Hepcidin is a key regulator of iron metabolism and a mediator of anemia in inflammation. Recent in vitro studies recognized prohepcidin as a type II acute phase protein regulating via interleukin-6. The aim of the present study was to investigate the time course of plasma prohepcidin after a large cardiac surgery in relation to IL-6 and other inflam matory parameters. Patients with chronic thromboembolic hypertension (n=22, males/females 14/8, age 51.9±10.2 years) underwent pulmonary endarterectomy using cardiopulmonary bypass and deep hypothermic circulatory arrest were included into study. Arterial concentrations of prohepcidin, IL-1β , IL-6, IL-8, tumor necrosis factor-α , and C-reactive protein were measured before/after sternotomy, after circulatory arrest, after separation from bypass, and then 12, 18, 24, 36, 48 h and 72 h after the separation from bypass. Hemodynamic parameters, hematocrit and markers of iron metabolism were followed up. Pulmonary endarterectomy induced a 48 % fall in plasma prohepcidin; minimal concentrations were detected after separation from cardiopulmonary bypass. Prohepcidin decline correlated with an extracorporeal circulation time (p<0.01), while elevated IL-6 levels were inversely associated with duration of prohepcidin decline. Postoperative prohepcidin did not correlate with markers of iron metabolism or hemoglobin concentrations within a 72-h period after separation from CPB. Prohepcidin showed itself as a negative acute phase reactant during systemic inflammatory response syndrome associated with a cardiac surgery. Results indicate that the evolution of prohepcidin in postoperative period implies the antagonism of stimulatory effect of IL-6 and contraregulatory factors inhibiting prohepcidin synthesis or increasing prohepcidin clearance., P. Maruna ... [et al.]., and Obsahuje seznam literatury
Tissue factor is a cell surface protein that is expressed constitutively by monocytes, macrophages and fibroblasts, but also by some other cells in response to a variety of stimuli. The main function of the tissue factor is to form a complex with factor VII/VIIa that converts factors IX and X to their active forms. Tissue factor is also involved in the pathophysiology of systemic inflammatory disorders, coagulopathies, atherosclerotic disease, tumor angiogenesis and metastasis. Increased tissue factor expression either locally in the coronary plaques or systematically on circulating blood elements of patients with acute coronary syndromes may be responsible for increased thrombin generation, thus leading to platelet activation and fibrin formation. Tissue factor therefore plays a pivotal role in the initiation of thrombotic complications in patients with coronary artery disease., J. Vojáček, J. Dušek, J. Bis, J. Šťásek, M. Blažek., and Obsahuje bibliografii a bibliografické odkazy
Idiopathic pes equinovarus (clubfoot) is a congenital deformity of the foot and lower leg defined as a fixation of the foot in plantar flexion, adduction, supination and varus. The deformity does not affect only the foot position, which is usually investigated by radiography, CT, micro-CT, MRI or ultrasound but logically influence the whole gait biomechanics. It is supposed, that clubfoot belongs to a group of fibroproliferative disorders whose origin and multi- hierarchical effect remain unknown. It has been suggested that fibroblasts and growth factors may be involved. To gain a more global view, direct analysis of the protein composition of extra cellular matrix, a proteomic approach was used. At present two principle methods are mostly used for the treatment of clubfoot: physiotherapy and the Ponseti method. The determination of the general biological and biomechanical parameters for various regio ns of the clubfoot can potentially help in the understanding of the mechanisms participating on this serious anomaly and thus contribute to the development of the more efficient therapeutic approach. This review summarizes the present knowledge on the poss ible pathogenetic mechanisms participating in the development of the clubfoot and their possible relation to the new therapeutic approaches., M. Ošťádal, J. Lišková, D. Hadraba, A. Eckhardt., and Obsahuje bibliografii
