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.
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.
Kruzliak P.,St Annes University Hospital Brno |
Kruzliak P.,Slovak Academy of Sciences |
Novak J.,St Annes University Hospital Brno |
Novak J.,Masaryk University |
Novak M.,St Annes University Hospital Brno
American Journal of Hypertension | Year: 2014
Hypertension is the most common adverse effect of the inhibitors of vascular endothelial growth factor (VEGF) pathway-based therapy (VEGF pathway inhibitors therapy, VPI therapy) in cancer patients. VPI includes monoclonal antibodies against VEGF, tyrosine kinase inhibitors, VEGF Traps, and so-called aptamers that may become clinically relevant in the future. All of these substances inhibit the VEGF pathway, which in turn causes a decrease in nitric oxide (NO) and an increase in blood pressure, with the consequent development of hypertension and its final events (e.g., myocardial infarction or stroke). To our knowledge, there is no current study on how to provide an optimal therapy for patients on VPI therapy with hypertension. This review summarizes the roles of VEGF and NO in vessel biology, provides an overview of VPI agents, and suggests a potential treatment procedure for patients with VPI-induced hypertension. © American Journal of Hypertension, Ltd 2013.
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.
Burkovics P.,Hungarian Academy of Sciences |
Burkovics P.,Masaryk University |
Sebesta M.,Masaryk University |
Sebesta M.,St Annes University Hospital Brno |
And 4 more authors.
Nucleic Acids Research | Year: 2014
Stalling of replication forks at unrepaired DNA lesions can result in discontinuities opposite the damage in the newly synthesized DNA strand. Translesion synthesis or facilitating the copy from the newly synthesized strand of the sister duplex by template switching can overcome such discontinuities. During template switch, a new primer-template junction has to be formed and two mechanisms, including replication fork reversal and D-loop formation have been suggested. Genetic evidence indicates a major role for yeast Rad5 in template switch and that both Rad5 and its human orthologue, Helicase-like transcription factor (HLTF), a potential tumour suppressor can facilitate replication fork reversal. This study demonstrates the ability of HLTF and Rad5 to form a D-loop without requiring ATP binding and/or hydrolysis. We also show that this strand-pairing activity is independent of RAD51 in vitro and is not mechanistically related to that of another member of the SWI/SNF family, RAD54. In addition, the 3′-end of the invading strand in the D-loop can serve as a primer and is extended by DNA polymerase. Our data indicate that HLTF is involved in a RAD51-independent D-loop branch of template switch pathway that can promote repair of gaps formed during replication of damaged DNA. © 2013 The Author(s) 2013. Published by Oxford University Press.
Giannopoulos S.,Columbia University |
Giannopoulos S.,University of Ioannina |
Katsanos A.H.,University of Ioannina |
Tsivgoulis G.,Democritus University of Thrace |
And 2 more authors.
Journal of Cerebral Blood Flow and Metabolism | Year: 2012
HMG-CoA reductase inhibitors (statins) are associated with improved stroke outcome. This observation has been attributed in part to the palliative effect of statins on cerebral hemodynamics and cerebral autoregulation (CA), which are mediated mainly through the upregulation of endothelium nitric oxide synthase (eNOS). Several animal studies indicate that statin pretreatment enhances cerebral blood flow after ischemic stroke, although this finding is not further supported in clinical settings. Cerebral vasomotor reactivity, however, is significantly improved after long-term statin administration in most patients with severe small vessel disease, aneurysmal subarachnoid hemorrhage, or impaired baseline CA. © 2012 ISCBFM All rights reserved.
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.