• MeSH
• Aspirin * farmakokinetika   farmakologie   terapeutické užití   MeSH
• diabetes mellitus * farmakoterapie   patologie   MeSH
• inhibitory agregace trombocytů MeSH
• komplikace diabetu MeSH
• lidé MeSH
• megakaryocyty patologie   MeSH
• trombocyty patologie   účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH

Androgen deprivation therapy has long been the first-line treatment for hormone-sensitive prostate cancer (HSPC). After progression to castration-resistant prostate cancer (CRPC), androgen receptor pathway inhibitors (ARPIs) are commonly used. Recently, combined therapy with androgen deprivation and an ARPI has been recommended for metastatic HSPC patients. Novel markers are urgently needed for monitoring this disease and for making therapeutic decisions. Plasma samples were collected from 140 patients with either metastatic HSPC (n = 72) or CRPC (n = 68) before the start of ARPI therapy. Digital PCR was used to assess AR gene amplification, while the expression levels of miR-375 were measured by quantitative PCR. Sixteen other clinical markers were also evaluated, including prostate-specific antigen (PSA), chromogranin A (CGA), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), C-reactive protein (CRP), lymphocyte-to-monocyte ratio, and platelet count. A multivariate analysis, adjusted for age and metastatic dissemination, identified miR-375 expression and lymphocyte-to-monocyte ratio to be the independent negative predictors of ARPI therapy failure in CRPC patients. Regarding the HSPC patients, this article reports the primary finding of the independent negative predictive value of platelet count, CRP, and CGA for the failure of combined androgen deprivation therapy and ARPI.

• MeSH
• androgenní receptory genetika   MeSH
• C-reaktivní protein * metabolismus   MeSH
• chromogranin A * krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• mikro RNA * genetika   krev   MeSH
• nádorové biomarkery krev   MeSH
• nádory prostaty rezistentní na kastraci * krev   genetika   patologie   farmakoterapie   diagnóza   MeSH
• neúspěšná terapie MeSH
• prognóza MeSH
• prostatický specifický antigen * krev   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• trombocyty * metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Metabolic syndrome is a significant pro-inflammatory and pro-coagulant condition. The clinical association of adiponectin, a mainly antidiabetogenic molecule, and its interaction with platelets and platelet indices remains insufficiently investigated. OBJECTIVE: The aim of our study was to investigate the association of adiponectin with platelets and platelet indices in patients with metabolic syndrome. METHODS: The investigation was conducted as a cross-sectional study involving 113 subjects: 63 patients with the diagnosis of metabolic syndrome, and 50 healthy controls - with clear inclusion and exclusion criteria. The group of patients with metabolic syndrome was divided into two subgroups according to the platelet/high-density lipoprotein (HDL) ratio. RESULTS: The subgroup with a higher platelet/HDL ratio was prediabetic. In the same subgroup of patients, a positive correlation between the adiponectin and mean platelet volume (MPV) was seen, while linear regression (95% CI) confirmed the association. CONCLUSION: Considering that MPV is the index that indicates average platelet volume and activity, we believe this association with adiponectin can represent a protective compensatory response in patients with metabolic syndrome and prediabetes. Our results provide a basis for a more precise selection of patients in whom the future therapeutic application of recombinant adiponectin would be most effective.

• MeSH
• adiponektin * krev   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolický syndrom * krev   MeSH
• průřezové studie MeSH
• střední objem trombocytu * MeSH
• studie případů a kontrol MeSH
• trombocyty metabolismus   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Chelation is the rational treatment modality in metal overload conditions, but chelators are often non-selective and can, hence, cause an imbalance in the homeostasis of physiological metals including calcium and magnesium. The aim of this study was to develop an affordable, rapid but sensitive and precise method for determining the degree of chelation of calcium and magnesium ions and to employ this method for comparison on a panel of known metal chelators. Spectrophotometric method using o-cresolphthalein complexone (o-CC) was developed and its biological relevance was confirmed in human platelets by impedance aggregometry. The lowest detectable concentration of calcium and magnesium ions by o-CC was 2.5 μM and 2 μM, respectively. The indicator was stable for at least 110 days. Four and seven out of twenty-one chelators strongly chelated calcium and magnesium ions, respectively. Importantly, the chelation effect of clinically used chelators was not negligible. Structure-activity relationships for eight quinolin-8-ols showed improvements in chelation particularly in the cases of dihalogen substitution, and a negative linear relationship between pKa and magnesium chelation was observed. Calcium chelation led to inhibition of platelet aggregation in concentrations corresponding to the complex formation. A novel method for screening of efficacy and safety of calcium and magnesium ion chelation was developed and validated.

