scholarly journals Animal Models of Peritoneal Dialysis: Thirty Years of Our Own Experience

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Krzysztof Pawlaczyk ◽  
Ewa Baum ◽  
Krzysztof Schwermer ◽  
Krzysztof Hoppe ◽  
Bengt Lindholm ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Animal Models ◽  
Experimental Animal ◽  
Bioactive Molecules ◽  
Technical Problems ◽  
Peritoneal Mesothelial Cells ◽  
Measure Concentration ◽  
Peritoneal Permeability ◽  
Kinetics Of

Experimental animal models improve our understanding of technical problems in peritoneal dialysis PD, and such studies contribute to solving crucial clinical problems. We established an acute and chronic PD model in nonuremic and uremic rats. We observed that kinetics of PD in rats change as the animals are aging, and this effect is due not only to an increasing peritoneal surface area, but also to changes in the permeability of the peritoneum. Changes of the peritoneal permeability seen during chronic PD in rats are comparable to results obtained in humans treated with PD. Effluent dialysate can be drained repeatedly to measure concentration of various bioactive molecules and to correlate the results with the peritoneal permeability. Additionally we can study inin vitroconditions properties of the effluent dialysate on cultured peritoneal mesothelial cells or fibroblasts. We can evaluate acute and chronic effect of various additives to the dialysis fluid on function and permeability of the peritoneum. Results from such study are even more relevant to the clinical scenario when experiments are performed in uremic rats. Our experimental animal PD model not only helps to understand the pathophysiology of PD but also can be used for testing biocompatibility of new PD fluids.

Glucose Degradation Products and Peritoneal Membrane Function

2001 ◽  
Vol 21 (2) ◽  
pp. 201-207 ◽  
Author(s):  
Janusz Witowski ◽  
Thorsten O. Bender ◽  
Gerhard M. Gahl ◽  
Ulrich Frei ◽  
Achim Jörres
Keyword(s):  
Peritoneal Dialysis ◽  
Cell Viability ◽  
Degradation Products ◽  
Membrane Function ◽  
Peritoneal Mesothelial Cells ◽  
Glucose Degradation Products ◽  
And Function ◽  
The Impact ◽  
Dialysis Fluids

Background The bioincompatibility of peritoneal dialysis fluids (PDF) in current use has been partially attributed to the presence of glucose degradation products (GDPs), which are generated during heat sterilization of PDF. Several of the GDPs have been identified and we have recently demonstrated that these GDPs per se may impair the viability and function of human peritoneal mesothelial cells (HPMC) in vitro. It is also possible that GDP-related toxicity is further exacerbated by the milieu of PDF. We review the current literature on GDP and present the results of experiments comparing the impact of heat- and filter-sterilized PDF on the viability and function of HPMC. Methods Peritoneal dialysis fluids with low (1.5%) and high (4.25%) glucose concentrations were laboratory prepared according to the standard formula and sterilized either by heat (H-PDF; 121°C, 0.2 MPa, 20 minutes) or filtration (F-PDF; 0.2 μ). The buildup of GDP was confirmed by UV absorbance at 284 nm. Confluent HPMC monolayers were exposed to these solutions mixed 1:1 with standard M199 culture medium. After 24 hours, cell viability was assessed with the MTT assay, and interleukin-1β–stimulated monocyte chemotactic protein-1 (MCP-1) release with specific immunoassay. Results Exposure of HPMC to H-PDF resulted in a significant decrease in cell viability, with solutions containing 4.25% glucose being more toxic than 1.5% glucose-based PDF (27.4% ± 3.4% and 53.4% ± 11.0% of control values, respectively). In contrast, viability of HPMC exposed to F-PDF was not different from that of control cells. Moreover, treatment with H-PDF impaired the release of MCP-1 from HPMC to a significantly greater degree compared to F-PDF (17.4% and 24.9% difference for low and high glucose PDF, respectively). Conclusions Exposure of HPMC to H-PDF significantly impairs cell viability and the capacity for generating MCP-1 compared to F-PDF. This effect is likely to be mediated by GDPs present in H-PDF but not in F-PDF.

