OBJECTIVE: The aim of our study was to establish whether or not tinnitus patients have higher platelet activity, as measured by plasma 11-dehydro-thromboxane B2 levels, compared with individuals without tinnitus. METHODS: The study group included patients without documented organic causes of tinnitus or a cause of non-vascular hearing impairment. Laboratory tests included complete blood count, biochemistry, coagulation activity, and thromboxane levels. To exclude a pathology in the cerebellopontine angle, CT and MRI were performed together with an X-ray scan of cervical vertebrae. For the purpose of this study, blood samples were screened for 11-dehydro-thromboxane B2 levels using commercial kits. RESULTS: A comparison of the main marker of increased platelet activity i.e., thromboxane levels of tinnitus patients with those of a control group, showed increased thromboxane levels in the former. The average plasma concentrations of 11-dehydro-thromboxane B2 were 2.0234±1.80 ng/ml in the group of tinnitus patients and 1.3247±1.33 ng/ml in the control group. Our results showed that patients with tinnitus have significantly higher values of 11-dehydro-thromboxane B2. CONCLUSION: Tinnitus patients showed higher levels of increased platelet activity, a marker that may play an important role in the pathogenesis of tinnitus.

• MeSH
• dospělí MeSH
• hemokoagulace MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• thromboxan B2 analogy a deriváty   krev   MeSH
• tinnitus krev   MeSH
• trombocyty metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Kyselina acetylsalicylová (aspirin, ASA) v sekundární prevenci kardiovaskulárních příhod u pacientů s aterosklerotickým postižením koronárních i periferních tepen snižuje výskyt úmrtí a závažných ischemických cévních příhod o 22 %. Pokud je však laboratorně měřena účinnost antiagregační terapie aspirinem, neodpovídá kolem jedné třetiny pacientů adekvátním způsobem. Pro tento fenomén se vžil název aspirinová rezistence. Většina studií a metaanalýzy, které se zabývaly aspirinovou rezistencí, potvrdily korelaci různými metodami zjištěné aspirinové rezistence s horšími klinickými výsledky. V metaanalýze dvaceti studií s témě? 3?000 pacienty ?inil pom?r ?anc? (pooled odds ratio) pro kardiovaskul?rn? p??hodu u?pacient? rezistentn?ch na terapii ASA 3,8. Frekvence v?skytu aspirinov? rezistence se v?jednotliv?ch studi?ch ?asto dramaticky li?? od?t?m?? nulov?ch hodnot po?hodnoty p?es 70?%. K?t?mto markantn?m rozd?l?m doch?z? p?edev??m v?z?vislosti na?pou?it? laboratorn? metod?, klinick? situaci (stabiln?, nebo akutn? onemocn?n?, p??padn? zdrav? dobrovoln?ci) a?dal??ch aspektech, jako jsou l?kov? interakce atd. V?n?sleduj?c?m textu se pokus?me nazna?it, jak? klinick? a?laboratorn? aspekty ovliv?uj? v?skyt aspirinov? rezistence a?jak?m zp?sobem naopak aspirinov? rezistence ovliv?uje progn?zu pacienta. V?sou?asn? dob? nen? dostupn? p?esv?d?iv? d?kaz o?efektivit? ?pravy medikace na?z?klad? laboratorn? zji?t?n? aspirinov? rezistence, uv?d?me v?ak postupy, kter? byly pou?ity v?klinick?ch studi?ch za???elem zv??en? laboratorn? odpov?di na?antiagrega?n? terapii. ř 3 000 pacienty činil poměr šancí (pooled odds ratio) pro kardiovaskulární příhodu u pacientů rezistentních na terapii ASA 3,8. Frekvence výskytu aspirinové rezistence se v jednotlivých studiích často dramaticky liší od téměř nulových hodnot po hodnoty přes 70 %. K těmto markantním rozdílům dochází především v závislosti na použité laboratorní metodě, klinické situaci (stabilní, nebo akutní onemocnění, případně zdraví dobrovolníci) a dalších aspektech, jako jsou lékové interakce atd. V následujícím textu se pokusíme naznačit, jaké klinické a laboratorní aspekty ovlivňují výskyt aspirinové rezistence a jakým způsobem naopak aspirinová rezistence ovlivňuje prognózu pacienta. V současné době není dostupný přesvědčivý důkaz o efektivitě úpravy medikace na základě laboratorně zjištěné aspirinové rezistence, uvádíme však postupy, které byly použity v klinických studiích za účelem zvýšení laboratorní odpovědi na antiagregační terapii.

