L-2-oxothiazolidine-4-carboxylic acids slow down dialysate-induced senescence in human peritoneal mesothelial cells.

Peritoneal dialysis induces an intraperitoneal inflammatory reaction, which in the long term may cause deterioration of the peritoneal structure and function as the dialysis membrane. We studied the effect of the overnight effluent dialysate from patients on chronic peritoneal dialysis on aging of the human peritoneal mesothelial cells in an in vitro model of replicative cellular senescence. In the control group cells were cultured in the standard medium and in the studied groups in culture medium mixed 1:1 v/v with the dialysate ± L-2-oxothiazolodine-4-carboxylic acid 1 mmol/L (OTZ). OTZ was used as the precursor for the synthesis of glutathione in these cells. Dialysate accelerated senescence of the mesothelial cells as reflected by elongation of their population doubling time, reduced expression of KI-67 gene, and increased ß-galactosidase activity. Also, expression of the genes regulating the production of the inflammatory mediators (interleukin-6, monocyte chemoattractant protein-1, metalloproteinase-2, hyaluronan), proangiogenic (VEGF) and profibrotic (fibronectin) factors was increased in that group. At the same time, these cells secreted more inflammatory mediators. Simultaneous treatment of the cells with the dialysate and OTZ slowed down their senescence, whose intensity was similar to that in the control group. The results presented in this manuscript prove that the intraperitoneal inflammatory reaction induced by repeated infusions of the dialysis fluid accelerates the senescence of the mesothelial cells, which may result in fibrosis and neoangiogenesis within the peritoneum. Simultaneous supplementation of the cells with a glutathione precursor (OTZ) may prevent the development of these pathological changes.

Post-operative Venous Thromboembolism in Patients Operated on for Aorto-iliac Obstruction and Abdominal Aortic Aneurysm, and the Application of Pharmacological Thromboprophylaxis.

OBJECTIVE/BACKGROUND: In light of the methods generally used to assess the risk of venous thromboembolism (VTE), major vascular operations should be regarded as high risk procedures. Nevertheless, no principles for implementing and maintaining thromboprophylaxis have so far been developed. The aim of this study was to determine the frequency and nature of VTE occurrence in patients routinely applying pharmacological thromboprophylaxis following implantation of an aorto-bifemoral prosthesis. METHODS: The prospective non-randomized study included 105 patients with aortoiliac obstruction and 119 patients with abdominal aortic aneurysm (AAA) treated surgically. During hospitalization pharmacological thromboprophylactic procedures were observed. A duplex test was performed on the day before surgery, on the day of discharge, and 30 days after the patients had left the hospital. RESULTS: VTE was detected in 18.1% of the patients with aortoiliac obstruction (9.5% of patients during hospitalization and 8.6% of patients after discharge). VTE was diagnosed in 21.0% of patients with AAA (15.1% of patients during hospitalization and 5.9% of patients after discharge). The incidence of VTE was comparable in both groups, both during hospitalization (p = .51) and in the 30 day period following the end of hospitalization (p = .48). It is advisable that before hospital discharge routine duplex ultrasonography tests should be conducted on the venous systems of all patients who have undergone major vascular operations. CONCLUSIONS: It is likewise advisable to consider whether thromboprophylaxis for vascular patients should be extended beyond their discharge from hospital.

Sulodexide suppresses inflammation in patients with chronic venous insufficiency.

AIM: According to previously performed studies, inflammation plays a crucial role in vein wall and leg tissue injury related to chronic venous insufficiency (CVI) development. Sulodexide (SUL) is a balanced mix of glycosaminoglycans with potential anticoagulant and profibrinolytic activity, also protecting endothelial cells and suppressing inflammatory reactions in various vascular disease-related conditions. The goal of the present study was to evaluate the anti-inflammatory action of SUL in patients with CVI. METHODS: The study was performed on a group of 11 patients with chronic venous disease (stage C5 according to CEAP classification). The mean age of the patients was 58.4±7.7 years, and none of them were diabetic. The patients were treated for 8 weeks with orally-administered SUL (2 x 500 LSU/day). Blood samples were collected at the start and at the end of the study for measurement of MMP-9, IL-6 and monocyte chemoattractant protein-1 (MCP-1). Additionally, the effect of the obtained serum samples on the function of human venous endothelial cells (HVEC) in in-vitro culture was evaluated. RESULTS: After treatment with SUL, the serum concentration of MMP-9 (ng/mL) decreased from 6.50±3.48 to 5.41±1.36, P<0.05, and the concentration of IL-6 (pg/mL) decreased from 11.5±3.4 to 10.1±2.3, P<0.005. There was also a trend of decreased serum MCP-1 (pg/mL) from 31.3±23.0 before treatment to 27.1±10.7 at the end. Intracellular generation of oxygen-derived free radicals in HVEC maintained in in-vitro culture was lower in the serum samples collected after treatment with SUL: 3.09±0.35 abs/µg protein vs. 3.63±0.32 abs/µg protein, at the start, P<0.05. Synthesis of IL-6 was lower in HVEC exposed in vitro to serum collected at the end of SUL treatment: 1.02±0.31 ng/µg cell protein vs. 1.32±0.41 ng/µg cell protein before SUL treatment. The proliferation rate of HVEC was similar in serum collected at the beginning and at the end of SUL treatment. CONCLUSION: We conclude that treatment with SUL in patients with CVI reduces intravascular inflammation and is protective for the endothelial cells and for the extracellular matrix changes related to metalloproteinase expression.

[Thrombophlebitis profunda in patients after conventional and laparoscopic cholecystectomy]. / Thrombophlebitis profunda bei Patienten nach der konventionellen und laparoskopischen Gallenblasenentfernung.

The purpose of this study was to compare the incidence of deep venous thrombosis (DVT) in patients undergoing uncomplicated laparoscopic cholecystectomy and in whom conversion to laparotomy was required. Using the Duplex Doppler examination, we found higher incidence of DVT in patients who required conversion than in those who did not (47 vs 58%). Prolonged prophylaxis with low-molecular weight heparin should be considered in these patients.