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71.
Kristina Svennerholm Michael Haney Bj?rn Biber Erik Ulfhammer Ott Saluveer Pia Larsson Elmir Omerovic Sverker Jern Niklas Bergh 《PloS one》2015,10(3)
The expression of the tissue plasminogen activator (t-PA) gene appears to be under epigenetic control and can be affected by histone deacetylation inhibition. The study aimed to test if histone deacetalyase inhibitor treatment lead to increased t-PA release or reduced exhaustion in t-PA release in response to stimulation, as well as change in plasminogen activator inhibitor-1 (PAI-1) in subjects with coronary disease. In this clinical study, 16 post-myocardial infarction subjects, the perfused forearm model was used with isoprenaline provocation during 20 minutes, to stimulate local t-PA release. Each subject was measured twice on the same day (repeated stimuli sequences) as well as on two different occasions, without treatment and after four weeks of treatment with valproic acid (500 mg, twice daily). Net forearm release for t-PA in response to isoprenaline at minutes 1.5, 3, 6, 9, 12, 15 and 18 was measured, allowing assessment of cumulative t-PA release. There was a reduction in the exhaustion of cumulative t-PA release during repeated and prolonged stimulation with valproic acid treatment compared to non-treatment. Plasma PAI-1 antigen was decreased following treatment compared to non-treatment (18.4 ± 10.0 vs. 11.0 ± 7.1 nanograms/ml respectively, mean with 95% confidence interval). These findings demonstrate that histone deacetylation inhibition increases the capacity for endogenous t-PA release in subjects with vascular disease. Furthermore, the fibrinolytic balance is favored with suppressed PAI-1 levels. More studies are needed to establish the clinical relevance of these findings.
Trial registration
EU Clinical Trials Register 2012-004950-27 相似文献72.
Genomic Resources Development Consortium Mariella Baratti Federica Cattonaro Tiziana Di Lorenzo Diana Maria Paola Galassi Valentina Iannilli Alessio Iannucci Just Jensen Peter Foged Larsen Rasmus O. Nielsen Cino Pertoldi Dragos Postolache Jose Martin Pujolar Ettore Randi Aritz Ruiz‐Gonzalez Janne Pia Thirstrup Giovanni Giuseppe Vendramin Andrzej Zalewski 《Molecular ecology resources》2015,15(2):458-459
73.
Robert Wunderlich Pia Lau Alwina Stein Alva Engell Andreas Wollbrink Claudia Rudack Christo Pantev 《PloS one》2015,10(9)
Tinnitus, the ringing in the ears that is unrelated to any external source, causes a significant loss in quality of life, involving sleep disturbance and depression for 1 to 3% of the general population. While in the first place tinnitus may be triggered by damage to the inner ear cells, the neural generators of subjective tinnitus are located in central regions of the nervous system. A loss of lateral inhibition, tonotopical reorganization and a gain-increase in response to the sensory deprivation result in hypersensitivity and hyperactivity in certain regions of the auditory cortex. In the tailor-made notched music training (TMNMT) patients listen to music from which the frequency spectrum of the tinnitus has been removed. This evokes strong lateral inhibition from neurons tuned to adjacent frequencies onto the neurons involved in the tinnitus percept. A reduction of tinnitus loudness and tinnitus-related neural activity was achieved with TMNMT in previous studies. As the effect of lateral inhibition depends on the bandwidth of the notch, in the current study we altered the notch width to find the most effective notch width for TMNMT. We compared 1-octave notch width with ½-octave and ¼-octave. Participants chose their favorite music for the training that included three month of two hours daily listening. The outcome was measured by means of standardized questionnaires and magnetoencephalography. We found a general reduction of tinnitus distress in all administered tinnitus questionnaires after the training. Additionally, tinnitus-related neural activity was reduced after the training. Nevertheless, notch width did not have an influence on the behavioral or neural effects of TMNMT. This could be due to a non-linear resolution of lateral inhibition in high frequencies. 相似文献
74.
Laura E. Jonkman Diana M. Rosenthal Maria Pia Sormani Laura Miles Joseph Herbert Robert I. Grossman Matilde Inglese 《PloS one》2015,10(10)
Multiple Sclerosis (MS) is a chronic inflammatory/demyelinating and neurodegenerative disease of the central nervous system (CNS). Most patients experience a relapsing-remitting (RR) course, while about 15–20% of patients experience a primary progressive (PP) course. Cognitive impairment affects approximately 40–70% of all MS patients and differences in cognitive impairment between RR-MS and PP-MS have been found. We aimed to compare RR-MS and PP-MS patients in terms of cognitive performance, and to investigate the MRI correlates of cognitive impairment in the two groups using measures of brain volumes and cortical thickness. Fifty-seven patients (42 RR-MS, 15 PP-MS) and thirty-eight matched controls underwent neuropsychological (NP) testing and MRI. PP-MS patients scored lower than RR-MS patients on most of the NP tests in absence of any specific pattern. PP-MS patients showed significantly lower caudate volume. There was no significant difference in MRI correlates of cognitive impairment between the two groups except for a prevalent association with MRI measures of cortical GM injury in RR-MS patients and with MRI measures of subcortical GM injury in PP-MS patients. This suggests that although cognitive impairment results from several factors, cortical and subcortical GM injury may play a different role depending on the disease course. 相似文献
75.
Niels Andreasen Monica Simeoni Henrik Ostlund Pia I. Lisjo Tormod Fladby Amy E. Loercher Gerard J. Byrne Frances Murray Paul T. Scott-Stevens Anders Wallin Yinghua Y. Zhang Lena H. Bronge Henrik Zetterberg Agneta K. Nordberg Astrid J. Yeo Shahid A. Khan Jan Hilpert Prafull C. Mistry 《PloS one》2015,10(3)
Objective
To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the Fc-inactivated anti-β amyloid (Aβ) monoclonal antibody (mAb) GSK933776 in patients with mild Alzheimer’s disease (AD) or mild cognitive impairment (MCI).Methods
This was a two-part, single blind, placebo-controlled, first-time-in-human (FTIH) study of single (n = 18) and repeat dose (n = 32) intravenous GSK933776 0.001–6 mg/kg (ClinicalTrials.gov: NCT00459550). Additional safety data from an open-label, uncontrolled, single dose study of intravenous GSK933776 1–6 mg/kg (n = 18) are included (ClinicalTrials.gov: NCT01424436).Results
There were no cases of amyloid-related imaging abnormalities-edema (ARIA-E) or –hemorrhage (ARIA-H) after GSK933776 administration in both studies. Three patients across the two studies developed anti-GSK933776 antibodies. Plasma GSK933776 half-life (t1/2) was 10–15 days after repeat dosing. After each of three administrations of GSK933776, plasma levels of total Aβ42 and Aβ increased whereas plasma levels of free Aβ decreased dose dependently; no changes were observed for placebo. For total Aβ42 the peak:trough ratio was ≤2 at doses ≥3 mg/kg; for total Aβ the ratio was ≤2 at 6 mg/kg. CSF concentrations of Aβ showed increases from baseline to week 12 for Aβ X–38 (week 12:baseline ratio: 1.65; 95%CI: 1.38, 1.93) and Aβ X–42 (week 12:baseline ratio: 1.18; 95%CI: 1.06, 1.30) for values pooled across doses.Conclusion
In this FTIH study the Fc-inactivated anti-Aβ mAb GSK933776 engaged its target in plasma and CSF without causing brain ARIA-E/H in patients with mild AD or MCI.Trial Registration
ClinicalTrials.gov NCT00459550 相似文献76.
Background
Several point-of-care (POC) tests are available for evaluation of febrile patients, but the data about their performance in acute care setting is sparse. We investigated the analytical accuracy and feasibility of POC tests for white blood cell (WBC) count and C-reactive protein (CRP) at the pediatric emergency department (ED).Methods
In the first part of the study, HemoCue WBC and Afinion AS100 CRP POC analyzers were compared with laboratory’s routine WBC (Sysmex XE-2100) and CRP (Modular P) analyzers in the hospital central laboratory in 77 and 48 clinical blood samples, respectively. The POC tests were then adopted in use at the pediatric ED. In the second part of the study, we compared WBC and CRP levels measured by POC and routine methods during 171 ED patient visits by 168 febrile children and adolescents. Attending physicians performed POC tests in capillary fingerprick samples.Results
In parallel measurements in the laboratory both WBC and CRP POC analyzers showed good agreement with the reference methods. In febrile children at the emergency department (median age 2.4 years), physician performed POC determinations in capillary blood gave comparable results with those in venous blood analyzed in the laboratory. The mean difference between POC and reference test result was 1.1 E9/L (95% limits of agreement from -6.5 to 8.8 E9/L) for WBC and -1.2 mg/L (95% limits of agreement from -29.6 to 27.2 mg/L) for CRP.Conclusions
POC tests are feasible and relatively accurate methods to assess CRP level and WBC count among febrile children at the ED. 相似文献77.
