Biomedical subjects

K Pawlak

Publications and source records attributed to K Pawlak.

At least 19 recordsLinked to original sources

PubMed2006

Hepcidin, an acute-phase protein and a marker of inflammation in kidney transplant recipients with and without coronary artery disease.

BACKGROUND: In kidney transplant recipients, endothelial dysfunction and atherosclerosis are almost universal, as are cardiovascular complications. Inflammatory markers have been shown to play a role in the pathogenesis and progression of atherosclerosis, regarded as a chronic inflammatory condition. Iron metabolism is disturbed in chronic inflammatory diseases such as atherosclerosis. Hepcidin, the liver-expressed antimicrobial peptide, LEAP-1, is an acute-phase reactant produced in the liver that displays intrinsic antimicrobial activity. Cross-sectional study was performed to assess possible relations between hepcidin and inflammatory markers in kidney transplant recipients with versus without coronary artery disease (CAD). METHODS: Iron status, complete blood count, creatinine, albumin, and lipids were estimated using standard laboratory methods. Glomerular filtration rate (GFR) was calculated using the MDRD formula. Hepcidin, high-sensitivity C-reactive protein (CRP), IL-6, TNFalpha, and soluble receptor of transferrin were measured using commercially available kits. RESULTS: Kidney transplant recipients with CAD were older, and showed higher hepcidin, hsCRP, IL-6, TNFalpha, sTFR, ferritin, and lower cholesterol levels than did patients without CAD. Univariate analysis of values in kidney transplant recipients showed hepcidin to correlate significantly with total protein, ferritin, time after transplantation, creatinine, eGFR (simplified MDRD), cholesterol, neutrophil count, hsCRP, and IL-6. There were tendencies to correlate with TNFalpha. Multiple regression analysis showed that hepcidin was independently related to GFR, cholesterol, and hsCRP. CONCLUSIONS: Elevated hepcidin values in kidney allograft recipients may be due not only to impaired renal function, but also to a low-grade inflammatory state, as reflected by hepcidin correlations with hsCRP, IL-6, and ferritin.

Adult↗

PubMed2006

Possible relations between thyroid function, endothelium, and kidney and liver function in kidney allograft recipients.

BACKGROUND: Renal function affects the thyroid gland in many ways. Disturbances in hemostasis and endothelial damage are common complications of kidney disease. Endothelial dysfunction may link these two processes. AIM AND METHODS: This cross-sectional study examined thyroid hormones in relation to markers of endothelial damage and inflammation among 80 kidney allograft recipients and 29 healthy volunteers. Thyroid hormones, markers of endothelial damage (vWF, thrombomodulin, intracellular adhesion molecule [ICAM] vascular adhesion molecule [VCAM], CD146), markers of inflammation (hsCRP), other hemostatic parameters (thrombin-antithrombin complexes [TAT], prothrombin fragments 1 + 2 [F1 + 2], plasmin-antiplasmin complexes, tissue plasminogen activator and its inhibitor, platelet glycoprotein [V-GPV]) as well as P-selectin were measured using commercially available kits. RESULTS: Total T3 was significantly lower among kidney allograft recipients, whereas markers of endothelial dysfunction and inflammation were significantly elevated over controls. In kidney allograft recipients total T3 was independently related to PAI-1, ICAM, and eGFR, whereas free T3 was independently related to thrombomodulin, aspartate, and alanine aminotransferases, hemoglobin, urea, eGFR, dose of cyclosporine and treatment with mycophenolate mofetil/azathioprine. Total T4 was related to aspartate and alanine aminotransferases, dose of cyclosporine, PAI-1, and ICAM. In multiple regression analysis the only correlates of T3 were PAI-1 and ICAM, whereas the only correlates of free T3 were thrombomodulin, aspartate aminotransferase, eGFR, and cyclosporine dose. In healthy volunteers GPV was related only to TSH. CONCLUSIONS: We described novel relations between thyroid hormones and markers of endothelial dysfunction in kidney transplant recipients. In kidney transplant recipients thyroid function metrics were associated with endothelial damage, immunosuppressive treatment, liver and kidney function. Therefore, the relations between thyroid axis and endothelium in kidney allograft recipients merit additional studies.

