Treatment with hyperbaric oxygen (HBO) has shown promising results in some models of ischemia, the major effect being a reduction in the local ischemic damage. The present study investigated the effects of HBO treatment on neutrophil activation and leukosequestration during reperfusion following intestinal ischemia in a rat model. The superior mesenteric artery was clamped for 2 h and subsequently reperfused for 90 min. One group of male Sprague-Dawley rats (n = 9) was given HBO and another group (n = 9) served as controls. Prior to ischemia, leukocytes and erythrocytes were separated, radiolabelled with 111ln and 51Cr, respectively, and reinfused. Leukocyte transit factor, the ratio between the mean passage time of leukocytes and erythrocytes was used to quantitate leukosequestration and the fraction of circulating, spontaneously nitroblue tetrazolium (NBT)-reducing neutrophils was used to measure the degree of neutrophil preactivation. HBO treatment reduced the level of leukocyte pooling significantly, especially in the lungs but also, to a minor degree, in the systemic vascular bed. The percentage of NBT-positive cells increased in all animals after reperfusion, but the increase was significantly reduced by HBO treatment. In conclusion, HBO treatment reduces leukosequestration and neutrophil preactivation following intestinal ischemia-reperfusion.
Objectives Clinical studies have demonstrated that the intraperitoneal (IP) complement and coagulation systems are activated in peritoneal dialysis (PD) patients. In animal models, low molecular weight heparin (LMWH) was seen to inhibit peritoneal angiogenesis, and related compounds have increased ultrafiltration volumes after repeated administration to PD patients. The present study evaluated the effects of LMWH on ultrafiltration, coagulation, and complement activation during a single PD dwell. Design Rats were exposed to a single dose of 20 mL 2.5% glucose-based, filter-sterilized PD fluid, with or without supplementation with LMWH. The PD fluid was administered either as an IP injection or as an infusion through an indwelling catheter. The dwell fluid was analyzed 2 hours later concerning activation of the complement and coagulation cascades, chemotactic activity, neutrophil recruitment, ultrafiltration volume, and glucose and urea concentrations. Results Exposure to PD fluid induced activation of IP complement [formation of C3a(desArg) and increase of C5a-dependent chemotactic activity] and coagulation (formation of thrombin–antithrombin complex) and recruitment of neutrophils. In the case of IP injection, neutrophil recruitment and complement activation were inhibited by LMWH. In both models, LMWH inhibited thrombin formation, reduced complement-dependent chemotactic activity, and increased the IP fluid volume, indicating an improved ultrafiltration. Conclusions The acute inflammatory reaction to PD fluid involves the complement and coagulation cascades. Addition of LMWH to the PD fluid improves ultrafiltration, inhibits formation of thrombin, and potentially blocks C5a activity. The present results motivate further investigations of the IP cascade systems in PD.
Peer-assisted learning has gained momentum in a variety of disciplines, including medical education. In Gothenburg, Sweden, medical students who have finished their compulsory anatomy courses have the option of working as teaching assistants (TAs). Teaching assistants provide small group teaching sessions as a complement to lectures given by faculty. Previously, TAs were left to handle the role as junior teachers by themselves, but since 2011, a continuation course in anatomy has been developed with the aim of providing the TAs better anatomy knowledge and guidance for teaching. The course was designed to comprise 7.5 ECTS credits (equivalent to 5 weeks of full-time studies), and today all TAs are required to take this course before undertaking their own teaching responsibilities. This study aims to compare course evaluations of TA teaching before and after the introduction of the anatomy continuation course, in order to understand how students perceived teaching performed by self-learned versus trained TAs. The results of this study demonstrate that there was a trend towards better teaching performed by trained TAs. The variability in rankings decreased significantly after the introduction of the continuation course. This was mainly due to an improvement among the TAs with the lowest levels of performance. In addition to comparing student rankings, TAs were interviewed regarding their experiences and perceptions within the continuation course. The course was generally positively regarded. The TAs described a sense of cohesion and appreciation since the institute invested in a course dedicated specifically for them. Anat Sci Educ 11: 403-409. © 2018 American Association of Anatomists.
Objective To evaluate the in vivo effects of heat-sterilized peritoneal dialysis (PD) fluids on the respiratory burst response of rat peritoneal leukocytes. Design Rats were exposed to intraperitoneal injections of a laboratory-made PD fluid that was either heat-sterilized (HPD) or filtered (F-PD). Control groups of animals were given Hank's buffer (HBSS) or saline (NaCI). Leukocytes were harvested by intraperitoneal lavage at different times in different animals and analyzed with respect to cell numbers, differential counts, and production of superoxide (chemiluminescence) in response to opsonized zymosan. The chemiluminescence responses of the macrophage and the neutrophil populations, respectively, were obtained by curve-fitting techniques from the responses of the mixed populations. Results All fluids induced a recruitment of neutrophils, the PD fluids causing a cell number increase that was more transient than that caused by NaCI and HBSS. Macrophage numbers were only slightly influenced, but were generally higher after NaCI and HBSS injections than after PD fluid injections. The H-PD exposure induced a significant inhibition of the macrophage chemiluminescence response after 2 and 12 hours, compared with the exposure to F-PD. The neutrophil chemiluminescence response was not significantly affected. Conclusion The toxins produced by heat-sterilization of glucose-containing PD fluids inhibit in vivo the respiratory burst response of peritoneal macrophages.
Objectives Long-term peritoneal dialysis (PD) leads to structural and functional changes in the peritoneum. The aim of the present study was to investigate the long-term effects of PD fluid components, glucose and glucose degradation products (GDP), and lactate-buffered solution on morphology and transport characteristics in a nonuremic rat model. Methods Rats were subjected to two daily intraperitoneal injections (20 mL/day) during 12 weeks of one of the following: commercial PD fluid (Gambrosol, 4%; Gambro AB, Lund, Sweden), commercial PD fluid with low GDP levels (Gambrosol trio, 4%; Gambro AB), sterile-filtered PD fluid (4%) without GDP, or a glucose-free lactate-buffered PD fluid. Punctured and untreated controls were used. Following exposure, the rats underwent a single 4-hour PD dwell (30 mL, 4% glucose) to determine peritoneal function. Additionally, submesothelial tissue thickness, percentage of high mesothelial cells (perpendicular diameter > 2 μm), vascular density, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF) β1 mRNA expression were determined. Submesothelial collagen concentration was estimated by van Gieson staining. Results Submesothelial tissue thickness and vascular density, mediated by VEGF and TGFβ production, in the diaphragmatic peritoneum increased significantly in rats exposed to any PD fluid. Gambrosol induced a marked increased fibrosis of the hepatic peritoneum. A significant increase in high mesothelial cells was observed in the Gambrosol group only. Net ultrafiltration was reduced in the Gambrosol and in the glucose-free groups compared to untreated controls. Small solute transport was unchanged, but all groups exposed to fluids showed significantly increased lymph flow. Conclusions Our results show that long-term exposure to different components of PD fluids leads to mesothelial cell damage, submesothelial fibrosis, and neoangiogenesis. Mesothelial cell damage could be connected to the presence of GDP; the other changes were similar for all fluids. Peritoneal transport characteristics did not change in any consistent way and the neoangiogenesis observed was not paralleled by increased solute transport.
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