Use of icodextrin solution to evaluate peritoneal transport capacity.

Peritoneal equilibration test (PET) is the gold standard for evaluating peritoneal transport, and measurement of the drain volume after 4-h dwell time with glucose 4.25% is a simple means of evaluating failure of ultrafiltration. The study objective was to verify if the measurement of the volume drained after 4 h dwell of icodextrin at 7.5% (ICO), has a better correlation with the parameters of PET. Patients in a peritoneal dialysis program (N = 35) underwent three procedures: PET; determination of the drain volume after a 4-h dwell with glucose 4.25%; and determination of the drain volume after a 4-h dwell with ICO. Among patients who were classified as high transporters, the ultrafiltration volume was greater after ICO use. The ICO ultrafiltration volume correlated negatively with the ratio between the 4- and 0-h dialysate glucose concentrations (D4/D0 ratio, r = -0.579; P = 0.002), correlating positively with the dialysate-to-plasma ratio for creatinine (D/PCr ratio, r = 0.474; P = 0.002). For ICO, the area under the receiver operating characteristic curve was 0.867 and 0.792 for the D/PCr and D4/D0 ratios (P < 0.0001 and P = 0.004, respectively), compared with 0.738 and 0.710 for glucose 4.25% (P = 0.020 and P = 0.041, respectively). A cut-off volume of 141 mL discriminated high/high-average transporters from low/low-average transporters. Volume drained after ICO use better predicts peritoneal transport patterns than does that drained after the use of glucose 4.25%.

[Dialysis monitoring: peritoneal equilibrium test, regional citrate anticoagulation and residual renal function]. / Suivi de la dialyse : test d'équilibration péritonéale, anticoagulation régionale au citrate, et fonction rénales résiduelle.

The SFBC working group aimed to deal with biological tests outside the French nomenclature that may be useful for the follow-up of dialysis patients. Our discussion was divided into 3 parts: 1) evaluation of peritoneal membrane characteristics; 2) monitoring of renal replacement therapy using regional citrate anticoagulation; 3) estimation of residual renal function (RRF). International recommendations underline the importance of assessing peritoneal membrane characteristics for peritoneal dialysis prescription. This peritoneal equilibrium test requires the measurement in dialysate of the following parameters: glucose, urea, creatinine and sodium. As part of the monitoring of continuous renal replacement therapy using regional citrate anticoagulation, the determination of ionized calcium assay is essential according to national and international guidelines to ensure a balance between effective anticoagulation and appropriate calcium levels. Finally, the RRF plays a key role in the dialysis adequacy and patient survival. European and international recommendations highlight the potential interest of RRF in peritoneal dialysis and hemodialysis. The RRF corresponds to the mean of urinary urea and creatinine clearance, assessed from a urine collection with measurement of urinary urea.

Decellularised porcine peritoneum as a tendon protector sheet.

Tissue grafts achieve high levels of compositional and mechanical integrity biomimicry and are often considered as the gold standard in clinical practice. Herein, we assessed the potential of decellularised porcine peritoneum (XenoMEM) as a tendon protector sheet and correlated its properties to a commercially available product (TenoGlide®). XenoMEM presented lower cross-linking ratio (p < 0.05), higher mechanical properties (p < 0.01), lower coefficient of friction (p < 0.01) and higher (p < 0.05) cytocompatibility with human tenocytes than TenoGlide®. In addition, XenoMEM exhibited lower (p < 0.05) immune response than TenoGlide® with macrophages. Collectively, these data support the use of XenoMEM in tendon tissue engineering.

Role of allograft inflammatory factor-1 in the regulation of inflammation and oxidative stress in primary peritoneal mesothelial cells.

Peritoneal dialysis (PD) is often used to treat patients with end stage renal disease, and its long-term complications include excessive inflammation and oxidative stress. Allograft inflammatory factor 1 (AIF-1), as a cytoplasmic protein, is originally identified from infiltrating macrophages, and it was associated with inflammation in the cells other than macrophages, such as endothelial cells and vascular smooth muscle cells. To clarify the molecular mechanisms of AIF-1-modulated pathological changes in the peritoneum during PD, we first detected the AIF-1 expression in peritoneal tissues from PD mice. Results revealed that the pro-fibrotic stimulation caused AIF-1 upregulation and triggered inflammation in peritoneal tissues, and that AIF-1 co-expressed with pan-cytokeratin (a marker of peritoneal mesothelial cells). We next treated primary mouse peritoneal mesothelial cells (pan-cytokeratin and intercellular adhesion molecule 1 positive cells) with 50 or 100 ng/mL recombinant AIF-1, and evaluated the direct effects of AIF-1 on these cells in vitro. We found that exogenous AIF-1 treatment induced inflammation and oxidative stress in mesothelial cells. Apart from the augmented IL-6 and TNF-α secretion, the level of ROS was upregulated and the activity of anti-oxidative SOD was reduced in cells exposed to AIF-1. Moreover, AIF-1 simulation triggered the activation of NF-κB pathway-enhanced the conversion of IκB to phosphorylated IκB and promoted the translocation of NF-κB p65 from cytoplasm into nucleus. Additionally, AIF-1-evoked inflammation in peritoneal mesothelial cells was attenuated by the addition of NF-κB inhibitor (BAY 11-7082). In brief, this study provides us novel information to understand the molecular regulation mechanisms of AIF-1 in peritoneal fibrosis.

Embryology, anatomy, physiology and pathophysiology of the peritoneum and the peritoneal vasculature.

The peritoneum is a large serous membrane with both epithelial and mesenchymal features, and is essential for maintaining an intra-abdominal homeostatic equilibrium. The peritoneum plays a central role in the pathogenesis of a number of disorders. Pathological processes affecting the peritoneum such as inflammation and carcinomatosis can have serious clinical consequences, but the pathophysiology of these conditions is poorly understood. Understanding peritoneal embryology, anatomy and physiology is crucial to comprehend pathophysiological mechanisms and to devise a new focus for research. The vascular response to pathological processes appears to be of considerable importance, since the peritoneal vasculature plays a pivotal role in most associated diseases. Therefore, this review summarizes currently available literature with special emphasis on the development, anatomy and function of the peritoneal vasculature. Pathological processes are described to illustrate physiological and pathophysiological characteristics of the peritoneum.

Epithelial-to-Mesenchymal Transition and Migration of Human Peritoneal Mesothelial Cells Undergoing Senescence.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) of human peritoneal mesothelial cells (HPMCs) contributes to fibrotic thickening of the peritoneum that develops in patients on peritoneal dialysis (PD). The process is thought to be largely mediated by transforming growth factor-beta (TGF-ß). As TGF-ß has also been implicated in senescence of HPMCs, we have performed an exploratory study to examine if senescent HPMCs can undergo EMT. METHODS: Omentum-derived HPMCs were rendered senescent by repeated passages in culture. Features of EMT were assessed by immunostaining and quantitative polymerase chain reaction (qPCR) at various stages of the HPMC lifespan and after treatment with or without TGF-ß. The motility of HPMCs was assessed in a scratch wound migration assay. RESULTS: Replicative senescence of HPMCs was associated with a gradual increase in the constitutive expression of EMT markers, including increased production of extracellular matrix proteins. However, senescent HPMCs also retained epithelial cell features such as cytokeratin, calretinin, and E-cadherin and showed decreased, rather than increased, motility. In contrast, exposure to TGF-ß resulted in an up-regulation of mesenchymal markers and down-regulation of epithelial markers. Such effects of TGF-ß occurred both in young and senescent cells, although they were less pronounced in senescence. CONCLUSIONS: Senescence of HPMCs is associated with spontaneous development of several EMT features. At the same time, senescent HPMCs preserve epithelial cell-like characteristics and are less prone to develop a full EMT phenotype in response to TGF-ß. These observations may support the concept of cellular senescence being antagonistically pleiotropic with regard to EMT.

miRNA Expression and Interaction with Genes Involved in Susceptibility to Pristane-Induced Arthritis.

Pristane-induced arthritis (PIA) in mice is an experimental model that resembles human rheumatoid arthritis, a chronic autoimmune disease that affects joints and is characterized by synovial inflammation and articular cartilage and bone destruction. AIRmax and AIRmin mouse lines differ in their susceptibility to PIA, and linkage analysis in this model mapped arthritis severity QTLs in chromosomes 5 and 8. miRNAs are a class of small RNA molecules that have been extensively studied in the development of arthritis. We analyzed miRNA and gene expression profiles in peritoneal cells of AIRmax and AIRmin lines, in order to evaluate the genetic architecture in this model. Susceptible AIRmax mice showed higher gene (2025 vs 1043) and miRNA (240 vs 59) modulation than resistant AIRmin mice at the onset of disease symptoms. miR-132-3p/212-3p, miR-106-5p, miR-27b-3p, and miR-25-3p were among the miRNAs with the highest expression in susceptible animals, showing a negative correlation with the expression of predicted target genes (Il10, Cd69, and Sp1r1). Our study showed that global gene and miRNA expression profiles in peritoneal cells of susceptible AIRmax and resistant AIRmin lines during pristane-induced arthritis are distinct, evidencing interesting targets for further validation.

The peritoneal "soil" for a cancerous "seed": a comprehensive review of the pathogenesis of intraperitoneal cancer metastases.

Various types of tumors, particularly those originating from the ovary and gastrointestinal tract, display a strong predilection for the peritoneal cavity as the site of metastasis. The intraperitoneal spread of a malignancy is orchestrated by a reciprocal interplay between invading cancer cells and resident normal peritoneal cells. In this review, we address the current state-of-art regarding colonization of the peritoneal cavity by ovarian, colorectal, pancreatic, and gastric tumors. Particular attention is paid to the pro-tumoral role of various kinds of peritoneal cells, including mesothelial cells, fibroblasts, adipocytes, macrophages, the vascular endothelium, and hospicells. Anatomo-histological considerations on the pro-metastatic environment of the peritoneal cavity are presented in the broader context of organ-specific development of distal metastases in accordance with Paget's "seed and soil" theory of tumorigenesis. The activity of normal peritoneal cells during pivotal elements of cancer progression, i.e., adhesion, migration, invasion, proliferation, EMT, and angiogenesis, is discussed from the perspective of well-defined general knowledge on a hospitable tumor microenvironment created by the cellular elements of reactive stroma, such as cancer-associated fibroblasts and macrophages. Finally, the paper addresses the unique features of the peritoneal cavity that predispose this body compartment to be a niche for cancer metastases, presents issues that are topics of an ongoing debate, and points to areas that still require further in-depth investigations.

A counterforce to diversion of cerebrospinal fluid during ventriculoperitoneal shunting: the intraperitoneal pressure. An observational study.

BACKGROUND: Intraperitoneal pressure (IPP) counteracts the diversion of cerebrospinal fluid (CSF) from the cranial to the peritoneal compartment during ventriculoperitoneal shunting. Animal studies suggest that the intrinsic IPP exceeds the intraperitoneal hydrostatic pressure. The intrinsic IPP in mobile patients is relevant for shunt therapy, but data about it is not available. METHODS: The IPP was measured indirectly in 25 mobile subjects (13 female) by applying a standard intravesical pressure measurement technique. Measurements were carried out in reference to the navel (supine position) and the xiphoid (upright position). Results were adjusted for the intraperitoneal hydrostatic pressure and correlated afterward with general body measures. RESULTS: The corrected mean (SD) IPP measured in the supine position was 4.4 (4.5) cm H2O, and the mean (SD) upright IPP was 1.6 (7.8) cm H2O (p = 0.02). A positive correlation was found between the body mass index (BMI) and the IPP in the upright (r = 0.51) and supine (r = 0.65) body positions, and between the abdominal circumference and the IPP in the supine position (r = 0.63). CONCLUSIONS: The intrinsic IPP in mobile subjects exceeds the intraperitoneal hydrostatic pressure. Thus, the intrinsic IPP counteracts the diversion of CSF into the peritoneal compartment. The intrinsic IPP is correlated with mobile patients' general body measures.

The Peritoneum: Health, Disease, and Perspectives regarding Tissue Engineering and Cell Therapies.

There are several pathologies associated with the peritoneum, such as mesothelioma and peritonitis. Moreover, the peritoneum is widely used in ultrafiltration procedures, i.e., peritoneal dialysis, presenting advantages over hemodialysis. On the other hand, ultrafiltration failure may lead to dialysis-induced fibrosis and hypervolemia. Therefore, the pathophysiological study of this tissue is of extreme biomedical importance. Studies investigating the biology of the cells dwelling in the peritoneum wall provide evidence of their plasticity and progenitor features. For instance, both mesothelial and submesothelial cells present characteristics similar to mesenchymal stem cells, including osteogenic and adipogenic differentiation potential, support of extramedullary hematopoiesis, modulation of inflammatory responses, and regulation of tumor progression. Indeed, the participation of each cell type in peritoneal pathological and physiological phenomena is still under debate, especially regarding a possible differentiation pathway connecting these peritoneal cells. The primary aim of this review is to raise this discussion. In order to do so, we will firstly provide an overview of the peritoneum anatomy, histology, and ontology, and finally we will address how a better understanding of peritoneal cell biology may contribute to future cell therapy and tissue engineering approaches.

The peritoneum: healing, immunity, and diseases.

The peritoneum defines a confined microenvironment, which is stable under normal conditions, but is exposed to the damaging effect of infections, surgical injuries, and other neoplastic and non-neoplastic events. Its response to damage includes the recruitment, proliferation, and activation of a variety of haematopoietic and stromal cells. In physiological conditions, effective responses to injuries are organized; inflammatory triggers are eliminated; inflammation quickly abates; and the normal tissue architecture is restored. However, if inflammatory triggers are not cleared, fibrosis or scarring occurs and impaired tissue function ultimately leads to organ failure. Autoimmune serositis is characterized by the persistence of self-antigens and a relapsing clinical pattern. Peritoneal carcinomatosis and endometriosis are characterized by the persistence of cancer cells or ectopic endometrial cells in the peritoneal cavity. Some of the molecular signals orchestrating the recruitment of inflammatory cells in the peritoneum have been identified in the last few years. Alternative activation of peritoneal macrophages was shown to guide angiogenesis and fibrosis, and could represent a novel target for molecular intervention. This review summarizes current knowledge of the alterations to the immune response in the peritoneal environment, highlighting the ambiguous role played by persistently activated reparative macrophages in the pathogenesis of common human diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Impact of Diabetes on Extracellular Volume Status in Patients Initiating Peritoneal Dialysis.

BACKGROUND: Recent reports have highlighted that diabetic patients with kidney failure are at increased risk of technique failure and transfer to haemodialysis within 90 days of initiating peritoneal dialysis (PD). We wished to determine whether there were differences between diabetic and non-diabetic patients within the first 3 months of starting PD. METHODS: We reviewed results of corresponding bioimpedance and the 1st test of peritoneal membrane function (PET) in consecutive patients, 6-10 weeks after initiating PD electively. RESULTS: Adult patients numbering 386 - 230 males (59.6%), 152 (39.4%) diabetic, 188 (48.7%) white, mean age 57.3 ±16.9 years - were studied. Although weight, residual renal function and peritoneal clearances were not different, diabetic patients had greater extracellular water to total body water (ECW/TBW; 40.4 ± 1.1 vs. 39.2 ± 1.4) and % ECW excess (9.6 [6.3-12.3] vs. 4.9 [0.7-8.9]), lower serum albumin (35.2 ± 4.7 vs. 37.8 ± 4.9 g/L), greater fat mass index (9.5 ± 4.2 vs. 7.7 ± 4.2), and although mean arterial blood pressure was similar, arterial pulse pressure was greater (66.9 ± 10.8 vs. 54.3 ± 17.3 mm Hg, all p < 0.001). On multivariate analysis, glycated haemoglobin was associated with pulse pressure (standardised ß 0.24, p < 0.001), N terminal brain natriuretic peptide (ß 0.24, p < 0.001), ECW/TBW (ß 0.19, p = 0.012) and negatively with serum albumin (ß -0.14, p = 0.033) and creatinine (ß -0.18, p = 0.02). CONCLUSION: Diabetic patients electively starting PD were found to have greater ECW/TBW ratios and ECW excess 6-10 weeks after starting PD compared to non-diabetics, despite similar PET. Increased ECW could predispose diabetic patients to be at greater risk of volume overload.

Contribution of leukocytes to the induction and resolution of the acute inflammatory response in chickens.

A successful immune response against invading pathogens relies on the efficient activation of host defense mechanisms and a timely return to immune homeostasis. Despite their importance, these mechanisms remain ill-defined in most animal groups. This study focuses on the acute inflammatory response of chickens, important both as an avian model with a unique position in evolution as well as an increasingly notable target of infectious zoonotic diseases. We took advantage of an in vivo self-resolving intra-abdominal challenge model to provide an integrative view of leukocyte responses during the induction and resolution phases of acute inflammation. Our results showed rapid leukocyte infiltration into the abdominal cavity post zymosan challenge (significant increase as early as 4 h), which was dominated by heterophils. Peak leukocyte infiltration and ROS production reached maximum levels at 12 h post challenge, which was significantly earlier than comparative studies in teleost fish and mice. Both heterophils and monocyte/macrophages contributed to ROS production. Local leukocyte infiltration was preceded by an increase in peripheral leukocytes and a drop in the number of bone marrow leukocytes. The proportion of apoptotic leukocytes increased following peak of acute inflammation, rising to significant levels within the abdominal cavity by 48 h, consistent with other indicators for the resolution of inflammation. Importantly, comparison of chicken phagocytic responses with those previously shown in agnathan, teleost and murine models suggested a progressive evolutionary shift towards an increased sensitivity to pro-inflammatory pathogen-derived particles and decreased sensitivity towards homeostatic stimuli. Thus, while significant conservation can be noted across the immune systems of endotherms, this study highlights additional unique features that govern the induction and resolution of acute inflammation in the avian system, which may be relevant to disease susceptibility and performance.

Regeneration of peritoneal mesothelial cells after placement of hyaluronate carboxymethyl-cellulose (Seprafilm®).

PURPOSE: To examine the regeneration of mesothelium under a bioresorbable membrane. METHODS: A 1 cm2 piece of peritoneum was resected from both sides of the abdominal wall of retired female mice. A piece of hyaluronate and carboxymethyl-cellulose (Seprafilm®) was placed over the wound on one side and the other side was left uncovered. We evaluated the degree of adhesion and regeneration of mesothelial cells macroscopically and histologically using immunohistochemistry at different times. RESULTS: Macroscopically, the degree of postoperative adhesion in the treated site was significantly less than that in the untreated site. The membrane was left in place for 7 postoperative days (PODs). By POD 5, the regenerated peritoneum mesothelial cells covered part of the area and by POD 7, they had regenerated over almost all of that area in the abdominal wall. CONCLUSION: The anti-adhesion membrane worked as a physical barrier to prevent postoperative adhesion until the mesothelial cells had regenerated completely. To our knowledge, this is the first study conducted to assess the regeneration of peritoneum mesothelial cells under a bioresorbable membrane using immunohistochemistry.

Hydrocortisone and dexamethasone dose-dependently stabilize mast cells derived from rat peritoneum.

BACKGROUND: Besides their anti-inflammatory properties, corticosteroid drugs exert anti-allergic effects. Exocytosis of mast cells is electrophysiologically detected as the increase in the whole-cell membrane capacitance (Cm). Therefore, the lack of such increase after exposure to the drugs suggests their mast cell-stabilizing effects. METHODS: We examined the effects of 1, 10, 100 and 200µM hydrocortisone or dexamethasone on the degranulation from rat peritoneal mast cells. Employing the whole-cell patch-clamp recording technique, we also tested their effects on the Cm during exocytosis. RESULTS: At relatively lower concentrations (1, 10µM), both hydrocortisone and dexamethasone did not significantly affect the degranulation from mast cells and the increase in the Cm induced by GTP-γ-S. Nevertheless, at higher doses (100, 200µM), these drugs inhibited the degranulation from mast cells and markedly suppressed the GTP-γ-S-induced increase in the Cm. CONCLUSIONS: Our results provided electrophysiological evidence for the first time that corticosteroid drugs, such as hydrocortisone and dexamethasone, inhibited the exocytotic process of mast cells in a dose-dependent manner. The mast cell-stabilizing effects of these drugs may be attributable to their "non-genomic" action, by which they exert rapid anti-allergic effects.

The Current State of Peritoneal Dialysis.

Technical innovations in peritoneal dialysis (PD), now used widely for the long-term treatment of ESRD, have significantly reduced therapy-related complications, allowing patients to be maintained on PD for longer periods. Indeed, the survival rate for patients treated with PD is now equivalent to that with in-center hemodialysis. In parallel, changes in public policy have spurred an unprecedented expansion in the use of PD in many parts of the world. Meanwhile, our improved understanding of the molecular mechanisms involved in solute and water transport across the peritoneum and of the pathobiology of structural and functional changes in the peritoneum with long-term PD has provided new targets for improving efficiency and for intervention. As with hemodialysis, almost half of all deaths on PD occur because of cardiovascular events, and there is great interest in identifying modality-specific factors contributing to these events. Notably, tremendous progress has been made in developing interventions that substantially reduce the risk of PD-related peritonitis. Yet the gains have been unequal among individual centers, primarily because of unequal clinical application of knowledge gained from research. The work to date has further highlighted the areas in need of innovation as we continue to strive to improve the health and outcomes of patients treated with PD.

Rapid reperitonealization and wound healing in a preclinical model of abdominal trauma repair with a composite mesh.

PURPOSE: Peritoneal tissue healing is characterized by the simultaneous repopulation of mesothelial cells and the formation of neoperitoneum. Despite the common use of mesh products for abdominal wall repair, there are few investigations of how these materials may impact the peritoneal healing process. Here, we utilized an animal model of abdominal trauma to specifically investigate the peritoneal healing process in conjunction with a composite (poliglecaprone 25-coated polypropylene) mesh. METHODS: Abdominal wall injury was simulated in New Zealand White rabbits and peritoneal tissue was covered with composite mesh and fixed with peripheral sutures. Animals were sacrificed at regular intervals (up to 28 days) for macroscopic and microscopic evaluation. RESULTS: Mesothelial cells were consistently identified on the surface of the central areas of the implanted mesh as early as 3-5 days after implantation. From day 7 onward, the entire mesh surface was covered by neoperitoneum which matured over the remaining study intervals. Fibroblast ingrowth of the mesh was apparent by day 5 and increased over time, concurrent with fragmentation of the film on the composite mesh. CONCLUSIONS: These results suggest that composite mesh products used for abdominal wall repair do not significantly delay mesothelial repopulation. Study results also support the hypothesis that mesothelial cells involved in healing are derived, at least in part in this model, from free-floating precursor cells located within the peritoneal cavity.