Electrophysiology and Glucose Transport of Human Peritoneal Mesothelial Cells: Implications for Peritoneal Dialysis (original) (raw)

Transperitoneal Transport of Glucose In Vitro

Artificial Organs, 2000

The effect of fluid mixing intensification, damage of mesothelial cells, gentamicin, and icodextrin on the diffusive glucose transport across the peritoneal membrane were evaluated in in vitro studies. A mathematical model of mass transport was used to calculate the diffusive permeability, expressed as a diffusive permeability coefficient (P). In the control conditions, the rate of glucose transfer from the interstitial to the mesothelial side of membrane (I→M) and in the opposite direction (M→I) remained constant, and the P value at mean was 2,731 ± 1,493 × 10 −4 (cm × s −1). The change of the stirring rate from 5.5 to 11 ml/min increased P values by about 74% for transport direction I→M and 58% for M→I, and the change from 11 to 22 ml/min enhanced P at mean by about 42% for both directions. The damage of the mesothelial layer, using sodium deoxycholate (2.5 mmol/L; 103.6 mg%), increased the glucose transfer from the interstitial

Peritoneal Transport of Glucose in Rat

Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, 1999

Objective To evaluate the convective transport characteristics of glucose and the effect of high glucose and insulin during experimental peritoneal dialysis in rat. Methods Male Sprague–Dawley rats weighing 300 – 400 g were used in this study. Mannitol (5%) was used as osmotic agent. Glucose was added to dialysis solution to yield a concentration of 100 mg/dL (group 1) or 300 mg/dL (group 2). Mannitol solution (5%) containing the same concentration of electrolytes and lactate but without glucose was used as control (group 3). In group 2, blood sugar was maintained at approximately 300 mg/dL by continuous intravenous infusion of 25% glucose solution and 0.9% NaCl solution. A 2-hour dwell study was performed with 30 mL of test solutions. Intraperitoneal volume was calculated by volume marker (18.5 kBq of 131I-human radioiodinated serum albumin, RISA) dilution with corrections made for the elimination of RISA from the peritoneal cavity (KE) and sample volume. The diffusive mass transpo...

Effect of pH and Glucose on Cultured Human Peritoneal Mesothelial Cells

Scandinavian Journal of Urology and Nephrology, 1999

We investigated the effects of various pH and glucose concentrations on the growth of human peritoneal mesothelial cells and on coagulation and fibrinolytic factors. Materials and methods: Cells were cultured at various pH values in Ham's F-12 medium containing 1.0% foetal calf serum and supplemented with D-glucose or D-mannitol at various concentrations. After 4-48 h, cell proliferation and 3 H-thymidine incorporation were determined. Coagulation and fibrinolytic factors were measured after 48 h. Results: Glucose caused concentration-dependent inhibition of cell growth at all pH values, but the deleterious effect of low pH on cell proliferation was faster and stronger than that of high glucose. At a similar osmolality, mannitol caused less inhibition of cell proliferation than glucose. There was a glucose concentration-dependent increase of thrombin-antithrombin III complex production at all pH values. At pH 5.2, tissue-type plasminogen activator production was far lower than at higher pH values, and production of the plasminogen activator inhibitor showed a glucose concentration-dependent increase. At pH 6.5 or 7.3, however, the plasminogen activator inhibitor production decreased and tissue-type plasminogen activator production increased in a glucose concentration-dependent manner. Conclusions: Low pH and/or high glucose culture medium had an inhibitory effect on peritoneal mesothelial cells, with the effect of high glucose being partially related to hyperosmolality. These cells may modulate peritoneal coagulant and fibrinolytic activity, with the balance between coagulation and fibrinolysis being disturbed by low pH and/or high glucose.

Permselectivity of the peritoneal membrane

Microvascular Research, 1985

To investigate the osmotic barrier characteristics of the peritoneal membrane during conditions similar to peritoneal dialysis in man, net transperitoneal fluid movement was measured in 20 cats following intraabdominal placement of isotonic saline and hypertonic solutions of NaCl, glucose, raffinose, and inulin. Also, isooncotic solutions of hemoglobin and albumin and two sulfated high-molecular-weight dextrans were investigated. Transperitoneal fluid movement was measured by a volume recovery method. Oncotic pressures of test solutions and plasma were measured by osmometry. Peritoneal osmotic conductances were calculated from the rate of transperitoneal water movement and the difference in osmotic pressures between the test solution and isotonic saline. The average glucose osmotic conductance per unit body surface area was found to be 2.3 2 0.18 x 10m3 ml mini' mm Hg-' m-2, m good agreement with previous reports, and the glucose osmotic reflection coefficient (o) was estimated to be 0.02. All the osmotic conductances measured could be fitted to a peritoneal equivalent pore radius of approximately 6 nm according to current hydrodynamic theories. The peritoneal membrane filtration coefficient was estimated to be 0.12 ml. min-'. mm Hg-' mm*, of which OS-l% was found to be due to transcellular water flow. In conclusion the results of this study indicate that the peritoneum is a highly selective membrane with restrictive properties comparable to those reported for continuous capillary beds.