• MeSH
• agregace trombocytů účinky léků   MeSH
• chelátory * chemie   MeSH
• hořčík * chemie   MeSH
• lidé MeSH
• preklinické hodnocení léčiv metody   MeSH
• trombocyty účinky léků   metabolismus   MeSH
• vápník * analýza   metabolismus   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

• MeSH
• akutní koronární syndrom komplikace   patofyziologie   MeSH
• enzymy klasifikace   metabolismus   MeSH
• epoprostenol fyziologie   MeSH
• intrakraniální embolie a trombóza * komplikace   patofyziologie   MeSH
• kyselina arachidonová metabolismus   MeSH
• lidé MeSH
• mastné kyseliny * fyziologie   metabolismus   MeSH
• nenasycené mastné kyseliny fyziologie   metabolismus   MeSH
• trombocyty enzymologie   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND AND PURPOSE: Although the amphiphilic nature of the widely used antithrombotic drug Ticagrelor is well known, it was never considered as a membranotropic agent capable of interacting with the lipid bilayer in a receptor-independent way. In this study, we investigated the influence of Ticagrelor on plasma membrane lipid order in platelets and if this modulates the potency of Ticagrelor at the P2Y12 receptor. EXPERIMENTAL APPROACH: We combined fluorescent in situ, in vitro and in silico approaches to probe the interactions between the plasma membrane of platelets and Ticagrelor. The influence of Ticagrelor on the lipid order of the platelet plasma membrane and large unilamellar vesicles was studied using the advanced fluorescent probe NR12S. Furthermore, the properties of model lipid bilayers in the presence of Ticagrelor were characterized by molecular dynamics simulations. Finally, the influence of an increased lipid order on the dose-response of platelets to Ticagrelor was studied. KEY RESULTS: Ticagrelor incorporates spontaneously into lipid bilayers and affects the lipid order of the membranes of model vesicles and isolated platelets, in a nontrivial composition and concentration-dependent manner. We showed that higher plasma membrane lipid order in platelets leads to a lower IC50 value for Ticagrelor. It is shown that membrane incorporation of Ticagrelor increases its potency at the P2Y12 receptor, by increasing the order of the platelet plasma membrane. CONCLUSION AND IMPLICATIONS: A novel dual mechanism of Ticagrelor action is suggested that combines direct binding to P2Y12 receptor with simultaneous modulation of receptor-lipid microenvironment.

• MeSH
• antagonisté purinergních receptorů P2Y farmakologie   chemie   MeSH
• buněčná membrána * účinky léků   metabolismus   MeSH
• lidé MeSH
• lipidové dvojvrstvy metabolismus   MeSH
• membránové lipidy metabolismus   MeSH
• purinergní receptory P2Y12 * metabolismus   účinky léků   MeSH
• simulace molekulární dynamiky MeSH
• ticagrelor * farmakologie   chemie   MeSH
• trombocyty * účinky léků   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cíl: Vliv autoplazmy obohacené o krevní destičky na tloušťku endometria a citlivost receptorů na estrogen a progesteron. Materiál a metody: Do této prospektivní studie bylo zařazeno 200 pacientek. Účastnice studie byly rozděleny do dvou skupin. První, kontrolní skupina dostávala hormonální substituční terapii (HRT – hormone replacement therapy). Druhá, studijní skupina dostávala intrauterinní infuzi autoplazmy obohacené o krevní destičky (PRP – platelet-rich autoplasma). Devatenáctý den menstruačního cyklu bylo provedeno ultrazvukové vyšetření s cílem zhodnotit tloušťku endometria a dále imunohistochemická analýza k stanovení citlivosti receptorů pro estrogen a progesteron. Výsledky: Během studie jsme zjistili, že po podání autoplazmy obohacené o krevní destičky se zvýšila tloušťka endometria o 0,85 mm; průměrná tloušťka endometria ve skupině na terapii PRP byla 8,25 mm (8,25–8,61 mm) a ve skupině pacientek, které dostávaly pouze HRT, byla 7,40 mm (7,34–7,65 mm). Citlivost receptorů pro estrogen se v experimentální skupině zvýšila o 3,5, přičemž v této skupině dosáhla hodnoty 75,00 (71,43–74,22) a v kontrolní skupině 71,50 (67,05–70,85). Citlivost receptorů pro progesteron se zvýšila o 9,0, hodnota v této skupině byla 95,0 (91,4–93,8) a v kontrolní skupině 86,0 (83,47–86,27). Závěr: Díky působení destičkových faktorů má terapie PRP pozitivní vliv na endometrium, kdy zvyšuje jeho tloušťku a zlepšuje receptivitu. Je tedy možné vyvodit závěr, že tato metoda zřejmě nalezne velké praktické uplatnění při zlepšování výsledků programů asistované reprodukce.

