938 research outputs found
Combination of cyclic nucleotide modulators with P2Y12 receptor antagonists as anti-platelet therapy
"This is the peer reviewed version of the following article: Armstrong, PC, Ferreira, PM, Chan, MV, et al. Combination of cyclic nucleotide modulators with P2Y12 receptor antagonists as anti‐platelet therapy. J Thromb Haemost. 2020 https://doi.org/10.1111/jth.14826 which has been published in final form at https://doi.org/10.1111/jth.14826BACKGROUND: Endothelium-derived prostacyclin and nitric oxide elevate platelet cyclic nucleotide levels and maintain quiescence. We previously demonstrated that a synergistic relationship exists between cyclic nucleotides and P2Y12 receptor inhibition. A number of clinically approved drug classes can modulate cyclic nucleotide tone in platelets including activators of NO-sensitive guanylyl cyclase (GC) and phosphodiesterase (PDE) inhibitors. However, the doses required to inhibit platelets produce numerous side effects including headache. OBJECTIVE: We investigated using GC-activators in combination with P2Y12 receptor antagonists as a way to selectively amplify the anti-thrombotic effect of both drugs. METHODS: In vitro light transmission aggregation and platelet adhesion under flow were performed on washed platelets and platelet rich plasma. Aggregation in whole blood and a ferric chloride-induced arterial thrombosis model were also performed. RESULTS: The GC-activator BAY-70 potentiated the action of the P2Y12 receptor inhibitor prasugrel active metabolite in aggregation and adhesion studies and was associated with raised intra-platelet cyclic nucleotide levels. Furthermore, mice administered sub-maximal doses of the GC activator cinaciguat together with the PDE inhibitor dipyridamole and prasugrel, showed significant inhibition of ex vivo platelet aggregation and significantly reduced in vivo arterial thrombosis in response to injury without alteration in basal carotid artery blood flow. CONCLUSIONS: Using in vitro, ex vivo, and in vivo functional studies, we show that low dose GC activators synergize with P2Y12 inhibition to produce powerful anti-platelet effects without altering blood flow. Therefore, modulation of intra-platelet cyclic nucleotide levels alongside P2Y12 inhibition can provide a strong, focused anti-thrombotic regimen while minimizing vasodilator side effects
The Reform of Employee Compensation in China’s Industrial Enterprises
Although employee compensation reform in Chinese industrial sector has been discussed in the literature, the real changes in compensation system and pay practices have received insufficient attention and warrant further examination. This paper briefly reviews the pre- and post-reform compensation system, and reports the results of a survey of pay practices in the four major types of industrial enterprises in China. The research findings indicate that the type of enterprise ownership has little influence on general compensation practices, adoption of profit-sharing plans, and subsidy and allowance packages. In general, pay is linked more to individual performance and has become an important incentive to Chinese employees. However, differences are found across the enterprise types with regard to performance-related pay. Current pay practices are positively correlated to overall effectiveness of the enterprise
Paradoxical euthyroid hormone profile in a case of Graves' disease with cardiac failure
Cardiac failure is an uncommon complication of juvenile hyperthyroidism. We describe an adolescent boy with Graves' disease who developed manifestations of heart failure while on antithyroid medications. There was no evidence of any underlying cardiac disease. He had paradoxical euthyroid hormone profile which rose to hyperthyroid range when the manifestations of the cardiac failure subsided. The case highlights several unusual features of Graves' disease
Greatly increased occurrence of breast cancers in areas of mammographically dense tissue
INTRODUCTION: Mammographic density is a strong, independent risk factor for breast cancer. A critical unanswered question is whether cancers tend to arise in mammographically dense tissue (i.e. are densities directly related to risk or are they simply a marker of risk). This question cannot be addressed by studying invasive tumors because they manifest as densities and cannot be confidently differentiated from the densities representing fibrous and glandular tissue. We addressed this question by studying ductal carcinoma in situ (DCIS), as revealed by microcalcifications. METHOD: We studied the cranio-caudal and the mediolateral-oblique mammograms of 28 breasts with a solitary DCIS lesion. Two experienced radiologists independently judged whether the DCIS occurred in a mammographically dense area, and determined the density of different areas of the mammograms. RESULTS: It was not possible to determine whether the DCIS was or was not in a dense area for six of the tumors. Of the remaining 22 lesions, 21 occurred in dense tissue (test for difference from expected taken as the percentage of density of the 'mammographic quadrant' containing DCIS; P < 0.0001). A preponderance of DCIS (17 out of 28) occurred in the mammographic quadrant with the highest percentage density. CONCLUSION: DCIS occurs overwhelmingly in the mammographically dense areas of the breast, and pre-DCIS mammograms showed that this relationship was not brought about by the presence of the DCIS. This strongly suggests that some aspect of stromal tissue comprising the mammographically dense tissue directly influences the carcinogenic process in the local breast glandular tissue
Evolutionary and pulsational properties of white dwarf stars
Abridged. White dwarf stars are the final evolutionary stage of the vast
majority of stars, including our Sun. The study of white dwarfs has potential
applications to different fields of astrophysics. In particular, they can be
used as independent reliable cosmic clocks, and can also provide valuable
information about the fundamental parameters of a wide variety of stellar
populations, like our Galaxy and open and globular clusters. In addition, the
high densities and temperatures characterizing white dwarfs allow to use these
stars as cosmic laboratories for studying physical processes under extreme
conditions that cannot be achieved in terrestrial laboratories. They can be
used to constrain fundamental properties of elementary particles such as axions
and neutrinos, and to study problems related to the variation of fundamental
constants.
In this work, we review the essentials of the physics of white dwarf stars.
Special emphasis is placed on the physical processes that lead to the formation
of white dwarfs as well as on the different energy sources and processes
responsible for chemical abundance changes that occur along their evolution.
Moreover, in the course of their lives, white dwarfs cross different
pulsational instability strips. The existence of these instability strips
provides astronomers with an unique opportunity to peer into their internal
structure that would otherwise remain hidden from observers. We will show that
this allows to measure with unprecedented precision the stellar masses and to
infer their envelope thicknesses, to probe the core chemical stratification,
and to detect rotation rates and magnetic fields. Consequently, in this work,
we also review the pulsational properties of white dwarfs and the most recent
applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and
Astrophysics Revie
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