Aldosterone receptor antagonist, spironolactone, has been shown to prevent remodeling of the heart in several models of left ventricular hypertrophy. The aim of the present study was to determine whether the treatment with spironolactone can prevent hypertension, reduction of tissue nitric oxide synthase activity and left ventricular (LV) and aortic remodeling in NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Four groups of rats were investigated: control, spironolactone (200 mg/kg), L-NAME (40 mg/kg) and L-NAME + spironolactone (in corresponding dosage). Animals were studied after 5 weeks of treatment. The decrease of NO-synthase activity in the LV and kidney was associated with the development of hypertension and LV hypertrophy, with increased DNA concentration in the LV, and remodeling of the aorta in the L-NAME group. Spironolactone prevented the inhibition of NO-synthase activity in the LV and kidney and partially attenuated hypertension and LVH development and the increase in DNA concentration. However, remodeling of the aorta was not prevented by spironolactone treatment. We conclude that the aldosterone receptor antagonist spironolactone improved nitric oxide production and partially prevented hypertension and LVH development without preventing hypertrophy of the aorta in NO-deficient hypertension. The reactive growth of the heart and aorta seems to be controlled by different mechanisms in L-NAMEinduced hypertension., F. Šimko, J. Matúšková, I. L'upták, T. Pinčíková, K. Krajčírovičová, S. Štvrtina, J. Pomšár, V. Pelouch, L'. Paulis, O. Pecháňová., and Obsahuje bibliografii
There is virtually no information on spontaneous variability of ECG body surface potential maps (BSPMs) and on dynamics of their reactive changes in healthy subjects. This study evaluated quantitatively the depolarization (QRS) and repolarization (QRST) parameters derived from the respective integral BSPMs, constructed beat-to-beat, from continual body surface ECG records in 9 healthy men resting supine, during head-up tilting and sitting. Spontaneous variability of the BSPMs parameters, both at rest and during postural reactions, was characterized by significant respiratory and low frequency oscillations, more pronounced when related to repolarization. Head-up tilting and sitting-up evoked significant decrease in the QRST-BSPM amplitudes, widening of the angle α and reduction of nondipolarity indexes, compared to the respective supine values. All these changes were gradual, characterized by transition phenomena and prolonged after-effect s. Tilting back to horizontal restored the resting supine va lues. The postural effects on depolarization were individually more variable and in the average showed a minimal QRS-BSPM amplitude increase. Beat-to-beat analysis of a train of ECG BSPMs provided the first evidence of spontaneous, non-random, respiratory and low frequency oscillations of the ventricula r repolarization pattern, and the first insight into the dynamics of body posture associated changes in ventricular recovery., E. Kellerová, V. Szathmáry, G. Kozmann, K. Haraszti, Z. Tarjányi., and Obsahuje bibliografii
NG-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is associated with protein remodeling of the left ventricle. The aim of the study was to show, whether aldosterone receptor blocker spironolactone and precursor of NOproduction L-arginine were able to reverse the protein rebuilding of the left ventricle. Six groups of male Wistar rats were investigated: control 4 (4 weeks placebo), L-NAME (4 weeks L-NAME), spontaneous-regression (4 weeks L-NAME + 3 weeks placebo), spironolactone-regression (4 weeks L-NAME + 3 weeks spironolactone), L-arginineregression (4 weeks L-NAME + 3 weeks arginine), control 7 (7 weeks placebo). L-NAME administration induced hypertension, hypertrophy of the left ventricle (LV), and the increase of metabolic and contractile as well as soluble and insoluble collagenous protein concentration. The systolic blood pressure and relative weight of the LV decreased in all three groups with regression, while the most prominent attenuation of the LVH was observed after spironolactone treatment. In the spontaneous-regression and L-arginine-regression groups the concentrations of individual proteins were not significantly different from the control value. However, in the spironolactone-regression group the concentration of metabolic, contractile and insoluble collagenous proteins remained significantly increased in comparison with the control group. The persistence of the increased protein concentration in the spironolactone group may be related to the more prominent reduction of myocardial water content by spironolactone., F. Šimko, A. Potáčová, V. Pelouch, L'. Paulis, J. Matúšková, K. Krajčírovičová, O. Pecháňová, M. Adamcová., and Obsahuje bibliografii
Early diagnosis of ongoing malignant disease is crucial to improve survival rate and life quality of the patients and requires sensitive detection of specific biomarkers e.g. prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), etc. In spite of current technological advances, malignant diseases are still identified in rather late stages, which have detrimental effect on the prognosis and treatment of the disease. Here, we present a biosensor able to detect fetuin-A, a potential multibiomarker. The biosensing platform is based on polymer brush combining antifouling monomer units of N -(2-hydroxypropyl)methacrylamide (HPMA) and carboxybetaine methacrylamide (CBMAA), statistically copolymerized by surfaceinitiated atom transfer radical polymerization. The copolymer poly(HPMA-co-CBMAA) exhibits excellent non-fouling properties in the most relevant biological media (i.e. blood plasma) as well as antithrombogenic surface properties by preventing the adhesion of blood components (i.e. leukocytes; platelets; and erythrocytes). Moreover, the polymer brush can be easily functionalized with biorecognition elements maintaining high resistance to blood fouling and the binding capacity can be regulated by tuning the ratio between CBMAA and HPMA units. The superior antifouling properties of the copolymer even after biofunctionalization were exploited to fabricate a new plasmonic biosensor for the analysis of fetuin-A in real clinical blood plasma samples. The assay used in this work can be explored as labelfree affinity biosensor for diagnostics of different biomarkers in real clinical plasma samples and to shift the early biomarker detection toward novel biosensor technologies allowing point of care analysis., Z. Riedelová, P. Májek, K. Pečánková, J. Kučerová, F. Surman, A. De Los Pereira, T. Riedel., and Obsahuje bibliografii
In this retrospective study we analysed changes of the ST segment in patients with arterial hypertension using multi-lead body surface mapping of the electric heart field as the ST segment often shows non-specific changes and is influenced by many different conditions. We constructed isointegral maps (IIM) of chosen intervals (the first 35 ms, the first 80 ms, and the whole ST segment) in 42 patients with arterial hypertension (with and without left ventricular hypertrophy) and in the control group involving 23 healthy persons. We analysed the position and values of map extrema. Spatial distribution of voltage integrals was similar in the control group and in the “pure” hypertensives. Patients with the left ventricular hypertrophy exhibited shifts of the integral minima. Despite our expectations, the highest extrema values were found in the control group and not in the left ventricular hypertrophy group. The extrema values were similar in all hypertensives, with or without left ventricular hypertrophy. Differences could be explained neither by the influence of the age, nor by the body habitus., K. Kozlíková, J. Martinka, J. Bulas., and Obsahuje seznam literaury
napsal Lad. Syllaba., KČSN (sg. S-L 403), Z I. kliniky nemocí vnitřních při Universitě Karlově, Předloženo II. třídě dne 4. dubna 1930, and Obsahuje bibliografii a rejstřík
Increased excitability of the spinal motor system has been observed after loud and unexpe cted acoustic stimuli (AS) preceding H-reflexes. The paradigm has been proposed as an electrophysiological marker of reticulospinal tract activity in humans. The brainstem reticular formation also maintains dense anatomical interconnections wi th the cortical motor system. When a startling AS is delivered, prior to transcranial magnetic stimulation (TMS), the AS produces a suppression of motor evoked potential (MEP) amplitud e in hand and arm muscles of healthy subjects. Here we analyzed the conditioning effect of a startling AS on MEP amplitude evoked by TMS to the primary motor leg area. Ten healthy volunteers participated in two experiments that used a conditioning-test paradigm. In the first experiment, a startling AS preceded a suprathreshold transcranial test stimulus. The interstimulus interval (ISI) varied between 20 to 160 ms. When given alone, the test stimulus evoked a MEP amplitude of approximately 0.5 mV in the slightly preinervated soleus muscle (SOL). In the seco nd experiment, the startling AS was used to condition the size of the H-reflex in SOL muscle. Mean MEP amplitude was calc ulated for each ISI. The conditioning AS suppressed MEP amplitude at ISIs of 30-80 ms. By contrast, H-reflex amplitude was augmented at ISIs of 100- 200 ms. In conclusions, acoustic stimulation exerts opposite and ISI-specific effects on the amplitude of MEPs and H-reflex in the SOL muscle, indicating different mechanism of auditory-to-motor interactions at cortical and spinal level of motor system., T: V. Ilic ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
We have found that short-term statin treatment plus stem cell transplantation in acutely infarcted hearts improves cardiac function because statins promote the efficacy of cellular cardiomyoplasty. Autologous Sca-1+ LinCD45- (CXCR+ ) very small embryonic-like stem cell (VSEL) mobilization in acute myocardial infarction (AMI) correlates with the preservation of cardiac function. Whether short-term atorvastatin (Ator) can enhance the mobilization or recruitment of VSELs in AMI is still unclear. We divided mice into 4 groups: 1) sham; 2) AMI; 3) AMI+resveratrol (RSV) as a positive control; and 4) AMI+Ator. There was an increase in the circulating VSEL/full population of leukocytes (FPL) ratio 48 hours after AMI, and AMI+RSV increased it further. Ator administration did not increase the VSEL/FPL ratio. The cardiac stromal cell-derived factor-1 (SDF-1) and SDF-1α levels were in agreement with the results of VSEL mobilization. One week after AMI, more Sca-1+ CXCR+ cells were recruited to the myocardium of AMI+RSV mice but not AMI+Ator mice. Short-term Ator administration failed to upregulate cardiac SDF-1 and could not enhance the recruitment of VSELs early after AMI., H. Wang ... [et al.]., and Obsahuje seznam literatury
Statin-associated myopathy (SAM) represents a broad spectrum of disorders from insignificant myalgia to fatal rhabdomyolysis. Its frequency ranges from 1-5 % in clinical trials to 15-20 % in everyday clinical practice. To a large extent, these variations can be explained by the definition used. Thus, we propose a scoring system to classify statin-induced myopathy according to clinical and biochemical criteria as 1) possible, 2) probable or 3) definite. The etiology of this disorder remains poorly understood. Most probably, an underlying genetic cause is necessary for overt SAM to develop. Variants in a few gene groups that encode proteins involved in: i) statin metabolism and distribution (e.g. membrane transporters and enzymes; OATP1B1, ABCA1, MRP, CYP3A4), ii) coenzyme Q10 production (e.g. COQ10A and B), iii) energy metabolism of muscle tissue (e.g. PYGM, GAA, CPT2) and several others have been proposed as candidates which can predispose to SAM. Pharmacological properties of individual statin molecules (e.g. lipophilicity, excretion pathways) and patients´ characteristics influence the likelihood of SAM development. This review summarizes current data as well as our own results., M. Vrablik, L. Zlatohlavek, T. Stulc, V. Adamkova, M. Prusikova, L. Schwarzova, J. A. Hubacek, R. Ceska., and Obsahuje bibliografii