The fibrinolytic capacity of the peritoneum plays a pivotal role in peritoneal wound healing. During surgery the balance between fibrin deposition and degradation is tilted towards deposition, leading to the formation of adhesions. In blood, carboxypeptidase U (CPU) stabilizes clots by retarding fibrinolysis. The purpose of this study was to investigate whether the more stable zymogen, proCPU, is also present in the peritoneal cavity and, if so, to examine its origin. Levels of proCPU were measured in plasma and serosal peritoneal fluid collected during surgery. Peritoneal biopsies were stained for proCPU. Two‐dimensional gel electrophoresis was performed to study the protein composition of the serosal fluid compared to plasma and Western blotting to identify differences in glycosylation of proCPU, indicating possible different cellular origin. Cultured human mesothelial cells were examined for proCPU production under normal conditions and conditions mimicking surgery. We found comparable and correlating levels of proCPU in serosal fluid and plasma. ProCPU was also found where fibrin covered the injured peritoneal surface. A protein composition very similar in serosal fluid and plasma was shown by two‐dimensional gel electrophoresis, and the proCPU pattern did not indicate a different origin. No proCPU production was found in cultured mesothelial cells. This is the first study to report on the presence of proCPU in the peritoneal cavity, which seems to be the result of plasma oozing out during the inflammatory reaction to the surgical trauma. This is likely to be important for the balance between fibrin deposition and degradation and thereby in the formation of postoperative adhesions.
HYPOTHESIS:Sodium hyaluronate interferes with the fibrin degrading capacity of human peritoneal mesothelial cells exposed to tumor necrosis factor (TNF) alpha.DESIGN:Controlled laboratory experiment.INTERVENTION:Human peritoneal mesothelial cells were harvested from 5 patients undergoing laparotomy and cultured in vitro. Cells were treated with TNF-alpha, a cytokine typically involved in peritoneal inflammation, and sodium hyaluronate was added in a final concentration of 0.1%, 0.2%, or 0.4%. Controls received medium only. After 24 hours' incubation, tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and plasminogen activator inhibitor type 1 (PAI-1) were measured in the medium and cell lysates using enzyme-linked immunosorbent assay techniques. Specific gene transcripts in cells treated with 0.4% sodium hyaluronate and controls were determined using a quantitative reverse transcription polymerase chain reaction.MAIN OUTCOME MEASURES:Concentrations of tPA, uPA, and PAI-1, and their specific gene transcripts.RESULTS:Sodium hyaluronate significantly increased tPA concentration in cell lysates without affecting its gene expression as determined after 24 hours (P =.02). The uPA concentration was significantly decreased by sodium hyaluronate in the medium but not in cell lysates (P<.0001). The uPA messenger RNA expression was 1000-fold increased compared with control. Sodium hyaluronate significantly decreased PAI-1 concentration in the medium and reduced its gene expression 500-fold (P =.04), while PAI-1 concentration in cell lysates did not change.CONCLUSION:Sodium hyaluronate affected the fibrinolytic response of TNF-alpha-stimulated human peritoneal mesothelial cells, most notably by decreasing PAI-1 transcription and release. This observation indicates that sodium hyaluronate counteracts the fibrinolytic decline induced by TNF-alpha and suggests a biological mechanism of action for sodium hyaluronate intra-abdominally.
In 1993-94 a nutritional survey of 15-year-old adolescents was carried out in Uppsala, a university city in eastern Sweden, and in Trollhättan, an industrial town in the western part of the country. The study was the beginning of a longitudinal nutritional survey of 193 boys and 218 girls randomly selected from the official population register. The dietary methods used were a food frequency questionnaire (FFQ) and a combined estimated and weighed 7-day dietary record. According to the FFQ both boys and girls consumed cereals, butter or margarine and something from the group meat/fish/eggs every day. Milk, milk products, sweets and snacks were consumed more than once per day. Vegetables and fruit/roots were consumed less often. There was relatively good correlation between the FFQ and the 7-day record results. The mean daily energy intakes of the 15-year-old boys and girls were 10.2 and 8.3 MJ, respectively, in Uppsala, and 9.8 and 7.4 MJ in Trollhättan. The mean daily intakes of sucrose were 74 and 58 g in boys and 64 and 52 g in girls. The average daily dietary fibre intake was 1.8 g/MJ. The daily intake of energy obtained from breakfast was 18% on weekdays and 22% on weekends; 18 and 11% from prepared lunch; 24 and 30% from dinner, 21 and 14% from light meals; and 16 and 28% from snacks, in Uppsala and Trollhättan respectively. The lowest energy intake from a prepared lunch meal was noted during weekends. On both weekdays and weekends, considerable energy was obtained from light meals and snacks. However, nearly 40% of the girls and 28% of the boys had an energy intake from fat of < 30 energy%. The mean intakes of vitamin D and selenium and, in the case of girls, iron and zinc, were below the official Swedish Nutrition Recommendations. The daily median intake of iron was 18.7 mg in boys and 14.1 mg in girls. The iron intakes varied between 6 and 35 mg per day. Low serum ferritin concentrations, defined as s-ferritin < 12 micrograms/L, were found in 7 boys (3.7% and in 29 girls (13.9%). Significant negative correlations were found between smoking and frequency of consumption of vegetables, roots, fruits and meat. A negative correlation was also found between smoking and the intake of energy and a number of nutrients. Socioeconomic factors seem to be less important for the food habits of teenagers than for those noted during childhood. Only frequent consumption of vegetables was positively correlated to the mothers' educational level.