Aim: The effect of platelet-rich autoplasma on endometrial thickness and receptor sensitivity to estrogen and progesterone. Materials and methods: This prospective clinical study included 200 patients. The participants in the study were divided into two groups. The first control group received hormone replacement therapy (HRT). The second study group received an intrauterine infusion of platelet-rich autoplasma (PRP group). On the 19th day of the menstrual cycle, an ultrasound examination was performed to assess endometrial thickness, as well as an immunohistochemical analysis to determine receptor sensitivity to estrogen and progesterone. Results: In the course of the study, we found that the use of platelet-rich autoplasma increased the thickness of the endometrium by 0.85 mm; the average thickness of the endometrium in the group who received PRP therapy was 8.25 (8.25–8.61) mm; and in the group of patients who only received HRT, it was 7.40 (7.34–7.65) mm. The sensitivity of receptors to estrogen in the experimental group increased by 3.5, in the experimental group it was 75.00 (71.43–74.22), and in the control group it was 71.50 (67.05–70.85). The sensitivity of receptors to progesterone also increased by 9.0, in the experimental group it was 95.0 (91.4–93.8), and in the control group it was 86.0 (83.47–86.27). Conclusion: Due to the action of platelet factors, PRP therapy has a positive effect on the endometrium, increasing its thickness and improving its receptivity. Therefore, it can be concluded that this method can find great practical application to improve the outcomes of assisted reproductive technology programs.

• Klíčová slova
• autoplazma,
• MeSH
• dospělí MeSH
• endometrium * anatomie a histologie   krevní zásobení   patologie   MeSH
• hormonální substituční terapie metody   MeSH
• imunohistochemie MeSH
• lidé MeSH
• parenterální infuze * metody   MeSH
• prospektivní studie MeSH
• statistika jako téma MeSH
• steroidní receptory MeSH
• trombocyty MeSH
• ultrasonografie MeSH
• velikost orgánu MeSH
• ženská infertilita etiologie   terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinická studie MeSH

Zhodnotit prognostickou hodnotu skóre s použitím hodnot hemoglobinu, albuminu, lymfocytů a trombocytů (hemoglobin, albumin, lymphocyte, and platelet, HALP) u akutní plicní embolie (APE). Metody: Retrospektivně jsme vyhodnotili údaje pacientů ve věku 18 let a starších, u nichž CT angiografické vyšetření plic na oddělení urgentního příjmu v období mezi lednem 2019 a lednem 2023 prokázalo APE. Byly vyhodnoceny klinické a demografické údaje pacientů a následně vypočítán zjednodušený index závažnosti jejich plicní embolie. Skóre HALP se vypočítávalo z prvního krevního vzorku odebraného po přivezení pacienta na oddělení urgentního příjmu; přitom se používala rovnice HALP: hemoglobin × albumin × lymfocyty / trombocyty. Výsledky: U 277 pacientů s APE, zařazených do studie, dosáhla nemocniční mortalita hodnoty 19,1 %. Skóre HALP zemřelých pacientů bylo statisticky významně vyšší než skóre přeživších (p < 0,001). Mezní hodnota skóre HALP na křivce ROC pro nemocniční mortalitu byla 3,21 (senzitivita: 81,13 %; specificita: 84,37 %; plocha pod křivkou ROC: 0,879; 95% interval spolehlivosti [confidence interval, CI] 0,827–0,930; p < 0,001). Na základě těchto mezních hodnot byla provedena logistická regresní analýza a multivariační logistická analýza prokázala, že skóre HALP (poměr šancí: 0,24; 95% CI: 0,17–0,96) je nezávislým ukazatelem mortality. Závěr: Zjistili jsme, že skóre HALP, zahrnující čtyři hematologické parametry, může sloužit jako cenný biomarker v predikci nemocniční mortality.

To investigate the prognostic value of the hemoglobin, albumin, lymphocyte, and platelet (HALP) score in acute pulmonary embolism (APE). Methods: We retrospectively evaluated patients aged 18 years and over who were diagnosed with APE by computed tomography pulmonary angiography at the emergency department (ED) between January 2019 and January 2023. The patients' clinical and demographic data were evaluated, and their simplified pulmonary embolism severity index values were calculated. The HALP score was obtained using the first blood sample measured after the patients were admitted to the ED. The HALP score was calculated according to the formula: HALP = hemoglobin × albumin × lymphocytes / platelets Results: The in-hospital mortality rate was 19.1% in 277 patients with APE included in the study. The HALP score of the patients who died was significantly lower than the HALP score of those who survived (p <0.001). The cut-off value of the HALP score on the receiver operating characteristic (ROC) curve for in-hospital mortality was 3.21 (sensitivity: 81.13%; specificity: 84.37%; area under the ROC curve [AUC]: 0.879, 95% confidence interval [CI]: 0.827-0.930, p <0.001). A logistic regression analysis was performed based on these cut-off values, and the multivariate logistic regression analysis revealed that the HALP score (odds ratio: 0.24, 95% CI: 0.17-0.96) was an independent indicator of mortality. Conclusion: Our findings showed that the HALP score, which comprises four hematological parameters, can be a valuable biomarker that can be used to predict in-hospital mortality.

• MeSH
• albuminy analýza   MeSH
• biologické markery * analýza   MeSH
• hemoglobiny analýza   MeSH
• lidé MeSH
• lymfocyty MeSH
• plicní embolie * diagnóza   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• trombocyty MeSH
• Check Tag
• lidé MeSH

BACKGROUND AND AIMS: It is well known that elevated cholesterol is associated with enhanced platelet aggregation and patients suffering from familial hypercholesterolemia (FH) have a high risk of thrombotic cardiovascular events. Although decreasing cholesterol level is associated with attenuation of platelet hyperactivity, there are currently no data on the effect of convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9ab) on platelet reactivity in FH. The aim of the study was to analyse the impact of different therapies including PCSK9ab on platelet aggregation in FH. METHODS: This study enrolled all 15 patients treated in the University Hospital Hradec Králové for FH. PCSK9ab have been administered in 12 of 15 patients while 8 patients were also undergoing lipid apheresis. Blood samples from all patients including pre- and post-apheresis period were tested for platelet aggregation triggered by 7 inducers, and the effect of 3 clinically used drugs (acetylsalicylic acid, ticagrelor and vorapaxar) was compared as well. RESULTS: Although apheresis decreased the reactivity of platelets in general, platelet responses were not different between non-apheresis patients treated with PCSK9ab and apheresis patients (post-apheresis values) with the exception of ristocetin. However, when compared to age-matched healthy population, FH patients had significantly lower platelet aggregation responses to 4 out of 7 used inducers and higher profit from 2 out of 3 used antiplatelet drugs even after exclusion of FH patients regularly receiving conventional antiplatelet treatment. CONCLUSION: This study showed for the first time the suitability of PCSK9ab treatment for reduction of platelet reactivity in FH patients.

• MeSH
• agregace trombocytů * účinky léků   MeSH
• dospělí MeSH
• hyperlipoproteinemie typ II * krev   terapie   farmakoterapie   MeSH
• inhibitory agregace trombocytů * terapeutické užití   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   farmakologie   MeSH
• PCSK9 inhibitory * MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 * imunologie   MeSH
• senioři MeSH
• separace krevních složek * MeSH
• trombocyty účinky léků   metabolismus   imunologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: We previously reported that the "Endothelial Activation and Stress Index" (EASIX; ((creatinine×lactate dehydrogenase)÷thrombocytes)) measured before start of conditioning predicts mortality after allogeneic hematopoietic stem cell transplantation (alloSCT) when used as continuous score. For broad clinical implementation, a prospectively validated EASIX-pre cut-off is needed that defines a high-risk cohort and is easy to use. METHOD: In the current study, we first performed a retrospective cohort analysis in n=2022 alloSCT recipients and identified an optimal cut-off for predicting non-relapse mortality (NRM) as EASIX-pre=3. For cut-off validation, we conducted a multicenter prospective study with inclusion of n=317 first alloSCTs from peripheral blood stem cell in adult patients with acute leukemia, lymphoma or myelodysplastic syndrome/myeloproliferative neoplasms in the European Society for Blood and Marrow Transplantation network. RESULTS: Twenty-three % (n=74) of alloSCT recipients had EASIX-pre ≥3 taken before conditioning. NRM at 2 years was 31.1% in the high EASIX group versus 11.5% in the low EASIX group (p<0.001). Patients with high EASIX-pre also had worse 2 years overall survival (51.6% vs 70.9%; p=0.002). We were able to validate the cut-off and found that EASIX ≥3 was associated with more than twofold increased risk for NRM in multivariate analysis (HR=2.18, 95% CI 1.2 to 3.94; p=0.01). No statistically significant difference could be observed for the incidence of relapse. CONCLUSIONS: The results of this study provide a prospectively validated standard laboratory biomarker index to estimate the transplant-related mortality risk after alloSCT. EASIX ≥3 taken before conditioning identifies a population of alloSCT recipients who have a more than twofold increased risk of treatment-related mortality.

• MeSH
• dospělí MeSH
• kreatinin MeSH
• lidé MeSH
• prospektivní studie MeSH
• retrospektivní studie MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   MeSH
• trombocyty MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH