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81.
Synthesis and biological evaluation of N‐acylated tyramine sulfamates containing C–F bonds as steroid sulfatase inhibitors
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Mateusz Daśko Janusz Rachon Maciej Masłyk Konrad Kubiński Sebastian Demkowicz 《Chemical biology & drug design》2017,90(1):156-161
Steroid sulfatase (STS) is responsible for the hydrolysis of biologically inactive sulfated steroids into their active un‐sulfated forms and promotes the growth of various hormone‐dependent cancers (e.g., breast cancer). Therefore, the STS enzyme is a promising therapeutic target for the treatment of steroid‐sensitive cancers. Herein, we report the synthesis and biological evaluation of sulfamate analogs as potential STS inhibitors based on N‐acylated tyramines that contain C–F bonds. The inhibitory effects of the analogs were tested using STS isolated from human placenta. Of the analogs tested, 4‐(2‐perfluoroundecanoylaminoethyl)‐phenyl sulfamate, 5r , demonstrated the greatest inhibitory effect, with an IC50 value of 2.18 μm (IC50 value of 2.13 μm for coumarin‐7‐O‐sulfamate was used as a reference). These findings were supported by the results our computational analyses performed using molecular docking techniques. 相似文献
82.
Background
Multiple disposable syringe designs are available both with and without silicone lubricant. Tc99m sestamibi variably adheres to certain syringe designs. In practice, this increases pre-injection activity to ensure constant acceptable image quality in the setting of high adherence.Methods
The residual activity following 35 Tc99m MDP injections was used as a proxy for the dead-space residual activity. This was compared to Tc99m sestamibi injections in the same syringe in 107 injections, a syringe without lubricant in 35 injections, and a syringe without lubricant or rubber gasket in 16 injections. The syringe with lubricated barrel was disassembled and each part separately assayed to see which part demonstrated the most adherence.Results
The standard design demonstrated a mean adherence of 26% (SD 7.0%). This was significantly more than the 6% (SD 3.7%) demonstrated with MDP. The two designs without silicone lubricant demonstrated mean adherence of 7.2% (SD 2.3%) and 6.4% (SD 2.3%). Disassembly of the three part syringe showed the greatest adherence to the rubber gasket.Conclusions
QC procedures determining adherence in the administration syringe are warranted for any change in syringe design or manufacturer. If adherence is present, conversion to non-lubricated plastic syringes with lower and more predictable retention of Tc99m sestamibi enables more precise titration of prescribed activities and reduction of overall patient absorbed doses.83.
Create a Chain of Survival: Extracorporeal Life Support Treatment of Severe Hypothermia Victims
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84.
Anna Maria Kubicka Jakub Stefaniak Przemysław Lubiatowski Jan Długosz Marcin Dzianach Marcin Redman Janusz Piontek Leszek Romanowski 《International orthopaedics》2016,40(12):2581-2588
Purpose
The main purpose of this study is to establish which of two methods is more reliable in glenoid assessment for instability in pre-operative planning. Accordingly, we have studied the intra- and inter-observer reliability of glenoid parameters with the use of two-dimensional (2D) and three-dimensional (3D) reconstructed computed tomography (CT) images.Methods
One hundred glenoids were measured with the use of 2D-CT and 3D-CT (in 3D orientation) by two independent observers (one experienced and one inexperienced). Measurements were repeated after one week for 30 randomly selected glenoids.Results
The intra-class correlation coefficient (ICC) for inter-observer reliability was significantly greater for 3D-CT (0.811 to 0.915) than for 2D-CT (0.523 to 0.925). All intra-observer reliability values for 3D-CT were near perfect (0.835 to 0.997), while those for 2D-CT were less reliable (0.704 to 0.960). A dependent t-test showed that, for both observers, almost all glenoid parameters (except R and d) differed significantly (p?<?0.05) between 2D and 3D measurement methods.Conclusions
Therefore, it can be concluded that 3D glenoid reconstructions are more reliable for glenoid bone loss assessment than 2D-CT. The results suggest that quantifying a glenoid defect with the use of 2D image only—even if performed by an experienced orthopaedic surgeon—is prone to errors. Differences in measurements between and within observers can be explained by plane setting and identifying glenoid rim in 2D-CT. Accordingly, we recommend that glenoid measurements should be performed in 3D orientation using 3D reconstruction obtained from CT images for pre-operative assessments, which are crucial for surgical planning.85.
Jansen van Vuren P Potgieter AC Paweska JT van Dijk AA 《Journal of virological methods》2007,140(1-2):106-114
This paper describes the cloning, sequencing and bacterial expression of the N protein of the Rift Valley fever virus (RVFV) ZIM688/78 isolate and its evaluation in indirect ELISAs (I-ELISA) for the detection of IgM and IgG antibodies in human and sheep sera. Sera used for the evaluation were from 106 laboratory workers immunised with an inactivated RVF vaccine, 16 RVF patients, 168 serial bleeds from 8 sheep experimentally infected with wild type RVFV and 210 serial bleeds from 10 sheep vaccinated with the live attenuated Smithburn RVFV strain. All human and animal sera that tested positive in the virus neutralisation test were also positive in the IgG I-ELISA. There was a high correlation (R2 = 0.8571) between virus neutralising titres and IgG I-ELISA readings in human vaccinees. In experimentally infected sheep IgG antibodies were detected from day 4 to 5 post-infection onwards and IgM antibodies from day 3 to 4. The IgG I-ELISA was more sensitive than virus neutralisation and haemagglutination-inhibition tests in detecting the early immune response in experimentally infected sheep. The I-ELISAs demonstrated that the IgG and IgM response to the Smithburn vaccine strain was slower and the levels of antibodies induced markedly lower than to wild type RVFV infection. 相似文献
86.