Adult↗

PubMed2006

Resistin, a new adipokine, is related to inflammation and renal function in kidney allograft recipients.

BACKGROUND: Among patients without chronic kidney disease, resistin, an adipocytokine, has been related to inflammatory markers, coronary artery disease, and cardiovascular disease in the metabolic syndrome. Moreover, resistin up-regulates adhesion molecules. Since inflammation and endothelial cell damage or injury are invariably associated with thrombosis, atherosclerosis, and their major clinical consequences, resistin may play a role to link inflammation and CVD. The aim of this study was to correlate resistin with markers of inflammation and endothelial cell injury in 96 kidney allograft recipients. METHODS: We measured resistin and the following markers of endothelial function/injury: vWF, thrombomodulin, VCAM, hsCRP, tumor necrosis factor alpha (TNFalpha), and interleukin-6 (IL-6). RESULTS: Triglycerides, CRP (assessed by high-sensitivity method), phosphate, creatinine, IL-6, TNFalpha, vWF, prothrombin fragments 1 + 2, and resistin were elevated among kidney transplant recipients compared with the control group. Kidney allograft recipients with coronary artery disease displayed significantly higher resistin levels than those in patients without this complication. Upon univariate analysis resistin levels in kidney allograft recipients were related to hsCRP, IL-6, thrombomodulin, red blood cell count, white blood cell count, platelet count, creatinine, urea, VCAM, CSA, dose and eGFR. Upon multiple regression analysis, resistin was independently related only to creatinine, hsCRP, and white blood cell count in kidney allograft recipients. CONCLUSIONS: The relation of elevated resistin levels to markers of inflammation may represent a novel link between these conditions and adipocytokines. Renal function was a major determinant of elevated resistin in kidney allograft recipients.

Adult↗

PubMed2006

P53 correlates positively with VEGF in preoperative sera of colorectal cancer patients.

Diversity of P53 impact on tumor angiogenesis is due to the fact that wild-type P53 decreases expression of vascular endothelial growth factor (VEGF), but mutant P53 upregulates it. Therefore, we aimed at uncovering relations between preoperative serum levels of VEGF and P53 in colorectal cancer (CRC) patients. Preoperative blood samples of 125 CRC patients and 16 control healthy volunteers were examined with an ELISA-kit for serum P53 levels and VEGF. P53 did not correlate with VEGF in the whole group of CRC patients. However, P53 associated with VEGF in case of colorectal cancer patients, whose serum values of VEGF were higher than in controls (VEGF{H} >5.9333 pg/ml) (r=0.274, p<0.009). We revealed a positive correlation between P53 and VEGF{H} in subsets of poorly differentiated (G3) cancers (p<0.02), lymph node positive (p<0.007), pT3 or pT4 patients (p<0.004) without analogous relation in moderately differentiated (G2) tumors, node negative patients or pT1 or pT2 patients. P53 and IGF-I negatively correlated in all CRC patients (p<0.04) and VEGF{H} individuals of pT3 or pT4 (p<0.05) without any significant linkage in tumors of pT1 or pT2. The positive correlation between serum P53 and VEGF points at mutation of P53 and is a highly probable sign of poor prognosis in colorectal cancer. For now it can not be excluded that the binary analysis of serum P53 and VEGF could help select CRC patients endangered by rapid growth and lymph node metastases.

Adenocarcinoma↗

PubMed2005

Anthranilic acid-uraemic toxin damaged red cell's membrane.

Normocytic normochromic anaemia is a common syndrome present in patients with chronic renal insufficiency (CRI). Simultaneously in these patients the increase in L-tryptophan (TRP) degradation via kynurenine pathway is observed. On the basis of these observations we tried to examine whether one of the TRP metabolites, anthranilic acid (AA), shows interaction with membranes of erythrocytes and because of that it may contribute to anaemia development. In patients with CRI we have observed changes characteristic for normocytic normochromic anaemia, such as the decrease in erythrocyte count, haemoglobin concentration, haematocrit and the decrease in erythrocyte osmotic resistance as well as the increase in AA concentration in plasma in comparison to healthy subjects. We have also noticed the existence of a positive correlation between anthranilic acid concentration and creatinine and urea concentrations and also negative relationships between anthranilic acid concentration and haematological parameters. Moreover, incubation of healthy erythrocytes with 10 and 100 microM AA caused haemolysis curve movement to the right, which shows decrease in osmotic resistance. In conclusion, the increase in plasma AA concentration might be one of many factors, which damage erythrocyte membrane, and thereby contributes to anaemia development in patients with CRI.

