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971.
972.
Grzegorz Gajos Aleksander Siniarski Joanna Natorska Michał Ząbczyk Jakub Siudut Krzysztof Piotr Malinowski Renata Gołębiowska-Wiatrak Paweł Rostoff Anetta Undas 《Cardiovascular diabetology》2018,17(1):146
Background
Little is known about factors that affect the composition of contracted blood clots in specific diseases. We investigated the content of polyhedral erythrocytes (polyhedrocytes) formed in blood clots and its determinants in type 2 diabetes (T2D) patients.Methods
In 97 patients with long-standing T2D [median HbA1c, 6.4% (interquartile range 5.9–7.8)], we measured in vitro the composition of blood clots, including a clot area covered by polyhedrocytes using scanning electron microscopy and the erythrocyte compression index (ECI), defined as a ratio of the mean polyhedrocyte area to the mean native erythrocyte area. Moreover, plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation, oxidative stress [total protein carbonyl (total PC), total antioxidant capacity and thiobarbituric acid reactive substances (TBARS)], and platelet activation markers were determined. The impact of glucose concentration on polyhedrocytes formation was assessed in vitro.Results
Polyhedrocytes content in contracted clots was positively correlated with glucose (r?=?0.24, p?=?0.028), glycated hemoglobin (r?=?0.40, p?=?0.024), total cholesterol (r?=?0.22, p?=?0.044), TBARS (r?=?0.60, p?=?0.0027), P-selectin (r?=?0.54, p?=?0.0078) and platelet factor-4, PF4 (r?=?0.59, p?=?0.0032), but not with thrombin generation, platelet count, Ks or CLT. Patients who formed more polyhedrocytes (≥?10th percentile) (n?=?83, 85.6%) had higher glucose (+?15.7%, p?=?0.018), fibrinogen (+?16.6%, p?=?0.004), lower red blood cell distribution width (RDW, ??8.8%, p?=?0.034), reduced plasma clot density (??21.8% Ks, p?=?0.011) and impaired fibrinolysis (+?6.5% CLT, p?=?0.037) when compared to patients with lesser amount of polyhedrocytes (<?10th percentile). ECI and the content of polyhedrocytes were strongly associated with total PC (r?=?0.79, p?=?0.036 and r?=?0.67, p?=?0.0004, respectively). In vitro an increase of glucose concentration by 10 mmol/L was associated with 94% higher polyhedrocytes content (p?=?0.033) when compared to the baseline (7.1 mM). After adjustment for age, sex and fibrinogen, multiple regression analysis showed that RDW was the only independent predictor of polyhedrocytes content in T2D (OR?=?0.61, 95% CI 0.39–0.92).Conclusions
Poor glycemic control, together with enhanced platelet activation and oxidative stress, increase the content of polyhedrocytes in blood clots generated in T2D patients.973.
Magdalena Markowicz-Piasecka Kristiina M. Huttunen Joanna Sikora 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1309-1322
The aim of this study was to assess in vitro the effects of sulphenamide and sulphonamide derivatives of metformin on the activity of human acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), establish the type of inhibition, and assess the potential synergism between biguanides and donepezil towards both cholinesterases (ChEs) and the effects on the β-amyloid aggregation. Sulphonamide 5 with para-trifluoromethyl- and ortho-nitro substituents in aromatic ring inhibited AChE in a mixed-type manner at micromolar concentrations (IC50?=?212.5?±?48.3?µmol/L). The binary mixtures of donepezil and biguanides produce an anti-AChE effect, which was greater than either compound had alone. A combination of donepezil and sulphonamide 5 improved the IC50 value by 170 times. Compound 5 at 200?µmol/L inhibited Aβ aggregation by ~20%. In conclusion, para-trifluoromethyl-ortho-nitro-benzenesulphonamide presents highly beneficial anti-AChE and anti-Aβ aggregation properties which could serve as a promising starting point for the design and development of novel biguanide-based candidates for AD treatment. 相似文献
974.
Jamshed Iqbal Mohammed I. El-Gamal Syeda Abida Ejaz Joanna Lecka Jean Sévigny 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):479-484
Tissue-nonspecific alkaline phosphatase (TNAP) is an important isozyme of alkaline phosphatases, which plays different pivotal roles within the human body. Most importantly, it is responsible for maintaining the balanced ratio of phosphate and inorganic pyrophosphate, thus regulates the extracellular matrix calcification during bone formation and growth. The elevated level of TNAP has been linked to vascular calcification and end-stage renal diseases. Consequently, there is a need to search for highly potent and selective inhibitors of alkaline phosphatases (APs) for treatment of disorders associated with the over-expression of APs. Herein, a series of tricyclic coumarin sulphonate 1a-za with known antiproliferative activity, was evaluated for AP inhibition against human tissue nonspecific alkaline phosphatase (h-TNAP) and human intestinal alkaline phosphatase (h-IAP). The methylbenzenesulphonate derivative 1f (IC50?=?0.38?±?0.01?μM) was found to be the most active h-TNAP inhibitor. Another 4-fluorobenzenesulphonate derivative 1i (IC50?=?0.45?±?0.02?μM) was found as the strongest inhibitor of h-IAP. Some of the derivatives were also identified as highly selective inhibitors of APs. Detailed structure-activity relationship (SAR) was investigated to identify the functional groups responsible for the effective inhibition of AP isozymes. The study was also supported by the docking studies to rationalise the most possible binding site interactions of the identified inhibitors with the targeted enzymes. 相似文献
975.
Assessing uncertainties in crop and pasture ensemble model simulations of productivity and N2O emissions 下载免费PDF全文
Fiona Ehrhardt Jean‐François Soussana Gianni Bellocchi Peter Grace Russel McAuliffe Sylvie Recous Renáta Sándor Pete Smith Val Snow Massimiliano de Antoni Migliorati Bruno Basso Arti Bhatia Lorenzo Brilli Jordi Doltra Christopher D. Dorich Luca Doro Nuala Fitton Sandro J. Giacomini Brian Grant Matthew T. Harrison Stephanie K. Jones Miko U. F. Kirschbaum Katja Klumpp Patricia Laville Joël Léonard Mark Liebig Mark Lieffering Raphaël Martin Raia S. Massad Elizabeth Meier Lutz Merbold Andrew D. Moore Vasileios Myrgiotis Paul Newton Elizabeth Pattey Susanne Rolinski Joanna Sharp Ward N. Smith Lianhai Wu Qing Zhang 《Global Change Biology》2018,24(2):e603-e616
Simulation models are extensively used to predict agricultural productivity and greenhouse gas emissions. However, the uncertainties of (reduced) model ensemble simulations have not been assessed systematically for variables affecting food security and climate change mitigation, within multi‐species agricultural contexts. We report an international model comparison and benchmarking exercise, showing the potential of multi‐model ensembles to predict productivity and nitrous oxide (N2O) emissions for wheat, maize, rice and temperate grasslands. Using a multi‐stage modelling protocol, from blind simulations (stage 1) to partial (stages 2–4) and full calibration (stage 5), 24 process‐based biogeochemical models were assessed individually or as an ensemble against long‐term experimental data from four temperate grassland and five arable crop rotation sites spanning four continents. Comparisons were performed by reference to the experimental uncertainties of observed yields and N2O emissions. Results showed that across sites and crop/grassland types, 23%–40% of the uncalibrated individual models were within two standard deviations (SD) of observed yields, while 42 (rice) to 96% (grasslands) of the models were within 1 SD of observed N2O emissions. At stage 1, ensembles formed by the three lowest prediction model errors predicted both yields and N2O emissions within experimental uncertainties for 44% and 33% of the crop and grassland growth cycles, respectively. Partial model calibration (stages 2–4) markedly reduced prediction errors of the full model ensemble E‐median for crop grain yields (from 36% at stage 1 down to 4% on average) and grassland productivity (from 44% to 27%) and to a lesser and more variable extent for N2O emissions. Yield‐scaled N2O emissions (N2O emissions divided by crop yields) were ranked accurately by three‐model ensembles across crop species and field sites. The potential of using process‐based model ensembles to predict jointly productivity and N2O emissions at field scale is discussed. 相似文献
976.
Vasyl V. Tkach Tyler J. Achatz Joanna Hildebrand Stephen E. Greiman 《Parasitology international》2018,67(4):501-508
The Dicrocoeliidae is a highly diverse family of digeneans parasitic in amniotic tetrapods. Detailed molecular phylogenetic analysis of dicrocoeliids is lacking and only a few dicrocoeliids from mammals have been included in previous studies. Sequence data were previously absent for the Anenterotrematidae that shares several morphological characteristics with dicrocoeliids. We examined phylogenetic affinities of several newly sequenced (nuclear 28S rDNA) taxa of dicrocoeliids and anenterotrematids collected from small mammals in Ecuador, Panama, Peru, USA and Vietnam. Our analyses demonstrated that the two anenterotrematid genera (Anenterotrema, Apharyngotrema) belong to the Dicrocoeliidae, placing the Anenterotrematidae into synonymy with the Dicrocoeliidae. Molecular data combined with morphological examination of type and new specimens provided evidence that Parametadelphis and Apharyngotrema are junior synonyms of Metadelphis, with all Metadelphis species lacking a digestive system. Phylogenetic analysis demonstrates that reduction of the alimentary tract in Lutztrema and its loss in Anenterotrema and Metadelphis represent at least two independent evolutionary events. Genera Brachylecithum, Brachydistomum, and Lyperosomum proved to be non-monophyletic, each likely representing more than a single genus. Furthermore, phylogenetic analysis did not support monophyly of the two largest subfamilies of the Dicrocoeliidae (Dicrocoeliinae and Leipertrematinae) with the other two subfamilies not included in this study. Therefore, we propose to abandon the current subfamily division of the Dicrocoeliidae. Analysis of host associations indicates multiple host-switching events throughout evolution of dicrocoeliids. Lastly, analysis of dicrocoeliid geographic distribution revealed that nearly all major clades included taxa from more than a single zoogeographic realm with the exception of the clade Anenterotrema?+?Metadelphis, found only in the Neotropics. 相似文献
977.