Glucose Degradation Products and the Peritoneal Mesothelium

2000 ◽  
Vol 20 (5_suppl) ◽  
pp. 19-22 ◽  
Author(s):  
Achim Jörres ◽  
Thorsten O. Bender ◽  
Janusz Witowski
Keyword(s):  
Peritoneal Dialysis ◽  
Degradation Products ◽  
Experimental Models ◽  
Buffer System ◽  
Peritoneal Fibrosis ◽  
High Concentration ◽  
Peritoneal Mesothelial Cells ◽  
Cell Functions ◽  
Glucose Degradation Products

Conventional heat-sterilized, glucose-based peritoneal dialysis (PD) fluids contain significant amounts of glucose degradation products (GDPs) such as aldehydes and dicarbonyl compounds (glyoxal, methylglyoxal). These GDPs have been shown to impair cell functions in various in vitro experimental models. In peritoneal mesothelial cells, GDPs dose-dependently inhibit cell proliferation and mediator synthesis. In addition, some GDPs potently promote generation of advanced glycation end-products (AGEs). Immunohistochemistry finds AGEs in the peritoneal membrane of chronic continuous ambulatory peritoneal dialysis (CAPD) patients, suggesting that peritoneal AGE accumulation may be involved in chronic peritoneal fibrosis. The formation of GDPs might be prevented by filter-sterilization of PD fluids. Another option is to separate the glucose and the buffer system in dual-chambered or multi-chambered containers. In these systems, the glucose is kept in a separate compartment at high concentration and very low pH—both conditions being known to minimize the degree of glucose decomposition during autoclaving. Initial experimental evidence suggests that these novel, multi-chambered fluids significantly improve in vitro biocompatibility; however, the clinical relevance of these results remains to be established in clinical trials.

Bicarbonate: The Alternative Buffer for Peritoneal Dialysis

1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 109-113 ◽  
Author(s):  
Jutta Passlick-Deetjen ◽  
Judith Kirchgessner
Keyword(s):  
Peritoneal Dialysis ◽  
Metabolic Acidosis ◽  
Cell Function ◽  
Multicenter Trial ◽  
The Body ◽  
Bicarbonate Concentration ◽  
Promising Alternative ◽  
Technical Problems ◽  
Cell Functions

For a long time bicarbonate, the physiological buffer of the body, was suggested to be the best buffer for peritoneal dialysis. However, since the production of bicarbonate containing solutions is associated with technical problems, lactate was favored. To avoid the well-known disadvantages of lactate solution concerning biocompatibility and possible metabolic side effects, different attempts have been made to use bicarbonate as a buffer in peritoneal dialysis. One of the major approaches was the total replacement of lactate by bicarbonate combined with storage of the fluid in a specially designed double-chamber bag. Further solutions of the above-mentioned problem were the on-line preparation of bicarbonate fluids for intermittent peritoneal dialysis, the addition of bicarbonate just before use, the combination of bicarbonate with organic acids, or its combination with the dipeptide glycylglycine as a stabilizing agent. By now, the beneficial effect of the neutral bicarbonate fluid, for example, on cell viability and cell functions, has been demonstrated in many different in vitro and animal studies. However, only few reports on clinical experience have been published. These investigations demonstrated independently that bicarbonate fluids diminish inflow pain, are well tolerated by the patients, and may correct metabolic acidosis of uremic patients. A controlled randomized multicenter trial using 34 mmol/L bicarbonate for at least three months confirmed that bicarbonate is as efficacious as lactate in equimolar concentrations. Concomitant investigations on energy metabolism and redox state of red blood cells and phospholipid secretion of mesothelial cells additionally demonstrated the improvement of cell function with bicarbonate solutions. For some patients with severe metabolic acidosis the bicarbonate concentration used in the multicenter trial seemed to be too low. Thus, a fluid containing a higher bicarbonate concentration was tested in a pilot study resulting in the expected significant increase of arterial bicarbonate levels. In summary, bicarbonate-containing peritoneal dialysis solutions are a promising alternative to lactate, especially if bicarbonate concentrations are adjusted individually to the patient's need.

scholarly journals Regulation of Synthesis and Roles of Hyaluronan in Peritoneal Dialysis

2015 ◽  
Vol 2015 ◽  
pp. 1-12
Author(s):  
Timothy Bowen ◽  
Soma Meran ◽  
Aled P. Williams ◽  
Lucy J. Newbury ◽  
Matthias Sauter ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
In Vivo Models ◽  
Peritoneal Mesothelial Cells ◽  
Glycosidic Bonds ◽  
Peritoneal Biopsy ◽  
Human Peritoneal Mesothelial Cells ◽  
Regulation Of Synthesis ◽  
Ha Synthase

Hyaluronan (HA) is a ubiquitous extracellular matrix glycosaminoglycan composed of repeated disaccharide units of alternating D-glucuronic acid and D-N-acetylglucosamine residues linked via alternatingβ-1,4 andβ-1,3 glycosidic bonds. HA is synthesized in humans by HA synthase (HAS) enzymes 1, 2, and 3, which are encoded by the correspondingHASgenes. Previous in vitro studies have shown characteristic changes in HAS expression and increased HA synthesis in response to wounding and proinflammatory cytokines in human peritoneal mesothelial cells. In addition, in vivo models and human peritoneal biopsy samples have provided evidence of changes in HA metabolism in the fibrosis that at present accompanies peritoneal dialysis treatment. This review discusses these published observations and how they might contribute to improvement in peritoneal dialysis.

