Non Anticoagulant Effects of Heparin: Implications for Animal Models of Peritoneal Dialysis

2001 ◽  
Vol 21 (3_suppl) ◽  
pp. 354-356 ◽  
Author(s):  
An S. De Vriese ◽  
Siska Mortier ◽  
Norbert H. Lameire
Keyword(s):  
Peritoneal Dialysis ◽  
Animal Models ◽  
Anticoagulant Activity ◽  
Experimental Studies ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Correct Interpretation ◽  
Peritoneal Membrane ◽  
Peritoneal Adhesions ◽  
Antiproliferative Effects

Heparin is a glycosaminoglycan with well-known anticoagulant activity. That property is used in animal models of peritoneal dialysis to maintain catheter patency and to prevent the development of peritoneal adhesions. However, heparin has a host of biologic actions beyond its role as an anticoagulant. Heparin modulates the activity of various inflammatory cells, affects the synthesis of extracellular matrix, has antiproliferative effects on several cell types, and influences neoangiogenesis. By virtue of those actions, intraperitoneally administered heparin may interfere with peritoneal membrane homeostasis. The potential side effects of heparin use in animal models of peritoneal dialysis should be recognized to permit correct interpretation of experimental studies conducted in those models.

Pathogenesis of Peritoneal Sclerosis

2005 ◽  
Vol 28 (2) ◽  
pp. 90-96 ◽  
Author(s):  
C. Pollock
Keyword(s):  
Peritoneal Dialysis ◽  
Large Scale ◽  
Clinical Decision Making ◽  
Inflammatory Cells ◽  
Clinical Decision ◽  
Cumulative Exposure ◽  
Peritoneal Membrane ◽  
Peritoneal Fibrosis ◽  
Histological Data ◽  
The Individual

Peritoneal sclerosis is an almost invariable consequence of peritoneal dialysis. In most circumstances it is “simple” sclerosis, manifesting clinically with an increasing peritoneal transport rate and loss of ultrafiltration capacity. In contrast, encapsulating peritoneal sclerosis is a life threatening and usually irreversible condition, associated with bowel obstruction, malnutrition and death. It is unknown whether common etiological factors underlie the development of these 2 clinically and pathologically distinct forms of peritoneal sclerosis. The majority of studies to date have investigated factors that contribute to “simple” sclerosis, although it remains possible that similar mechanisms are amplified in patients who develop encapsulated peritoneal sclerosis. The cellular elements that promote peritoneal sclerosis include the mesothelial cells, peritoneal fibroblasts and inflammatory cells. Factors that stimulate these cells to promote peritoneal fibrosis and neoangiogenesis, both inherent in the development of peritoneal sclerosis, include cytokines that are induced by exposure of the peritoneal membrane to high concentrations of glucose, advanced glycation of the peritoneal membrane and oxidative stress. The cumulative exposure to bioincompatible dialysate is likely to have an etiological role as the duration of dialysis correlates with the likelihood of developing peritoneal sclerosis. Indeed peritoneal dialysis using more biocompatible fluids has been shown to reduce the development of peritoneal sclerosis. The individual contribution of the factors implicated in the development of peritoneal sclerosis will only be determined by large scale peritoneal biopsy registries, which will be able to prospectively incorporate clinical and histological data and support clinical decision making.

scholarly journals A novel computational sheep atria model for the study of atrial fibrillation

2013 ◽  
Vol 3 (2) ◽  
pp. 20120067 ◽  
Author(s):  
Timothy D. Butters ◽  
Oleg V. Aslanidi ◽  
Jichao Zhao ◽  
Bruce Smaill ◽  
Henggui Zhang
Keyword(s):  
Atrial Fibrillation ◽  
Animal Models ◽  
Pulmonary Veins ◽  
Experimental Studies ◽  
Three Dimensional ◽  
Cell Types ◽  
Underlying Mechanisms ◽  
Detailed Computer ◽  
Atrial Cell ◽  
Atrial Excitation

Sheep are often used as animal models for experimental studies into the underlying mechanisms of cardiac arrhythmias. Previous studies have shown that biophysically detailed computer models of the heart provide a powerful alternative to experimental animal models for underpinning such mechanisms. In this study, we have developed a family of mathematical models for the electrical action potentials of various sheep atrial cell types. The developed cell models were then incorporated into a three-dimensional anatomical model of the sheep atria, which was recently reconstructed and segmented based on anatomical features within different regions. This created a novel biophysically detailed computational model of the three-dimensional sheep atria. Using the model, we then investigated the mechanisms by which paroxysmal rapid focal activity in the pulmonary veins can transit to sustained atrial fibrillation. It was found that the anisotropic property of the atria arising from the fibre structure plays an important role in facilitating the development of fibrillatory atrial excitation waves, and the electrical heterogeneity plays an important role in its initiation.

