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1.
J Med Biochem ; 43(4): 397-405, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-39139153

RESUMEN

Background: Post-operative atrial fibrillation (POAF) is a frequent complication after cardiac surgery. It is associated with prolonged hospital stay, increased morbidity, mortality rate and economic costs. The aim of the study was to determine the association between the values of Galectin3 and N-terminal pro-B-type natriuretic peptide (NTproBNP) with POAF after cardiac surgery. Methods: A prospective study enrolled patients aged 18-85 years old admitted due to elective coronary artery bypass graft surgery (CABG) or CABG + aortic valve replacement. The plasma Galectin-3 and NT-proBNP levels were measured one day before surgery postoperative days 1 and 7. Results: The study included a total of 103 patients. POAF was registered in 45 patients. The mean age of patients in whom POAF occurred was 68.8 years, while other patients' mean age was 65.5 years (p=0.028). Patients with POAF did not differ from the group without POAF in the values of Galectin-3 and NT-proBNP preoperatively as well as on the first and seventh postoperative days. Changes in Galectin-3 levels on the first postoperative day had statistically significant value for predicting POAF (AUC=0.627 0.509-0.745 , p<0.05). Decrease in Galectin-3 level con centration on the first postoperative day over 17% increases the risk of developing AF. Conclusions: Preoperative values of Galectin-3 and NTproBNP are not associated with POAF development after cardiac surgery.

3.
Diagnostics (Basel) ; 13(21)2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37958244

RESUMEN

BACKGROUND: Galectin-3 (Gal-3) is a biomarker involved in a wide range of diseases including cardiac remodeling following acute myocardial infarction (AMI). Identification of prognostic markers in patients with AMI can guide strategies towards improved survival and quality of life. METHODS: Our study included 59 patients with AMI and a preserved ejection fraction. We determined the Gal-3 plasma concentration within 24 h of chest pain onset from the aortic root, femoral/radial artery, coronary sinus and cubital vein. Major adverse cardiovascular events (MACEs) were evaluated at six months follow-up. RESULTS: MACE at six months post-AMI was recorded in 20 patients (34%). The Gal-3 plasma concentration from the aortic root and the femoral/radial artery were independent predictors of MACE at six months follow-up after the first AMI (OR 1.228; 95%CI: 1.011-1.491; p = 0.038; OR 3.438; 95%CI: 1.275-9.265; p = 0.015). ROC analysis identifies the Gal-3 plasma concentration from the aortic root as a better predictor of MACE or death (cut-off ≥ 10.86 ng/mL; AUC 0.858; 95%CI: 0.744-0.973; p < 0.001) than Gal-3 plasma concentration from the femoral/radial artery (cut-off ≥ 10.18 ng/mL; AUC 0.742; 95%CI: 0.596-0.888; p = 0.006). CONCLUSION: the Gal-3 plasma concentration in patients with AMI determined during coronary angiography, especially from the aortic root, within 24 h after chest pain onset is a valuable biomarker of prognosis at six months follow-up.

4.
Ceska Gynekol ; 88(4): 291-293, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37643911

RESUMEN

Pure uterine lipomas are extremely rare benign uterine tumors. This paper presents the case of a 68-year-old patient with symptomatic leiomyoma-like fundus formation on ultrasound. A hysterectomy was performed with anterior vaginal plastic surgery as a treatment option for concomitant cystocele grade II. Histological diagnosis of pure uterine lipoma with S-100 positive immunohistochemical staining was confirmed. This case shows us that uterine lipoma clinically and diagnostically mimics myoma very well. We believe that surgery as a therapeutical approach is justified in symptomatic patients.


Asunto(s)
Leiomioma , Lipoma , Femenino , Humanos , Anciano , Útero , Histerectomía , Lipoma/diagnóstico , Lipoma/cirugía , Vagina , Proteínas S100
5.
Sci Rep ; 13(1): 6770, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-37185606

RESUMEN

The aim of this study was to compare QT dispersion (QTd) and echocardiographic parameters in male athletes competing across different sports (long-distance running, volleyball, football, powerlifting, and bodybuilding) and a control population. Significant moderate-strong differences (p < 0.001, [Formula: see text] = 0.52-0.71) were found in corrected QTd, intraventricular septal wall thickness (ISWT), posterior wall thickness (PWT), relative wall thickness (RWT) and LV (left ventricular) index between groups. Corrected QTd, ISWT, PWT, and RWT were significantly (p < 0.001) higher in powerlifters and bodybuilders compared to other athlete groups and controls. While all athlete groups displayed a significantly higher LV index (p < 0.05) compared to controls, corrected QTd was significantly lower (p < 0.001) only in long-distance runners, volleyball athletes, and football athletes compared to controls. Normal or eccentric LV hypertrophy (LVH) was observed in most long-distance runners (58% and 33%), volleyball athletes (50% and 50%), and football athletes (56% and 41%). In contrast, concentric LVH was observed in most powerlifters (58%) and bodybuilders (54%). Advanced LVH, predominantly concentric in nature, appears to be accompanied with increased QTd in powerlifters and bodybuilders. On the other hand, runners, volleyball athletes, and football athletes experienced LVH toward the upper threshold of the normal reference range alongside reduced QTd compared to other groups.


Asunto(s)
Fútbol Americano , Carrera , Humanos , Masculino , Ecocardiografía , Atletas , Ventrículos Cardíacos , Hipertrofia Ventricular Izquierda
6.
Biomed Chromatogr ; 37(9): e5663, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37113052

RESUMEN

A simple HPLC method was developed for the determination of antiplatelet drug ticagrelor (TCG) in blood. Sample preparation and extraction conditions were investigated and optimized. The preparation of blood plasma was investigated by protein precipitation using perchloric acid, methanol, acetonitrile (ACN), and trifluoroacetic acid. Protein precipitation using ACN was found to be the most suitable. Chromatographic separation of TCG was performed on a C18 column with a mobile phase consisting of ACN and 15 mM ammonium acetate buffered at pH 8.0. The method was applied to determine TCG in blood plasma of patients who had a heart attack. Blood samples were collected 1.5 h after the administration of the initial loading dose of the antiplatelet drug. The average concentration of TCG was found to be 0.97 ± 0.53 µg/ml. The developed method proved to be very selective, without interferences from other endogenous substances and the influences of possible coadministered drugs. The limits of detection and quantification estimated by the signal-to-noise ratio in real samples were 0.24 and 0.4 µg/ml, respectively. The developed method is simple and can be easily applied in clinics and emergency cardiac situations after the initial loading dose of TCG in the first few hours of a heart attack.


Asunto(s)
Síndrome Coronario Agudo , Infarto del Miocardio , Humanos , Ticagrelor , Inhibidores de Agregación Plaquetaria , Cromatografía Líquida de Alta Presión/métodos , Síndrome Coronario Agudo/tratamiento farmacológico , Plasma
7.
Biomolecules ; 13(2)2023 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-36830764

RESUMEN

Heart failure (HF) is the leading cause of hospitalisations worldwide, with only 35% of patients surviving the first 5 years after diagnosis. The pathogenesis of HF with preserved ejection fraction (HFpEF) is still unclear, impeding the implementation of effective treatments. FK506-binding protein like (FKBPL) and its therapeutic peptide mimetic, AD-01, are critical mediators of angiogenesis and inflammation. Thus, in this study, we investigated-for the first time-FKBPL's role in the pathogenesis and as a biomarker of HFpEF. In vitro models of cardiac hypertrophy following exposure to a hypertensive stimulus, angiotensin-II (Ang-II, 100 nM), and/or AD-01 (100 nM), for 24 and 48 h were employed as well as human plasma samples from people with different forms of HFpEF and controls. Whilst the FKBPL peptide mimetic, AD-01, induced cardiomyocyte hypertrophy in a similar manner to Ang-II (p < 0.0001), when AD-01 and Ang-II were combined together, this process was abrogated (p < 0.01-0.0001). This mechanism appears to involve a negative feedback loop related to FKBPL (p < 0.05). In human plasma samples, FKBPL concentration was increased in HFpEF compared to controls (p < 0.01); however, similar to NT-proBNP and Gal-3, it was unable to stratify between different forms of HFpEF: acute HFpEF, chronic HFpEF and hypertrophic cardiomyopathy (HCM). FKBPL may be explored for its biomarker and therapeutic target potential in HFpEF.