Aged↗

PubMed2005

Correlations between leptin, body composition, bone mineral density, and bone metabolism in kidney transplant recipients.

INTRODUCTION: In kidney transplant recipients leptin levels are often elevated and bone mineral density (BMD) decreased. However, to date there are no about correlations between leptin and BMD in this population. It has been suggested that leptin is a predictor of BMD in postmenopausal women. Moreover, leptin acts as a marker of fat stores. We examined the relationships between leptinemia, some markers of nutritional status, BMD, and bone metabolism in kidney transplant recipients. We also assessed whether leptin was a significant and independent predictor of BMD in this population. METHODS: BMD and fat content (global, percentage, trunk) were measured using dual-energy X-ray absorptiometry in 27 kidney allograft recipients. Markers of bone turnover and leptin were studied using commercially available kits. RESULTS: Leptin correlated with the percentage of body fat, trunk fat, lean body mass, serum creatinine, and urea. Insulin growth factor binding protein 1 was negatively related to waist-hip ratio and global and trunk fat, whereas BMD of the lumbar spine was correlated with the daily dose of prednisone, azathioprine, cyclosporine trough levels, serum calcium, as well as osteoprotegerin level. CONCLUSIONS: Leptin levels are associated with graft function and body fat in kidney allograft recipients. Leptin is not related to nutritional status, BMD, or bone metabolism in kidney allograft recipients, but is associated with the current dosage of immunosuppressants and the serum calcium.

Absorptiometry, Photon↗

PubMed2004

Extended pneumonectomy for non small cell lung cancer--should we still do it?

The aim of the study was to assess the early and late results of extended pneumonectomies in lung cancer patients with T3 and T4 disease. Between Jan. 1995 and Dec. 1999--445 pneumonectomies were performed in patients with lung cancer. In 37 patients without preoperative N2 involvement a standard pneumonectomy was extended to include the following additional resections: chest wall (10), pericardium (9), diaphragm (5), VCS (3), descending aorta (2), left atrium (5), esophagus (1) and tracheal bifurcation (2). The effect of various factors on general mortality and morbidity was analyzed with the use of binary logistic regression. There were two early postoperative deaths (6.8%). Major complications occurred in 10 patients (29%). Overall survival rates at 1, 2, and 3 years were 43, 30 and 24%, respectively. The survival rates for the subgroup with chest involvement only were 50, 42 and 30%, respectively. Eight patients survived beyond the 36 month follow-up. The only factor significantly affecting mortality was incomplete resection, as revealed by postoperative microscopic examination (R1, p<0.05). Extended operations are justified by a relatively low mortality rate and low number of severe postoperative complications, specially in patients with chest wall involvement only. The result of this treatment predominantly depends upon the completeness of the resection.

Aged↗

PubMed2004

Protein Z and vitamin K in kidney disease.

PURPOSE: Disturbances in hemostasis are common complications of kidney diseases. Both bleeding diathesis and thromboembolism may complicate the course of chronic uremia. As far as we know, there is a limited data about protein Z in kidney disease. MATERIAL AND METHODS: The aim of our work was to examine plasma protein Z and vitamin K concentrations in nephrotic syndrome (n = 34), glomerulonephritis (n = 48), kidney transplant recipients (n = 80), peritoneally dialyzed patients (n = 42) and in the healthy volunteers (n = 27). RESULTS: Vitamin K was significantly lower in nephrotic syndrome when compared to non-nephrotic patients, CAPD and healthy volunteers (p < 0.05). Protein Z was the highest in CAPD and kidney transplant recipients when compared to any other group. In nephrotic syndrome protein Z was significantly lower when compared to the healthy volunteers, but it did not differ significantly between two groups of patients with chronic renal failure (with and without nephrotic syndrome). Protein Z correlated only with fibrinogen in CAPD, glomerulonephritis and nephrotic patients. Vitamin K correlated with age and albumin in patients with glomerulonephritis, nephrotic syndrome as well as with albumin in CAPD. CONCLUSIONS: Alterations in protein Z might contribute to the enhanced risk of thromboembolic complications in nephrotic syndrome, CAPD and Tx via different and unknown mechanisms. This phenomenon seems to be unrelated to vitamin K status in these patients.

Adult↗

PubMed2004

Plasma VEGF-A and its soluble receptor R1 correlate with the clinical stage of colorectal cancer.

UNLABELLED: Our aim was to assess plasma VEGF-A and its soluble receptor R1 (sVEGF-R1) in patients with colorectal cancer, in comparison with apparently healthy subjects. METHODS: Samples of plasma were collected from 26 patients with colorectal cancer before surgery and on post-operative day 3 and 10, frozen and eventually assessed, using ELISA kits. RESULTS: We found an increase in VEGF-A in colorectal cancer patients and a strong positive correlation between metastatic spread and postoperative VEGF-A, which also correlated with CA19.9. Soluble VEGF-R1 showed a positive correlation with lymph node involvement. CONCLUSIONS: Our findings may suggest that the patients with high postoperative VEGF-A should be scanned for metastases. In view of our finding that sVEGFR-1 correlates with lymph node involvement, precautions must be taken in studies of sVEGFR-1 as a potential therapeutic agent.

Biomarkers, Tumor↗

PubMed2001

Accumulation of toxic products degradation of kynurenine in hemodialyzed patients.

In patients that developed a chronic renal failure the augmentation in tryptophan degradation is reflected in the increase in plasma metabolites of kynurenine pathway. Hemodialysis is one of therapeutic approaches that significantly reduce all plasma kynurenine metabolites in uremic patients. In spite of haemodialysis, plasma concentration of kynurenine, kynurenic acid, 3-hydroxykynurenine, anthranilic acid, xanthurenic acid and quinolinic acid were still elevated in uremic patients in comparison with healthy volunteers. These data shows significant disturbances in kynurenine metabolism in uremic patients. Accumulation of these substances in uremic blood is capable to account for certain uremic symptoms.

Female↗

PubMed2001

Correlation between carotid intima-media thickness and hematocrit and hemoglobin values in renal transplant recipients.

BACKGROUND: Cardiovascular diseases are the main causes of morbidity and mortality in kidney transplant recipients. Blood viscosity plays an important role in the development of arteriosclerosis in the general population. Since hematocrit (Ht) and hemoglobin (Hb) values are determinants of blood viscosity, we decided to perform a study to check the possible relevance between these hemorheological factors and carotid intima-media thickness (IMT) in renal transplant recipients. PATIENTS AND METHODS: The study was performed on 33 clinically stable renal transplant recipients and 19 healthy persons. All subjects underwent ultrasonographic measurements of IMT. Analyzed clinical parameters included: age, sex, body mass index (BMI), mean arterial blood pressure (MAP), pulse pressure (PP) time from renal transplantation, and time on dialysis. The following biochemical parameters were assessed: Hb, Ht, fibrinogen (Fbg), and homocysteine (tHcy) concentrations (estimated by enzyme immunoassay). RESULTS: The two analyzed groups did not differ in respect to age and BMI. Mean concentrations of Hb and Ht values were lower in the patients group. Mean carotid IMT, Fbg, tHcy, MAP, and PP were significantly higher in the renal transplant recipients group when compared to the control group. IMT was positively correlated with age (r=0.55; p=0.001), Hb (r=0.36; p=0.04), Ht (r=0.34; p<0.05), PP (r=0.35; p<0.05), Fbg (r=0.4; p=0.02), and time on dialysis prior to transplantation (r=0.50; p=0.003) in the patients group. Multiple regression analysis in renal transplant recipients showed that the IMT was independently related to age, Hb or Ht values, and Fbg. CONCLUSIONS: The results for the first time show positive association between IMT and Ht and Hb values in renal transplant recipients. The results may implicate the role of these rheological factors in progression and acceleration of arterial remodeling in renal transplant recipients.

Adult↗

PubMed2001

Soluble thrombomodulin is associated with viral hepatitis, blood pressure, and medications in haemodialysis patients.

BACKGROUND: The level of soluble thrombomodulin (sTM), a traditional marker of endothelial injury, is also dependent on renal excretory function. We studied serum sTM in chronic haemodialysis (HD) patients to determine which factors are predictive of its levels in this population. METHODS AND RESULTS: sTM levels of 10.7 (5.72-30.7) ng/ml in 100 HD patients were higher than in 30 controls (P<0.0001). In a bivariate regression analysis, immunoreactive sTM was positively associated with the presence of hepatitis B virus surface antigen and/or anti-hepatitis C virus antibodies measured by third generation ELISAs (P<0.0001), and was related to certain markers of liver injury and biosynthetic dysfunction. sTM was also directly associated with time on dialysis (P=0.001), or use of unfractionated heparin (UFH) (vs enoxaparin) (P=0.0007), erythropoietin (P=0.008), ACE-inhibitors (P=0.034), acetate-buffered dialysate (vs bicarbonate) (P=0.040), pre-dialysis systolic (P=0.012), and diastolic blood pressure (P=0.043). It was negatively associated with lipoprotein(a) (P=0.029). sTM was not related to age, sex, smoking, cause of renal failure, prevalence of cardiovascular disease, amount of HD delivered, preserved residual renal function, ferritin, C-reactive protein, and other vasoactive medications used. In a multivariable analysis, a positive hepatitis marker (P=0.0002), the use of UFH (P=0.030) and erythropoietin (P=0.019), and raised pre-dialysis blood pressure (P=0.024) were positive independent predictors of high sTM level. CONCLUSION: These data indicate that, in addition to endothelial activation, elevated sTM levels in HD patients may be related to viral infection and/or liver dysfunction, and influenced by modifiable factors such as increased blood pressure, and the type of heparin and erythropoietin treatment used.

Adult↗

PubMed2001

Endothelial dysfunction marker von Willebrand factor antigen in haemodialysis patients: associations with pre-dialysis blood pressure and the acute phase response.

BACKGROUND: Increased plasma soluble von Willebrand factor antigen (vWF : Ag) level, a marker of vascular endothelial cell dysfunction, is a strong predictor of atherosclerotic cardiovascular disease (CVD) in the general population. We studied cross-sectional associations between vWF : Ag level, prevalence of CVD, and related factors including pre-dialysis arterial blood pressure (BP) and some markers of inflammation in maintenance haemodialysis (HD) patients. Methods and results. Plasma vWF : Ag level measured by an enzyme-linked immunosorbent assay (ELISA) was higher in 110 HD patients than in 20 controls. On bivariate regression analysis, vWF : Ag level was directly associated with the presence of CVD, age, fibrinogen and the use of enoxaparin (vs unfractionated heparin) during HD procedures, and inversely with albumin and pre-dialysis BP. The patients with prevalent CVD were older, had higher vWF : Ag, white blood cell and platelet counts, fibrinogen and triglycerides, lower albumin levels, and were less frequently on combination antihypertensive therapy. Multivariable analyses identified low pre-dialysis BP, hypoalbuminaemia and hyperfibrinogenaemia (in descending order of significance) as independent predictors of high vWF : Ag level. There were no associations between vWF : Ag levels and gender, ABO blood type, smoking, body mass index, renal failure cause, duration of HD therapy, K(t)/V, normalized protein catabolic rate, dialysate buffers, dialysers, viral hepatitis, erythropoietin treatment, specific antihypertensive drugs, haemoglobin, white blood cell and platelet counts, liver enzymes, phosphorous, total cholesterol, and triglycerides. CONCLUSION: Elevated plasma levels of endothelial dysfunction marker vWF : Ag in maintenance HD patients are associated with established cardiovascular mortality risk factors such as low pre-dialysis blood pressure and the activated acute phase response.

Adult↗

PubMed2001

A possible role of thrombin-activatable fibrinolysis inhibitor in disturbances of fibrinolytic system in renal transplant recipients.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of death in renal transplant recipients (RTR). Suppression of fibrinolysis plays a role in the progression of atherosclerosis. Accelerated progression of atherosclerosis and fibrinolytic system suppression has been observed in RTR. Despite many years of intensive research, the reason for impaired fibrinolysis in this patient population is not fully understood. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a recently discovered glycoprotein combining coagulation and fibrinolysis. This study was conducted to evaluate concentrations of TAFI, markers of thrombin generation, endothelial injury, and some standard laboratory parameters in RTR receiving triple immunosuppressive drug regimen. METHODS: The study was performed in 29 stable, non-diabetic kidney transplant recipients treated with cyclosporin A, azathioprine, and prednisone and in 18 age- and sex-matched healthy volunteers. Soluble thrombomodulin (sTM), prothrombin fragments F1+2 (F1+2), thrombin--antithrombin complexes (TAT), plasmin--antiplasmin complexes (PAP), and TAFI were measured with commercially available kits. RESULTS: The RTR group had significantly higher plasma levels of TAT, F1+2, sTM and TAFI than the healthy volunteers. There were no differences in PAP concentrations between the two groups. Plasma sTM correlated inversely with creatinine clearance, body mass index, haemoglobin, and albumin. Plasma TAT level was positively associated with total cholesterol. TAFI antigen influenced negatively PAP antigen concentration. CONCLUSIONS: On the basis of our research, we concluded that elevated circulating TAFI antigen might be a new link in the pathogenesis of impaired fibrinolysis in RTR, and thus atherosclerosis progression. In the patient group there is also evidence of endothelial injury, followed by secondary activation of the coagulation cascade. Hypercholesterolaemia in RTR is associated with enhanced thrombin activity.

Adult↗

PubMed2001

[Platelet aggregation and P-selectin concentration in patients on peritoneal dialysis treated with erythropoietin].

In chronic renal failure disturbances of hemostasis are predominantly due to the defective platelet function and platelet/vessel wall interactions. Erythropoietin, used for treatment of renal anemia, affect hemostasis in dialyzed patients. The aim of the work was to assess platelet aggregation and P-selectin concentration in patients on continuous ambulatory peritoneal dialysis (CAPD) during erythropoietin therapy. The studied were performed on 12 CAPD patients, administered with subcutaneous erythropoietin in a dose of 2000 U three times a week for 3 months. Hemoglobin, hematocrit and erythrocyte count increased significantly after 1 month of the treatment. Platelet aggregation in platelet-rich plasma induced by collagen, ristocetin and serotonin increased significantly after 3 months of erythropoietin therapy when compared to the baseline values. Whole blood platelet aggregation and P-selectin concentration did not change significantly during 3 months of erythropoietin therapy. Erythropoietin treatment in CAPD patients did not affect significantly platelet aggregation and activation.

Adult↗

PubMed2000

Early post-pneumonectomy complications in the elderly.

OBJECTIVE: The surgical treatment of non-small cell lung cancer (NSCLC) in elderly patients presents a serious challenge to thoracic surgeons. As there is considerable divergence of opinion about both the mortality and morbidity rates, it is important to set guidelines for proper patient selection. METHODS: Early post-operative complications in 42 patients aged over 70 years who had undergone pneumonectomy because of NSCLC (Group I) were analyzed. The control group (Group II) consisted of 48 patients, also aged over 70 years, but who had undergone lobectomy or wedge resections. In both groups, the pre-operative conditions and 30-day morbidity and mortality were evaluated. RESULTS: Postoperative complications occurred significantly more frequently in pneumonectomy patients (78.5%) than in Group II (58%). Transient or long-standing arrhythmias were noted in 20 patients (47.6%) from Group I and in 17 (35.4%) from Group II. Pulmonary complications occurred in 17 patients (40.4%) from Group I and 16 (33.3%) from Group II. The most important factors contributing to post-operative complications in pneumonectomy patients were performance status (WHO), chronic obstructive pulmonary disease (COPD) and elevated level of blood urea nitrogen (BUN). The highest impact on early mortality in pneumonectomy patients was exerted by COPD, arterial hypertension, formation of broncho-pleural fistula (BPF), the need for re-thoracotomy and high level of BUN. CONCLUSIONS: (1) Pneumonectomy in patients over the age of 70 carries a considerable risk of severe post-operative complications and death, when compared to patients with less extensive pulmonary resections. (2) Elderly patients with impaired Performance Status (WHO 2 or more) and co-existing arterial hypertension, COPD and elevated level of BUN should be considered for pneumonectomy very carefully and cautiously.

Aged↗

PubMed2000

Importance of serotonergic mechanisms in the thrombotic complications in hemodialyzed patients treated with erythropoietin.

So far it is not clear how erythropoietin affects the anticoagulant properties of vascular endothelium in uremia. Since serotonin is also thought to play a role in the pathogenesis of thrombosis, the aim of the study was to evaluate major components of extrinsic coagulation pathway, markers of endothelial cell injury, lipoprotein (a) and peripheral serotonergic mechanisms during rHuEPO therapy in hemodialyzed patients. The study was performed on chronically hemodialyzed patients divided into two groups: with rHuEPO treatment and without rHuEPO therapy in relation to the control group. In uremic patients, thrombomodulin and von Willebrand factor, activity of factor VII, tissue factor pathway inhibitor (TFPI) activity, TFPI and tissue factor (TF) concentrations, lipoprotein (a) level were significantly higher when compared to healthy volunteers. Treatment with rHuEPO resulted in a further significant rise in markers of endothelial cell injury: thrombomodulin and von Willebrand factor and TFPI concentration. Extrinsic coagulation factors: activities of factor VII and X, TFPI activity and TF activity and concentration, lipoprotein (a) and vitronectin remained unchanged during rHuEPO therapy. Platelet serotonin content and whole blood serotonin were significantly lower in uremic patients relative to healthy volunteers and during rHuEPO treatment they increased significantly. Whole blood serotonin reached normal values. Plasma serotonin, significantly elevated in uremia, did not change during rHuEPO therapy. Serotonin uptake by uremic platelets was significantly impaired and remained unaltered during rHuEPO administration. Serotonin release by uremic platelets was also significantly depressed but a significant improvement was observed in rHuEPO-treated patients. Our data suggest that endothelial injury, TF pathway components and peripheral serotonergic system disturbances may predispose to thromboembolic complications and play a role in the pathogenesis of atherosclerosis in uremic patients, particularly treated with rHuEPO. Increase in TFPI may compensate the increase in TF in these patients.

Adult↗

PubMed1998

A potent 5-hydroxytryptamine receptor (5-HT2A) antagonist, DV-7028, delays arterial thrombosis development in rats.

In our study, we demonstrated that DV-7028: (3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-6, 7,8,9-tetrahydro-2H-pyrido [1,2,-a]-1,3,5-triazine-2, 4(3H)-dione maleate)--a selective 5-HT2A receptor antagonist, inhibited thrombus formation in the arterial thrombosis model and was completely ineffective in the prevention of venous thrombosis in the rat. In washed platelets prelabelled with 3H-serotonin, DV-7028 inhibited, in a dose-dependent manner, the collagen-induced secretion of serotonin. However, the uptake of serotonin into platelets was not affected by this substance. Administration of DV-7028 also inhibited platelet aggregation in the whole blood and platelet-rich plasma (PRP) induced by collagen, and diminished serotonin-induced aggregation of rat platelets in the presence of a sensitizing but nonaggregating amount of ADP, whereas it did not modify aggregation in PRP when induced by ADP. DV-7028 caused a concentration-dependent, almost parallel shift to the right of the concentration-response to serotonin for its pressor effect in the rat perfused tail artery. The present data demonstrate that DV-7028 exhibits 5-HT2A receptor antagonistic properties in the rat cardiovascular system, exhibits antithrombotic effect in the model of arterial but not venous thrombosis in rats. These results constitute further evidence of the possible importance of serotonin as a mediator of platelet thrombosis in arteries. Moreover, they can provide a useful tool for the prevention of various thrombotic diseases.

Animals↗