Atherosclerosis and vascular aging as modifiers of tumor progression, angiogenesis, and responsiveness to therapy 总被引:1,自引:0,他引:1
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Klement H St Croix B Milsom C May L Guo Q Yu JL Klement P Rak J 《The American journal of pathology》2007,171(4):1342-1351
It is rarely considered that age-related common vascular co-morbidities may affect therapeutic outcomes of antiangiogenic therapy in cancer. Indeed, the accepted model of human disease consists of 4- to 8-week-old (young) tumor-bearing, but otherwise healthy, experimental mice, yet human cancers are diagnosed and treated in later decades of life when atherosclerosis and vascular diseases are highly prevalent. Here we present evidence that tumor growth and angiogenesis are profoundly altered in mice affected by natural aging and with genetically induced atherosclerosis (in ApoE(-/-) mice). Thus, transplantable tumors (Lewis lung carcinoma and B16F1) grew at higher rates in young (4 to 8 weeks old) ApoE(+/+) and ApoE(-/-) nonatherosclerotic syngeneic recipients than in their old (12 to 18 months old) or atherosclerotic (old/ApoE(-/-)) counterparts. These age-related changes were paralleled by reduced tumor vascularity, lower expression of tumor endothelial marker 1, increased acute tumor hypoxia, depletion of circulating CD45(-)/VEGFR(+) cells, and impaired endothelial sprouting ex vivo. Exposure of tumor-bearing mice to metronomic therapy with cyclophosphamide exerted antimitotic effects on tumors in young hosts, but this effect was reduced in atherosclerotic mice. Collectively, our results suggest that vascular aging and disease may affect tumor progression, angiogenesis, and responses to therapy. 相似文献
87.
88.
Ryszard Pluta Anna Bogucka-Kocka Marzena Ułamek-Kozioł Jacek Bogucki Sławomir Januszewski Janusz Kocki Stanisław J. Czuczwar 《Pharmacological reports : PR》2018,70(5):881-884
Background
Tauopathies are a class of neurodegenerative illnesses associated with the aberrant accumulation of the tau protein in the brain. The best known out of these diseases is Alzheimer’s disease, a disorder where the microtubule associated tau protein becomes hyperphosphorylated (which lowers its binding affinity to microtubules) and accumulates inside neurons in the form of tangles. In this study, we attempt to find out whether brain ischemia may play an important role in tau protein gene alterations.Methods
We have investigated the relationship between hippocampal ischemia and Alzheimer’s disease by means of a transient 10-min global brain ischemia in rats and determining the effect on Alzheimer’s disease tau protein gene expression during 2, 7 and 30?days post injury.Results
We found the significant overexpression of tau protein gene on the 2nd day, but on day’s 7 and 30 post-ischemia there a significant opposite tendency was observed.Conclusion
The obtained results offer a novel insight into tau protein gene in regulating delayed neuronal death in the ischemic hippocampus. Finally, these findings further elucidate the long-term impact of brain ischemia on Alzheimer’s disease development. 相似文献89.
90.
Intracellular distribution of differentially phosphorylated dual‐specificity tyrosine phosphorylation‐regulated kinase 1A (DYRK1A)
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Wojciech Kaczmarski Madhabi Barua Bozena Mazur‐Kolecka Janusz Frackowiak Wieslaw Dowjat Pankaj Mehta David Bolton Yu‐Wen Hwang Ausma Rabe Giorgio Albertini Jerzy Wegiel 《Journal of neuroscience research》2014,92(2):162-173
The gene encoding dual‐specificity tyrosine phosphorylation‐regulated kinase 1A (DYRK1A) is located within the Down syndrome (DS) critical region of chromosome 21. DYRK1A interacts with a plethora of substrates in the cytosol, cytoskeleton, and nucleus. Its overexpression is a contributing factor to the developmental alterations and age‐associated pathology observed in DS. We hypothesized that the intracellular distribution of DYRK1A and cell‐compartment‐specific functions are associated with DYRK1A posttranslational modifications. Fractionation showed that, in both human and mouse brain, almost 80% of DYRK1A was associated with the cytoskeleton, and the remaining DYRK1A was present in the cytosolic and nuclear fractions. Coimmunoprecipitation revealed that DYRK1A in the brain cytoskeleton fraction forms complexes with filamentous actin, neurofilaments, and tubulin. Two‐dimensional gel analysis of the fractions revealed DYRK1A with distinct isoelectric points: 5.5–6.5 in the nucleus, 7.2–8.2 in the cytoskeleton, and 8.7 in the cytosol. Phosphate‐affinity gel electrophoresis demonstrated several bands of DYRK1A with different mobility shifts for nuclear, cytoskeletal, and cytosolic DYRK1A, indicating modification by phosphorylation. Mass spectrometry analysis disclosed one phosphorylated site in the cytosolic DYRK1A and multiple phosphorylated residues in the cytoskeletal DYRK1A, including two not previously described. This study supports the hypothesis that intracellular distribution and compartment‐specific functions of DYRK1A may depend on its phosphorylation pattern. © 2013 Wiley Periodicals, Inc. 相似文献