respond to norepinephrine, suggesting that the sympathetic nervous system (SNS) influences immune activity in the intestines, particularly in diseases like inflammatory bowel disease.
  • A study using sympathetic denervation revealed increased activated macrophages and monocytes, along with changes in cytokine levels that promote inflammation and affect the intestinal barrier.
  • The findings indicate that the SNS is crucial for maintaining healthy intestinal immune functions, as a loss of sympathetic input can lead to increased inflammation and decreased barrier integrity in the intestines.
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  • Interactions between the peripheral nervous system and resident macrophages (MMs) are essential for maintaining intestinal health, with β2-adrenergic receptor activation on MMs helping to combat bacterial threats.
  • The study investigates how the sympathetic nervous system (SNS) influences MMs during postoperative ileus (POI), a noninfectious inflammation-related disorder, using techniques like RNA sequencing and flow cytometry.
  • Findings reveal that SNS activity plays a crucial role in modulating inflammation, as denervation leads to decreased anti-inflammatory genes in MMs and a shift towards proinflammatory responses, ultimately affecting bowel recovery during POI.
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Different nonhypothermic preservation modalities have shown beneficial effects in liver transplantation models. This study compares controlled oxygenated rewarming (COR) to normothermic machine perfusion (NMP) to resuscitate liver grafts following cold storage (CS). Porcine livers were preserved for 18 hours by CS.

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Early graft dysfunction due to preservation/reperfusion injury still represents a notable issue after kidney transplantation, affecting long term prognosis of graft viability. One trigger of postischemic cell dysfunction could be recognized in the abrupt temperature shift from hypo- to normothermia, leading to mitochondrial dysfunction and proapoptotic signal transduction. Here we propose a technique to cope with this "rewarming injury" by interposing a period of gentle warming up by hypo- to subnormothermic machine perfusion of the isolated graft prior to warm reperfusion.

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Custodiol-N, a new preservation solution, has been shown particularly suitable for hypothermic machine perfusion preservation (HMP) in isolated porcine kidneys. These preliminary results should be confirmed in an actual transplant model in vivo. Kidney function after 21 h of HMP was studied in an autotransplant model using Landrace pigs (25-30 kg; n = 6 per group).

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Background: Activation of the Rho-Rho-kinase pathway has been shown to cause vasoconstriction in renal afferent arterioles. Vascular dysfunction plays a pivotal role in triggering reperfusion injury after kidney transplantation. Therefore, the effect of a Rho-kinase inhibitor, added to the preservation solution, on renal function after 18 h of storage at 4 °C was evaluated.

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In-house machine perfusion after cold storage (hypothermic reconditioning) has been proposed as convenient tool to improve kidney graft function. This study investigated the role of machine perfusion duration for early reperfusion parameters in porcine kidneys. Kidney function after cold preservation (4 °C, 18 h) and subsequent reconditioning by one or 4 h of pulsatile, nonoxygenated hypothermic machine perfusion (HMP) was studied in an isolated kidney perfusion model in pigs (n = 6, respectively) and compared with simply cold-stored grafts (CS).

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The effect of adding pulsatility to gaseous oxygen persufflation during liver preservation was studied in an isolated rat liver model. Livers from male Wistar rats were retrieved 30 min after cardiac arrest of the donor and subjected to 18 h of cold storage. Some grafts were subjected to nonpulsatile or pulsatile gaseous oxygen persufflation.

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Background: Brief in-house machine perfusion after cold storage (CS) (hypothermic reconditioning) has been proposed as a convenient tool to improve kidney graft function. The present study aimed to investigate the mechanistic role of vascular pulsatility in this context.

Methods: Kidney function after cold preservation (4°C, 18 hr) and subsequent reconditioning by 90 min of pulsatile machine perfusion (PP) (30/20 mm Hg) or nonpulsatile machine perfusion (NPP) (30 mm Hg) was studied in an isolated kidney perfusion model in pigs (n=6 for both) and compared with simply CS grafts.

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Unlabelled: Dynamic preservation of organ grafts by hypothermic machine perfusion (HMP) has regained broader interest to provide better outcome after transplantation. One pivotal aspect still under debate is the role of oxygenation during HMP. The present study investigates functional and molecular aspects of active oxygenation during HMP of kidneys from heart beating donors.

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Background: Delayed graft function still represents a major complication in clinical kidney transplantation. Here we tested the possibility to improve functional outcome of cold stored kidneys a posteriori by hypothermic reconditioning using retrograde oxygen persufflation (ROP) immediately prior to reperfusion.

Methods: Kidneys from female German Landrace pigs were flushed with Histidine-Tryptophan-Ketoglutarate (HTK) solution and cold-stored for 18 h (control).

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Background: Gaseous insufflation of oxygen via the venous vascular system has proven to be an effective tool for preventing anoxic tissue injury after extended time periods of ischemic liver preservation. Most experimental studies so far have been undertaken in rat models and include a series of pinpricks into postsinusoidal venules as an outlet for the insufflated gas. Here, we describe a simplified technique for minimally invasive liver oxygenation in porcine grafts, representing a hassle-free access to organ oxygenation without vascular lesions.

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Background: Clinical trial data suggest that continuous hypothermic machine perfusion (HMP) during the entire preservation period reduces the incidence of delayed graft function and improves graft survival. This study evaluates whether short-term MP after cold storage (CS) is also effective.

Methods: Kidney function after cold preservation (4°C, 21 hr) and transplantation was studied in an autotransplant model using Landrace pigs (25-30 kg; n=5 per group) with 1 week follow-up.

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Background: Hypothermic machine preservation (HMP) is currently reconsidered as alternative to standard cold storage of organs from non-heart-beating donors. The present study was aimed at investigating the possible synergistic effect of HMP and the addition of dopamine to the circulating perfusate during preservation.

Methods: Cardiac arrest was induced in male Wistar rats (250-300 g) by phrenotomy.

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Background: Quality of cold-stored livers declines beyond 12 hr of ischemia, increasing the risk of primary dysfunction. Here we evaluate the potential and optimal treatment interval of gaseous oxygen persufflation for grafts reconditioning after long storage times in an experimental pig liver model.

Method: Porcine livers (n=6/group) were cold stored at 4°C for 18 hr in histidine-tryptophan-ketoglutarate solution.

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Grafts from non-heart-beating donors are thought to be best preserved by hypothermic machine perfusion (HMP). Controversy exists concerning the role of oxygenation during HMP. In this study, we wanted to evaluate the relative role of oxygenation for graft integrity during and after HMP.

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