A new non-uremic rat model of long-term peritoneal dialysis

Together with the development of peritoneal dialysis (PD), appropriate animal models play an important role in the investigation of physiological, pathophysiological and clinical aspects of PD. However, there is still not an ideal experimental PD animal model. In this study, 45 Sprague-Dawley rats were divided into three groups. Group 1 (n=15) was receiving daily peritoneal injection through the catheter connected to the abdominal cavity, using PD solution containing 3.86 % D-glucose. Group 2 (n=15) was receiving daily peritoneal injection of 0.9 % physiological saline through a catheter. Group 3 (n=15), which was subjected to sham operation, served as controls. Our results showed that WBC counts in peritoneal effluent of Group 1 were slightly higher than those of Group 2 and control group, respectively (p<0.05). However, there was no episode of infection in any group. In addition, there was no significant difference in neutrophils fractions among these three groups. Hematoxylin-eosin and Masson's trichrome staining demonstrated a dramatic increase in thickness of the mesothelium-to-muscle layer of peritoneum exposed to high glucose (Group 1) compared to Group 2 and controls (p<0.01). These data indicated that we established a novel rat model of PD with a modified catheter insertion method. This model is more practical, easy to operate, not too expensive and it will facilitate the investigate of long-term effects of PD.     

Continuous ambulatory peritoneal dialysis: no longer experimental.

Many patients with end-stage renal disease have now been maintained for 5 years or more with continuous ambulatory peritoneal dialysis (CAPD). Viewed initially as an experimental alternative to be used only when hemodialysis was not feasible, CAPD is now seen as the treatment of choice in an increasing number of situations. CAPD is suitable for self-care. The main concern in the early years--peritonitis--is now less frightening and less frequent (one episode occurring every 18 patient-months as compared with every 8 initially), and this has allowed chronic complications of CAPD, such as malnutrition and loss of the peritoneum''s capacity for ultrafiltration, to come to light. As would be expected, among patients of advanced age and those who have heart disease or diabetes, survival rates tend to be lower than among other CAPD patients. However, hypertension seems to be more easily controlled, pre-existing anemia can be significantly ameliorated, and young children grow more normally than they do with hemodialysis. Diabetes-related changes in vision stabilize in most CAPD patients, and control of the blood glucose level is good; insulin is administered intraperitoneally. CAPD is thus showing itself to be a feasible form of long-term treatment for end-stage renal disease.     

Bactericidal activity of human peritoneal macrophages from patients undergoing peritoneal dialysis

Peritoneal macrophages (PM) play an essential role in the pathogenesis of bacterial peritonitis, the main complication of peritoneal dialysis (PD). We determined the antibacterial activity of PM from 31 PD patients using gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and gram-negative (Escherichia coli, Pseudomonas aeruginosa) test organisms. In an 8-hour test assay, PM revealed the highest antibacterial activity against E. coli [median bactericidal index (Bi) = 5.46 representing 0.74 log growth inhibition compared to controls] and the lowest against P. aeruginosa (Bi = 1.63, 0.21 log growth inhibition, p less than 0.05). The antibacterial activity against S. aureus (Bi = 1.99, 0.3 log growth inhibition) and S. epidermidis (Bi = 2.0, 0.31 log growth inhibition) was within this range. When compared to peripheral blood polymorphonuclear leukocytes, PM reached only 4% (S. aureus) and 8.1% (E. coli) of their antibacterial activity (p less than 0.05). Using E. coli as a test organism, PM isolated after a 4-hour dialysis period revealed the highest antibacterial activity when compared to PM isolated after longer dialysis periods (p less than 0.05). Increasing the duration of PD to 6 and 8 h subsequently decreased the antibacterial activity of PM, suggesting that unphysiologic concentrations of toxic metabolites in the peritoneal effluent might have a harmful influence on PM functions.     

Curvularia lunata peritonitis complicating peritoneal dialysis

A case of peritonitis due toCurvularia lunata during continuous ambulatory peritoneal dialysis is reported. Diagnosis was established by culture of dialysis effluent and peritoneal exudate, and was also confirmed through histological examination.     

Cytology of peritoneal fluid from patients on continuous ambulatory peritoneal dialysis

Peritoneal fluids from 41 patients on continuous ambulatory peritoneal dialysis (CAPD) were examined. The patients were divided into a short-term group (18 patients with CAPD up to one year) and a long-term group (23 patients with CAPD for one to seven years). Peritoneal fluids from a control group, consisting of ten nondialysis patients with ascites, were also examined. The cellular background of the peritoneal fluids and, in particular, the morphology of the mesothelial cells were studied. The following were found to be significantly increased in the CAPD groups: background lymphocytes, mesothelial exfoliation in three-dimensional clusters, mesothelial nuclear size and the number of mesothelial nucleoli. All of these features increased slightly with an increased duration of the dialysis. These findings emphasize that peritoneal dialysis of any duration can induce significantly atypical changes in mesothelial cells.     

Lavage fluid from continuous ambulatory peritoneal dialysis. A model for mesothelial cell changes

Continuous ambulatory peritoneal dialysis (CAPD) lavage can be interpreted as an artificial short-term ascites. The cellular content of 362 CAPD specimens from 32 patients was investigated. Irregular inflammatory reactions were seen in 85.3% of the specimens and eosinophilia in 27.6%. Mesothelial aggregates of great variability were registered in 59.4% of the specimens and mainly atypical mitoses in 7.5%. The cytologic changes seen in those patients from whom lavage fluids were examined over 10 to 12 months did not correlate with the changes in blood chemistry (BUN and creatinine) in those cases.     

Proteomic analysis in peritoneal dialysis patients with different peritoneal transport characteristics

Peritoneal membranes can be categorized as high, high average, low average, and low transporters, based on the removal or transport rate of solutes. In this study, we used proteomic analysis to determine the differences in proteins removed by different types of peritoneal membranes. Peritoneal transport characteristics in patients who received peritoneal dialysis therapy were assessed by a peritoneal equilibration test. Two-dimensional differential gel electrophoresis technology followed by quantitative analysis was performed to study the variation in protein expression from peritoneal dialysis effluents (PDE) among different groups. Proteins were identified by MALDI-TOF-MS/MS analyses. Further validation in PDE or serum was performed utilizing ELISA analysis. Proteomics analysis revealed ten protein spots with significant differences in intensity levels among different groups, including vitamin D-binding protein, complement C3, apolipoprotein-A1, complement factor C4A, haptoglobin, alpha-1 antitrypsin, immunoglobulin kappa light chain, alpha-2-microglobulin, retinol-binding protein 4 and transthyretin. The levels of vitamin D-binding protein, complement C3, and apolipoprotein-A1 in PDE derived from different groups were greatly varied (P < 0.05). However, no significant difference was found in the serum levels of these proteins among different groups (P > 0.05 for all groups). This study provides a novel overview of the differences in PDE proteomes of four types of peritoneal membranes. Vitamin D-binding protein, complement C3, and apolipoprotein-A1 showed enhanced expression in PDE of patients with high transporter.     

An experimental model of pulmonary aspergillosis

The model of experimental chronic pulmonary aspergillosis has been obtained in mice and guinea pigs by the intrapulmonary infection of the animals with the suspension of Aspergillus mycelium and spores in complete Freund's adjuvant. Such method of infection has made it possible to produce chronic local mycotic process. Morphologically, focal inflammatory changes of the lung tissue with the subsequent formation of a multitude of small abscesses in these areas have been observed as characteristic manifestations of aspergillosis.     

An experimental model of tardive dyskinesias

Rats treated continually and chronically with trifluoperazine (ca 3 mg/kg/day) for six months initially developed mild catalepsy and an inhibition of spontaneous locomotor activity; both effects disappeared by three months. An initial increase in dopamine turnover (as measured by levels of homovanillic acid and dihydroxyphenylacetic acid) also disappeared by three months. Apomorphine-induced stereotypy was completely inhibited in drug-treated animals at two weeks, but progressively returned to normal after three months of drug intake. An exaggerated response to apomorphine developed in animals after six months of drug administration. Inhibition of striatal dopamine-stimulated adenylate cyclase found during the first month of drug intake was reversed at three months, a trend exaggerated after continuous drug administration for six months. Specific striatal ³H-spiperone binding affinity decreased acutely, but was increased after six months drug intake; no change in number of receptor sites occurred.These changes suggest that at least striatal dopamine receptors may become “supersensitive” during chronic neuroleptic treatment.     

An experimental model of DIC syndrome

Disseminated intravascular coagulation syndrome (DIC-syndrome) is experimentally reproduced by introduction of 30% aqueous solution "Desoxon-3" (2800-300 mg/kg) into the organism of laboratory animals (rabbits). The preparation was perorally introduced once on an empty stomach for 1 min. Biochemical and pathomorphological studies testify to the development of the typical DIC-syndrome in rabbits. It is concluded that the model suggested makes it possible to thoroughly study genesis, course, consequences of the development and preventive measures of disseminated intravascular blood coagulation, a complex pathological process.