scholarly journals Mechanisms of Crystalloid versus Colloid Osmosis across the Peritoneal Membrane

2018 ◽  
Vol 29 (7) ◽  
pp. 1875-1886 ◽  
Author(s):  
Johann Morelle ◽  
Amadou Sow ◽  
Charles-André Fustin ◽  
Catherine Fillée ◽  
Elvia Garcia-Lopez ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Water Flow ◽  
Molecular Mechanisms ◽  
Experimental Models ◽  
Peritoneal Membrane ◽  
Aquaporin 1 ◽  
Dialysis Solution ◽  
Osmotic Water ◽  
Osmotic Agents

Background Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated.Methods We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin.ResultsIn silico modeling and in vivo studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, colloidal fractions, with a reflection coefficient close to unity, a low diffusion capacity, and a minimal effect on dialysate osmolality. Combining crystalloid and colloid osmotic agents in the same dialysis solution strikingly enhanced water and sodium transport across the peritoneal membrane, improving ultrafiltration efficiency over that obtained with either type of agent alone.Conclusions These data cast light on the molecular mechanisms involved in colloid versus crystalloid osmosis and characterize novel osmotic agents. Dialysis solutions combining crystalloid and colloid particles may help restore fluid balance in patients treated with peritoneal dialysis.

Quantification of osmotic water transport in vivo using fluorescent albumin

2014 ◽  
Vol 307 (8) ◽  
pp. F981-F989 ◽  
Author(s):  
Johann Morelle ◽  
Amadou Sow ◽  
Didier Vertommen ◽  
François Jamar ◽  
Bengt Rippe ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Water Transport ◽  
Molecular Mechanisms ◽  
Water Channel ◽  
Transgenic Animals ◽  
Peritoneal Membrane ◽  
Intraperitoneal Pressure ◽  
Alexa Fluor ◽  
Osmotic Water

Osmotic water transport across the peritoneal membrane is applied during peritoneal dialysis to remove the excess water accumulated in patients with end-stage renal disease. The discovery of aquaporin water channels and the generation of transgenic animals have stressed the need for novel and accurate methods to unravel molecular mechanisms of water permeability in vivo. Here, we describe the use of fluorescently labeled albumin as a reliable indicator of osmotic water transport across the peritoneal membrane in a well-established mouse model of peritoneal dialysis. After detailed evaluation of intraperitoneal tracer mass kinetics, the technique was validated against direct volumetry, considered as the gold standard. The pH-insensitive dye Alexa Fluor 555-albumin was applied to quantify osmotic water transport across the mouse peritoneal membrane resulting from modulating dialysate osmolality and genetic silencing of the water channel aquaporin-1 (AQP1). Quantification of osmotic water transport using Alexa Fluor 555-albumin closely correlated with direct volumetry and with estimations based on radioiodinated (125I) serum albumin (RISA). The low intraperitoneal pressure probably accounts for the negligible disappearance of the tracer from the peritoneal cavity in this model. Taken together, these data demonstrate the appropriateness of pH-insensitive Alexa Fluor 555-albumin as a practical and reliable intraperitoneal volume tracer to quantify osmotic water transport in vivo.

Transgenic Mouse Models

2007 ◽  
Vol 27 (6) ◽  
pp. 625-633 ◽  
Author(s):  
Tomoya Nishino ◽  
Jie Ni ◽  
Olivier Devuyst
Keyword(s):  
Peritoneal Dialysis ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Experimental Models ◽  
The Body ◽  
In Vivo Studies ◽  
Limiting Factor ◽  
Peritoneal Membrane ◽  
Pharmacological Agents

The development of peritoneal dialysis has been paralleled by a growing interest in establishing suitable experimental models to better understand the functional and structural processes operating in the peritoneal membrane. Thus far, most investigations have been performed in rat and rabbit models, with mechanistic insights essentially based on intervention studies using pharmacological agents, blocking antibodies, or transient expression systems. Since the body size of a species is no longer a limiting factor in the performance of in vivo studies related to peritoneal dialysis, it has been considered that mice, particularly once they have been genetically modified, could provide an attractive tool to investigate the molecular mechanisms operating in the peritoneal membrane. The purpose of this review is to illustrate how investigators in peritoneal dialysis research, catching up with other fields of biomedical research, are increasingly taking advantage of mouse models to provide direct evidence of basic mechanisms involved in the major complications of peritoneal dialysis.

Polymers as Osmotic Agents for Peritoneal Dialysis

1984 ◽  
Vol 4 (2_suppl) ◽  
pp. 125-131 ◽  
Author(s):  
Zbylut J. Twardowski ◽  
Harold L. Moore ◽  
Terry J. McGary ◽  
Mira Poskuta ◽  
Charalambos Stathakis ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Membrane ◽  
Small Molecular Weight ◽  
Plasma Substitutes ◽  
Dialysis Solution ◽  
Osmotic Agent ◽  
Peritoneal Dialysis Solution ◽  
Solute Absorption ◽  
Osmotic Agents ◽  
Dialysis Solutions

A sustained ultrafiltration during long-dwell peritoneal dialysis exchanges cannot be obtained with rapidly absorbable small molecular weight osmotic agents. Slowly absorbable synthetic poly ions tested on rats and rabbits yielded high and sustained ultrafiltration, but were toxic. Gelatin solutions were not toxic in acute rat studies and produced sustained ultrafiltration but were difficult to work with because of gelation. A review of the literature on the properties of gelatin derivatives, used as plasma substitutes, led us to believe that they may be also useful as osmotic agents in the peritoneal dialysis solutions. In the peritoneal dialysis system, hydrostatic pressure in the blood compartment cannot be readily manipulated. Therefore, traditionally a solute (osmotic agent) is added to the peritoneal dialysis solution to create an osmotic driving force. During the process of ultrafiltration (Figure I), the rate of ultrafiltration decreases with time due to dilution by ultrafiltrate and absorption of the osmotic agent. Thus, ultrafiltration will eventually cease after the dialysis solution is infused. The bigger the molecule of the osmotic agent, the longer ultrafiltration lasts because solute absorption through the peritoneal membrane is slower. Thus, to achieve sustained ultrafiltration, an osmotic agent with a bigger molecule would be more advantageous than the smaller one at comparable osmotic gradients.

scholarly journals Experimental Models of Hepatocellular Carcinoma—A Preclinical Perspective

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3651
Author(s):  
Alexandru Blidisel ◽  
Iasmina Marcovici ◽  
Dorina Coricovac ◽  
Florin Hut ◽  
Cristina Adriana Dehelean ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Prediction Models ◽  
3D Models ◽  
Experimental Models ◽  
Health Concern ◽  
Liver Carcinoma ◽  
Tumor Type

Hepatocellular carcinoma (HCC), the most frequent form of primary liver carcinoma, is a heterogenous and complex tumor type with increased incidence, poor prognosis, and high mortality. The actual therapeutic arsenal is narrow and poorly effective, rendering this disease a global health concern. Although considerable progress has been made in terms of understanding the pathogenesis, molecular mechanisms, genetics, and therapeutical approaches, several facets of human HCC remain undiscovered. A valuable and prompt approach to acquire further knowledge about the unrevealed aspects of HCC and novel therapeutic candidates is represented by the application of experimental models. Experimental models (in vivo and in vitro 2D and 3D models) are considered reliable tools to gather data for clinical usability. This review offers an overview of the currently available preclinical models frequently applied for the study of hepatocellular carcinoma in terms of initiation, development, and progression, as well as for the discovery of efficient treatments, highlighting the advantages and the limitations of each model. Furthermore, we also focus on the role played by computational studies (in silico models and artificial intelligence-based prediction models) as promising novel tools in liver cancer research.

Potential Health Benefits Of A Pomegranate Extract, Rich In Phenolic Compounds, In Intestinal Inflammation

2021 ◽  
Vol 17 ◽  
Author(s):  
Marco Raffaele ◽  
Khaled Greish ◽  
Luca Vanella ◽  
Giuseppe Carota ◽  
Fatemah Bahman ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Molecular Mechanisms ◽  
Intestinal Inflammation ◽  
Inflammatory Marker ◽  
Experimental Models ◽  
Cellular Damage ◽  
Experimental Conditions ◽  
Potential Health

Background: Pomegranate is a fruit rich in bioactive compounds such as punicalagins, gallic acid, and ellagic acid derivatives. It has been widely used since ancient times in traditional medicine for a wide variety of diseases. It has been reported that bioactive compounds, such as polyphenols, are able to induce the expression of cytoprotective enzymes, including HO-1. The contribution of HO-1 activity to the prevention of intestinal inflammation has been shown in different models of Inflammatory bowel diseases (IBD). Objective: Aim of the present research was to investigate the molecular mechanisms involved in the beneficial effects of a pomegranate extract (PE), rich in bioactive compounds in intestinal inflammation. Methods: Caco-2 cells exposed to LPS and DSS induced colitis were chosen as convenient experimental models of intestinal inflammation. Results: Results obtained in our experimental conditions, showed that PE in vitro was able to induce HO-1 and to reduce cellular damage and oxidative stress through increase of GSH levels. Moreover, PE was able to decrease the pro-inflammatory marker IL-8 levels and to activate TIGAR pathway. The results obtained in vivo, in agreement with the data obtained in vitro, highlighted the ability of PE to reduce intestinal inflammation, preserve the colon length and histological features and reduce IL-6 levels compared to the DSS treated group. Conclusion: PE, rich in bioactive compounds, could contribute, as supportive therapy, to enhance the effects of the conventional therapeutic strategies to the management of IBD.

Peritoneal Solute Clearances after four Years of Continuous Ambulatory Peritoneal Dialysis (CAPD)

1989 ◽  
Vol 9 (1) ◽  
pp. 75-78 ◽  
Author(s):  
Min Sun Park ◽  
Jean Lee ◽  
Moon Sung Lee ◽  
Seung Ho Baick ◽  
Seung Duk Hwang ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Glucose Absorption ◽  
Peritoneal Membrane ◽  
Vasoactive Agents ◽  
Membrane Function ◽  
Dialysis Solution ◽  
Before And After ◽  
Dialysate Volume

In order to evaluate peritoneal membrane function and responsiveness of peritoneal microcirculation to vasoactive agents in long-term continuous ambulatory peritoneal dialysis (CAPD) patients, we studied peritoneal clearances of urea (Curea) and creatinine (Ccr), protein concentrations in drained dialysate (D PC), peritoneal glucose absorption (% GA), and drained dialysate volume ( VD) before and after nitroprusside (NP) addition to dialysis solution in 17 long-term CAPD patients (mean duration of CAPD: 52 months) and the results were compared to those of 18 patients who were just trained for CAPD (mean duration: 0.6 month). There were no differences in the control (without NP) Curea, Ccr, D PC, %GA, and VD between the new and long-term CAPD patients. Curea, Ccr, and D PC increased significantly with NP in both new and long-term patients. Curea and Ccr with NP were not different between the new and long-term patients but D PC with NP was significantly lower in the long-term CAPD patients. The results of this study suggest that peritoneal solute clearances and the responsiveness of peritoneal microcirculation to NP remain unchanged after four years of CAPD, despite recurrent episodes of peritonitis.

In vivo inhibition of transcellular water channels (aquaporin-1) during acute peritoneal dialysis in rats

1996 ◽  
Vol 271 (6) ◽  
pp. H2254-H2262 ◽  
Author(s):  
O. Carlsson ◽  
S. Nielsen ◽  
el-R. Zakaria ◽  
B. Rippe
Keyword(s):  
Peritoneal Dialysis ◽  
Water Transport ◽  
Water Flow ◽  
Peritoneal Cavity ◽  
Critical Role ◽  
Water Channels ◽  
Capillary Endothelium ◽  
Tissue Fixation ◽  
Solute Permeability ◽  
Aquaporin 1

During peritoneal dialysis (PD), a major portion of the osmotically induced water transport to the peritoneum can be predicted to occur through endothelial water-selective channels. Aquaporin-1 (AQP-1) has recently been recognized as the molecular correlate to such channels. Aquaporins can be inhibited by mercurials. In the present study, HgCl2 was applied locally to the peritoneal cavity in rats after short-term tissue fixation, used to protect the tissues from HgCl2 damage. Dianeal (3.86%) was employed as dialysis fluid, 125I-albumin as an intraperitoneal volume marker, and 51Cr-EDTA (constantly infused intravenously) to assess peritoneal small-solute permeability characteristics. Immunocytochemistry and immunoelectron microscopy revealed abundant AQP-1 labeling in capillary endothelium in peritoneal tissues, representing sites for HgCl2 inhibition of water transport. HgCl2 treatment reduced water flow and inhibited the sieving of Na+ without causing any untoward changes in microvascular permeability, compared with that of fixed control rats, in which the peritoneal cavity was exposed to tissue fixation alone. In fixed control rats, the mean intraperitoneal volume (IPV) increased from 20.5 +/- 0.15 to 25.0 +/- 0.52 ml in 60 min, whereas in the HgCl2-treated rats, the increment was only from 20.7 +/- 0.23 to 23.5 +/- 0.4 ml. In fixed control rats, the dialysate Na+ fell from 135.3 +/- 0.97 to 131.3 +/- 1.72 mM, whereas in the HgCl2-treated rats the dialysate Na+ concentration remained unchanged between 0 and 40 min, further supporting that water channels had been blocked. Computer simulations of peritoneal transport were compatible with a 66% inhibition of water flow through aquaporins. The observed HgCl2 inhibition of transcellular water channels strongly indicates a critical role of aquaporins in PD and provides evidence that water channels are crucial in transendothelial water transport when driven by crystalloid osmosis.

Animal Models in Peritoneal Dialysis Research: A Need for Consensus

2005 ◽  
Vol 25 (1) ◽  
pp. 16-24 ◽  
Author(s):  
Siska Mortier ◽  
Norbert H. Lameire ◽  
An S. De Vriese
Keyword(s):  
Animal Model ◽  
Peritoneal Dialysis ◽  
Animal Models ◽  
Solute Transport ◽  
Experimental Models ◽  
Research Groups ◽  
Experimental Animals ◽  
Collective Effort ◽  
Study Duration

The development of an adequate animal model for peritoneal research remains an object of concern. In vivo peritoneal dialysis (PD) research is hampered by the large variety of available models that make interpretation of results and comparison of studies very difficult. Species and strain of experimental animals, method of peritoneal access, study duration, measures of solute transport and ultrafiltration, and sampling for histology differ substantially among the various research groups. A collective effort to discuss the shortcomings and merits of the different experimental models may lead to a consensus on a standardized animal model of PD.

scholarly journals P1238EVALUATION OF AN IN VITRO CO-CULTURE MODEL FOR TESTING EFFECTS OF CYTOPROTECTIVE ADDITIVES IN PERITONEAL DIALYSIS FLUIDS ON CARDIOVASCULAR OUTCOME

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Juan Manuel Sacnun ◽  
Rebecca Herzog ◽  
Maria Bartosova ◽  
Claus Schmitt ◽  
Klaus Kratochwill
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Peritoneal Dialysis ◽  
Cardiovascular Risk ◽  
Cell Damage ◽  
Peritoneal Membrane ◽  
Cytoskeleton Reorganization ◽  
Harmful Effects

Abstract Background and Aims The composition of all currently available peritoneal dialysis (PD) fluids triggers morphological and functional changes in the peritoneal membrane. Periodic exposure leads to vasculopathy, hypervascularization, and diabetes-like damage of vessels, eventually leading to failure of the technique. Patients undergoing dialysis generally, have a high risk of cardiovascular events. It is currently unclear if there is a mechanistic link between peritoneal membrane failure and cardiovascular risk. In vitro and in vivo studies have shown that cytoprotective additives (e.g. dipeptide alanyl-glutamine (AlaGln) or kinase inhibitor lithium chloride (LiCl)) to PDF reduce peritoneal damage. Here, we developed an experimental model for investigating effects of these cytoprotective additives in PDF in the cardiovascular context. Method For modelling the peritoneal membrane in vitro, mesothelial and endothelial cells were co-cultured in transwell plates. Mesothelial cells were grown in the upper compartment and primary human umbilical vein endothelial cells (HUVEc) or primary microvascular cells were grown in the lower compartment. PDF with or without cytoprotective compounds, was added to the upper compartment to only expose mesothelial cells directly to different dilutions of the fluid. Effects on cell damage was assessed by quantification of lactate-dehydrogenase (LDH) release and live-dead staining of cells. Proteome profiles were analysed for both cell-types separately and in combination using two-dimensional difference gel electrophoresis (2D-DiGE) and liquid chromatography coupled to mass spectrometry (LC-MS). In vitro findings were related to PD-induced arteriolar changes based on abundance profiles of micro-dissected omental arterioles of children treated with conventional PD-fluids and age-matched controls with normal renal function. Results Marked cellular injury of HUVEc after PD-fluid exposure was associated with a molecular landscape of the enriched biological process clusters ‘glucose catabolic process’, ‘cell redox homeostasis’, ‘RNA metabolic process’, ‘protein folding’, ‘regulation of cell death’, and ‘actin cytoskeleton reorganization’ that characterize PD-fluid cytotoxicity and counteracting cellular repair process respectively. PDF-induced cell damage was reduced by AlaGln and LiCl both in mesothelial and endothelial cells. Proteome analysis revealed perturbation of major cellular processes including regulation of cell death and cytoskeleton reorganization. Selected markers of angiogenesis, oxidative stress, cell junctions and transdifferentiation were counter-regulated by the additives. Co-cultured cells yielded differently regulated pathways following PDF exposure compared to separate culture. Comparison to human arterioles confirmed overlapping protein regulation between endothelial cells in vitro and in vivo, proving harmful effects of PD-fluids on endothelial cells leading to drastic changes of the cellular process landscape. Conclusion In summary, this study shows harmful effects of PD-fluids also effecting endothelial cells and elucidates potential mechanisms by which cytoprotective additives may counteract the signalling axis between local peritoneal damage and systemic vasculopathy. An in vitro co-culture system may be an attractive approach to simulate the peritoneal membrane for testing direct and indirect effects of cytoprotective additives in PDF. When cultured and stressed in close proximity cells may respond differently. Characterisation of PD-induced perturbations will allow identifying molecular mechanisms linking the peritoneal and cardiovascular context, offering therapeutic targets to reduce current limitations of PD and ultimately decreasing cardiovascular risk of dialysis patients.

Integrating Network Pharmacology and Experimental Models to Investigate the Efficacy of Coptidis and Scutellaria Containing Huanglian Jiedu Decoction on Hepatocellular Carcinoma

2020 ◽  
Vol 48 (01) ◽  
pp. 161-182 ◽  
Author(s):  
Jihan Huang ◽  
Wei Guo ◽  
Fan Cheung ◽  
Hor-Yue Tan ◽  
Ning Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Experimental Models ◽  
Network Pharmacology ◽  
Disease Networks ◽  
Cycle Arrest ◽  
Single Target ◽  
Induced Apoptosis

Unlike Western medicines with single-target, the traditional Chinese medicines (TCM) always exhibit diverse curative effects against multiple diseases through its “multi-components” and “multi-targets” manifestations. However, discovery and identification of the major therapeutic diseases and the underlying molecular mechanisms of TCM remain to be challenged. In the current study, we, for the first time, applied an integrated strategy by combining network pharmacology with experimental evaluation, for exploration and demonstration of the therapeutic potentials and the underlying possible mechanisms of a classic TCM formula, Huanglian Jiedu decoction (HLJDD). First, the herb–compound, compound–protein, protein–pathway, and gene–disease networks were constructed to predict the major therapeutic diseases of HLJDD and explore the underlying molecular mechanisms. Network pharmacology analysis showed the top one predicted disease of HLJDD treatment was cancer, especially hepatocellular carcinoma (HCC) and inflammation-related genes played an important role in the treatment of HLJDD on cancer. Next, based on the prediction by network pharmacology analysis, both in vitro HCC cell and in vivo orthotopic HCC implantation mouse models were established to validate the curative role of HLJDD. HLJDD exerted its antitumor activity on HCC in vitro, as demonstrated by impaired cell proliferation and colony formation abilities, induced apoptosis and cell cycle arrest, as well as inhibited migratory and invasive properties of HCC cells. The orthotopic HCC implantation mouse model further demonstrated the remarkable antitumour effects of HLJDD on HCC in vivo. In conclusion, our study demonstrated the effectiveness of integrating network pharmacology with experimental study for discovery and identification of the major therapeutic diseases and the underlying molecular mechanisms of TCM.

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