Decreased leukocyte recruitment in the mesenteric microcirculation of rats with cirrhosis is partially restored by treatment with peginterferon: an in vivo study.

Background/aims: Patients with liver cirrhosis are predisposed to develop bacterial infections. An essential process in inflammatory responses is the recruitment of circulating leukocytes through the activation of adhesion molecules. Interferon-alpha2a is a cytokine reported to influence the expression of adhesion molecules.

Increased angiogenesis and permeability in the mesenteric microvasculature of rats with cirrhosis and portal hypertension: an in vivo study.

Background: In vivo evidence for angiogenesis in the splanchnic vasodilation in portal hypertension (PHT) and cirrhosis is lacking. Vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) are mediators of angiogenesis. The present study visualises in vivo structural changes (angiogenesis and vascular hyperpermeability) and examines the presence of VEGF and eNOS in the mesenteric microvasculature of animal models of PHT with and without cirrhosis.

Myofibroblast transdifferentiation of mesothelial cells is mediated by RAGE and contributes to peritoneal fibrosis in uraemia.

Background: Uraemia is associated with fibrosis of the peritoneal membrane, even prior to the start of peritoneal dialysis. Increased carbonyl stress and the resultant formation of advanced glycation end-products (AGEs) are potentially involved. The interaction of AGEs with their cell surface receptor for AGE (RAGE) induces sustained cellular activation, including the production of the fibrogenic growth factor-beta (TGF-beta).

What did we learn from animal models in peritoneal dialysis?

The development of animal models in peritoneal dialysis has led to some breakthroughs in the application of this dialysis modality in clinical practice. These breakthroughs are (1) a better understanding of the physiology and pathophysiology of solute transport and ultrafiltration mechanisms, (2) the observation and integration of the long-term structural and functional alterations of the membrane, (3) a better understanding of the biocompatibility issues involved in PD, leading to the clinical introduction of more biocompatible dialysis solutions and finally, (4) the development of colloid osmotic solutions containing polyglucose polymers for application in the long dwells. Intravital miscroscopy provides information in live animals about diverse functional parameters, such as blood flow rate, vessel diameter, permeability to macromolecules, leukocyte-endothelium interaction, capillary recruitment, and lymph vessel kinetics.

Effects of new peritoneal dialysis solutions on leukocyte recruitment in the rat peritoneal membrane.

Objectives: Peritonitis remains a principal cause of dropout in peritoneal dialysis (PD). The physiological host response to a peritoneal infection involves a rise in numbers of circulating leukocytes to the peritoneal cavity. We evaluated the effects of (1) conventional peritoneal dialysis fluid (PDF), (2) bicarbonate-based PDF, low in glucose degradation products, and (3) non-glucose PDF on peritoneal leukocyte recruitment in response to an inflammatory stimulus using intravital microscopy.

Benefits of switching from a conventional to a low-GDP bicarbonate/lactate-buffered dialysis solution in a rat model.

Background: Long-term exposure to standard peritoneal dialysis fluid (PDF) results in alterations in peritoneal morphology and function. Studies investigating the long-term effects on the peritoneum of a low-glucose degradation product (GDP) bicarbonate/lactate-buffered PDF demonstrated its superior biocompatibility. We examined the potential of the low-GDP bicarbonate/lactate-buffered solution to reverse or reduce standard PDF-induced peritoneal alterations.

Animal models in peritoneal dialysis research: a need for consensus.

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.

Long-term exposure to new peritoneal dialysis solutions: Effects on the peritoneal membrane.

Background: Chronic exposure to peritoneal dialysis fluid (PDF) affects the peritoneum, but precise causative factors are incompletely understood. We examined the effects of standard and new PDF on peritoneal function and structure.

Methods: Female Wistar rats received twice daily intraperitoneal infusions of a standard lactate-buffered 3.

The effects of peritoneal dialysis solutions on peritoneal host defense.

Conventional peritoneal dialysis fluid (PDF) is a bioincompatible solution owing to the acidic pH, the high glucose concentrations and the associated hyperosmolarity, the high lactate concentrations, and the presence of glucose degradation products (GDPs). This unphysiologic composition adversely affects peritoneal host defense and may thus contribute to the development of PD-related peritonitis. The viability of polymorphonuclear leukocytes, monocytes, peritoneal macrophages, and mesothelial cells is severely depressed in the presence of conventional PDF.

Endothelium-derived hyperpolarizing factor-mediated renal vasodilatory response is impaired during acute and chronic hyperhomocysteinemia.

Background: Endothelial dysfunction is an early event in the development of vascular complications in hyperhomocysteinemia. Endothelial cells release a number of vasodilators, including NO and prostacyclin. Several lines of evidence have indicated the existence of a third vasodilator pathway, mediated by endothelium-derived hyperpolarizing factor (EDHF).

Antibiotic administration in an animal model of chronic peritoneal dialysate exposure.

Objectives: The high incidence of intraperitoneal infection remains an important problem in animal models of chronic dialysate exposure. Prophylactic antibiotic administration can be used to resolve this problem, but the isolated effects of antibiotics on peritoneal membrane function and structure are unknown. The present study examined the effects of prophylactic antibiotics on infection rate and peritoneal membrane function and structure in a rat model of chronic dialysate exposure.

Inhibition of the interaction of AGE-RAGE prevents hyperglycemia-induced fibrosis of the peritoneal membrane.

The peritoneal membrane of long-term peritoneal dialysis patients is characterized by a loss of ultrafiltration capacity, associated morphologically with submesothelial fibrosis and neoangiogenesis. Exposure to high glucose concentrations in peritoneal dialysate and the resultant advanced glycation end-products (AGE) accumulation have been implicated in the development of these changes, but their exact pathophysiological role is unknown. We examined the effect of the interaction of AGE with one of their receptors (i.

Effects of conventional and new peritoneal dialysis fluids on leukocyte recruitment in the rat peritoneal membrane.

Peritonitis remains an important cause of morbidity and technique failure in peritoneal dialysis (PD). Conventional peritoneal dialysate fluids (PDF) inhibit peritoneal leukocyte function in vitro and may thus adversely affect the immune response to peritonitis. New PDF have been designed with neutral pH, low glucose degradation product (GDP) contents, and bicarbonate as buffer.

Recent concepts in the molecular biology of the peritoneal membrane - implications for more biocompatible dialysis solutions.

This paper reviews some important recent findings on the molecular biology of the peritoneal membrane. It attempts to correlate in vitro and in vivo experimental results with the possible clinical consequences. The most common functional alteration during long-term CAPD is increased peritoneal small-solute transport rate, resulting in impaired ultrafiltration and decreased dialysis efficiency.

The effects of heparin administration in an animal model of chronic peritoneal dialysate exposure.

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.

Hemodynamic effects of peritoneal dialysis solutions on the rat peritoneal membrane: role of acidity, buffer choice, glucose concentration, and glucose degradation products.

Conventional peritoneal dialysis fluids (PDF) are unphysiologic because of their hypertonicity, high glucose and lactate concentrations, acidic pH, and presence of glucose degradation products (GDP). Long-term exposure to conventional PDF may cause functional and structural alterations of the peritoneal membrane. New PDF have a neutral pH, a low GDP content, and contain bicarbonate or lactate as the buffer.