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81.
82.
Doonan RJ Scheffler P Yu A Egiziano G Mutter A Bacon S Carli F Daskalopoulos ME Daskalopoulou SS 《PloS one》2011,6(10):e26151
Background
Studies showed that long-standing smokers have stiffer arteries at rest. However, the effect of smoking on the ability of the vascular system to respond to increased demands (physical stress) has not been studied. The purpose of this study was to estimate the effect of smoking on arterial stiffness and subendocardial viability ratio, at rest and after acute exercise in young healthy individuals.Methods/Results
Healthy light smokers (n = 24, pack-years = 2.9) and non-smokers (n = 53) underwent pulse wave analysis and carotid-femoral pulse wave velocity measurements at rest, and 2, 5, 10, and 15 minutes following an exercise test to exhaustion. Smokers were tested, 1) after 12h abstinence from smoking (chronic condition) and 2) immediately after smoking one cigarette (acute condition). At rest, chronic smokers had higher augmentation index and lower aortic pulse pressure than non-smokers, while subendocardial viability ratio was not significantly different. Acute smoking increased resting augmentation index and decreased subendocardial viability ratio compared with non-smokers, and decreased subendocardial viability ratio compared with the chronic condition. After exercise, subendocardial viability ratio was lower, and augmentation index and aortic pulse pressure were higher in non-smokers than smokers in the chronic and acute conditions. cfPWV rate of recovery of was greater in non-smokers than chronic smokers after exercise. Non-smokers were also able to achieve higher workloads than smokers in both conditions.Conclusion
Chronic and acute smoking appears to diminish the vascular response to physical stress. This can be seen as an impaired ‘vascular reserve’ or a blunted ability of the blood vessels to accommodate the changes required to achieve higher workloads. These changes were noted before changes in arterial stiffness or subendocardial viability ratio occurred at rest. Even light smoking in young healthy individuals appears to have harmful effects on vascular function, affecting the ability of the vascular bed to respond to increased demands. 相似文献83.
Some hereditary diseases, such as retinitis pigmentosa, lead to blindness due to the death of photoreceptors, though the rest of the visual system might be only slightly affected. Optogenetics is a promising tool for restoring vision after retinal degeneration. In optogenetics, light-sensitive ion channels ("channelrhodopsins") are expressed in neurons so that the neurons can be activated by light. Currently existing variants of channelrhodopsin – engineered for use in neurophysiological research – do not necessarily support the goal of vision restoration optimally, due to two factors: First, the nature of the light stimulus is fundamentally different in "optogenetic vision" compared to "optogenetic neuroscience". Second, the retinal target neurons have specific properties that need to be accounted for, e.g. most retinal neurons are non-spiking. In this study, by using a computational model, we investigate properties of channelrhodopsin that might improve successful vision restoration. We pay particular attention to the operational brightness range and suggest strategies that would allow optogenetic vision over a wider intensity range than currently possible, spanning the brightest 5 orders of naturally occurring luminance. We also discuss the biophysical limitations of channelrhodopsin, and of the expressing cells, that prevent further expansion of this operational range, and we suggest design strategies for optogenetic tools which might help overcoming these limitations. Furthermore, the computational model used for this study is provided as an interactive tool for the research community. 相似文献
84.
Ying-zi Xu Andrei W. Konradi Frederique Bard Michael Dappen Lilibeth Dofiles Mark Dreyer Ian Gallager Caroline Garrido Mike Krimm Zhenmei Liao Elizabeth Messersmith Linda Mutter Michael A. Pleiss Bhushan Samant Christopher M. Semko Jennifer Smith Frank Stappenbeck Brian Stupi Ted Yednock 《Bioorganic & medicinal chemistry letters》2013,23(10):3070-3074
A series of (S)-2-(2-(diethylamino)-5-(N-alkyl-N-sulfonamido)pyrimidin-4-ylamino)-3-(4-(carbamoyloxy)phenyl)propanoic acid is discovered as orally available VLA-4 antagonists. Representative compounds 11b and 11p showed efficacy in multiple in vivo animal models. The in vitro selectivity of 11p is also described. 相似文献
85.