Asunto(s)
Insuficiencia Cardíaca , Hipertensión , Humanos , Insuficiencia Cardíaca/diagnóstico , Volumen Sistólico , Proteínas de Unión a Tacrolimus/uso terapéutico , Biomarcadores , Proteínas de Ciclo Celular , Fragmentos de Péptidos
8.
Diabet Med ; 40(5): e15064, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36782075

RESUMEN

AIMS: The aim of this scoping review is to evaluate the current biomarkers used in the assessment of adverse cardiac remodelling in people with diabetes mellitus (DM) and in the diagnosis and prognosis of subsequent cardiovascular disease. We aim to discuss the biomarkers' pathophysiological roles as a reflection of the cardiac remodelling mechanisms in the presence of DM. METHODS: We performed the literature search to include studies from 2003 to 2021 using the following databases: MEDLINE, Scopus, Web of Science, PubMed, and Cochrane library. Articles that met our inclusion criteria were screened and appraised before being included in this review. The PRISMA guidelines for Scoping Reviews were followed. RESULTS: Our literature search identified a total of 43 eligible articles, which were included in this scoping review. We identified 15 different biomarkers, each described by at least two studies, that were used to determine signs of cardiac remodelling in cardiovascular disease (CVD) and people with DM. NT-proBNP was identified as the most frequently employed biomarker in this context; however, we also identified emerging biomarkers including hs-CRP, hs-cTnT, and Galectin-3. CONCLUSION: There is a complex relationship between DM and cardiovascular health, where more research is needed. Current biomarkers reflective of adverse cardiac remodelling in DM are often used to diagnose other CVDs, such as NT-proBNP for heart failure. Hence there is a need for identification of specific biomarkers that can detect early signs of cardiac remodelling in the presence of DM. Further research into these biomarkers and mechanisms can deepen our understanding of their role in DM-associated CVD and lead to better preventative therapies.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus , Humanos , Pronóstico , Remodelación Ventricular , Biomarcadores
9.
Biomolecules ; 12(10)2022 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-36291628

RESUMEN

Heart failure with preserved ejection fraction (HFpEF) accounts for around 50% of all heart failure cases. It is a heterogeneous condition with poorly understood pathogenesis. Here, we aimed to identify unique pathogenic mechanisms in acute and chronic HFpEF and hypertrophic cardiomyopathy (HCM). We performed unbiased, comprehensive proteomic analyses of plasma samples from gender- and BMI-matched patients with acute HFpEF (n = 8), chronic HFpEF (n = 9) and HCM (n = 14) using liquid chromatography-mass spectrometry. Distinct molecular signatures were observed in different HFpEF forms. Clusters of biomarkers differentially abundant between HFpEF forms were predominantly associated with microvascular inflammation. New candidate protein markers were also identified, including leucine-rich alpha-2-glycoprotein 1 (LRG1), serum amyloid A1 (SAA1) and inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3). Our study is the first to apply systematic, quantitative proteomic screening of plasma samples from patients with different subtypes of HFpEF and identify candidate biomarkers for improved management of acute and chronic HFpEF and HCM.


Asunto(s)
Insuficiencia Cardíaca , Humanos , Volumen Sistólico , Proteómica , Leucina , Biomarcadores/metabolismo , Fenotipo , Glicoproteínas
10.
Int J Clin Pract ; 2022: 5913712, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36177364

RESUMEN

Aim: A retrospective study of the occurrence of liver damage and obstetric outcomes in pregnant women diagnosed with pruritus. Methods: The following parameters were monitored in patients: aspartate aminotransferase (AST), alanine aminotransferase, gamma-glutamyl transferase, bilirubin (direct and total), hemoglobin, platelets, serum bile acid level, age of pregnant women, parity, pregnancy weight gain, birth weight, and gestational age at delivery. A total of 107 patients were included during a five-year period (2016-2020) and classified into three groups. Group A included 17 pregnant women with pruritus without elevated liver enzymes and bilirubin. Group B included 50 pregnant women with pruritus, elevated liver enzymes, and bilirubin. Group C included 40 pregnant women with pruritus and elevated bile acids (regardless of liver enzyme levels). Results: The groups did not significantly differ in patients' age and parity, but there was a statistically significant between-group difference in weight gain during pregnancy. The values of AST, ALT, GGT, LDH, and direct bilirubin were the highest in group B, and serum bile acids were expectedly the highest in group C. There was no statistically significant variation in the onset of labor and mode of delivery between groups. However, groups significantly differed in gestational age at delivery, newborn birthweight, and pregnancy prolongation from the onset of pruritus to delivery. Conclusion: Further study is needed to assess the pathophysiologic mechanisms underlying intrahepatic cholestasis of pregnancy as well as any significant liver damage associated with pregnancy.


Asunto(s)
Hígado , Complicaciones del Embarazo , Prurito , Alanina Transaminasa , Aspartato Aminotransferasas , Ácidos y Sales Biliares , Bilirrubina , Femenino , Humanos , Recién Nacido , Hígado/patología , Embarazo , Prurito/complicaciones , Prurito/epidemiología , Estudios Retrospectivos
11.
Curr Pharm Des ; 28(20): 1660-1668, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35593361

RESUMEN

BACKGROUND: Beta-adrenergic (ß-AR) receptor blockers (BBs) are an essential class of drugs as they have numerous indications. On the other hand, they have numerous unwanted effects that decrease the compliance, adherence, and persistence of this very useful group of drugs. OBJECTIVE: The paper aims to analyze the possibility that an unnoticed side effect may contribute to a less favorable pharmacologic profile of BBs, e.g., a diminished reaction to a sudden fall in BP. METHODS: We searched two medical databases for abstracts and citations (Medline and SCOPUS). Moreover, we searched the internet for drug prescription leaflets (of the individual BBs). RESULTS: Whichever cause of stress is considered, the somatic manifestations of stress will be (partially) masked if a patient takes BB. Stress-induced hypercatecholaminemia acts on ß-AR of cardiomyocytes; it increases heart rate and contractility, effects suppressed by BBs. The answers of the organism to hypoglycemia and hypotension share the main mechanisms such as sympathetic nervous system activation and hypercatecholaminemia. Thus, there is a striking analogy: BBs can cover up symptoms of both hypoglycemia (which is widely known) and of hypotension (which is not recognized). It is widely known that BBs can cause hypotension. However, they can also complicate recovery by spoiling the defense mechanisms in hypotension as they interfere with the crucial compensatory reflex to increase blood pressure in hypotension. CONCLUSION: Beta blockers can cause hypotension, mask it, and make recovery more difficult. This is clinically important and deserves to be more investigated and probably to be stated as a warning.


Asunto(s)
Hipoglucemia , Hipotensión , Antagonistas Adrenérgicos beta/efectos adversos , Presión Sanguínea , Frecuencia Cardíaca , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/tratamiento farmacológico , Hipotensión/inducido químicamente , Hipotensión/tratamiento farmacológico
12.
Medicina (Kaunas) ; 58(2)2022 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-35208606

RESUMEN

Background and Objectives: Given the fact that galectin-3 has a predictive significance on the development of myocardial dysfunction after acute myocardial infarction, the aim of our study was to examine potential factors that could be important for the dynamics of the concentration of this biomarker in the early postinfarction period. Materials and Methods: This study included 89 patients with a diagnosis of stable angina pectoris (SAP) or the first non-ST elevation (NSTEMI) or ST-elevation (STEMI) myocardial infarction, who underwent percutaneous coronary intervention (PCI). The study group included 23 patients with the first NSTEMI and 42 patients with STEMI, while the control group consisted of 24 patients with SAP hospitalized for elective PCI without a previous MI. All patients had preserved left ventricular ejection fraction. Galectin-3 levels were determined on days 1, 5, and 30 after PCI. The significance of various independent variables as predictors of galectin-3 concentration was analyzed after a series of univariate linear regression modeling in a multivariate linear regression model. Results: The average patients' age was 63.99 ± 9.13 years. Statistically significantly higher values of C-reactive protein were established in STEMI compared to SAP (p < 0.01) or NSTEMI (p < 0.001), whereas WBC count was significantly lower in SAP than in STEMI (p < 0.001) and NSTEMI (p < 0.01) group. Although there were no statistically significant differences in measured galectin-3 concentrations between the examined groups on days 1, 5, and 30 after PCI, HTA, triglyceride level, LA size, treatment with trimetazidine and long-acting nitrates, as well as percentage of LM stenosis and E/A ratio were identified as independent predictors of galectin-3 concentration. Conclusions: In the post-MI period, very early values of galectin-3 correlate mostly with atherosclerosis factors, while on day 30 this biomarker correlates with diastolic dysfunction and "announces" left ventricular remodeling.


Asunto(s)
Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Anciano , Galectina 3 , Humanos , Persona de Mediana Edad , Sistema de Registros , Infarto del Miocardio con Elevación del ST/cirugía , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular Izquierda
14.
Int J Cardiovasc Imaging ; 37(3): 881-887, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33044719

RESUMEN

Objective We sought to investigate left ventricular (LV) structure, function and mechanics in the patients with leukemia and lymphoma before initiation of chemotherapy, as well as the relationship between hematological malignancies and reduced LV longitudinal strain. Methods This retrospective investigation included 71 patients with leukemia and lymphoma before chemotherapy and 36 healthy controls. All participants underwent echocardiographic examination before initiation of chemotherapy and radiotherapy. Results LV global longitudinal strain (- 20.2 ± 1.7% vs. - 17.9 ± 3.0%, p < 0.001) was significantly lower in the patients with hematological malignancies than in controls. There was no difference in LV circumferential and radial strains between two observed groups. Subendocardial and subepicardial longitudinal strains were significantly lower in the patients with hematological malignancies (- 20.5 ± 3.6% vs. - 22.5 ± 3.8%, p = 0.001 for subendocardial strain; - 18.0 ± 1.5% vs. - 15.8 ± 2.6%, p < 0.001 for subepicardial strain). Hematological malignancies were associated with reduced global LV longitudinal strain (OR 21.0; 95%CI 2.04-215.0, p = 0.010) independently of age, gender, heart rate, body mass index, left ventricular ejection fraction, left ventricular mass index, and glucose level. Conclusions LV longitudinal strain was impaired in the patients with leukemia and lymphoma even before initiation of chemotherapy. Endocardial and epicardial LV layers are equally affected in the patients with hematological malignancies. Newly diagnosed hematological malignancies were related with reduced LV global longitudinal strain independently of common clinical and echocardiographic parameters.


Asunto(s)
Antineoplásicos/uso terapéutico , Ecocardiografía Doppler , Ventrículos Cardíacos/diagnóstico por imagen , Leucemia/terapia , Linfoma/terapia , Disfunción Ventricular Izquierda/diagnóstico por imagen , Función Ventricular Izquierda , Adulto , Antineoplásicos/efectos adversos , Femenino , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Valor Predictivo de las Pruebas , Radioterapia/efectos adversos , Estudios Retrospectivos , Disfunción Ventricular Izquierda/fisiopatología
15.
Curr Vasc Pharmacol ; 18(1): 12-24, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-30289080

RESUMEN

A considerable amount of data supports a 1.8-7.4-fold increased mortality associated with Cushing's syndrome (CS). This is attributed to a high occurrence of several cardiovascular disease (CVD) risk factors in CS [e.g. adiposity, arterial hypertension (AHT), dyslipidaemia and type 2 diabetes mellitus (T2DM)]. Therefore, practically all patients with CS have the metabolic syndrome (MetS), which represents a high CVD risk. Characteristically, despite a relatively young average age, numerous patients with CS display a 'high' or 'very high' CVD risk (i.e. risk of a major CVD event >20% in the following 10 years). Although T2DM is listed as a condition with a high CVD risk, CS is not, despite the fact that a considerable proportion of the CS population will develop T2DM or impaired glucose tolerance. CS is also regarded as a risk factor for aortic dissection in current guidelines. This review considers the evidence supporting listing CS among high CVD risk conditions.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Síndrome de Cushing/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/fisiopatología , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/mortalidad , Síndrome de Cushing/fisiopatología , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Hipertensión/epidemiología , Síndrome Metabólico/epidemiología , Pronóstico , Medición de Riesgo , Factores de Riesgo
16.
Sci Rep ; 9(1): 13145, 2019 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-31511537

RESUMEN

Our study investigates association between Galectin-3 levels and adverse left ventricular remodelling (LVR) at six months. Fifty-seven patients following first acute myocardial infarction (AMI) were enrolled in this study and blood samples collected on day 1 from the femoral vein and artery, the right atrium near the coronary sinus and the aortic root, and on day 30, from the cubital vein. Patients with LVESV ≥20% at six months, were included in the LVR group. On day 1, Galectin-3 plasma levels in the femoral vein (10.34 ng/ml ± 3.81 vs 8.22 ng/ml ± 2.34, p = 0.01), and near coronary sinus (10.7 ng/ml ± 3.97 vs 8.41 ng/ml ± 2.56, p = 0.007) were higher in the LVR group. Positive correlations between Galectin-3 levels from aortic root and coronary sinus, aortic root and femoral vein, and coronary sinus and femoral vein, were observed in both groups. On day 30, Galectin-3 concentration in the cubital vein was an independent risk factor of LVR six months post-AMI, demonstrating 1.5-fold increased risk. Day-30 Galectin-3 also showed positive correlations with echocardiography parameters indicative of diastolic and systolic dysfunction. Determining Galectin-3 plasma concentration on day 30 following AMI could have beneficial prognostic value in predicting LVR.