Tuula Salo Marilena Vered Ibrahim O. Bello Pia Nyberg Carolina Cavalcante Bitu Ayelet Zlotogorski Hurvitz Dan Dayan 《Experimental cell research》2014
The research on oral cancer has focused mainly on the cancer cells, their genetic changes and consequent phenotypic modifications. However, it is increasingly clear that the tumor microenvironment (TME) has been shown to be in a dynamic state of inter-relations with the cancer cells. The TME contains a variety of components including the non-cancerous cells (i.e., immune cells, resident fibroblasts and angiogenic vascular cells) and the ECM milieu [including fibers (mainly collagen and fibronectin) and soluble factors (i.e., enzymes, growth factors, cytokines and chemokines)]. Thus, it is currently assumed that TME is considered a part of the cancerous tissue and the functionality of its key components constitutes the setting on which the hallmarks of the cancer cells can evolve. Therefore, in terms of controlling a malignancy, one should control the growth, invasion and spread of the cancer cells through modifications in the TME components. This mini review focuses on the TME as a diagnostic approach and reports the recent insights into the role of different TME key components [such as carcinoma-associated fibroblasts (CAFs) and inflammation (CAI) cells, angiogenesis, stromal matrix molecules and proteases] in the molecular biology of oral carcinoma. Furthermore, the impact of TME components on clinical outcomes and the concomitant need for development of new therapeutic approaches will be discussed. 相似文献
78.
Telomeres are specialized nucleoprotein complexes that provide protection to the ends of eukaryotic chromosomes. Telomeric DNA consists of tandemly repeated G-rich sequences that terminate with a 3′ single-stranded overhang, which is important for telomere extension by the telomerase enzyme. This structure, as well as most of the proteins that specifically bind double and single-stranded telomeric DNA, are conserved from yeast to humans, suggesting that the mechanisms underlying telomere identity are based on common principles. The telomeric 3′ overhang is generated by different events depending on whether the newly synthesized strand is the product of leading- or lagging-strand synthesis. Here, we review the mechanisms that regulate these processes at Saccharomyces cerevisiae and mammalian telomeres. 相似文献
79.
Rajani Sarojam Pia G. Sappl Alexander Goldshmidt Idan Efroni Sandra K. Floyd Yuval Eshed John L. Bowman 《The Plant cell》2010,22(7):2113-2130
In seed plants, leaves are born on radial shoots, but unlike shoots, they are determinate dorsiventral organs made of flat lamina. YABBY genes are found only in seed plants and in all cases studied are expressed primarily in lateral organs and in a polar manner. Despite their simple expression, Arabidopsis thaliana plants lacking all YABBY gene activities have a wide range of morphological defects in all lateral organs as well as the shoot apical meristem (SAM). Here, we show that leaves lacking all YABBY activities are initiated as dorsiventral appendages but fail to properly activate lamina programs. In particular, the activation of most CINCINNATA-class TCP genes does not commence, SAM-specific programs are reactivated, and a marginal leaf domain is not established. Altered distribution of auxin signaling and the auxin efflux carrier PIN1, highly reduced venation, initiation of multiple cotyledons, and gradual loss of the SAM accompany these defects. We suggest that YABBY functions were recruited to mold modified shoot systems into flat plant appendages by translating organ polarity into lamina-specific programs that include marginal auxin flow and activation of a maturation schedule directing determinate growth. 相似文献
80.
Martin Flajšhans David Gela Martin Kocour Hana Buchtová Marek Rodina Martin Pšenička Vojtěch Kašpar Veronika Piačková Eliška Sudová Otomar Linhart 《Reviews in Fish Biology and Fisheries》2010,20(3):317-329
Performance and physiological traits and health of spontaneous and induced triploid tench are reviewed. Triploidy is best
induced with cold shock; with triploids exhibiting 13.5–51.5% better weight gain, 2.69–3.94% higher slaughtering value, 20–60%
lower gonadosomatic index, 0.9–4.5% higher dry matter in flesh and up to 107% more flesh fat than diploids, if farmed untill
post sexual maturity. Triploids exhibit more abdominal fat and less polyunsaturated fatty acids of the n-3 and n-6 groups
in the flesh. Triploid females are sterile, while triploid males may produce aneuploid spermatozoa with varying DNA content
(1–1.9n) which may initiate development of embryos. Triploids have milder seasonal dynamics in their erythrocyte profile than
the diploids. Thinner diffusion distance in gills of triploids than in diploids is interpreted as adaptation to lower aerobic
capacity. Triploids show neither stronger tendencies to anatomic malformations, nor have bigger affinity to parasitic diseases
than the diploids. Production of triploid tench could be an economically interesting method of farming to higher marketable
weight, bringing a relatively high product quality. 相似文献