Is Normal Saline Harmful to the Peritoneum?

2005 ◽  
Vol 25 (4_suppl) ◽  
pp. 67-70 ◽  
Author(s):  
Andrzej Breborowicz ◽  
Dimitrios G. Oreopoulos
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Cavity ◽  
Normal Saline ◽  
Experimental Studies ◽  
Nacl Solution ◽  
Peritoneal Adhesions ◽  
Surgical Interventions ◽  
Peritoneal Mesothelial Cells

♦ Background Normal saline (0.9% NaCl) is used during various abdominal surgical interventions and during peritoneal dialysis to rinse the peritoneal cavity. Although no clear clinical evidence exists for the bioincompatibility of normal saline, various experimental studies have suggested that 0.9% NaCl solution can initiate fibrosis of peritoneum. ♦ Material and Methods We review the data derived from in vitro and in vivo experimental studies demonstrating the cytotoxic effect of 0.9% NaCl and its ability to initiate peritoneal adhesions. ♦ Results Normal saline reduces the viability and fibrinolytic activity of peritoneal mesothelial cells. Use of normal saline to wash the peritoneal cavity during abdominal operations or after chronic peritoneal dialysis is more likely to produce adhesions than is no irrigation at all. Chronic exposure of the peritoneum to normal saline causes overgrowth of the connective tissue and formation of new blood vessels within that tissue. Conclusion ♦ Normal saline is a bioincompatible solution that predisposes to the formation of peritoneal adhesions and fibrosis of the peritoneum. A 0.9% NaCl solution should therefore not be used to rinse the peritoneal cavity after interruption of peritoneal dialysis.

Pathogenesis and Treatment of Encapsulating Peritoneal Sclerosis: Basic and Translational Research

2008 ◽  
Vol 28 (5_suppl) ◽  
pp. 10-15 ◽  
Author(s):  
Darren W. Schmidt ◽  
Michael F. Flessner
Keyword(s):  
Peritoneal Dialysis ◽  
Animal Models ◽  
Early Diagnosis ◽  
Translational Research ◽  
Effective Means ◽  
Disease Process ◽  
Molecular Pathways ◽  
Dialysis Patients ◽  
Peritoneal Adhesions

Encapsulating peritoneal sclerosis is a devastating condition in long-term peritoneal dialysis patients. Animal models have employed chemical insults to simulate its pathology and have provided insights into its pathophysiology, which appears to include inflammation, angiogenesis, and fibrosis. Monitoring of biomarkers and interruption of molecular pathways have provided potential interventions to slow or prevent the disease process. However, there remain many questions concerning the trigger that alters chronic peritoneal inflammation in peritoneal dialysis to severe sclerosis, peritoneal adhesions, and bowel obstruction. Further advances in therapy will likely require an effective means of an early diagnosis through related biomarkers, which in turn will require further advances in the understanding of the pathogenesis of this disease process.

scholarly journals IL-17A as a Potential Therapeutic Target for Patients on Peritoneal Dialysis

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1361
Author(s):  
Vanessa Marchant ◽  
Antonio Tejera-Muñoz ◽  
Laura Marquez-Expósito ◽  
Sandra Rayego-Mateos ◽  
Raul R. Rodrigues-Diez ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Therapeutic Target ◽  
Experimental Studies ◽  
Γδ T Cells ◽  
Peritoneal Membrane ◽  
Potential Therapeutic Target ◽  
Membrane Injury ◽  
Membrane Function ◽  
Mesenchymal Transition ◽  
Compact Zone

Chronic kidney disease (CKD) is a health problem reaching epidemic proportions. There is no cure for CKD, and patients may progress to end-stage renal disease (ESRD). Peritoneal dialysis (PD) is a current replacement therapy option for ESRD patients until renal transplantation can be achieved. One important problem in long-term PD patients is peritoneal membrane failure. The mechanisms involved in peritoneal damage include activation of the inflammatory and immune responses, associated with submesothelial immune infiltrates, angiogenesis, loss of the mesothelial layer due to cell death and mesothelial to mesenchymal transition, and collagen accumulation in the submesothelial compact zone. These processes lead to fibrosis and loss of peritoneal membrane function. Peritoneal inflammation and membrane failure are strongly associated with additional problems in PD patients, mainly with a very high risk of cardiovascular disease. Among the inflammatory mediators involved in peritoneal damage, cytokine IL-17A has recently been proposed as a potential therapeutic target for chronic inflammatory diseases, including CKD. Although IL-17A is the hallmark cytokine of Th17 immune cells, many other cells can also produce or secrete IL-17A. In the peritoneum of PD patients, IL-17A-secreting cells comprise Th17 cells, γδ T cells, mast cells, and neutrophils. Experimental studies demonstrated that IL-17A blockade ameliorated peritoneal damage caused by exposure to PD fluids. This article provides a comprehensive review of recent advances on the role of IL-17A in peritoneal membrane injury during PD and other PD-associated complications.

The Effects of Heparin Administration in an Animal Model of Chronic Peritoneal Dialysate Exposure

2002 ◽  
Vol 22 (5) ◽  
pp. 566-572 ◽  
Author(s):  
An S. De Vriese ◽  
Siska Mortier ◽  
Maria Cornelissen ◽  
Els Palmans ◽  
Nele J. Vanacker ◽  
...  
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Cellular Proliferation ◽  
Anticoagulant Activity ◽  
Peritoneal Membrane ◽  
Peritoneal Dialysate ◽  
Technique Survival ◽  
Heparin Administration ◽  
Study Results ◽  
Biological Actions

Diverse modes of heparin administration have been used in animal models of chronic peritoneal dialysate exposure to maintain catheter patency and prevent fibrinous adhesions. Heparin has biological actions independent of its well-known anticoagulant activity, including the ability to modulate extracellular matrix synthesis, cellular proliferation, angiogenesis, and inflammation. These actions may interfere with peritoneal membrane homeostasis. The present study evaluated the influence of the mode of heparin administration on technique survival and infection rate in a rat model of chronic dialysate exposure. Further, the incorporation of heparin in the peritoneal membrane was examined. A 3.86% glucose dialysate was injected twice daily into Wistar rats with a heparin-coated catheter (group A1), or with a standard catheter with heparin injections during the entire exposure time (group A2) or only during 1 week (group A3). Sham manipulations were performed in a fourth group and a fifth group was left untreated. Technique survival was 80% in group A1, 60% in group A2, and 40% in group A3. The rate of infection was highest in group A1 and lowest in group A2. Intraperitoneally administered heparin accumulated in the peritoneal membrane, whereas dextran, with a molecular weight similar to that of heparin, was not incorporated in the peritoneum. In conclusion, intraperitoneal heparin reduced the incidence of infection in an animal model of chronic dialysate exposure. The best technique survival was, however, obtained using a heparin-coated catheter. Heparin is incorporated in the peritoneal membrane, where it may exert diverse biological actions and thus bias study results. The use of a heparin-coated catheter in combination with antibiotics may be the optimal approach to obtaining peritoneal access in animal models of chronic dialysate exposure.

scholarly journals Microvesicles and Cancer Associated Thrombosis

2019 ◽  
Vol 45 (06) ◽  
pp. 593-603 ◽  
Author(s):  
Romaric Lacroix ◽  
Loris Vallier ◽  
Amandine Bonifay ◽  
Stephanie Simoncini ◽  
Diane Mege ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Animal Models ◽  
Fibrinolytic Activity ◽  
Molecular Mechanisms ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Different Types ◽  
Clinical Interest ◽  
Cancer Associated Thrombosis

