Endothelins - clinical perspectives

Endothelins (ET) are a group of endogenous peptides, which have a strong and long-lasting vasocon-strictive effect. Three isoforms of endothelins coded by three different genes have been identified to date. Endothelin-1 (ET-1) is the most potent vasoconstrictive agent currently identified, and it was originally isolated and characterized from the culture media of aortic endothelial cells. Two other iso-forms, named endothelin-2 (ET-2) and endothelin-3 (ET-3), were subsequently identified, along with structural homologues isolated from the venom of Actractapis engaddensis known as the sarafotoxins. The biological effects of endothelin production are determined via activation of one or two G-protein coupled receptors, endothelin receptors A (ETRA) and B (ETRB1 and ETRB2). Recently endothelin receptor C (ETRC) was discovered, however, its functions and distribution still remain unclear. The effects mediated by ET-1 via ETRA are vasoconstriction, bronchoconstriction and secretion of aldosterone. Agonists related to the ETRB1 activation cause vasodilatation by stimu-lating NO, PGI2 and endothelium-derived hyperpolarizing factor (EDHF). In contrast, coupling to ETRB2 causes vasoconstriction. Involvement of ET has been demonstrated in the pathophysiology of certain disorders. In this review, we discuss the physiological and pathophysiological role of endothe-lium-derived ET-1, the pharmacology of its two receptors, focusing on the role of ET-1 in the develo-pment of some pathophysiological conditions

Use of biochemical parameters for non-invasive screening of oesophageal varices in comparison to elastography-based approach in patients with compensated advanced chronic liver disease

Oesophageal varices are routinely diagnosed by esophagogastroduodenoscopy (EGD), and their bleeding has high mortality. We aimed to evaluate diagnostic performance of biochemical tests in comparison to elastography-based approaches, as non-invasive alternatives to EGD, for ruling-out high risk oesophageal varices (HRV). Retrospective analysis of patients (N = 861) who underwent liver stiffness measurement (LSM) by transient elastography (TE) in a single centre over 5-year period, with available results of EGD (within 3 months from LSM). Only patients with suspicion of compensated advanced chronic liver disease (cACLD) defined by LSM ≥ 10 kPa were included comprising the final cohort of 73 subjects. Original and expanded Baveno VI criteria (B6C), controlled attenuation parameter (CAP), platelet count (PLT), aspartate aminotransferase to PLT ratio index (APRI), Fibrosis-4 index (FIB4), model for end stage liver disease (MELD) score were evaluated against the results of EGD that served as the reference method. Analysed patients had median age 62 years, 59/73 (0.81) were males, 54/73 (0.74) had alcoholic/non-alcoholic fatty liver disease, and 21/73 (0.29) had HRV. In multivariate logistic regression analysis only LSM and PLT were independently associated with HRV. The best performing tests for ruling-out HRV (% of spared EGD; % of missed HRV) were respectively: LSM 214x109/L (21.9%; 0%); FIB4 ≤ 1.8 (21.4%; 0%), APRI ≤ 0.34 (12.3%; 0%). CAP, MELD = 6 alone or combined with PLT > 150(x109/L) did not show acceptable performance. The best performing biochemical tests for ruling-out HRV in our cohort of patients were PLT and FIB-4, but they were still outperformed by elastography-based approaches

Analytical evaluation of the clinical chemistry analyzer Olympus AU2700 plus

Background: The objective of this study was to perform the analytical evaluation of the clinical chemistry analyzer Olympus AU2700 plus. The evaluation was performed according to the guidelines of the European Committee for Clinical Laboratory Standards (ECCLS). Materials and methods: The evaluation consisted of determination of within-run and between-run imprecision, inaccuracy and comparison with Olympus AU2700. The tested analytes were: glucose, creatinine, urate, total bilirubin, cholesterol, tryglicerides, calcium, phosphate, iron, unsatura-ted iron binding capacity, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, alpha-amylase, alkaline phosphatase, potassium, sodium, chloride, C-reactive protein, antistreptolysin O and rheumatoid factor. Results: The results showed low within-run and between-run imprecision and acceptable inaccuracy for all analytes. High correlation with AU2700 analyzer was found. Intercept and slope (with 95% confidence interval) met the preferences of Passing-Bablok regression for all of the analytes except alanine aminotransferase, sodium, rheumatoid factor, creatine kinase, total bilirubin and tryglicerides. Conclusions: Olympus AU2700 plus analyzer shows acceptable precision and accuracy for majority of analytes, with the exception of sodium and chloride. Instrument is fully comparable with Olympus AU2700 analyzer for all but several analytes (ALT, RF, sodium, CK, total bilirubin and tryglicerides), where only some minor deviations (constant and proportional difference) were observed

Anti-citrullinated protein antibody and rheumatoid factor in patients with end-stage renal disease

Background: Patients with end-stage renal disease (ESRD) and on hemodialysis (HD) are at increased risk for developing rheumatoid arthritis (RA), as a result of defective immunity. Our aim was to examine if ESRD and the length of HD treatment impact the clinical utility of antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor (RF) as diagnostic tools for RA. Methods: We included 94 subjects in our study: 37 healthy volunteers and 57 patients with ESRD who had been undergoing HD for 1–12 years, and without confirmed RA. In order to test our hypothesis, we measured and correlated anti-CCP and RF as laboratory markers of RA. Results: Our study showed that there is no significant difference between values for anti-CCP (p=0.11) and RF (p=0.98) in control subjects as well as in patients undergoing HD, regardless of the length of time that patients had been undergoing HD treatment. Conclusions: Our study indicates that HD does not impair the specificity of anti-CCP and RF for RA in patients where the disease has not yet developed. Future prospective studies may show whether there is any use in determinating RF, and especially anti-CCP, as early predictors of RA in patients with ESRD who are at greater risk of developing this condition. Clin Chem Lab Med 2009;47:959–62.Peer Reviewe

Endothelins - clinical perspectives

Endothelins (ET) are a group of endogenous peptides, which have a strong and long-lasting vasocon-strictive effect. Three isoforms of endothelins coded by three different genes have been identified to date. Endothelin-1 (ET-1) is the most potent vasoconstrictive agent currently identified, and it was originally isolated and characterized from the culture media of aortic endothelial cells. Two other iso-forms, named endothelin-2 (ET-2) and endothelin-3 (ET-3), were subsequently identified, along with structural homologues isolated from the venom of Actractapis engaddensis known as the sarafotoxins. The biological effects of endothelin production are determined via activation of one or two G-protein coupled receptors, endothelin receptors A (ETRA) and B (ETRB1 and ETRB2). Recently endothelin receptor C (ETRC) was discovered, however, its functions and distribution still remain unclear. The effects mediated by ET-1 via ETRA are vasoconstriction, bronchoconstriction and secretion of aldosterone. Agonists related to the ETRB1 activation cause vasodilatation by stimu-lating NO, PGI2 and endothelium-derived hyperpolarizing factor (EDHF). In contrast, coupling to ETRB2 causes vasoconstriction. Involvement of ET has been demonstrated in the pathophysiology of certain disorders. In this review, we discuss the physiological and pathophysiological role of endothe-lium-derived ET-1, the pharmacology of its two receptors, focusing on the role of ET-1 in the develo-pment of some pathophysiological conditions