Semko CM Chen L Dressen DB Dreyer ML Dunn W Farouz FS Freedman SB Holsztynska EJ Jefferies M Konradi AW Liao A Lugar J Mutter L Pleiss MA Quinn KP Thompson T Thorsett ED Vandevert C Xu YZ Yednock TA 《Bioorganic & medicinal chemistry letters》2011,21(6):1741-1743
A series of N-(pyrimidin-4-yl)-phenylalanine VLA-4 antagonists is described. Optimization of substituents at the 2 and 5 positions of the pyrimidine ring gave 14, a very potent VLA-4 inhibitor which is orally active in a sheep asthma model. 相似文献
86.
A novel type of water-soluble prodrugs of cyclosporine A (CsA) is described, featuring a modular system of an enzyme-cleavable group, a solubilizing moiety and a chemodegradable spacer attached to the hydroxyl function of (4R)-4-[(E)-2-butenyl]-4-,N-dimethyl-l-threonine (MeBmt)-1 of CsA. The chemical synthesis of these double prodrugs proceeds in high yield and purity and allows for a systematic study of the influence of the structural parameters upon physicochemical and pharmacological properties. The evaluation of the chemical and enzymatic stability results in differential values of the conversion rates (minutes to several hours) in support of an enzyme-triggered release of the parent drug as the rate-limiting step. In vitro studies show that the designed prodrug systems can be regarded as soft prodrugs in being devoid of cyclophiline A (CypA) binding and that complete conversion to the parent drug occurs in whole rat blood, setting the stage for therapeutic use. 相似文献
87.
Hernández Pérez A E Cerna Chávez JC Delgado Ortiz M Beltrán Beache LM Tapia Vargas YM Ochoa Fuentes 《Phyton》2019,88(1):11-13
Mexico is the main producer, consumer and exporter
of avocado in the world, being Michoacan the main producer state
contributing more than 80% of the national production. There
are phytopathogens that decimate the production causing the
death of the tree. Root samples were collected in avocado trees
that showed the characteristic symptomatology of the disease
known as avocado sadness, the sampling was carried out in four
of the main avocado producing towns, in the state of Michoacan,
Mexico. The isolation consisted in sowing root tissue in Petri
dishes with V8®-PARPH culture medium, subsequently they were
identified morphologically and for species level it was determined
by molecular biology, with the PCR-ITS technique. Pathogenicity
tests were performed in triplicate with avocado seedlings with more
than six leaves. After 24 hours, the inoculated plants expressed
decay in the apical part, after 120 hours the leaves showed yellowing
and after 15 days there was a generalized wilt on the stem and
leaves, re-isolating the phytopathogen Phytopythium vexans.
This study confirms the first report of the oomycete P. vexans
affecting avocado trees in the most important producing region of
the Mexican Republic. 相似文献
88.
Y Deng J Zhao D Sakurai KM Kaufman JC Edberg RP Kimberly DL Kamen GS Gilkeson CO Jacob RH Scofield CD Langefeld JA Kelly ME Alarcón-Riquelme BIOLUPUS GENLES Networks JB Harley TJ Vyse BI Freedman PM Gaffney KM Sivils JA James TB Niewold RM Cantor W Chen BH Hahn EE Brown PROFILE BP Tsao 《Arthritis research & therapy》2012,14(Z3):A5
89.
Regulation of cellular adhesion molecule expression in murine oocytes, peri-implant ation and post-implantation embryos 总被引:2,自引:0,他引:2
DAVID P LU LINA TIAN CHRIS O'''' NEILL NICHOLAS JC KING Department of Pathology University of Sydney NSW AustraliaHuman Reproduction Unit Department of Physiology University of Sydney Royal North Shore Hospital NSW Australia 《Cell research》2002,(Z2)
Expression of the adhesion molecules, ICAM-1, VCAM-1, NCAM, CD44, CD49d (VLA-4, a chain), and CDlla (LFA-1, a chain) on mouse oocytes, and pre- and peri-implantation stage embryos was examined by quantitative indirect immunofluorescence microscopy. ICAM-1 was most strongly expressed at the oocyte stage, gradually declining almost to undetectable levels by the expanded blastocyst stage. NCAM, also expressed maximally on the oocyte, declined to undetectable levels beyond the morula stage. On the other hand, CD44 declined from highest expression at the oocyte stage to show a second maximum at the compacted 8-cell/morula. This molecule exhibited high expression around contact areas between trophecto-derm and zona pellucida during blastocyst hatching. CD49d was highly expressed in the oocyte, remained significantly expressed throughout and after blastocyst hatching was expressed on the polar trophecto-derm. Like CD44, CD49d declined to undetectable levels at the blastocyst outgrowth stage. Expression of both 相似文献
90.