In the central nervous system (CNS), monocarboxylate transporter 1 (MCT1) is expressed in astrocytes and endothelial cells but also in oligodendroglia. Oligodendroglia support neurons and axons through lactate transportation by MCT1. Limited information is available on the MCT1 expression changes in candidate cells in the developing rat brain, especially in corpus callosum which is the most vulnerable area in demyelinating diseases. In the present study, we investigated the expression pattern of MCT1 during postnatal development in the rat corpus callosum using immunofluorescene staining, Western blotting analysis and RT-PCR. We reported that MCT1 gene and protein were consistently expressed in the rat corpus callosum from birth to adult. MCT1/CNPase and MCT1/GFAP immunofluorescence staining demonstrated that most of MCT1 positive cells were co-labeled with cyclic nucleotide 3′ phosphodiesterase (CNPase) in rat corpus callosum from P7 to adult, whereas MCT1+/GFAP+ cells preserve the dominate position before P7. Moreover, there were significant associations between the expression of MCT1 protein and the expression of myelin basic protein (MBP) (correlation coefficient: r=0.962, P=0.009) from P7 to adult. Similarly, the MCT1 mRNA expression was also significantly associated with MBP mRNA expression (r=0.976, P=0.005). Our results are proposing that in the developing brain white matter, MCT1 is predominately expressed in oligodendrocyte though it mainly expressed in astrocyte in early postnatal, which indicate that MCT1 may involve in the oligodendrocyte development and myelination., F. Dong, Y. Liu, Z. Zhang, R. Guo, L. Ma, X. Qu, H. Yu, H. Fan, R. Yao., and Obsahuje bibliografii
The objective of this prospective double-blind study was to determine whether postoperative residual paralysis (PORP) after pancuronium or vecuronium results in hypoxemia and hypercapnia in the immediate admission period to the recovery ward. Eighty-three consecutive surgical patients received balanced or intravenous anesthesia with pancuronium for operations lasting longer than one hour or vecuronium for those lasting less than 60 min, both combined with neostigmine at the end of anesthesia. Standard clinical criteria assessed neuromuscular function intraoperatively. Postoperatively, we determined neuromuscular function (acceleromyography with supramaximal train-of-four (TOF) stimulation of the ulnar nerve, and a 5-s head lift) and pulmonary function (pulse oximetry: SpO2, and blood gas analysis: SaO2, PaCO2). We defined PORP as a TOF-ratio 70 %, hypoxemia as a postoperative SpO2³ 5 % below the pre-anesthestic level together with a postoperative SaO293 %, and hypercapnia as a PaCO2³ 46 mm Hg. Among the 49 pancuronium and 27 vecuronium patients studied, the PORP rates were 20 % in the pancuronium group and 7 % in the vecuronium group (p>0.05). Hypoxemia and hypercapnia occurred more often in pancuronium patients with PORP than in those without PORP namely 60 % vs. 10% (p<0.05) and 30 % vs. 8 % (p>0.05), respectively. We conclude that PORP after pancuronium is a significant risk factor for hypoxemia., U. Bissinger, F. Schimek, G. Lenz., and Obsahuje bibliografii
Hypoventilation, as one of ventilatory disorders, decreases the electrical stability of the heart similarly as ischemia. If preconditioning by short cycles of ischemia has a cardioprotective effect against harmful influences of a prolonged ischemic period, then preconditioning by hypoventilation (HPC) can also have a similar effect. Anesthetized rats (ketamine 100 mg/kg + xylasine 15 mg/kg i.m., open chest experiments) were subjected to 20 min of hypoventilation followed by 20 min of reoxygenation (control group). The preconditioning (PC) was induced by one (1PC), two (2PC) or three (3PC) cycles of 5-min hypoventilation followed by 5-min reoxygenation. The electrical stability of the heart was measured by a ventricular arrhythmia threshold (VAT) tested by electrical stimulation of the right ventricle. Twenty-minute hypoventilation significantly decreased the VAT in the control and 1PC groups (p<0.05) and non-significantly in 2PC vs. the initial values. Reoxygenation reversed the VAT values to the initial level only in the control group. In 3PC, the VAT was increased from 2.32±0.69 mA to 4.25±1.31 mA. during hypoventilation (p<0.001) and to 4.37±1.99 mA during reoxygenation (p<0.001). It is concluded that cardioprotection against the hypoventilation/ reoxygenation-induced decrease of VAT proved to be effective only after three cycles of HPC., P. Švorc, I. Bračoková., and Obsahuje bibliografii
n previous studies, one of the systolic time intervals - preejection period (PEP) - was used as an index of sympathetic activity reflecting the cardiac contractility. However, PEP could be also influenced by several other cardiovascular variables including preload, afterload and diastolic blood pressure (DBP). The aim of this study was to assess the behavior of the PEP together with other potentially confounding cardiovascular system characteristics in healthy humans during mental and orthostatic stress (head-up tilt test - HUT). Forty-nine healthy volunteers (28 females, 21 males, mean age 18.6 years (SD=1.8 years)) participated in the study. We recorded finger arterial blood pressure by volume-clamp method (Finome ter Pro, FMS, Netherlands), PEP, thoracic fluid content (TFC) - a measure of preload, and cardiac output (CO) by impedance cardiography (CardioScreen ®2000, Medis, Germany). Systemic vascular resistance (SVR) - a measure of afterload - was calculated as a ratio of mean arterial pressure and CO. We observed that during HUT, an expected decrease in TFC was accompanied by an increase of PEP, an increase of SVR and no significant change in DBP. During mental stress, we observed a decrease of PEP and an increase of TFC, SVR and DBP. Correlating a change in assessed measures (delta values) between mental stress and previous supinerest, we found that ΔPEP correlated negatively with ΔCO and positively with ΔSVR. In orthostasis, no significant correlation between ΔPEP and ΔDBP, ΔTFC, ΔCO, ΔMBP or ΔSVR was found. We conclude that despite an expected increase of sympathetic activity during both challenges, PEP behaved differently indicating an effect of other confounding factors. To interpret PEP values properly, we recommend simultaneously to measure other variables influencing this cardiovascular measure., J. Krohova, B. Czippelova, Z. Turianikova, Z. Lazarova, I. Tonhajzerova, M. Javorka., and Obsahuje bibliografii
The levels of four pregnanolone isomers and their polar conjugates and pregnenolone sulfate were measured in the plasma of 13 and 7 women at delivery with subarachnoidal and epidural analgesia, respectively, and in corresponding samples of umbilical plasma using a simple quadrupole GC/MS system with electron impact ionization (pregnenolone isomers), RIA following HPLC separation (pregnenolone) and specific RIA (pregnanolone sulfate). The concentration of epipregnanolone (3b-hydroxy-5b-pregnan-20-one) in both maternal and umbilical plasma was much lower than that of other pregnanolone isomers. The levels of 3b-hydroxy-pregnanolone isomers were significantly higher in the umbilical plasma than in the maternal, while the differences in 3a-hydroxy-isomers were insignificant. The differences in conjugates were insignificant with the exception of allopregnanolone, the levels of which were lower in umbilical plasma. In all the pregnanolone isomers, a significantly lower conjugated/unconjugated steroid ratio was found in the umbilical plasma than in the maternal plasma. In addition, time profiles of the steroids were measured around parturition and in the postpartum period in the maternal serum. Similarly, the levels of polar conjugates of all pregnanolone isomers were followed during parturition. Changes in concentrations of free steroids exhibited a similar pattern, with a fall primarily within the first hour after delivery. The decrease in conjugated steroids was shifted to the interval within the first hour and first day after delivery, and the changes were more pronounced. The time profiles of the conjugated/free steroid ratio exhibited a significant decrease within the first hour and the first day after delivery in all of the isomers investigated. A decrease was also observed in the ratio of 3a/3b- isomers and 5a/5b- isomers around parturition.The possible physiological consequences of the findings are indicated., J. Klak, M. Hill, A. Pařízek, H. Havlíková, M. Bičíková, R. Hampl T. Fait, J. Šulcová V. Pouzar, R. Kancheva, L. Stárka., and Obsahuje bibliografii
Pregnenolone sulfate (PS), an endogenously occurring neurosteroid, has been shown to modulate the activity of several neurotransmitter-gated channels, including the NMDA receptor (NMDAR). NMDARs are glutamate-gated ion channels involved in excitatory synaptic transmission, synaptic plasticity, and excitotoxicity. In this study, we analyzed the effects of PS on calcium signaling in cultured hippocampal neurons and HEK293 cells expressing NMDAR. The ce lls were loaded with the Ca 2+ sensor Fura-2. In agreement with previous electrophysiological experiments, PS potentiated the increases in intracellular Ca 2+ induced by an exogenous application of glutamate; however, PS also increased intracellular Ca 2+ in the absence of exogenous NMDA agonist. The agonist-independent effect of PS was induced in all neurons studied and in HEK293 cells expressing GluN1/GluN2A-B receptors in a neurosteroid-specific manner. We conclude that PS is an endogenous NMDA agonist that activates the GluN1/GluN2A-B receptors., E. Adamusová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy