Marie Nováková

Sleep scoring using artificial neural networks

Rapid development of computer technologies leads to the intensive automation of many different processes traditionally performed by human experts. One of the spheres characterized by the introduction of new high intelligence technologies substituting analysis performed by humans is sleep scoring. This refers to the classification task and can be solved - next to other classification methods - by use of artificial neural networks (ANN). ANNs are parallel adaptive systems suitable for solving of non-linear problems. Using ANN for automatic sleep scoring is especially promising because of new ANN learning algorithms allowing faster classification without decreasing the performance. Both appropriate preparation of training data as well as selection of the ANN model make it possible to perform effective and correct recognizing of relevant sleep stages. Such an approach is highly topical, taking into consideration the fact that there is no automatic scorer utilizing ANN technology available at present.

Inotropic action of σ receptor ligands in isolated cardiac myocytes from adult rats

High affinity binding sites for sigma receptor ligands were found in membranes of cardiac myocytes from adult rats. The sigma receptor ligand (+)-3-hydroxyphenyl-N-(1-propyl)piperidine ((+)-3-PPP) binds with a Kd of 17.9 +/- 4.0 nM and a Bmax of 275 +/- 32.1 fmol/mg protein. Competition experiments of (+)-pentazocine with [3H]1,3-di-O-tolylguanidine ([3H]DTG) binding yielded a Ki of 6.1 +/- 1.3 nM. The majority of the sites (> 80%) were of the sigma 1 subtype. Exposure of isolated cardiomyocytes from adult rats to (+)-3-PPP (10 nM-1.0 microM) caused a marked concentration-dependent increase in the amplitude of systolic cell contraction, reaching 149% of control level, with an apparent ED50 value of 4.5 nM. The increase in the contraction amplitude was markedly inhibited by pretreatment with verapamil or thapsigargin. An increase in the amplitude of [Ca2+]i transients, similar to that in the amplitude of cell contraction, was observed in indo-1-loaded cardiomyocytes exposed to 0.1 microM (+)-3-PPP. Exposure to 10 nM of haloperidol or (+)-pentazocine induced an increase in the amplitude of contraction, reaching 188% and 138% (respectively) of control level. A lower concentration of haloperidol or (+)-pentazocine (1 nM) did not induce an increase in the contraction amplitude but rather reduced the amplitude to 70-80% of control.

Intra-Dialytic Electrostimulation of Leg Extensors May Improve Exercise Tolerance and Quality of Life in Hemodialyzed Patients

Hemodialyzed (HD) patients with end-stage renal disease (ESRD) exhibit lower fitness as a consequence of chronic uremic changes that trigger various structural, metabolic, and functional abnormalities in skeletal muscles. The aim of this randomized study was to compare the effect of rehabilitation (RHB) training on a bicycle ergometer and electromyostimulation (EMS) of leg extensors in HD patients with ESRD. Thirty-two HD patients (18 men/14 women; mean age 61.1 ± 8.8 years) were randomized into three groups: (i) exercise training (ET; n = 11) on bicycle ergometer 2 × 20 min; (ii) EMS (n = 11) where stimulation (10 Hz) of leg extensors was applied for 60 min; and (iii) controls (CON; n = 10) without exercise. Exercising was performed between the 2nd and the 3rd hour of HD, three times a week, 20 weeks in total. Ergometric test was performed in order to evaluate peak workload (W(peak)), 6-min corridor walking test (CWT) to evaluate the distance walked, and dynamometry of leg extensors to assess muscle power (F(max)). Urea clearance was monitored and expressed as standard parameters: spKt/V, spKt/V equilibrated (spKt/V-e), and the urea removal ratio (URR). Quality of life (QoL) was assessed by the questionnaire SF-36. A significant increase of F(max) (P = 0.040 in group ET; P = 0.032 in group EMS), of 6-min CWT (P < 0.001 in ET group; P = 0.042 in EMS group), and of W(peak) (P = 0.041 in ET group) was observed. In both exercising groups, significant increase of spKt/V, spKt/V-e, and URR was found as compared with initial values (P < 0.05). In both exercising groups, highly significant changes in summarized mental functions were found (P = 0.001); in summarized physical components, significant improvement was observed in the ET group (P = 0.006). Intradialytic RHB showed comparable positive effects on functional parameters, urea clearance, and QoL. Intradialytic EMS might represent wide therapeutic possibility in the near future.

