The effects of N-terminal part modification of arginine vasopressin analogues with 2-aminoindane-2-carboxylic acid: a highly potent V2 agonist

In this study we present the synthesis and some pharmacological properties of nine new analogues of arginine vasopressin modified in the N-terminal part of the molecule with 2-aminoindane-2-carboxylic acid (Aic). The peptides were tested for their in vitro uterotonic and in vivo pressor and antidiuretic activities. One of the new peptides, [Mpa1,Aic2,Val4,D-Arg8]VP, exhibited an antidiuretic activity similar to that of [Mpa1,D-Arg8]VP, thus being one of the most potent antidiuretic vasopressin analogues reported to date.     

Effects of long-term erythropoietin therapy on fibrinolytic system in haemodialyzed patients

INTRODUCTION: Recombinant human erythropoietin (rHuEPO) is the cornerstone of anaemia therapy in uraemic patients however the effects of this hormone on fibrinolytic system are difficult to interpret. MATERIALS AND METHODS: Assessment of fibrinolytic parameters: tissue-type plasminogen activator (tPA) antigen, urokinase-type plasminogen activator (uPA) and its soluble receptor (suPAR), plasminogen activator inhibitor 1 (PAI-1) and plasmin/antiplasmin (PAP) complexes were performed in haemodialyzed (HD) patients without rHuEPO therapy: Group I (n=8, Hg<10 g/dl); Group II (n=12, Hg>10 g/dl); and in HD patients treated with rHuEPO for more than 6 months (Group III, n=10) or for more than 12 months (Group IV, n=9) in relation to the healthy controls. RESULTS: Patients of Group I had the significantly lower haematological parameters than those of Groups II, III and IV. All the fibrinolytic parameters studied, except PAI-1, were significantly higher in HD patients without rHuEPO therapy when compared to the controls. There were no significant differences in fibrinolytic system between the Groups I and II. Erythropoietin therapy resulted in progressive decrease in antigenic tPA levels, which reach normal range values after 6 months rHuEPO administration. uPA and PAP concentrations were also decreased and reached normal values after 12 months of rHuEPO therapy. In these patients a significant decrease in uPAR levels was also observed. Therapy with rHuEPO did not alter PAI-1 concentrations in HD patients. CONCLUSIONS: These results suggest that long-term rHuEPO therapy can correct fibrinolytic parameters in patients undergoing regular HD irrespective from haemoglobin levels and in the absence of concomitant iron supplementation.     

The urokinase-type plasminogen activator/its soluble receptor system is independently related to carotid atherosclerosis and associated with CC-chemokines in uraemic patients

INTRODUCTION: The urokinase-type plasminogen activator (uPA)/its soluble receptor (suPAR) and CC-chemokines are two systems contributing in the atherosclerosis. We try to establish whether these two systems were associated among themselves, and the significance of this potential association in relation to carotid atherosclerosis in uraemic patients. MATERIALS AND METHODS: We determined uPA, suPAR, CC-chemokines: monocyte chemoattractant protein-1 (CCL2), macrophage inflammatory proteins (CCL3, CCL4), regulated upon activation, normal T cell expressed and secreted (CCL5) and the intima-media thickness (IMT) values in uraemic patients on peritoneal dialysis (CAPD), haemodialysis (HD) and healthy controls. RESULTS: The values of the uPA/suPAR system, CCL2, CCL4 and IMT in the patients significantly exceeded those in controls, whereas CCL5 were lower in the patients than in the controls. CCL3 concentrations were similar in all investigated groups. CCL2, CCL4 and CCL5 were positively associated with uPA/suPAR system. CCL2 and CCL4 were associated with IMT. Multivariate analysis showed that uPA, suPAR and age were the strong independent variables linked to IMT values. CONCLUSIONS: The carotid atherosclerosis is independently related to uPA/its soluble receptor system in dialysis patients. In addition, the strong positive associations existed between uPA/suPAR system and CC-chemokines suggesting that these two systems could cooperate and influence of atherosclerosis in these patients.     

The alteration of Microcystis aeruginosa biomass and dissolved microcystin-LR concentration following exposure to plant-producing phenols

Plant-producing phenols could strongly inhibit the growth of toxic cyanobacteria genera, but the ecological consequences of this action are still unknown. In this work, the activity of selected phenols in relation to the strain Microcystis aeruginosa was investigated. We have found that the mechanism of the growth inhibition could involve both the inhibition of the photosynthetic system and the alkaline phosphatase activity. The excretion of a high amount of microcystin-LR to the environment was observed as a final result of the application of phenols to the cyanobacterial culture. This finding suggests that first of all an algicidal effect of phenols was probably the reason of the cyanobacterial biomass decreasing.     

Significance of aspirin and clopidogrel resistance in patients undergoing percutaneous coronary interventions

Dual antiplatelet therapy (aspirin plus clopidogrel) is mandatory in patients treated with coronary stent implantation. This strategy is highly effective in prevention of stent thrombosis until its struts are covered with endothelium. However, a substantial number of patients still suffer from recurrent ischemic coronary events despite adequate antiplatelet therapy. These events fall into three categories: stent thrombosis, in stent restenosis and events related to other non-stented coronary lesions. Some data suggest that beside other local and systemic factors resistance to aspirin and clopidogrel may be a possible cause of stent thrombosis and ischemic events in patients after coronary interventions. Several mechanisms of antiplatelet drug resistance have been reported including poor compliance, interactions with other drugs, genetic polymorphism or increased platelet turnover. More research is needed to adequately assess the clinical significance and prognostic value of antiplatelet drug resistance detected by laboratory tests in patients undergoing percutaneous intervention. We review published data on mechanisms and the clinical significance of aspirin and clopidogrel resistance in patients after coronary interventions.     

Carotid intima-media thickness as a marker of cardiovascular risk in hypertensive patients with coronary artery disease

BACKGROUND: The aim of this study was to examine the significance of ultrasound-measured carotid intima-media thickness (CIMT) in high-risk patients with hypertension and coronary artery disease (CAD), as an independent prognostic factor in determining the risk of all-cause death or future cardiovascular events. METHODS: The study included 297 consecutive patients (mean age +/- SD, 57 +/- 9.4 years) with diagnosed hypertension and CAD, referred for coronary angiography. The mean of maximal CIMT in two arterial segments bilaterally was calculated. The primary endpoint was a patient's death from all causes. Death, stroke, or myocardial infarction comprised the secondary, composite endpoint. RESULTS: There was a follow-up of 1 to 79 (mean, 41) months. The predictors of death in a multivariate Cox proportional hazards model were the number of stenosed coronary arteries (P = .007) and CIMT (P = .001). The risk of the secondary, composite endpoint (death, stroke, or myocardial infarction) was determined by diabetes (P = .008) and CIMT (P = .010). Nearly 99% of patients with "low CIMT" (< or =1.13 mm) survived for 5 years, versus 78% with "high CIMT" >1.13 mm (log-rank test; P < .001). For the secondary, composite endpoint (death, stroke, or myocardial infarction), the event-free survival rate was 95% (low CIMT), versus 74% after 5 years (high CIMT) (P < .008). CONCLUSIONS: Intima-media thickness of the carotid arteries is a strong and independent predictor of death and serious cardiovascular events in hypertensive patients with CAD referred for coronary angiography.