scholarly journals In Vitro Activities of the Ketolides Telithromycin (HMR 3647) and HMR 3004 Compared to Those of Clarithromycin against Slowly Growing Mycobacteria at pHs 6.8 and 7.4

2000 ◽  
Vol 44 (10) ◽  
pp. 2848-2852 ◽  
Author(s):  
Nalin Rastogi ◽  
Khye Seng Goh ◽  
Mylene Berchel ◽  
André Bryskier
Keyword(s):  
Animal Models ◽  
Mycobacterium Bovis ◽  
Experimental Animal ◽  
Intracellular Accumulation ◽  
Experimental Animal Models ◽  
High Level

ABSTRACT The in vitro activities of HMR 3647 (telithromycin) and HMR 3004, two novel semisynthetic ketolides, were investigated and compared with that of the reference macrolide drug, clarithromycin, against 34 strains of slowly growing mycobacteria at pHs 6.8 and 7.4, as determined radiometrically. The MICs at pH 7.4 were about 1 to 2 dilutions lower than those observed at pH 6.8. In terms of the highest to the lowest activity, the three antibiotics could be classified as follows: clarithromycin > HMR 3004 > HMR 3647. Among the species tested, Mycobacterium bovis BCG, M. ulcerans, M. avium, and M. paratuberculosis were moderately susceptible to HMR 3004 and HMR 3647 (MICs at pH 7.4, ≤5.0 and ≤20.0 μg/ml, respectively, versus ≤1.25 μg/ml for clarithromycin), whereas M. tuberculosis, M. africanum, M. bovis, andM. simiae were resistant (MICs, ≥10.0 and ≥40.0 μg/ml, respectively, at pH 7.4). Although not more active than clarithromycin in vitro, the high level of intracellular accumulation of the two ketolides inside phagocytes warrants further screening in experimental animal models.

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.

Development of Animal Models, Presenting Appropriate Analogues to Respective Human Systems

2021 ◽  
Author(s):  
Iskra V Sainova
Keyword(s):  
Animal Models ◽  
Experimental Animal ◽  
Normal Mouse ◽  
Recombinant Dna ◽  
Embryonic Stem ◽  
Human Origin ◽  
Experimental Animal Models ◽  
Cellular Types

The main idea of the current study was directed to developed appropriate experimental animal models, imitating respective systems with the human origin, and giving a possibility when the last is not available, experiments about necessary applications to humans to be performed. So, an additional copy of oncogene Dcn1 in normal mouse embryonic stem cells (mESCs), was inserted, by appropriate recombinant DNA-constructs, based on the AAV DNA-genome. All derived genetically-manipulated cellular types were co-cultivated with early myeloid and lymphoid progenitors, derived from non-transfected mESCs in the presence of GM-CSF (for induction of initial stages of both myeloid and lymphoid differentiation), and subsequently, malignant antigens were added (about further phagocyte and plasmatic cell differentiation, respectively). The derived and selected mESCs, containing an additionally-inserted copy of oncogene Dcn1, which indicated preserved normal/non-malignant characteristics both in vitro and in vivo, presented appropriate experimental normal mouse cellular analog of the cited in the scientific literature human embryonic trophoblasts, immortalized by infection with virus SV40. Additionally, the results obtained showed a possibility about the expression of membrane receptor glycoproteins by non-lymphoid and non-myeloid cellular types inappropriate conditions. Also, the presented study demonstrated the importance of the blood-testes barrier (BTB) for the prevention of malignancy development in the experimental hamster Graffi tumor model. The role of bio-molecules, as well as of intra- and extra-cellular inter-molecular interactions in cascade regulatory mechanisms, inactivation of the differentiation of embryonic and adult stem/progenitor cells in normal types, as well as for suppression of malignant transformation, was suggested. The established analogy of the developed and investigated in the current study experimental animal models gives a possibility for their application about performing of specific experiments when the respective systems with human origin are not available.

Gonadotrophic Hormones – An Overview of their Involvement in Gonadal and Extragonadal Tumours

2010 ◽  
Vol 7 (1) ◽  
pp. 8 ◽  
Author(s):  
Ilpo Huhtaniemi ◽  
Maria Alevizaki ◽  
◽  
Keyword(s):  
Animal Models ◽  
Experimental Animal ◽  
Clinical Evidence ◽  
Critical Evaluation ◽  
Regulatory Action ◽  
Experimental Animal Models ◽  
Direct Involvement ◽  
Long Time

The concept of the direct involvement of gonadotrophins in tumorigenesis has been around for a long time. First, because the gonads are direct targets of gonadotrophin action, their tumours have been proposed to be gonadotrophin-dependent. Second, the recent findings of gonadotrophin receptors in extragonadal tissues has prompted the hypothesis that some extragonadal tumours (e.g. breast, uterus, prostate, pituitary and adrenal) could also be under the direct regulatory action of gonadotrophins. However, although supported by numerousin vitroexperiments and experimental animal models, the clinical evidence for a direct tumorigenic role of gonadotrophins remains weak. The purpose of this brief review is to present a critical evaluation of current information, both clinical and experimental, about the involvement of gonadotrophins in the induction and growth of gonadal and extragonadal tumours.

scholarly journals Protection of the Peritoneal Membrane by Peritoneal Dialysis Effluent-Derived Mesenchymal Stromal Cells in a Rat Model of Chronic Peritoneal Dialysis

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Lan Zhou ◽  
Ming Zong ◽  
Qiunong Guan ◽  
Gerald da Roza ◽  
Hao Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peritoneal Dialysis ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Flow Cytometric Analysis ◽  
Peritoneal Membrane ◽  
Peritoneal Mesothelial Cells

Peritoneal dialysis (PD) is a renal replacement option for patients with end-stage renal disease. However, a long-term exposure to hypertonic PD solutions leads to peritoneal membrane (PM) injury, resulting in ultrafiltration (UF) failure. This study was designed to primarily evaluate efficacy of PD effluent-derived mesenchymal stromal cells (pMSCs) in the prevention of PM injury in rats. The pMSCs were isolated from PD effluent. Male Wistar rats received daily intraperitoneal (IP) injection of 10 mL of Dianeal (4.25% dextrose) and were treated with pMSCs (1.2‐1.5×106/rat/wk, IP). UF was determined by IP injection of 30 mL of Dianeal (4.25% dextrose) with dwell time of 1.5 h, and PM injury was examined by histology. Apoptosis was quantitated by using flow cytometric analysis, and gene expression by using the PCR array and Western blot. Here, we showed that as compared to naive control, daily IP injection of the Dianeal PD solution for 6 weeks without pMSC treatment significantly reduced UF, which was associated with an increase in both PM thickness and blood vessel, while pMSC treatment prevented the UF loss and reduced PM injury and blood vessels. In vitro incubation with pMSC-conditioned medium prevented cell death in cultured human peritoneal mesothelial cells (HPMCs) and downregulated proinflammatory (i.e., CXCL6, NOS2, IL1RN, CCL5, and NR3C1) while upregulated anti-inflammatory (i.e., CCR1, CCR4, IL9, and IL-10) gene expression in activated THP1 cells. In conclusion, pMSCs prevent bioincompatible PD solution-induced PM injury and UF decline, suggesting that infusing back ex vivo-expanded pMSCs intraperitoneally may have therapeutic potential for reduction of UF failure in PD patients.

scholarly journals Translating Neurobehavioral Toxicity Across Species From Zebrafish to Rats to Humans: Implications for Risk Assessment

2021 ◽  
Vol 3 ◽  
Author(s):  
Charles V. Vorhees ◽  
Michael T. Williams ◽  
Andrew B. Hawkey ◽  
Edward D. Levin
Keyword(s):  
Risk Assessment ◽  
Animal Models ◽  
Experimental Animal ◽  
High Throughput ◽  
Clinical Studies ◽  
Drugs Of Abuse ◽  
Toxicant Exposure ◽  
Essential Information ◽  
Experimental Animal Models

There is a spectrum of approaches to neurotoxicological science from high-throughput in vitro cell-based assays, through a variety of experimental animal models to human epidemiological and clinical studies. Each level of analysis has its own advantages and limitations. Experimental animal models give essential information for neurobehavioral toxicology, providing cause-and-effect information regarding risks of neurobehavioral dysfunction caused by toxicant exposure. Human epidemiological and clinical studies give the closest information to characterizing human risk, but without randomized treatment of subjects to different toxicant doses can only give information about association between toxicant exposure and neurobehavioral impairment. In vitro methods give much needed high throughput for many chemicals and mixtures but cannot provide information about toxicant impacts on behavioral function. Crucial to the utility of experimental animal model studies is cross-species translation. This is vital for both risk assessment and mechanistic determination. Interspecies extrapolation is important to characterize from experimental animal models to humans and between different experimental animal models. This article reviews the literature concerning extrapolation of neurobehavioral toxicology from established rat models to humans and from zebrafish a newer experimental model to rats. The functions covered include locomotor activity, emotion, and cognition and the neurotoxicants covered include pesticides, metals, drugs of abuse, flame retardants and polycyclic aromatic hydrocarbons. With more complete understanding of the strengths and limitations of interspecies translation, we can better use animal models to protect humans from neurobehavioral toxicity.

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