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61.
Jararhagin is a 52 kDa hemorrhagic P-III metalloproteinase isolated from the venom of the medically important Brazilian pit-viper Bothrops jararaca. It is a member of the reprolysin family of zinc metalloproteinases containing a catalytic metalloproteinase domain followed by a disintegrin-like and a cysteine-rich domain. The impact of jararhagin on hemostasis has been extensively studied using in vitro and in vivo model systems as well as in clinical studies. Jararhagin-induced hemorrhage is the result of the degradation of sub-endothelial matrix proteins leading to the disruption of the blood vessel endothelium, with accompanying disturbances in platelet function. The versatility of jararhagin is further demonstrated by its direct action on von Willebrand factor, the degradation of fibrinogen, by its inhibition of platelet adhesion to collagen and by its inability to be affected by the plasma inhibitor 2-macroglobulin. Collagen-induced platelet aggregation is inhibited by jararhagin though the binding of the molecule to the 2 subunit I domain of the platelet surface 2β1 integrin (collagen receptor). Jararhagin also cleaves the β1 subunit of the same integrin, inhibiting platelet interaction and ultimately causing impairment of signal transduction. The effect of jararhagin on cell systems other than platelets is evaluated; in fibroblasts, jararhagin functions as a collagen-mimetic substrate and, in endothelial cells, it causes apoptosis and indirectly inhibits cell proliferation by release of angiostatin-like compounds. Jararhagin induces a strong pro-inflammatory response characterized by intense leukocyte accumulation at the site of the injection. Although hemorrhage and edema are a response to the direct effect of jararhagin, jararhagin-induced inflammation and necrosis are dependent on macrophages and key pro-inflammatory cytokines or their receptors. Some data also indicate that the toxin possesses anti-tumorgenic properties. Methods for inhibiting jararhagin are reviewed; this encompasses the use of synthetic peptides to the isolation of naturally occurring mammalian peptides and the development of toxin-specific antibodies through DNA immunisation and monoclonal antibody technologies. The availability of jararhagin makes it an important tool for research into the mechanisms of action of similar toxins, for insights into cellular interactions and for clinical investigations into the treatment of envenomings from B. jararaca. 相似文献
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Francesca Galeffi Simone Degan Gavin Britz Dennis A Turner 《Journal of cerebral blood flow and metabolism》2016,36(4):696-701
We investigated microvascular reactivity to synaptic train stimulation after induction of subarachnoid hemorrhage in adult rats, analyzing tissue oxygen levels [pO2] in intact hippocampus. In control rats, hippocampal pO2 averaged 11.4 mm Hg whereas hemodynamic responses averaged 13.1 mm Hg (to a 25 s train). After subarachnoid hemorrhage (at 2 days), we recorded a dramatic elevation in baseline pO2 in the hippocampus (to 68.4 mm Hg) accompanied by inverted pO2 responses to synaptic train stimulation (−9.46 mm Hg). These significant changes in baseline hippocampal pO2 and inverted pO2 responses after subarachnoid hemorrhage indicate severe alterations of neurovascular coupling and neuronal viability. 相似文献
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Gavin G. Enck 《Medicine, health care, and philosophy》2014,17(1):23-28
Emerging data indicates the prevalence and increased use of pharmaceutical enhancements by young medical professionals. As pharmaceutical enhancements advance and become more readily available, it is imperative to consider their impact on medical professionals. If pharmaceutical enhancements augment a person’s neurological capacities to higher functioning levels, and in some situations having higher functioning levels of focus and concentration could improve patient care, then might medical professionals have a responsibility to enhance? In this paper, I suggest medical professionals may have a responsibility to use pharmaceutical enhancements. In some situations, having higher functioning levels of focus and concentration is conducive to providing the best possible care to a patient. In these circumstances medical professionals should use pharmaceutical cognitive enhancements. I conclude by examining the limitations and implications of this responsibility in the practice of medicine and areas for future research. 相似文献
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Alison E. Brown Ellen Heinsbroek Meaghan M. Kall Hester Allen Kazim Beebeejaun Paula Blomquist Ines Campos-Matos Colin N.J. Campbell Hamish Mohammed Katy Sinka Theresa Lamagni Nicholas Phin the PHE COVID- Mortality Working Group Gavin Dabrera 《Emerging infectious diseases》2021,27(5):1468
Of the 58,186 coronavirus deaths among adults in England during March–December 2020, 77% occurred in hospitals, 93% were in patients >60 years, and 91% occurred within 28 days of positive specimen. Cumulative mortality rates were highest among persons of Black, Asian, other, or mixed ethnicities and in socioeconomically deprived areas. 相似文献
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Carly Wood Caroline Angus Jules Pretty Gavin Sandercock Jo Barton 《International journal of environmental health research》2013,23(4):311-320
This study assessed whether exercising whilst viewing natural or built scenes affected self-esteem (SE) and mood in adolescents. Twenty-five adolescents participated in three exercise tests on consecutive days. A graded exercise test established the work rate equivalent to 50% heart rate reserve for use in subsequent constant load tests (CLTs). Participants undertook two 15-min CLTs in random order viewing scenes of either natural or built environments. Participants completed Rosenberg’s SE scale and the adolescent profile of mood states questionnaire pre- and post-exercise. There was a significant main effect for SE (F(1) = 6.10; P < 0.05) and mood (F(6) = 5.29; P < 0.001) due to exercise, but no effect of viewing different environmental scenes (P > 0.05). Short bouts of moderate physical activity can have a positive impact on SE and mood in adolescents. Future research should incorporate field studies to examine the psychological effects of contact with real environments. 相似文献