Acetylsalicylic acid (aspirin, ASA) reduces mortality and major adverse cardiovascular events by 22% when used in coronary and peripheral artery disease secondary prevention. Laboratory assessed aspirin antiplatelet therapy effectiveness showed an inadequate response to the ASA treatment in about one third of patients. This phenomenon is often called “aspirin resistance”. Most of the studies and metaanalyses regarding the aspirin resistance proved a certain correlation between the ASA resistance assessed by various laboratory methods and the worst clinical outcomes. In the metaanalysis with nearly 3,000 patients the pooled odds ratio of cardiovascular events in ASA resistant patients was 3.8. The ASA resistance frequency shown in various clinical studies varies from almost zero values to as much as 70% of resistant patients. The distinct differences in the ASA resistance frequency are caused by variability in used laboratory methods, different clinical situations in particular studies (stable or acute cardiovascular disease or healthy volunteers) and other aspects as drug interactions etc. In the text as follows, we describe the clinical and laboratory aspects influencing the ASA resistance incidence and the influence of the ASA resistance on patient prognosis. Nowadays, there is no solid proof available which would confirm the fact that the ASA resistance guided treatment modification is associated with better clinical outcomes. Nevertheless, herein we describe various methods of therapy modification used in clinical studies for improving the laboratory ASA treatment response.

• Klíčová slova
• aspirinová rezistence, agregometrie,
• MeSH
• antiflogistika nesteroidní MeSH
• Aspirin * farmakologie   terapeutické užití   MeSH
• cyklooxygenasa 1 metabolismus   MeSH
• cyklooxygenasa 2 metabolismus   MeSH
• inhibitory agregace trombocytů farmakologie   MeSH
• inhibitory protonové pumpy MeSH
• kardiovaskulární nemoci prevence a kontrola   MeSH
• léková rezistence * MeSH
• lékové interakce * MeSH
• lidé MeSH
• monitorování léčiv MeSH
• thromboxan B2 metabolismus   MeSH
• vyšetření funkce trombocytů metody   MeSH
• Check Tag
• lidé MeSH

Cardiovascular patients take acetylsalicylic acid (ASA) for preventing myocardial infarction and other thromboembolic complications. It is already known that in some patients this therapy is not effective. The aim of this study was to assess the percentage of ASA resistance on the sample of patients with coronary artery bypass grafting. Our study included 105 patients with coronary artery bypass grafting treated with ASA 150 mg/day or lesser. Platelet aggregation was measured by serum thromboxane B2 level as well as impedance aggregometry from whole blood to determine ASA antiaggregation effect. The percentage of ASA resistance was 41.9% with impedance aggregometry, and after determining the serum thromboxane B2 level this percentage was only 8.6%. The correlation between these two methods was weak (r = 0.443; P < 0.0001). Thromboembolic complications still occur in ASA-treated patients because some patients are resistant to ASA therapy. It would be useful to monitor the effectiveness of ASA therapy and give another antiaggregation drug to these patients to reduce adverse events. The problem is which test is ideal because different tests show different percentages of ASA resistance.

• MeSH
• agregace trombocytů účinky léků   MeSH
• Aspirin terapeutické užití   MeSH
• dospělí MeSH
• inhibitory agregace trombocytů terapeutické užití   MeSH
• koronární bypass * MeSH
• léková rezistence MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování léčiv přístrojové vybavení   metody   MeSH
• nemoci koronárních tepen krev   patologie   chirurgie   MeSH
• rozvrh dávkování léků MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• thromboxan B2 krev   MeSH
• trombocyty účinky léků   MeSH
• vyšetření funkce trombocytů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Citalopram, a selective serotonin reuptake inhibitor (SSRi), is widely used to treat major depression. Patients treated with SSRIs suffer more frequently from bleeding disorders caused by the antiplatelet effect of SSRIs. METHODS: To investigate the potential suppressive effect of citalopram treatment on plasma thromboxane B2 levels and its possible correlation with actual plasma concentration of citalopram. Plasma concentrations of thromboxane B2 and citalopram were examined in a cohort of 77 aspirin-treated geriatric patients before and in the third week of citalopram therapy. RESULTS: Citalopram therapy led to a significant decrease of plasma concentrations of thromboxane B2 compared to its levels before initiation of the therapy. Furthermore, we have shown negative correlation in thromboxane B2 levels and actual plasma concentration of citalopram. Actual plasma concentrations of citalopram were significantly higher compared to younger adult patients treated with similar dose. CONCLUSIONS: In this study we have shown that even short-term citalopram therapy led to a suppression of thromboxane B2 production in aspirin-treated patients. This suppressive effect correlates with actual plasma concentration of citalopram.

• MeSH
• Aspirin farmakologie   MeSH
• citalopram krev   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• selektivní inhibitory zpětného vychytávání serotoninu krev   farmakologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• thromboxan B2 krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIMS: Platelet function testing is often affected by the existence of different pre-analytical variables that can cause platelet activation. The aim of this study was to assess the effect of such variables that are present when samples are taken (different anticoagulants, incubation temperature, and storage conditions) to select those which enable to reach optimal range of measured plasma concentrations of the two stable thromboxane A₂ metabolites, that is, thromboxane B₂ (TxB₂) and 11-dehydrothromboxane B₂ (11-dTxB₂). MATERIALS AND METHODS: For the purpose of this study, whole blood samples obtained from 20 volunteers were screened for TxB₂ and 11-dTxB₂ concentrations using commercial EIA kits (Cayman Chemicals™; Neogen™) in relation to the effect of different anticoagulants, using different incubation temperatures and storage conditions. RESULTS: Trisodium citrate has been shown not to be affecting the TxB₂ and 11-dTxB₂ concentrations compared with the values measured in the serum. Incubation of the samples for 1 h at 37 °C and freezing at -20 °C or -80 °C give the most suitable concentration range of both thromboxanes in the used EIA measurement. CONCLUSION: This study describes the setup of such pre-analytical phase conditions that enable the screening of platelet function in terms of the plasma concentrations of TxB₂ and 11-dTxB₂ in selected EIA measurement.

• MeSH
• antikoagulancia farmakologie   MeSH
• Aspirin terapeutické užití   MeSH
• časové faktory MeSH
• citráty farmakologie   MeSH
• imunoenzymatické techniky MeSH
• inhibitory agregace trombocytů farmakologie   MeSH
• inhibitory cyklooxygenasy farmakologie   MeSH
• lidé MeSH
• odběr biologického vzorku * MeSH
• teplota MeSH
• thromboxan A2 krev   metabolismus   MeSH
• thromboxan B2 analogy a deriváty   krev   metabolismus   MeSH
• trombocyty účinky léků   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• srovnávací studie MeSH

BACKGROUND: Thromboxane B2 (TxB2) and particularly 11-dehydrothromboxane B2 (11-dTxB2) are widely used as prognostic risk markers of platelet activation in cardiovascular diseases. The main errors in TxB2 and 11-dTxB2 determination include either low concentrations of circulating TxB2 (1 - 2 pg/mL) and 11-dTxB2 (0.9 - 4.3 pg/mL) or rather high transiency (mean TxB2 half-life is approximately 5 minutes) as well as an incorrect pre-analytical phase set up. The aim of this study was to investigate the impact of a widely used purification step on the results of enzyme immunosorbent assay (EIA)--based measurement of the two selected thromboxanes. METHODS: For the purpose of this study, 20 plasma samples (10 healthy donors, 10 patients under treatment with acetylsalicylic acid) were screened for TxB2 and 11-dTxB2 concentrations using commercial competitive EIA kits (Cayman Chemicals, Tallinn, Estonia; Neogen, Lexington, KY, USA) with or without the introduction of the purification procedure. RESULTS: The purification step does not significantly affect the results of EIA measurements of the two of TxA2 metabolites (TxB2, 11-dTxB2) in human plasma. The levels of TxB2 and 11-dTxB2 determined in the plasma samples were not significantly changed (p < 0.05) when the purification step was omitted compared to the purified samples. CONCLUSIONS: This study establishes a protocol allowing for reliable and reproducible plasma TxB2 and 11-dTxB2 EIA measurement for routine basic screening of platelet function.

• MeSH
• aktivace trombocytů účinky léků   MeSH
• antiflogistika nesteroidní farmakologie   MeSH
• Aspirin farmakologie   MeSH
• extrakce na pevné fázi metody   MeSH
• imunoenzymatické techniky metody   MeSH
• kardiovaskulární nemoci krev   diagnóza   MeSH
• lidé MeSH
• prognóza MeSH
• reagenční diagnostické soupravy MeSH
• reprodukovatelnost výsledků MeSH
• thromboxan B2 analogy a deriváty   krev   MeSH
• trombocyty účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Aspirin therapy decreases mortality and ischemic complication rates after coronary artery bypass grafting (CABG). However, platelet inhibition after oral aspirin seems to be insufficient in the early postoperative period. There are incomplete data reporting aspirin efficacy early after CABG. The aim of this study was to assess the pharmacologic effect of aspirin on platelets in the first postoperative days using the most specific laboratory tests for the evaluation of aspirin efficacy. DESIGN: A prospective study. SETTING: A clinical study in one cardiac surgery center and measurements in two pharmacologic institutions. PARTICIPANTS: Thirty patients. INTERVENTIONS: Postoperative aspirin efficacy (200 mg/d) was assessed by the suppression of serum thromboxane B(2) (TxB(2)) and by arachidonic acid-induced aggregometry using the MULTIPLATE analyzer. Samples were collected before surgery and on postoperative days 1-5. METHODS AND MAIN RESULTS: The median baseline value (range) of serum TxB(2) was 1.6 ng/mL (1.4-1.9). The median TxB(2) inhibition >90% (the value required for full platelet inhibition) was not achieved until day 5 (-91%, 0.13 ng/mL [0.08-0.22], p < 0.001) and in only 55% of patients. The median baseline ASPI value was 805 (640-975) aggregation units (AU)*min. A significant decrease in aspirin insufficiency was not seen before postoperative day 5 (390 [243-621], p < 0.003) and only 34% of patients reached an effective platelet inhibition on day 5 (cutoff < 300 AU*min). CONCLUSIONS: The effect of aspirin on inhibition of TxB(2) production and arachidonic acid-induced platelet aggregation is impaired during the first postoperative days after CABG. A more effective antiplatelet strategy presumably could increase early graft patency and improve clinical outcomes after CABG.

• MeSH
• agregace trombocytů účinky léků   MeSH
• Aspirin farmakologie   MeSH
• inhibitory agregace trombocytů farmakologie   MeSH
• koronární bypass MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři MeSH
• thromboxan B2 biosyntéza   MeSH
• trombocyty účinky léků   fyziologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIM: Elevated urinary 11-dehydrothromboxane levels place patients at an increased risk for experiencing cardiovascular events. Statins exert an inhibitory effect on platelets. The aim of our study was to determine the effect of 3-month statin therapy on 11-dehydrothromboxane elimination in two groups of patients, one not receiving antiplatelet therapy with acetylsalicylic acid and the other receiving 100 mg acetylsalicylic acid per day. METHODS: We examined the urinary levels of 11-dehydrothromboxane in a total of 58 patients before and after 3-month therapy with a statin at standard doses (simvastatin, fluvastatin, atorvastatin). We also examined the plasma levels of total cholesterol, triglycerides, LDL- and HDL-cholesterol, C-reactive protein, and blood glucose. RESULTS: After 3-month statin therapy, both groups of patients (with and without antiplatelet therapy) showed a significant decrease in urinary 11-dehydrothromboxane levels. Significant decreases were also seen in LDL- and total cholesterol, and C-reactive protein. Changes in the other parameters were not significant. CONCLUSION: Three-month statin therapy significant reduces the rate of 11-dehydrothromboxane elimination, even in patients on acetylsalicylic acid. In addition to its usual lipid-lowering effect, it significantly decreases the plasma levels of C-reactive protein. Combination therapy with a statin plus acetylsalicylic acid may be effective even in patients with incomplete thromboxane inhibition on antiplatelet therapy with acetylsalicylic acid.

• MeSH
• Aspirin terapeutické užití   MeSH
• biologické markery krev   moč   MeSH
• C-reaktivní protein metabolismus   MeSH
• časové faktory MeSH
• down regulace MeSH
• HDL-cholesterol krev   MeSH
• indoly terapeutické užití   MeSH
• inhibitory agregace trombocytů terapeutické užití   MeSH
• krevní glukóza metabolismus   MeSH
• kyseliny heptylové terapeutické užití   MeSH
• kyseliny mastné mononenasycené terapeutické užití   MeSH
• LDL-cholesterol krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pyrroly terapeutické užití   MeSH
• senioři MeSH
• simvastatin terapeutické užití   MeSH
• statiny terapeutické užití   MeSH
• thromboxan B2 analogy a deriváty   moč   MeSH
• triglyceridy krev   MeSH
• trombocyty účinky léků   metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH

The role of platelets in hemostasis may be influenced by alteration of the platelet redox state-the presence of antioxidants and the formation of reactive oxygen and nitrogen species. We investigated the effects of two antioxidants, resveratrol and trolox, on platelet activation. Trolox and resveratrol inhibited aggregation of washed platelets and platelet-rich plasma activated by ADP, collagen, and thrombin receptor-activating peptide. Resveratrol was a more effective agent in reducing platelet static and dynamic adhesion in comparison with trolox. The antioxidant capacity of resveratrol was, however, the same as that of trolox. After incubation of platelets with antioxidants, the resveratrol intraplatelet concentration was about five times lower than the intracellular concentration of trolox. Although both antioxidants comparably lowered hydroxyl radical and malondialdehyde production in platelets stimulated with collagen, TxB(2) levels were decreased by resveratrol much more effectively than by trolox. Cyclooxygenase 1 was inhibited by resveratrol and not by trolox. Our data indicate that antioxidants, apart from nonspecific redox or radical-quenching mechanisms, inhibit platelet activation also by specific interaction with target proteins. The results also show the importance of studying platelet activation under conditions of real blood flow in contact with reactive surfaces, e.g., using dynamic adhesion experiments.

• MeSH
• agregace trombocytů fyziologie   účinky léků   MeSH
• antioxidancia farmakologie   MeSH
• buněčná adheze fyziologie   účinky léků   MeSH
• chromany (dihydrobenzopyrany) farmakologie   MeSH
• cyklooxygenasa 1 metabolismus   MeSH
• hemostáza účinky léků   MeSH
• kolagen MeSH
• kultivované buňky MeSH
• lidé MeSH
• malondialdehyd metabolismus   MeSH
• stilbeny farmakologie   MeSH
• thromboxan B2 metabolismus   MeSH
• trombocyty fyziologie   účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

• MeSH
• androstadieny farmakologie   MeSH
• dinoproston biosyntéza   MeSH
• financování organizované MeSH
• inhibitory cyklooxygenasy MeSH
• kyseliny mastné neesterifikované krev   MeSH
• ledviny enzymologie   MeSH
• membránové proteiny MeSH
• obezita enzymologie   MeSH
• potkani Zucker MeSH
• prostaglandinové endoperoxidy syntetické analýza   MeSH
• thromboxan B2 biosyntéza   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH