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https://www.readbyqxmd.com/read/29778894/new-n-phenylpyrrolamide-dna-gyrase-b-inhibitors-optimization-of-efficacy-and-antibacterial-activity
#1
Martina Durcik, Denise Lovison, Žiga Skok, Cristina Durante Cruz, Päivi Tammela, Tihomir Tomašič, Davide Benedetto Tiz, Gábor Draskovits, Ákos Nyerges, Csaba Pál, Janez Ilaš, Lucija Peterlin Mašič, Danijel Kikelj, Nace Zidar
The ATP binding site located on the subunit B of DNA gyrase is an attractive target for the development of new antibacterial agents. In recent decades, several small-molecule inhibitor classes have been discovered but none has so far reached the market. We present here the discovery of a promising new series of N-phenylpyrrolamides with low nanomolar IC50 values against DNA gyrase, and submicromolar IC50 values against topoisomerase IV from Escherichia coli and Staphylococcus aureus. The most potent compound in the series has an IC50 value of 13 nM against E...
May 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29678315/effects-of-carvedilol-therapy-in-patients-with-heart-failure-with-preserved-ejection-fraction-results-from-the-croatian-heart-failure-cro-hf-registry
#2
Markovic Domagoj, Jurcevic Zidar Branka, Macanovic Jelena, Milicic Davor, Glavas Duska
BACKGROUND AND OBJECTIVE: According to recent guidelines, the best approach for treatment of heart failure patients with preserved ejection function is still not defined. The aim of this study was to investigate how carvedilol therapy influences the survival rate, ejection fraction and NYHA class in these patients. PATIENTS AND METHODS: We conducted study on heart failure patients with preserved systolic function from the Croatian heart failure registry who were hospitalized in the period between 2005 and 2010...
April 17, 2018: Medicina Clínica
https://www.readbyqxmd.com/read/29670510/differential-expression-of-several-mirnas-and-the-host-genes-aatk-and-dnm2-in-leukocytes-of-sporadic-als-patients
#3
Katarina Vrabec, Emanuela Boštjančič, Blaž Koritnik, Lea Leonardis, Leja Dolenc Grošelj, Janez Zidar, Boris Rogelj, Damjan Glavač, Metka Ravnik-Glavač
Genetic studies have managed to explain many cases of familial amyotrophic lateral sclerosis (ALS) through mutations in several genes. However, the cause of a majority of sporadic cases remains unknown. Recently, epigenetics, especially miRNA studies, show some promising aspects. We aimed to evaluate the differential expression of 10 miRNAs, including miR-9, miR-338, miR-638, miR-663a, miR-124a, miR-143, miR-451a, miR-132, miR-206, and let-7b, for which some connection to ALS was shown previously in ALS culture cells, animal models or patients, and in three miRNA host genes, including C1orf61 (miR-9), AATK (miR-338), and DNM2 (miR-638), in leukocyte samples of 84 patients with sporadic ALS...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29618798/differential-expression-of-micrornas-and-other-small-rnas-in-muscle-tissue-of-patients-with-als-and-healthy-age-matched-controls
#4
Anja Kovanda, Lea Leonardis, Janez Zidar, Blaž Koritnik, Leja Dolenc-Groselj, Stanislava Ristic Kovacic, Tomaž Curk, Boris Rogelj
Amyotrophic lateral sclerosis is a late-onset disorder primarily affecting motor neurons and leading to progressive and lethal skeletal muscle atrophy. Small RNAs, including microRNAs (miRNAs), can serve as important regulators of gene expression and can act both globally and in a tissue-/cell-type-specific manner. In muscle, miRNAs called myomiRs govern important processes and are deregulated in various disorders. Several myomiRs have shown promise for therapeutic use in cellular and animal models of ALS; however, the exact miRNA species differentially expressed in muscle tissue of ALS patients remain unknown...
April 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29599444/environmental-complexity-buffers-against-stress-induced-negative-judgement-bias-in-female-chickens
#5
Josefina Zidar, Irene Campderrich, Emelie Jansson, Anette Wichman, Svante Winberg, Linda Keeling, Hanne Løvlie
Cognitive processes are often biased by emotions. In humans, affective disorders are accompanied by pessimistic judgement, while optimistic judgement is linked to emotional stability. Similar to humans, animals tend to interpret ambiguous stimuli negatively after experiencing stressful events, although the long-lasting impact on judgement bias has rarely been investigated. We measure judgement bias in female chicks (Gallus gallus domesticus) after exposure to cold stress, and before and after exposure to additional unpredictable stressors...
March 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29566560/overcoming-problems-of-poor-drug-penetration-into-bacteria-challenges-and-strategies-for-medicinal-chemists
#6
Davide Benedetto Tiz, Danijel Kikelj, Nace Zidar
Bacterial cell walls and membranes provide essential protection for bacteria against environmental influences. Different bacteria possess different cell envelopes and understanding each of these structures is crucial for the design of effective antibacterial drugs whose targets are intracellular. Optimal properties of drugs that are required for their entry into bacteria are still hard to predict. The guidelines that are suitable and well established for the penetration of a drug into eukaryotic cells are poorly adaptable to the complex world of pathogens...
March 23, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29369112/anisocytosis-and-leukocytosis-are-independently-related-to-survival-after-transcatheter-aortic-valve-replacement
#7
Guilherme F Attizzani, Sadeer G Al-Kindi, Jarrod E Dalton, Ahmad Alkhalil, Anthony DeCicco, Myttle Mayuga, Nicholas T Funderburg, Eugene H Blackstone, Sahil Parikh, Chris T Longenecker, Michael M Lederman, Daniel I Simon, Marco A Costa, David A Zidar
No abstract text is available yet for this article.
January 23, 2018: Journal of Cardiovascular Medicine
https://www.readbyqxmd.com/read/29361236/%C3%AE-arrestin-2-dependent-signaling-promotes-ccr4-mediated-chemotaxis-of-murine-t-helper-type-2-cells
#8
Rui Lin, Yeon Ho Choi, David A Zidar, Julia K L Walker
Allergic asthma is a complex inflammatory disease that leads to significant healthcare costs and reduction in quality of life. Although many cell types are implicated in the pathogenesis of asthma, CD4+ T helper type 2 cells (Th2) are centrally involved. We previously reported that the asthma phenotype is virtually absent in ovalbumin-sensitized and -challenged mice that lack global expression of βarrestin-2 and that CD4+ T cells from these mice displayed significantly reduced C-C motif chemokine 22 (CCL22)-mediated chemotaxis...
January 23, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29324314/down-regulation-of-mir-133a-b-in-patients-with-myocardial-infarction-correlates-with-the-presence-of-ventricular-fibrillation
#9
Emanuela Boštjančič, Tanisa Brandner, Nina Zidar, Damjan Glavač, Dušan Štajer
MicroRNAs (miRNAs) are important regulators of physiologic and pathologic conditions of the heart. Animal models of heart diseases have shown that miRNAs may contribute to the development of arrhythmias. However, little is known about the expression of muscle- and cardiac-specific miRNAs in patients with myocardial infarction (MI) who have developed ventricular fibrillation (VF). Our study included 47 patients who had died from myocardial infarction (MI), 23 with clinically proven VF and 24 without VF. Autopsy samples of infarcted tissue and remote myocardium were available (n = 94)...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29304380/the-fate-of-benzotriazole-pollutants-in-an-urban-oxic-intergranular-aquifer
#10
Branka Trček, Dušan Žigon, Vlasta Kramarič Zidar, Primož Auersperger
Benzotriazoles (BTs) are considered as Contaminants of Emerging Concern (CECs); however, information about their fate in aquifers continues to be absent. This was the focus of the present study, which provides the first evidence for relevant BTs' degradation products (BTTPs) in urban aquifers that may impact the groundwater quality. The mechanisms and biotransformation pathways of BTs were investigated in an oxic intergranular medium. The BTs and BTTPs were identified and quantified by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) analytical techniques based on reference standards and internal materials...
December 26, 2017: Water Research
https://www.readbyqxmd.com/read/29239018/design-synthesis-and-biological-evaluation-of-1-ethyl-3-thiazol-2-yl-urea-derivatives-as-escherichia-coli-dna-gyrase-inhibitors
#11
Tihomir Tomašič, Michaela Barančoková, Nace Zidar, Janez Ilaš, Päivi Tammela, Danijel Kikelj
Discovery of novel DNA gyrase B inhibitors remains an attractive field in the search for new antibacterial drugs to overcome the known bacterial resistance mechanisms. In the present study, we designed and synthesized novel ethylurea derivatives of 4,5,6,7-tetrahydrobenzo[1,2-d]thiazole-2,6-diamine, 2-(2-aminothiazol-4-yl)acetic acid, and benzo[1,2-d]thiazole-2,6-diamine and evaluated their Escherichia coli DNA gyrase inhibition. The most potent DNA gyrase inhibitors in the prepared library of compounds were benzo[1,2-d]thiazoles 32-34, 36, and 37 with IC50 values in the low micromolar range...