AbstractMicrovesicles (MVs) are small membrane enclosed structures released into the extracellular space by virtually all cell types. Their composition varies according to the cell origin and the stimulus which caused their formation. They harbor functional molecules and participate in intercellular communication. Endothelium, inflammatory cells, and cancer cells produce procoagulant MVs which contribute to cancer-associated thrombosis (CAT) in animal models. The tissue factor (TF) conveyed by these MVs was shown to play a key role in different animal models of experimental CAT. Alternatively, other molecular mechanisms involving polyphosphates or phosphatidylethanolamine could also be involved. In clinical practice, an association between an increase in the number of TF-positive or the procoagulant activity of these MVs and the occurrence of CAT has indeed been demonstrated in pancreatic-biliary cancers, suggesting that they could behave as a biomarker predictive for CAT. However, to date, this association was not confirmed in other types of cancer. Potential causes explaining this limited associated between MVs and CAT are (1) the diversity of mechanisms associating MVs and different types of cancer; (2) a more complex role of MVs in hemostasis integrating their anticoagulant and fibrinolytic activity; and (3) the lack of sensitivity, reproducibility, and standardization of current methodologies permitting measurement of MVs. Each of these hypotheses constitutes an interesting exploration path for a future reassessment of the clinical interest of the MVs in CAT.

The Need for Using An Enzymatic Colorimetric Assay in Creatinine Determination of Peritoneal Dialysis Solutions

1990 ◽  
Vol 10 (1) ◽  
pp. 89-92 ◽  
Author(s):  
Liliane Larpent ◽  
Christian Verger
Keyword(s):  
Peritoneal Dialysis ◽  
Reliable Method ◽  
Colorimetric Assay ◽  
Colorimetric Method ◽  
Peritoneal Membrane ◽  
Creatinine Kinetics ◽  
Dialysis Solutions ◽  
Peritoneal Dialysis Solutions ◽  
Enzymatic Test

The fate of the peritoneal membrane on continuous ambulatory peritoneal dialysis (CAPD) is usually evaluated through the modification of its permeability to various solutes as glucose, creatinine, and urea. Therefore, the accuracy of the methods used for measurements of creatinine is of great importance. A particular problem does exist for creatinine determination as it may be influenced by the presence of glucose. We studied a new enzymatic colorimetric method for creatinine determination in peritoneal dialysis solutions which contain high dextrose concentrations. Creatinine was measured in plasma, urine, and dialysate from 18 patients on CAPD and in pure dextrose solutions, with an enzymatic test (Boehringer Mannheim) and with Jaffe's reaction on two different analyzers: Astra (Beckman) and Eris (Merck). Creatinine results were similar with both assays (Jaffe's reaction and enzymatic test) when measured in blood and urine. However the Jaffe's reaction gave higher creatinine results than the enzymatic test (p < 0.001), when assays were performed in peritoneal dialysis solutions and in pure glucose solutions. In addition, it appeared that other components of dialysis solutions, mainly calcium chloride, influenced unpredictably the results of creatinine with the Jaffe's reaction. We conclude that specific enzymatic test is a more accurate and reliable method to evaluate creatinine kinetics through the peritoneal membrane when determined in CAPD solutions.

scholarly journals Heme Oxygenase-1 Deficiency and Oxidative Stress: A Review of 9 Independent Human Cases and Animal Models

2021 ◽  
Vol 22 (4) ◽  
pp. 1514 ◽  
Author(s):  
Akihiro Yachie
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Heme Oxygenase ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Pharmacological Intervention ◽  
Heme Oxygenase 1 ◽  
Inflammatory Reactions

Since Yachie et al. reported the first description of human heme oxygenase (HO)-1 deficiency more than 20 years ago, few additional human cases have been reported in the literature. A detailed analysis of the first human case of HO-1 deficiency revealed that HO-1 is involved in the protection of multiple tissues and organs from oxidative stress and excessive inflammatory reactions, through the release of multiple molecules with anti-oxidative stress and anti-inflammatory functions. HO-1 production is induced in vivo within selected cell types, including renal tubular epithelium, hepatic Kupffer cells, vascular endothelium, and monocytes/macrophages, suggesting that HO-1 plays critical roles in these cells. In vivo and in vitro studies have indicated that impaired HO-1 production results in progressive monocyte dysfunction, unregulated macrophage activation and endothelial cell dysfunction, leading to catastrophic systemic inflammatory response syndrome. Data from reported human cases of HO-1 deficiency and numerous studies using animal models suggest that HO-1 plays critical roles in various clinical settings involving excessive oxidative stress and inflammation. In this regard, therapy to induce HO-1 production by pharmacological intervention represents a promising novel strategy to control inflammatory diseases.

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