St Annes University Hospital Brno

Brno, Czech Republic

St Annes University Hospital Brno

Brno, Czech Republic
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Mayo Foundation For Medical Education And Research and St Annes University Hospital Brno | Date: 2017-01-25

Systems and methods for epicardial pacing are provided. For example, this document provides epicardial pacing using a percutaneously delivered bifurcated pacing lead that has multiple electrodes that are directionally insulated to prevent extracardiac stimulation, including prevention of phrenic stimulation. In addition, the devices, systems, and methods provided can be used for ablation, defibrillation, and/or defibrillation in combination with pacing.

Mayo Foundation For Medical Education And Research and St Annes University Hospital Brno | Date: 2015-03-20

Systems and methods for epicardial pacing are provided. For example, this document provides epicardial pacing using a percutaneously delivered bifurcated pacing lead that has multiple electrodes that are directionally insulated to prevent extracardiac stimulation, including prevention of phrenic stimulation. In addition, the devices, systems, and methods provided can be used for ablation, defibrillation, and/or defibrillation in combination with pacing.

Jorda R.,Palacky University | Paruch K.,Masaryk University | Paruch K.,St Annes University Hospital Brno | Krystof V.,Palacky University
Current Pharmaceutical Design | Year: 2012

Roscovitine is a synthetic inhibitor of cyclin-dependent kinases that is currently undergoing clinical trials as a candidate drug for some oncological indications. Its discovery prompted many research teams to further optimize its structure or to initiate their own related but independent studies. This article reviews known roscovitine bioisosteres that have been prepared as CDK inhibitors using different core heterocycles. The individual bioisostere types have been described and explored to a different extent, which complicates direct comparisons of their biochemical activity - only six direct analogs containing different purine bioisosteres have been prepared and evaluated side by side with roscovitine. Only four types of bioisosteres have demonstrated improved biological properties, namely pyrazolo[ 1,5-a]-1,3,5-triazines, pyrazolo[1,5-a]pyrimidines, pyrazolo[1,5-a]pyridines and pyrazolo[4,3-d]pyrimidines. © 2012 Bentham Science Publishers.

Vlcek K.,Academy of Sciences of the Czech Republic | Vlcek K.,St Annes University Hospital Brno | Laczo J.,St Annes University Hospital Brno | Laczo J.,Charles University
Frontiers in Behavioral Neuroscience | Year: 2014

Although the memory impairment is a hallmark of Alzheimer's disease (AD), AD has also been characterized by spatial disorientation, which is present from its early stages. Spatial disorientation in AD manifests itself in getting lost in familiar and unfamiliar places and have been characterized more specifically using spatial navigation tests in both real space and virtual environments as an impairment in multiple spatial abilities, including allocentric and egocentric navigation strategies, visuo-spatial perception, or selection of relevant information for successful navigation. Patients suffering mild cognitive impairment (MCI), who are at a high risk of development of dementia, show impairment in a subset of these abilities, mainly connected with allocentric and egocentric processing. While spatial disorientation in typical AD patients probably reflects neurodegenerative changes in medial and posterior temporal, parietal, and frontal lobes, and retrosplenial cortex, the impairment of spatial navigation in MCI seem to be connected mainly with the medial temporal and also parietal brain changes. In this review, we will summarize the signs of brain disease in most MCI and AD patients showing in various tasks of spatial memory and navigation. © 2014 Vlček and Laczó.

Skoumalova A.,Charles University | Hort J.,Charles University | Hort J.,St Annes University Hospital Brno
Journal of Cellular and Molecular Medicine | Year: 2012

Alzheimer′s disease (AD) represents a highly common form of dementia, but can be diagnosed in the earlier stages before dementia onset. Early diagnosis is crucial for successful therapeutic intervention. The introduction of new diagnostic biomarkers for AD is aimed at detecting underlying brain pathology. These biomarkers reflect structural or biochemical changes related to AD. Examination of cerebrospinal fluid has many drawbacks; therefore, the search for sensitive and specific blood markers is ongoing. Investigation is mainly focused on upstream processes, among which oxidative stress in the brain is of particular interest. Products of oxidative stress may diffuse into the blood and evaluating them can contribute to diagnosis of AD. However, results of blood oxidative stress markers are not consistent among various studies, as documented in this review. To find a specific biochemical marker for AD, we should concentrate on specific metabolic products formed in the brain. Specific fluorescent intermediates of brain lipid peroxidation may represent such candidates as the composition of brain phospholipids is unique. They are small lipophilic molecules and can diffuse into the blood stream, where they can then be detected. We propose that these fluorescent products are potential candidates for blood biomarkers of AD. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Marini V.,Masaryk University | Krejci L.,Masaryk University | Krejci L.,St Annes University Hospital Brno
DNA Repair | Year: 2012

The budding yeast Srs2 protein possesses 3' to 5' DNA helicase activity and channels untimely recombination to post-replication repair by removing Rad51 from ssDNA. However, it also promotes recombination via a synthesis-dependent strand-annealing pathway (SDSA). Furthermore, at the replication fork, Srs2 is required for fork progression and prevents the instability of trinucleotide repeats. To better understand the multiple roles of the Srs2 helicase during these processes, we analysed the ability of Srs2 to bind and unwind various DNA substrates that mimic structures present during DNA replication and recombination. While leading or lagging strands were efficiently unwound, the presence of ssDNA binding protein RPA presented an obstacle for Srs2 translocation. We also tested the preferred directionality of unwinding of various substrates and studied the effect of Rad51 and Mre11 proteins on Srs2 helicase activity. These biochemical results help us understand the possible role of Srs2 in the processing of stalled or blocked replication forks as a part of post-replication repair as well as homologous recombination (HR). © 2012 Elsevier B.V.

Gora A.,Masaryk University | Brezovsky J.,Masaryk University | Damborsky J.,Masaryk University | Damborsky J.,St Annes University Hospital Brno
Chemical Reviews | Year: 2013

The dynamic motion of enzymes during catalytic events is one of the many aspects of protein chemistry that are currently insufficiently well understood. On one hand, proteins need to have well-defined and organized structures in order to maintain stable functionality in the intracellular environment. On the other hand, some degree of flexibility is often required for catalytic activity. Molecular dynamics simulations have provided key insights into the importance of protein dynamics in catalysis, such as the observation of substrate access and product exit pathways that cannot be identified by inspecting crystal structures. Spatial localization of the hydrophobic and hydrophilic regions within the structure of a protein is important in maintaining its proper fold and can also be crucial for catalytic function. The various steps of an enzymatic reaction may require different environments.

Mansukhani M.P.,Affiliated Communities Medical Center | Kara T.,St Annes University Hospital Brno | Kara T.,Mayo Medical School | Caples S.M.,Center for Sleep Medicine | Somers V.K.,Mayo Medical School
Current Hypertension Reports | Year: 2014

Obstructive sleep apnea (OSA) and hypertension are closely linked conditions. Disordered breathing events in OSA are characterized by increasing efforts against an occluded airway while asleep, resulting in a marked sympathetic response. This is predominantly due to hypoxemia activating the chemoreflexes, resulting in reflex increases in sympathetic neural outflow. In addition, apnea – and the consequent lack of inhibition of the sympathetic system that occurs with lung inflation during normal breathing – potentiates central sympathetic outflow. Sympathetic activation persists into the daytime, and is thought to contribute to hypertension and other adverse cardiovascular outcomes. This review discusses chemoreflex physiology and sympathetic modulation during normal sleep, as well as the sympathetic dysregulation seen in OSA, its extension into wakefulness, and changes after treatment. Evidence supporting the role of the peripheral chemoreflex in the sympathetic dysregulation seen in OSA, including in the context of comorbid obesity, metabolic syndrome, and systemic hypertension, is reviewed. Finally, alterations in cardiovascular variability and other potential mechanisms that may play a role in the autonomic imbalance in OSA are also discussed. © 2014, Springer Science+Business Media New York.

Hahn E.A.,Brandeis University | Wang H.-X.,University of Stockholm | Andel R.,University of South Florida | Andel R.,St Annes University Hospital Brno | Fratiglioni L.,University of Stockholm
American Journal of Geriatric Psychiatry | Year: 2014

Objective Sleep problems may adversely affect neuronal health. We examined a subjective report of change (reduced duration and/or depth) in sleep pattern in relation to subsequent risk of incident all-cause dementia and Alzheimer disease (AD) over 9 years. Methods This longitudinal study used data from a population-based sample of 214 Swedish adults aged 75 and over who were dementia-free both at baseline and at first follow-up (3 years later). The sample was 80% female and, on average, 83.4 years of age at baseline. All participants underwent a thorough clinical examination to ascertain all-cause dementia and AD. Results Forty percent of participants reported a change in sleep duration at baseline. Between the 6th and 9th year after baseline, 28.5% were diagnosed with all-cause dementia, 22.0% of whom had AD. Reduced sleep was associated with a 75% increased all-cause dementia risk (hazard ratio: 1.75; 95% confidence interval: 1.04-2.93; Wald = 4.55, df = 1, p = 0.035) and double the risk of AD (hazard ratio: 2.01; 95% confidence interval: 1.12-3.61; Wald = 5.47, df = 1, p = 0.019) after adjusting for age, gender, and education. The results remained after adjusting for lifestyle and vascular factors but not after adjusting for depressive symptoms. No evidence supported a moderating effect of the use of sleeping pills, and the sleep-dementia relationship remained after controlling for the presence of the apolipoprotein E ε4 allele. Conclusion Self-reported sleep problems may increase the risk for dementia, and depressive symptoms may explain this relationship. Future research should determine whether treatment, in particular, behavioral or nonpharmacologic treatment, may represent one avenue toward reduction of dementia risk in late life. © 2014 American Association for Geriatric Psychiatry.

Novak M.,St Annes University Hospital Brno
Current cardiology reviews | Year: 2015

Atrial fibrillation is the most common sustained arrhythmia. Because of the sub-optimal outcomes and associated risks of medical therapy as well as the recent advances in non-pharmacologic strategies, a multitude of combined (hybrid) algorithms have been introduced that improve efficacy of standalone therapies while maintaining a high safety profile. Antiarrhythmic administration enhances success rate of electrical cardioversion. Catheter ablation of antiarrhythmic drug-induced typical atrial flutter may prevent recurrent atrial fibrillation. Through simple ablation in the right atrium, suppression of atrial fibrillation may be achieved in patients with previously ineffective antiarrhythmic therapy. Efficacy of complex catheter ablation in the left atrium is improved with antiarrhythmic drugs. Catheter ablation followed by permanent pacemaker implantation is an effective and safe treatment option for selected patients. Additional strategies include pacing therapies such as atrial pacing with permanent pacemakers, preventive pacing algorithms, and/or implantable dual-chamber defibrillators are available. Modern hybrid strategies combining both epicardial and endocardial approaches in order to create a complex set of radiofrequency lesions in the left atrium have demonstrated a high rate of success and warrant further research. Hybrid therapy for atrial fibrillation reviews history of development of non-pharmacological treatment strategies and outlines avenues of ongoing research in this field.

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