January 2018: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29216997/the-state-of-the-absorb-bioresorbable-scaffold-consensus-from-an-expert-panel
#12
REVIEW
Sripal Bangalore, Hiram G Bezerra, David G Rizik, Ehrin J Armstrong, Bruce Samuels, Srihari S Naidu, Cindy L Grines, Malcolm T Foster, James W Choi, Barry D Bertolet, Atman P Shah, Rebecca Torguson, Surendra B Avula, John C Wang, James P Zidar, Aziz Maksoud, Arun Kalyanasundaram, Steven J Yakubov, Bassem M Chehab, Anthony J Spaedy, Srini P Potluri, Ronald P Caputo, Ashok Kondur, Robert F Merritt, Amir Kaki, Ramon Quesada, Manish A Parikh, Catalin Toma, Fadi Matar, Joseph DeGregorio, William Nicholson, Wayne Batchelor, Raghava Gollapudi, Ethan Korngold, Riyaz Sumar, George S Chrysant, Jun Li, John B Gordon, Rajesh M Dave, Guilherme F Attizzani, Tom P Stys, Osvaldo S Gigliotti, Bruce E Murphy, Stephen G Ellis, Ron Waksman
Significant progress has been made in the percutaneous coronary intervention technique from the days of balloon angioplasty to modern-day metallic drug-eluting stents (DES). Although metallic stents solve a temporary problem of acute recoil following balloon angioplasty, they leave behind a permanent problem implicated in very late events (in addition to neoatherosclerosis). BRS were developed as a potential solution to this permanent problem, but the promise of these devices has been tempered by clinical trials showing increased risk of safety outcomes, both early and late...
December 11, 2017: JACC. Cardiovascular Interventions
https://www.readbyqxmd.com/read/29206345/synthesis-and-evaluation-of-n-phenylpyrrolamides-as-dna-gyrase-b-inhibitors
#13
Martina Durcik, Päivi Tammela, Michaela Barančoková, Tihomir Tomašič, Janez Ilaš, Danijel Kikelj, Nace Zidar
ATP-competitive inhibitors of DNA gyrase and topoisomerase IV are among the most interesting classes of antibacterial drugs that are unrepresented in the antibacterial pipeline. We developed 32 new N-phenylpyrrolamides and evaluated them against DNA gyrase and topoisomerase IV from E. coli and Staphylococcus aureus. Antibacterial activities were studied against Gram-positive and Gram-negative bacterial strains. The most potent compound displayed an IC50 of 47 nm against E. coli DNA gyrase, and a minimum inhibitory concentration (MIC) of 12...
January 22, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29189208/extraneuraxial-hemangioblastoma-clinicopathologic-features-and-review-of-the-literature
#14
Michele Bisceglia, Lucia A Muscarella, Carlos A Galliani, Nina Zidar, David Ben-Dor, Gianandrea Pasquinelli, Annamaria la Torre, Angelo Sparaneo, Julie C Fanburg-Smith, Janez Lamovec, Michal Michal, Carlos E Bacchi
Extraneuraxial hemangioblastoma occurs in nervous paraneuraxial structures, somatic tissues, and visceral organs, as part of von Hippel-Lindau disease (VHLD) or in sporadic cases. The VHL gene plausibly plays a key role in the initiation and tumorigenesis of both central nervous system and extraneuraxial hemangioblastoma, therefore, the underlying molecular and genetic mechanisms of the tumor growth are initially reviewed. The clinical criteria for the diagnosis of VHLD are summarized, with emphasis on the distinction of sporadic hemangioblastoma from the form fruste of VHLD (eg, hemangioblastoma-only VHLD)...
May 2018: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/29112065/the-effects-of-hiv-and-smoking-on-aortic-and-splenic-inflammation
#15
Chris T Longenecker, Claire E Sullivan, Justin Morrison, Corrilynn O Hileman, David A Zidar, Robert Gilkeson, James O'Donnell, Grace A McComsey
OBJECTIVE: To determine the association of smoking and HIV status with tissue-specific inflammation measured by flurodeoxyglucose positron emission tomography (PET). DESIGN: A cross-sectional study. METHODS: We prospectively enrolled 55 HIV study participants on stable antiretroviral therapy and 19 age-matched HIV-uninfected controls without known cardiovascular disease. We measured aortic target-to-background ratio (TBR) and spleen standardized uptake values (SUV) 3-h post-FDG, and used regression models to examine the independent association of HIV and smoking status with PET variables...
January 2, 2018: AIDS
https://www.readbyqxmd.com/read/29098203/prospective-analysis-of-lipid-composition-changes-with-antiretroviral-therapy-and-immune-activation-in-persons-living-with-hiv
#16
Martha A Belury, Emily Bowman, Janelle Gabriel, Brandon Snyder, Manjusha Kulkarni, Marilly Palettas, Xiaokui Mo, Jordan E Lake, David Zidar, Scott F Sieg, Benigno Rodriguez, Martin P Playford, Adriana Andrade, Daniel R Kuritzkes, Nehal N Mehta, Michael M Lederman, Nicholas T Funderburg
Background: Lipid profiles are altered by HIV infection and antiretroviral therapy (ART). Among HIV-uninfected (HIV-) populations the concentrations of various lipid classes (ie, lyso-phosphatidylcholine, LPC) and their saturated (SaFA), mono-unsaturated (MUFA), and polyunsaturated fatty acid (PUFA) composition are related to cardiometabolic disease risk. Associations between changes in the lipidome and immune activation in HIV-infected (HIV+) individuals beginning ART have not been described...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28847012/accuracy-of-cardiovascular-risk-prediction-varies-by-neighborhood-socioeconomic-position-a-retrospective-cohort-study
#17
Jarrod E Dalton, Adam T Perzynski, David A Zidar, Michael B Rothberg, Claudia J Coulton, Alex T Milinovich, Douglas Einstadter, James K Karichu, Neal V Dawson
Background: Inequality in health outcomes in relation to Americans' socioeconomic position is rising. Objective: First, to evaluate the spatial relationship between neighborhood disadvantage and major atherosclerotic cardiovascular disease (ASCVD)-related events; second, to evaluate the relative extent to which neighborhood disadvantage and physiologic risk account for neighborhood-level variation in ASCVD event rates. Design: Observational cohort analysis of geocoded longitudinal electronic health records...
October 3, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28845283/a32%C3%A2-search-for-viral-integration-insertion-sites-into-the-human-genome-strategy-matters
#18
T M Zorec, L Hošnjak, B Kocjan, N Gale, N Zidar, P Strojan, M Poljak
No abstract text is available yet for this article.
March 2017: Virus Evolution
https://www.readbyqxmd.com/read/28808819/separating-the-idea-from-the-action-a-sloreta-study
#19
Martin Rakusa, Pierpaolo Busan, Piero Paolo Battaglini, Janez Zidar
Simple imaginary movements activate similar cortical and subcortical areas to actual movements, chiefly in the sensory-motor network. However, only a few studies also examined the imagery of more skilful movements such as reaching. Ten volunteers performed reaching movements or imagined the same movements. EEG was simultaneously recorded and analysed with sLORETA, which compared the preparation for actual and imagined reaching with respect to their baseline and between tasks. Major differences between them were found at three time intervals after target presentation, always in favour of the actual reaching condition...
March 2018: Brain Topography
https://www.readbyqxmd.com/read/28802123/clathrodin-hymenidin-and-oroidin-and-their-synthetic-analogues-as-inhibitors-of-the-voltage-gated-potassium-channels
#20
Nace Zidar, Aleš Žula, Tihomir Tomašič, Marc Rogers, Robert W Kirby, Jan Tytgat, Steve Peigneur, Danijel Kikelj, Janez Ilaš, Lucija Peterlin Mašič
We have prepared three alkaloids from the Agelas sponges, clathrodin, hymenidin and oroidin, and a series of their synthetic analogues, and evaluated their inhibitory effect against six isoforms of the Kv1 subfamily of voltage-gated potassium channels, Kv1.1-Kv1.6, expressed in Chinese Hamster ovary (CHO) cells using automated patch clamp electrophysiology assay. The most potent inhibitor was the (E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-4,5-dichloro-1H-pyrrole-2-carboxamide (6g) with IC50 values between 1...
October 20, 2017: European Journal of Medicinal Chemistry
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