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PURPOSE: The study aimed to determine the typical clearance and volume of distribution values of tamsulosin in patients with benign prostatic hyperplasia (BPH), and to identify factors with a measurable impact on the drug's elimination. METHODS: This open-label, single-arm population pharmacokinetic study involved 65 adult men with BPH who had been on tamsulosin therapy for at least seven days. The steady-state serum concentrations of tamsulosin were measured using liquid chromatography-tandem quadrupole mass spectrometry. Population pharmacokinetic parameters, their variability, and influencing factors were estimated based on a two-compartment pharmacokinetic model using NONMEM software. RESULTS: The estimated tamsulosin clearance in BPH patients was 0.719 L/h, and the steady-state volume of distribution was 32 L. Neither renal nor liver function parameters had a statistically significant effect on tamsulosin clearance. However, a positive correlation was observed between hemoglobin levels and tamsulosin clearance in the BPH patient cohort. CONCLUSION: Our investigation reveals significant associations between tamsulosin pharmacokinetics and specific characteristics of patients with lower urinary tract symptoms (LUTS) due to BPH. The study highlights that tamsulosin clearance is associated with hemoglobin levels in patients with LUTS/BPH. This study underscores the importance of considering patient-specific factors when managing BPH treatment with tamsulosin, emphasizing associations rather than causative relationships.
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Hiperplasia Prostática , Tansulosina , Humanos , Hiperplasia Prostática/tratamento farmacológico , Masculino , Tansulosina/farmacocinética , Tansulosina/uso terapêutico , Idoso , Pessoa de Meia-Idade , Antagonistas de Receptores Adrenérgicos alfa 1/farmacocinética , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Idoso de 80 Anos ou mais , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/etiologiaRESUMO
Preeclampsia is a pregnancy-specific cardiovascular disorder, involving significant maternal endothelial dysfunction. Although inappropriate placentation due to aberrant angiogenesis, inflammation and shallow trophoblast invasion are the root causes of preeclampsia, pathogenic mechanisms are poorly understood, particularly in early pregnancy. Here, we first confirm the abnormal expression of important vascular and inflammatory proteins, FK506-binding protein-like (FKBPL) and galectin-3 (Gal-3), in human plasma and placental tissues from women with preeclampsia and normotensive controls. We then employ a three-dimensional microfluidic placental model incorporating human umbilical vein endothelial cells (HUVECs) and a first trimester trophoblast cell line (ACH-3P) to investigate FKBPL and Gal-3 signaling in inflammatory conditions. In human samples, both circulating (n = 17 controls; n = 30 preeclampsia) and placental (n ≥ 6) FKBPL and Gal-3 levels were increased in preeclampsia compared to controls (plasma: FKBPL, p < 0.0001; Gal-3, p < 0.01; placenta: FKBPL, p < 0.05; Gal-3, p < 0.01), indicative of vascular dysfunction in preeclampsia. In our placenta-on-a-chip model, we show that endothelial cells are critical for trophoblast-mediated migration and that trophoblasts effectively remodel endothelial vascular networks. Inflammatory cytokine tumour necrosis factor-α (10 ng/mL) modulates both FKBPL and Gal-3 signaling in conjunction with trophoblast migration and impairs vascular network formation (p < 0.005). Our placenta-on-a-chip recapitulates aspects of inappropriate placental development and vascular dysfunction in preeclampsia.
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Placenta , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Placenta/metabolismo , Galectina 3/genética , Galectina 3/metabolismo , Trofoblastos/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Proteínas de Ciclo Celular/metabolismo , Dispositivos Lab-On-A-Chip , Proteínas de Ligação a Tacrolimo/metabolismoRESUMO
AIM: To investigate the factors affecting metformin concentrations after chronic administration in patients with polycystic ovary syndrome (PCOS), focusing on the pharmacokinetic variability and its implications for personalized therapy. METHODS: This study enrolled 53 PCOS patients undergoing long-term metformin treatment at the Clinic for Gynecology and Obstetrics in Nis, Serbia, from February to December 2019. Pharmacokinetic parameters were measured from blood samples, and metformin concentrations were determined with validated analytical techniques. RESULTS: There was a significant variability in metformin concentrations among PCOS patients, with body mass index (BMI) identified as a major influencing factor. Higher BMI was associated with lower plasma metformin levels, a finding suggesting an altered pharmacokinetic profile in obese patients. CONCLUSIONS: This study highlights the critical role of BMI in influencing metformin pharmacokinetics in PCOS patients and underscores the need for personalized treatment strategies in patients with PCOS.
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Índice de Massa Corporal , Hipoglicemiantes , Metformina , Síndrome do Ovário Policístico , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/sangue , Metformina/farmacocinética , Metformina/sangue , Metformina/administração & dosagem , Metformina/uso terapêutico , Feminino , Adulto , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/sangue , Hipoglicemiantes/uso terapêutico , Sérvia , Adulto Jovem , ObesidadeRESUMO
Sertraline is one of the most prescribed antidepressants, but its pharmacokinetic (PK) properties are still not completely characterized. Using nonlinear mixed-effects modeling, we examined factors influencing sertraline PK variability in outpatients with major depressive disorder. Blood samples from 53 male and female adults treated with sertraline orally were collected at a steady state. Various demographic and clinical covariates were tested by stepwise regression procedure. We found that sertraline clearance is significantly influenced by serum concentrations of its main metabolite N-desmethylsertraline, whereas clearance of N-desmethylsertraline is affected by both creatinine clearance and drug daily dose. These results were confirmed by the reduction of points dispersion in goodness-of-fit plots for their predicted versus measured concentrations and with bootstrapping analyses. This finding can serve to inform sertraline dosing optimization, especially when changes in kidney function occur in treated individuals, to prevent adverse drug reactions and maximize therapeutic benefits.
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Transtorno Depressivo Maior , Sertralina , Adulto , Humanos , Masculino , Feminino , Sertralina/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Depressão/tratamento farmacológico , Antidepressivos/uso terapêuticoRESUMO
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.
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Síndrome Coronariana Aguda , Infarto do Miocárdio , Humanos , Ticagrelor , Inibidores da Agregação Plaquetária , Cromatografia Líquida de Alta Pressão/métodos , Síndrome Coronariana Aguda/tratamento farmacológico , PlasmaRESUMO
Research background: The consumption of whole grain cereal flour contributes to increased intake of dietary fibre and phenolic compounds beneficial to human health. However, whole grain flour also has some disadvantages, such as poor baking properties and lower technological quality. Applying ultrasonic and hydrothermal treatments can provide new opportunities to modify and improve the baking and biofunctionality of flour as well as the quality of baked goods. Experimental approach: The whole grain flour samples of six wheat varieties with different amylose content were studied. The original chemical composition and viscosity profiles of the flour were determined. The flour samples were subjected to ultrasonic treatment at a frequency of 30 kHz and temperature of 40 °C for 10 min and hydrothermal treatment on a magnetic stirrer with heating for 3 min after reaching the boiling point. The treatments were carried out to determine their influence on the studied digestible and antioxidant properties of the flour. A multistep in vitro enzymatic digestibility protocol simulating the digestion process in the human gastrointestinal tract was applied to the untreated and treated whole grain flour samples. Total free phenolic compound content and total antioxidant capacity were also determined. Results and conclusions: Hydrothermal treatment had a positive effect on the digestibility of the whole grain flour, especially in waxy wheat genotypes compared to those with high amylose content, due to the formation of resistant starch. The hydrothermal treatment had an overall negative effect on the antioxidant capacity of the flour samples, while ultrasonic treatment generally increased the analytical values of total free phenolic compounds by enhancing their extractability. These findings can provide valuable information for the development of new whole wheat foods. Novelty and scientific contribution: To the best of our knowledge, this type of study of the effects of ultrasound and hydrothermal treatment on the digestibility and antioxidant properties has not yet been performed on whole wheat flour with different amylose content. Waxy and high-amylose wheat varieties are considered novel raw materials because of their unique properties in bread making, such as improved bread texture and increased dietary ï¬bre content.
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OBJECTIVE: There is a low incidence of the medullary infarctions and sparse data about the vascular territories, as well as a correlation among the anatomic, magnetic resonance imaging (MRI) and neurologic signs. MATERIALS AND METHODS: Arteries of the 10 right and left sides of the brain stem were injected with India ink, fixed in formalin and microdissected. The enrolled 34 patients with medullary infarctions underwent a neurologic, MRI and Doppler examination. RESULTS: Four types of the infarctions were distinguished according to the involved vascular territories. The isolated medial medullary infarctions (MMIs) were present in 14.7%. The complete MMIs comprised one bilateral infarction (2.9%), whilst the incomplete and partial MMIs were observed in 5.9% and 8.9%, respectively. The anterolateral infarctions (ALMIs) were very rare (2.9%). The complete and incomplete lateral infarctions (LMIs), noted in 35.3%, comprised 11.8% and 23.6%, respectively, that is, the anterior (5.9%), posterior (8.9%), deep (2.9%), and peripheral (5.9%). Dorsal ischemic lesions (DMIs) occurred in 11.8%, either as a complete (2.9%), or isolated lateral (5.9%) or medial infarctions (2.9%). The remaining ischemic regions belonged to various combined infarctions of the MMI, ALMI, LMI and DMI (35.3%). The infarctions most often affected the upper medulla (47.1%), middle (11.8%), or both (29.5%). Several motor and sensory signs were manifested following infarctions, including vestibular, cerebellar, ocular, sympathetic, respiratory and auditory symptoms. CONCLUSIONS: There was a good correlation among the vascular territories, MRI ischemia features, and neurologic findings regarding the medullary infarctions.
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Infartos do Tronco Encefálico , Infartos do Tronco Encefálico/etiologia , Cerebelo/irrigação sanguínea , Formaldeído , Humanos , Imageamento por Ressonância Magnética/efeitos adversos , Bulbo/irrigação sanguínea , Bulbo/diagnóstico por imagemRESUMO
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.
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Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Idoso , Galectina 3 , Humanos , Pessoa de Meia-Idade , Sistema de Registros , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Volume Sistólico , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
PURPOSE: Given that it has been reported that type 2 diabetes mellitus may affect the pharmacokinetics of a large number of drugs and that there are still no published population pharmacokinetic (PopPK) analyses in routinely treated patients with hypertension and type 2 diabetes mellitus as comorbid condition, the aim of this study was to determine PK variability of bisoprolol in 70 Serbian patients using the PopPK approach. METHODS: PopPK analysis was conducted using a nonlinear mixed effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In our patients, a total daily dose of bisoprolol ranged from 1.25 to 10 mg. The drug was administrated orally as a single daily dose or in two divided doses per day. RESULTS: A wide range of the drug concentrations were noted (1-103 ng/mL) in the population consisted of the adult patients with type 2 diabetes mellitus. From a total of 21 separately assessed covariates, our results indicated that only creatinine clearance could have a potential impact on the variability of the clearance of bisoprolol. CONCLUSION: Routine assessment of renal function should be carried out before the initiation of treatment with bisoprolol in order to individualize the dose and to prevent possible accumulation and adverse drug reactions.
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Bisoprolol/farmacocinética , Diabetes Mellitus Tipo 2/metabolismo , Hipertensão/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Citocromo P-450 CYP3A/fisiologia , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-IdadeRESUMO
To date, many questions about the extent and cause of pharmacokinetic (PK) variability of even the most widely studied and prescribed ß1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was conducted using a nonlinear mixed-effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In each patient, the same formulation of bisoprolol was administered once or twice daily at a total daily dose of 0.625-7.5 mg. We separately assessed the effects of 31 covariates on the PKs of bisoprolol, and our results indicated that only 2 covariates could have possible influence on the variability of the clearance of bisoprolol: the mean daily dose of the drug and smoking habits of patients. These findings suggest that possible autoinduction of drug metabolism by higher total daily doses and induction of cytochrome P450 isoform 3A4 (CYP3A4) by cigarette smoke in liver could be the potential causes of increased total clearance of bisoprolol in patients with ACS.
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Síndrome Coronariana Aguda/tratamento farmacológico , Antagonistas de Receptores Adrenérgicos beta 1/farmacocinética , Bisoprolol/farmacocinética , Modelos Biológicos , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Bisoprolol/administração & dosagem , Bisoprolol/sangue , Citocromo P-450 CYP3A/biossíntese , Indução Enzimática , Feminino , Humanos , Fígado/enzimologia , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Dinâmica não Linear , Sérvia , Fumantes , Fumar/efeitos adversos , Fumar/sangueRESUMO
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.â©.
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Clopidogrel/efeitos adversos , Clopidogrel/sangue , Isquemia/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Ticlopidina/efeitos adversos , Ticlopidina/sangue , Humanos , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/sangue , Resultado do TratamentoRESUMO
OBJECTIVE: Atrial fibrillation (AF) is common in acute myocardial infarction (AMI), and galectin-3 is possibly involved in its occurrence. Galectin-3 has been shown to play a central role in fibrosis and tissue remodeling and has a role in inflammatory and proliferative responses. The aim of our study was to measure galectin-3 levels in patients with myocardial infarction and to compare its levels in patients with or without AF, in order to investigate the potential predictive role of galectin-3 in this setting. SUBJECTS AND METHODS: The study included 51 consecutive AMI patients with AF; 27 AMI patients (52.9%) had permanent/persistent AF, and 24 patients (47.1%) had paroxysmal AF. Thirty-eight consecutive AMI patients without AF were used as a control group. Blood samples were obtained from venous blood on the third day after reperfusion. RESULTS: Patients with AF had higher levels of C-reactive protein (p < 0.01) and galectin-3 (p < 0.05) than those without AF. Patients with high galectin-3 had 4.4 times greater odds of having AF. Galectin-3 levels were lower in patients without AF (p < 0.01) than in those with permanent/persistent AF. CONCLUSION: AMI patients with AF had higher levels of galectin-3 than those without this arrhythmia. This biomarker of inflammation and fibrosis could be a potential target for treating AMI patients at high risk.
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Fibrilação Atrial/sangue , Fibrilação Atrial/etiologia , Galectina 3/análise , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROCRESUMO
The aim of our study was to estimate clearance of bisoprolol and reveal the factors that could influence its pharmacokinetic (PK) variability in hypertensive patients on hemodialysis, using the population PK analysis. Parameters associated with plasma concentration of bisoprolol at steady state were analyzed in 63 patients (mean age 62.12 years, mean total weight 69.63 kg) who were hypertensive and on hemodialysis due to severe renal failure using non-linear mixed-effect modeling with ADVAN1 subroutine. The final regression model for the clearance of the drug included only creatinine clearance (CLcr) out of 12 tested covariates. The equation that describes CL of bisoprolol is the following: CL (l/h) = 0.12 + 6.33 * CLcr. These findings suggest that the routine measuring of serum creatinine level may be used to facilitate administration of bisoprolol in patients on hemodialysis.
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Antagonistas de Receptores Adrenérgicos beta 1/farmacocinética , Anti-Hipertensivos/farmacocinética , Bisoprolol/farmacocinética , Creatinina/sangue , Hipertensão/metabolismo , Diálise Renal , Antagonistas de Receptores Adrenérgicos beta 1/sangue , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/sangue , Anti-Hipertensivos/uso terapêutico , Bisoprolol/sangue , Bisoprolol/uso terapêutico , Feminino , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Modelos BiológicosRESUMO
BACKGROUND/AIMS: One of the most common polymorphisms of ABCB1 gene, a synonymous mutation C3435T (rs1045642), is associated with increased in vivo activity. The main goal of this study was to determine the association of C3435T polymorphism with clopidogrel and 2-oxo-clopidogrel concentrations in plasma. METHODS: The patients were recruited upon acute myocardial infarction diagnosis. They were all tested for ABCB1 C3435T polymorphism. In plasma, drawn 1 h after the drug administration, concentrations of clopidogrel and 2-oxo-clopidogrel were measured using UHPLC-DAD-MS analysis. RESULTS: Due to differences in the maintenance doses, we have calculated the dose-adjusted concentrations of clopidogrel (0.2 ng/ml/mg (0.1-0.4)) and 2-oxo-clopidogrel (2.1 ng/ml/mg (0.5-4.6)). Patients carrying at least one C allele achieved significantly higher serum concentration of clopidogrel (p < 0.001), as well as dose-adjusted clopidogrel (p < 0.001) and 2-oxo-clopidogrel concentrations (p < 0.05). CONCLUSION: The ABCB1 3435CC genotype is associated with increased clopidogrel and 2-oxo-clopidogrel dose-adjusted concentrations. Therefore, the ABCB1 C3435T genotyping should be one of the parameters taken into account when deciding about the dosing regimen of clopidogrel.
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Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/farmacocinética , Ticlopidina/análogos & derivados , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Clopidogrel , Estudos Transversais , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Inibidores da Agregação Plaquetária/sangue , Polimorfismo Genético , Ticlopidina/administração & dosagem , Ticlopidina/sangue , Ticlopidina/farmacocinéticaRESUMO
PURPOSE: Knowledge of the incompletely studied microsurgical anatomy of the extracapsular part of the middle genicular artery (MGA) could imply an educational value and clinical significance because of the possible risk of injury during knee surgery. METHODS: Thirty formol-fixed cadaveric lower limbs in full extension were dissected and used for the measurements of MGA parameters. A second group of measurements was performed on distal ends of 30 adult femurs. Two fresh injected cadaveric lower limbs were explored by means of multidetector computed tomographic angiography (MDCTA). RESULTS: The MGA originated from the popliteal artery (PA), facing the lateral half of the intercondylar fossa in 16 (53.4 %) specimens, together with the superior lateral genicular artery (SLGA) in ten (33.3 %) cases, or from the same point of origin with SLGA and superior medial genicular artery (SMGA) in 4 (13.3 %) cases. The MGA averaged 15.6 mm in length and 1.8 mm in the outer diameter. After its curved direction the MGA entered the posterior capsule. The average distances of the point of MGA entrance into the joint capsule were as follows: to the lateral femoral epicondyle it was 34.88 mm, to the medial femoral epicondyle 46.38 mm, 5.74 mm lateral to the posterior midline, with an average vertical distance to the femoral subcondylar plane of 28.73 mm. CONCLUSION: This detailed anatomical examination with measurements of the extracapsular part of a MGA could be of clinical importance and useful in knee surgery for the prevention of vascular injury of MGA and PA, as well as in radiological examination of the knee region.
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Articulação do Joelho/irrigação sanguínea , Artéria Poplítea/anatomia & histologia , Lesões do Sistema Vascular/etiologia , Adulto , Angiografia , Cadáver , Feminino , Humanos , Articulação do Joelho/cirurgia , Masculino , Microcirurgia , Tomografia Computadorizada Multidetectores , Artéria Poplítea/cirurgia , Lesões do Sistema Vascular/prevenção & controleRESUMO
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.
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PURPOSE: The aim of the study was to develop a population pharmacokinetic (PK) model for clearance of bisoprolol in patients with congestive heart failure (CHF). METHODS: Parameters associated with the plasma concentrations of bisoprolol at steady-state were analyzed in 61 patients (mean age 66.21 ± 9.49 years; mean total body weight 8.90 ± 12.26 kg) with CHF using non-linear mixed-effect modeling (NONMEM). A validation set of 17 patients with heart failure was used to estimate the predictive performance of the pharmacokinetic model. RESULTS: The typical mean value for bisoprolol clearance (CL), estimated by the base model (without covariates), in our population was 11.4 l h(-1). In the full model, covariates such as bisoprolol total daily dose (DD) and creatinine clearance were included. The final regression model for the clearance of bisoprolol was the following: CL (l h(-1)) = 4.68 + 0.859 * DD. CONCLUSION: The derived PK model describes the clearance of bisoprolol in patients with CHF, showing that the total daily dose of bisoprolol is the most important covariate. This finding will provide the basis for future PK studies on beta blockers in this specific patient population and lead to better overall management of heart failure.
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Antagonistas de Receptores Adrenérgicos beta 1/farmacocinética , Bisoprolol/farmacocinética , Insuficiência Cardíaca/tratamento farmacológico , Modelos Biológicos , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bisoprolol/administração & dosagem , Bisoprolol/uso terapêutico , Doença Crônica , Feminino , Insuficiência Cardíaca/sangue , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-IdadeRESUMO
PURPOSE: It has been demonstrated that the semitendinosus tendon can regenerate after being harvested in its whole length and thickness for anterior cruciate ligament (ACL) reconstruction. Ultrasound studies and guided biopsies of the regenerated tendon have shown compatibility and resembling features of the normal tendon. The question is if this neo-tendon is biologically and functionally adequate for re-use? METHODS: Two randomised groups of 150 volunteers were followed up for two years after harvesting the semitendinosus only (25) or the semitendinosus and gracilis tendons (25) in ACL reconstruction. The patients were followed up with clinical and ultrasound examinations, biopsies and histological tests. Surgical exploration was done in three patients for macroscopic verification. The injected arteries of four lower limbs were dissected and the tendon's arterial supplies were examined. RESULTS: Seventy-two percent of the cases showed regeneration of the semitendinosus tendons. The neotendons were inserted mostly below the knee joint (83.3%) where they had fused with the gracilis tendon, and above the joint (60%) when the gracilis was harvested as well. The isokinetic strength of the hamstrings and quadriceps was not significantly diminished on the operated side. A macroscopic and histological analysis of the regenerated tendons demonstrates close resemblance to normal anatomy, with focal areas of fibrosis. In one patient the regenerated tendon was used for medial patellofemoral ligament reconstruction. CONCLUSION: The semitendinosus muscle can recover and the tendon has great potential to regenerate after harvesting for ACL reconstruction. Our data suggest that the regenerated tendons could be used for iterative ligament reconstruction.
Assuntos
Reconstrução do Ligamento Cruzado Anterior/métodos , Regeneração/fisiologia , Tendões/fisiologia , Tendões/cirurgia , Adolescente , Adulto , Ligamento Cruzado Anterior/diagnóstico por imagem , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior , Feminino , Seguimentos , Humanos , Masculino , Ruptura/diagnóstico por imagem , Ruptura/cirurgia , Tendões/irrigação sanguínea , Resultado do Tratamento , Ultrassonografia , Adulto JovemRESUMO
Considering the great potential of black soybean seed coat as a source of bioactive compounds, the objective of this study was to investigate the effect of anthocyanin-rich brine from the seed coat on functional properties of pickled baby corn, as well as its sensory properties. Given that the ears of sweet corn, popping corn and semi-flint corn were used for pickling in the pre-pollination phase, the effect of genotype and its growing stage on the chemical composition of Baby corn product was also taken into consideration. The brine of black soybean with a total anthocyanins content of 11,882.9 mg CGE/kg (cyanidin 3-glucoside equivalent) and an antioxidant capacity of 399.5 mmol Trolox Eq/kg determined by QUENCHER method had a positive impact on the functional potential of baby corn products. The content of total anthocyanins in the obtained products ranged from 748.6 to 881.2 mg CGE/kg, the predominant anthocyanin was cyanidin-3-glucoside (184.6 to 247.5 µg/g), while their colour was red. Compared to the commercial sample, baby corn products pickled in the enriched solution had a 26% to 46% and 17% to 26% higher content of total free phenolic compounds and antioxidant capacity, respectively. Contrarily, the control sample had higher sugar and fibre content. As established, pickled popping corn had the best sensory properties.
RESUMO
An anthocyanin-rich blue maize waste product was used for anthocyanin extraction. To preserve bioactive phenolic compounds, a spray-drying technique was employed using conventional wall material maltodextrin (MD), with novel one, hydroxypropyl-ß-cyclodextrin (HPBCD). The obtained spray-dried maize extract (SME) and microencapsulates were analyzed based on physicochemical powder properties, chemical analysis, antioxidant activity, and digestibility. The examined microencapsulates demonstrated good powder properties, exhibited a high powder yield (up to 83%), and had a low moisture content (less than 5%). HPBCD and MD + HPBCD combinations demonstrated superior powder properties in the terms of decreasing the time necessary for rehydration (133.25 and 153.8 s, respectively). The mean average particle diameter ranged from 4.72 to 21.33 µm. DSC analyses signified high powder thermal stability, around 200 °C, related to the increasing preservation with biopolymer addition. The total phenolic and anthocyanin compounds ranged from 30,622 to 32,211 mg CE/kg (CE-catechin equivalents) and from 9642 to 12,182 mg CGE/kg (CGE-cyanidin 3-glucoside equivalents), respectively, associated with good bioactive compound protection. Microencapsulates with both carriers (15% MD and 15% HPBCD) had the highest digestibility (73.63%). Our results indicated that the microencapsulates created with the active ingredient and the wall materials (MD and HPBCD) could protect phenolic compounds/anthocyanins against ABTS radicals (63.53 and 62.47 mmol Trolox Eq/kg, respectively).