Asunto(s)
Arteria Femoral/metabolismo , Vena Femoral/metabolismo , Galectina 3/metabolismo , Infarto del Miocardio/metabolismo , Volumen Sistólico , Remodelación Ventricular , Anciano , Proteínas Sanguíneas , Seno Coronario/metabolismo , Ecocardiografía , Femenino , Galectina 3/sangre , Galectinas , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/fisiopatología , Pronóstico , Factores de Tiempo
17.
Comput Biol Chem ; 79: 55-62, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30716601

RESUMEN

Rho kinases, one of the best-known members of the serine/threonine (Ser/Thr) protein kinase family, can be used as target enzymes for the treatment of many diseases such as cancer or multiple sclerosis, and especially for the treatment of cardiovascular diseases. This study presents QSAR modeling for a series of 41 chemical compounds as Rho kinase inhibitors based on the Monte Carlo method. QSAR models were developed for three random splits into the training and test set. Molecular descriptors used for QSAR modeling were based on the SMILES notation and local invariants of the molecular graph. The statistical quality of the developed model, including robustness and predictability, was tested with different statistical approaches and satisfying results were obtained. The best calculated QSAR model had the following statistical parameters: r2 = 0.8825 and q2 = 0.8626 for the training set and r2 = 0.9377 and q2 = 0.9124 for the test set. Novel statistical metric entitled as the index of ideality of correlation was used for the final model assessment, and the obtained results were 0.6631 for the training and 0.9683 for the test set. Molecular fragments responsible for the increases and decreases of the studied activity were defined and they were further used for the computer-aided design of new compounds as potential Rho kinase inhibitors. The final assessment of the developed QSAR model and designed inhibitors was achieved with the application of molecular docking. An excellent correlation between the results from QSAR and molecular docking studies was obtained.


Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Simulación por Computador , Diseño Asistido por Computadora , Inhibidores de Proteínas Quinasas/farmacología , Urea/farmacología , Quinasas Asociadas a rho/antagonistas & inhibidores , Enfermedades Cardiovasculares/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Modelos Moleculares , Método de Montecarlo , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad Cuantitativa , Urea/análogos & derivados , Urea/química
18.
Int J Clin Pharmacol Ther ; 57(2): 82-93, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30431425

RESUMEN

BACKGROUND AND OBJECTIVES: A significant number of ischemic events occur after acute myocardial infarction (MI), even when adhering to dual antiplatelet therapy including aspirin and clopidogrel. The aim of our study was to investigate the association between the concentration of the prodrug clopidogrel and its intermediary metabolite 2-oxo-clopidogrel plasma as well as demographic and clinical factors, and the long-term clinical outcome in patients with their first acute MI, ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction NSTEMI, treated with percutaneous coronary intervention (PCI). MATERIALS AND METHODS: This study included 172 consecutive patients with their first acute MI, 88 STEMI, and 84 NSTEMI, treated with PCI. On the third day of hospitalization, blood samples were collected from each patient to measure the concentration of clopidogrel and its metabolite 2-oxo-clopidogrel using the UHPLC-DAD-MS method. The following clinical outcomes were registered during the 28-month follow-up: mortality from cardiovascular causes, nonfatal MI, nonfatal stroke, and hospitalization for urgent myocardial revascularization or heart failure. RESULTS: Lower dose-adjusted clopidogrel concentrations (p < 0.05) were measured in NSTEMI patients with a composite of the hard clinical endpoint events of cardiovascular mortality, non-fatal MI, or a nonfatal stroke. During the follow-up, there was a 3.4 times higher risk of hard clinical endpoint events (p < 0.05) for each unit decrement of the dose-adjusted clopidogrel plasma concentration. Lower dose-adjusted concentrations of clopidogrel in these patients were associated with lower left ventricular ejection fraction (p < 0.001), and fentanyl (p < 0.001) and pantoprazole administration (p < 0.01) during the acute phase of MI. CONCLUSION: In patients with acute MI treated with PCI, lower dose-adjusted clopidogrel and dose-adjusted 2-oxo-clopidogrel plasma concentrations were associated with an increased risk of ischemic events.
.


Asunto(s)
Clopidogrel/efectos adversos , Clopidogrel/sangre , Isquemia/inducido químicamente , Infarto del Miocardio/tratamiento farmacológico , Ticlopidina/efectos adversos , Ticlopidina/sangre , Humanos , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/sangre , Resultado del Tratamiento
19.
Int J Clin Pharm ; 40(6): 1482-1489, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30367373

RESUMEN

Background A significant number of ischemic events occur even when adhering to dual antiplatelet therapy including aspirin and clopidogrel. Objectives The aim of our study was to determine predictors of long-term patient clinical outcome, among variables such as prodrug clopidogrel and intermediary metabolite 2-oxoclopidogrel concentrations, as well as patients' clinical characteristics. Setting Department for the Treatment of Acute Coronary Syndrome in tertiary teaching hospital, Serbia. Methods This study enrolled 88 consecutive patients with first STEMI, treated with primary PCI, within 6 h of the chest pain onset and followed them 40 months. On the third day of hospitalization, blood samples were collected from each patient to measure clopidogrel and its metabolite 2-oxo-clopidogrel concentration by UHPLC-DAD-MS method. Main outcome measure Mortality from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke or hospitalization for urgent myocardial revascularization or heart failure. Results The composite clinical outcome of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for urgent myocardial revascularization or heart failure, was registered in 31 patients (35.2%) during the 40-month follow-up. Lower clopidogrel (p < 0.05) and dose-adjusted clopidogrel concentrations (p < 0.05) were associated with the higher incidence of composite outcome events. Their low plasma concentrations may be predicted by fentanyl administration (p < 0.001) and creatinine clearance (p < 0.01). The decrease in dose-adjusted clopidogrel unit for each ng/ml/mg increases the risk 21.7 times (p < 0.05). Conclusion Clopidogrel dose-adjusted plasma concentration in STEMI patients, as well as multivessel coronary artery disease, showed significance in predicting an unfavorable composite clinical outcome after 40-month follow-up.


Asunto(s)
Clopidogrel/sangre , Clopidogrel/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/cirugía , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/sangre , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticlopidina/análogos & derivados , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/mortalidad , Síndrome Coronario Agudo/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Dolor en el Pecho/tratamiento farmacológico , Dolor en el Pecho/mortalidad , Enfermedad de la Arteria Coronaria/mortalidad , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Infarto del Miocardio con Elevación del ST/mortalidad , Infarto del Miocardio con Elevación del ST/cirugía , Ticlopidina/sangre , Resultado del Tratamiento
20.
Sci Rep ; 7(1): 15106, 2017 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-29118378

RESUMEN

Increased galectin-3 plasma concentration has been linked to an unfavorable outcome in patients with heart failure or atrial fibrillation (AF). There are no published data about the prognostic utility of galectin-3 and high-sensitivity C-reactive protein (hs-CRP) for long-term clinical outcome in the Non-ST elevation acute myocardial infarction (NSTEMI) patients with preexisting AF. Thirty-two patients with the first acute NSTEMI and preexisting AF and 22 patients without preexisting AF, were prospectively followed for fifteen months. Patients with AF had significantly higher galectin-3 plasma levels (p < 0.05) and hs-CRP concentration (p < 0.01), compared with patients without AF. Galectin-3 plasma concentration was not a significant covariate of the composite outcomes (p = 0.913). Patients with high hs-CRP (above 4.55 mg/L) showed 2.5 times increased risk (p < 0.05) of the composite outcome occurrence (p < 0.05). Besides, three-vessel coronary artery disease, creatinine serum level, and creatinine clearance were significant covariates (p < 0.05; p < 0.05; p < 0.01) of the composite outcome, respectively. Creatinine clearance, solely, has been shown to be an independent predictor of unfavorable prognosis after a 15-month follow-up. Galectin-3 and hs-CRP plasma levels were elevated in NSTEMI patients with AF, but with differential predictive value for an unfavorable clinical outcome. Only hs-CRP was associated with increased risk of composite outcome occurrence.


Asunto(s)
Fibrilación Atrial/sangre , Proteína C-Reactiva/metabolismo , Galectina 3/sangre , Infarto del Miocardio sin Elevación del ST/sangre , Adulto , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/patología , Proteínas Sanguíneas , Femenino , Galectinas , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infarto del Miocardio sin Elevación del ST/patología , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Pronóstico , Estudios Prospectivos , Factores de Riesgo
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