Electrolyte and Fluid Transport in Mesothelial Cells

Journal of Epithelial Biology & Pharmacology, 2008

Mesothelial cells are specialized epithelial cells, which line the pleural, pericardial, and peritoneal cavities. Accumulating evidence suggests that the monolayer of mesothelial cells is permeable to electrolyte and fluid, and thereby govern both fluid secretion and re-absorption in the serosal cavities. Disorders in these salt and fluid transport systems may be fundamental in the pathogenesis of pleural effusion, pericardial effusion, and ascites. In this review, we discuss the location, physiological function, and regulation of active transport (Na + -K + -ATPase) systems, cation and anion channels (Na + , K + , Cl − , and Ca 2+ channels), antiport (exchangers) systems, and symport (co-transporters) systems, and water channels (aquaporins). These secretive and absorptive pathways across mesothelial monolayer cells for electrolytes and fluid may provide pivotal therapeutical targets for novel clinical intervention in edematous diseases of serous cavities.

Measuring transport of water across the peritoneal membrane

Kidney International, 2003

Measuring transport of water across the peritoneal membrane. Introduction. Mechanisms of water flow across the peritoneal membrane include diffusion, convection, and reabsorption. Objectves. To understand these processes more clearly we have developed a method to measure transport of water across the peritoneal membrane. Methods. An artificial gradient of deuterated water (HDO) between blood and dialysate compartments was created in five subjects who took 0.3g per kg of body weight of D 2 O, which was allowed to equilibrate with total body water. During a test dwell (2 L, bicarbonate:lactate buffer, 1.36% glucose to minimize convection), frequent dialysate samples were drawn to determine the abundance of deuterium and other solutes and to calculate their time constants. Dialysate deuterium abundance was measured using flowing afterglow mass spectrometry (FA-MS). The method was combined with 125 iodinelabeled albumin (RISA) to enable simultaneous estimates of intraperitoneal volume and thus calculation of the mass transfer area coefficient (MTAC) for small solutes using the Garred equation. Results. The appearance of HDO in dialysate in four subjects is described by a single exponential fit with residuals of Ͻ1%, similar to method precision. In a fifth subject, the resolution of this method demonstrated that the best fit was a double exponential. When compared to other solutes, the time constant for water was as predicted by its molecular weight, with a MTAC of 38.7 Ϯ 4.4 mL/min. Total body water could also be estimated from the equilibrated dialysate deuterium abundance, with repeat estimates within 0.5%. Conclusion. Transport of water across the peritoneum can be measured with remarkable accuracy and when combined with an intraperitoneal volume estimation can be used to determine mass transfer. In conditions of low convection, the relative rate of deuterium appearance and mass transfer compared to other solutes suggests that water diffuses predominantly through the intercellular small pores. Variability in membrane function is the only intrinsic aspect of peritoneal dialysis treatment that has been

Characterization of epithelial-to-mesenchymal transition of mesothelial cells in a mouse model of chronic peritoneal exposure to high glucose dialysate

Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis, 2008

Animal models of peritoneal dialysis fluid (PDF) exposure are key tools in the study of mechanisms involved in alterations of the peritoneal membrane and in the design of therapies. We recently developed a mouse model of chronic peritoneal exposure to high glucose dialysate. Herein, we make a sequential analysis of the effects of glucose-based PDF on mouse peritoneal membrane and on mesothelium. We demonstrate that chronic exposure to PDF induces thickness and fibrosis of the peritoneal membrane in a time-dependent manner. We also show that mesothelial cells progressively detach and lose cytokeratin expression. In addition, we demonstrate that some mesothelial cells invade the submesothelial space, where they appear as cytokeratin- and alpha-smooth muscle actin-positive cells. These findings demonstrate that epithelial-to-mesenchymal transition (EMT) of mesothelial cells takes place in mouse peritoneum exposed to PDF, validating this model for the study of effects of drugs on the EM...