Electrical Stimulation of Skeletal Muscles

The aim of this study was to investigate whether electrical stimulation of skeletal muscles could represent a rehabilitation alternative for patients with chronic heart failure (CHF). Thirty patients with CHF and NYHA class II-III were randomly assigned to a rehabilitation program using either electrical stimulation of skeletal muscles or bicycle training. Patients in the first group (n = 15) had 8 weeks of home-based low-frequency electrical stimulation (LFES) applied simultaneously to the quadriceps and calf muscles of both legs (1 h/day for 7 days/week); patients in the second group (n = 15) underwent 8 weeks of 40 minute aerobic exercise (3 times a week). After the 8-week period significant increases in several functional parameters were observed in both groups: maximal VO2 uptake (LFES group: from 17.5 +/- 4.4 mL/kg/min to 18.3 +/- 4.2 mL/kg/min, P < 0.05; bicycle group: from 18.1 +/- 3.9 mL/kg/min to 19.3 +/- 4.1 mL/kg/min, P < 0.01), maximal workload (LFES group: from 84.3 +/- 15.2 W to 95.9 +/- 9.8 W, P < 0.05; bicycle group: from 91.2 +/- 13.4 W to 112.9 +/- 10.8 W, P < 0.01), distance walked in 6 minutes (LFES group: from 398 +/- 105 m to 435 +/- 112 m, P < 0.05; bicycle group: from 425 +/- 118 m to 483 +/- 120 m, P < 0.03), and exercise duration (LFES group: from 488 +/- 45 seconds to 568 +/- 120 seconds, P < 0.05; bicycle group: from 510 +/- 90 seconds to 611 +/- 112 seconds, P < 0.03). These results demonstrate that an improvement of exercise capacities can be achieved either by classical exercise training or by home-based electrical stimulation. LFES should be considered as a valuable alternative to classical exercise training in patients with CHF.

Induction of carbonic anhydrase IX by hypoxia and chemical disruption of oxygen sensing in rat fibroblasts and cardiomyocytes

CA IX is an active transmembrane carbonic anhydrase isoform functionally implicated in cell adhesion and pH control. Human CA IX is strongly induced by hypoxia and frequently associated with various tumors. In this study, we investigated the expression of the rat CA IX in response to chronic hypoxia and to treatment with chemical compounds that disrupt oxygen sensing, including dimethyloxalylglycine, dimethylester succinate, diazoxide, and tempol. We brought the evidence that expression of CA IX is regulated by hypoxia and hypoxia-mimicking compounds in immortalized Rat2 fibroblasts and BP6 rat fibrosarcoma cells in a cell-type-specific manner. We also demonstrated, for the first time, that CA IX is expressed in hypoxic primary rat cardiomyocytes and in immortalized H9c2 cardiomyocytes exposed to physiological or chemical hypoxia and that CA IX expression is increased in hypoxic rat tissues in vivo. Our findings suggest that CA IX expression is not limited to cancer but may be also induced in other pathological situations associated with ischemia or metabolic disturbances leading to activation of the HIF pathway. These data support the view that rats can represent useful model for studies of CA IX as a component of endogenous protection mechanisms associated with hypoxia or perturbed oxygen sensing.

Increased Cardio-ankle Vascular Index in Hyperlipidemic Patients without Diabetes or Hypertension

AIM The cardio-ankle vascular index (CAVI) is a sensitive non-invasive marker of arterial stiffness and atherosclerosis. The aim of this work was to compare the CAVI values in patients with dyslipidemia (without diabetes mellitus and hypertension) and healthy controls. METHODS A Total 248 subjects with dyslipidemia (104 men, 144 women), 55.0 (95% CI 30-70) years of age with combined hyperlipidemia or primary hypercholesterolemia and 537 healthy controls (244 men, 293 women) 40.0 (95% CI 26-62) years of age were included in this study. Fasting blood samples were collected to measure the serum total cholesterol, triglyceride, HDL-cholesterol and apolipoprotein A1 and B levels. The LDL cholesterol level was also calculated, and the CAVI was measured using the VaSera(®) 1500 system. RESULTS The CAVI values were significantly higher in the dyslipidemic patients (8.08, 95% CI 6.00-10.05) than in the controls (7.11, 95% CI 5.77-9.05; p < 0.01). In addition, the CAVI values were elevated in both subgroups of patients with hypercholesterolemia (7.95, 95% CI 5.85-6.90; p < 0.01) and combined hyperlipidemia (8.30, 95% CI 6.60-10.15; p < 0.01) in comparison with those observed in the controls. After adopting the propensity score method in order to balance the confounding factors (age, gender, body mass index) and adjust the analysis for diastolic blood pressure, the CAVI values in the dyslipidemic patients remained significantly high (7.78, 95% CI 5.80-9.69) compared to that observed in the controls (7.31, 95% CI 5.44-9.35; p < 0.001). However, the CAVI values did not differ significantly between the controls and both subgroups of dyslipidemic patients(primary hypercholesterolemia, combined hyperlipidemia). CONCLUSIONS The present findings demonstrated that dyslipidemia increases the CAVI values in comparison to that seen in healthy subjects.

Haloperidol cytotoxicity and its relation to oxidative stress.

Haloperidol (HP) is used for the symptomatic treatment of psychosis, manic phases, hyperactivity, aggressiveness, and acute delirium. Long-term use leads to various adverse side effects, especially to severe impairment of extrapyramidal nerve tracts and in particular, altered QT interval and increased incidence of arrhytmias. It is believed that cytotoxicity of HP and its metabolites is responsible for both neurotoxicity and cardiotoxicity. Extrapyramidal and cardiac adverse side effects may be explained by the HP-induced oxidative stress, as implicated by many studies. HP was reported to induce lipid peroxidation with subsequent membrane changes, responsible for cell death. Vice versa, cells resistant to oxidative stress are also resistant to the toxic effects of HP. Similarly, high percentage of patients suffering from extrapyramidal symptoms treated by vitamin E and other lipid-soluble antioxidants demonstrates diminishing of these adverse side effects. HPs ability to induce oxidative stress by multi-modal action (increased metabolism of dopamine, decrease of glutathione content, induction of NF-κB transcription factor, and inhibition of complex I of respiratory chain) has been established just recently. This review brings summarizing view on the cytotoxicity of haloperidol and involvement of reactive oxygen species and oxidative stress HP-induced cytotoxicity.

Electro-optical recording system for myocardial ischemia studies in animal experiments

Myocardial ischemia is the most common cause of death in the developed countries. The most severe manifestation is sudden death due to electrical instability, terminating in ventricular fibrillation or heart arrest. This study is based on experiments in which electrograms and monophasic action potentials are recorded from isolated guinea pig hearts perfused according to Langendorff during various phases of acute ischemia and reperfusion. The data are then processed by a wavelet transform in order to obtain complex-valued time-frequency patterns.

Modulation by 6-hydroxydopamine of expression of the phenylethanolamine N-methyltransferase (PNMT) gene in the rat heart during immobilization stress

Phenylethanolamine N-methyltransferase (PNMT) is the final enzyme in the catecholamine synthesizing cascade that converts noradrenaline (NA) to adrenaline (Adr). Both of these catecholamines are physiologically important hormones and neurotransmitters in mammals with profound influence on the activity of the cardiovascular system. Although PNMT activity and gene expression have been reported in the neonatal and also adult rat heart, little is known about the identity of the cells expressing PNMT mRNA. In this study, we have shown that besides PNMT in neuronal and intrinsic cardiac cells, this enzyme is expressed also in rat cardiomyocytes, as shown by immunofluorescence in isolated cardiomyocytes. To determine which cells in the heart more sensitively show stress-induced changes in PNMT mRNA expression, we performed chemical sympathectomy by administration of 6-hydroxydopamine (6-OHDA), which destroys catecholaminergic terminals. We determined PNMT mRNA levels in the left atria and ventricles of control and stressed rats. In the rats treated with 6-OHDA, PNMT mRNA levels were not changed under normal, physiological conditions compared to vehicle treated rats. Similar results were observed on isolated cardiomyocytes from control and 6-OHDA treated rats. However, 6-OHDA treatment prevented immobilization-induced increase in PNMT mRNA expression. The results allow us to propose that in the heart, the immobilization-induced increase in PNMT gene expression is probably not in cardiomyocytes, but in neuronal cells.

Hidden Markov model in wavelet analysis of myocardial ischemia in rabbit

Deals with analysis of myocardial ischemia caused by left anterior coronary artery occlusion. A system based on hidden Markov models has been designed. The vectorcardiograms recorded before and during the episode of local ischemia were preprocessed by wavelet transform to reveal short-time events during ventricular depolarization. To verify the models, 11 Langendorf-perfused rabbit hearts have been used. The presented results show that models can detect early ischemia in one of three orthogonal electrocardiograms in more than 90% of cases.