Joanna Bielewicz Anna Szczepańska-Szerej Magdalena Ogórek Piotr Dropko Katarzyna Wojtal Konrad Rejdak 《朊病毒》2018,12(2):143-146
We reported the case of a patient with Wernicke-Korsakoff syndrome (WKs) as an early clinical manifestation of sporadic Creutzfeld-Jakob disease (sCJD). The 66-year-old female complained of dizziness and imbalance which mostly occurred while walking. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk as well as memory disturbances with confabulations. The disturbances increased during the course of the disease, which led to the death of the patient four months after the appearance of the signs. The patient was finally diagnosed with sCJD disease. The most useful ancillary examination results supporting sCJD diagnosis were brain diffusion DWI MRI (diffusion weighted magnetic resonance imaging) and the presence of 14–3-3 protein in CSF (cerebrospinal fluid). Since that manifestation of sCJD is very unique other causes should be taken into consideration while making a final diagnosis. 相似文献
978.
979.
Joanna Cymerys A. Słońska A. Tucholska A. Golke A. Chmielewska M. W. Bańbura 《Folia microbiologica》2018,63(1):1-11
Equine herpesvirus 1 (EHV-1), like other members of the Alphaherpesvirinae subfamily, is a neurotropic virus causing latent infections in the nervous system of the natural host. In the present study, we have investigated EHV-1 replication (wild-type Jan-E strain and Rac-H laboratory strain) during long-term infection and during the passages of the virus in cultured neurons. The studies were performed on primary murine neurons, which are an excellent in vitro model for studying neurotropism and neurovirulence of EHV-1. Using real-time cell growth analysis, we have demonstrated for the first time that primary murine neurons are able to survive long-term EHV-1 infection. Positive results of real-time PCR test indicated a high level of virus DNA in cultured neurons, and during long-term infection, these neurons were still able to transmit the virus to the other cells. We also compared the neurovirulence of Rac-H and Jan-E EHV-1 strains after multiple passages of these strains in neuron cell culture. The results showed that multiple passages of EHV-1 in neurons lead to the inhibition of viral replication as early as in the third passage. Interestingly, the inhibition of the EHV-1 replication occurred exclusively in neurons, because the equine dermal (ED) cells co-cultivated with neuroculture medium from the third passage showed the presence of large amount of viral DNA. In conclusion, our results showed that certain balance between EHV-1 and neurons has been established during in vitro infection allowing neurons to survive long-term infection. 相似文献
980.
The differences in the eyelids microstructure and the conjunctiva‐associated lymphoid tissue between selected ornamental and wild birds as a result of adaptation to their habitat 下载免费PDF全文
Joanna E. Klećkowska‐Nawrot Karolina Goździewska‐Harłajczuk Dariusz Łupicki Krzysztof Marycz Tomasz Nawara Karolina Barszcz Artur Kowalczyk Joanna Rosenberger Ewa Łukaszewicz 《Acta zoologica》2018,99(4):367-394
The aim of the study was to describe the morphology of the upper, lower and third eyelid and characterize the organized lymphoid follicles and diffuse lymphocytes from ornamental and wild birds. The goal of these examinations was also to identify avian conjunctiva‐associated lymphoid tissue (CALT) and lymphoid tissue that contained specialized high endothelial venules. The upper, lower and third eyelid from 30 species of ornamental and wild birds representing 21 families were examined under light microscopy and using scanning electron microscopy. The third eyelid in all of the examined birds was composed of a free margin, which was divided into two parts. The largest tarsal plate of the third eyelid was observed in the greater rhea (Rheimorphae), the white‐tailed eagle and steppe eagle (Accipitrimorphae) and was approximately 13–15 mm wide and 9–11 mm long, respectively. In all of the examined birds, the CALT was associated with a rich network of small vessels. In addition, the presence of characteristic high endothelial venules and roundish bright endothelial cells was confirmed in the upper and lower eyelids or only in the lower eyelid (Phoenicopterimorphae, Procellariimorphae and Strigimorphae). 相似文献