45 research outputs found
Mutant Prourokinase with Adjunctive C1-Inhibitor Is an Effective and Safer Alternative to tPA in Rat Stroke
A single-site mutant (M5) of native urokinase plasminogen activator (prouPA) induces effective thrombolysis in dogs with venous or arterial thrombosis with a reduction in bleeding complications compared to tPA. This effect, related to inhibition of two-chain M5 (tcM5) by plasma C1-inhibitor (C1I), thereby preventing non-specific plasmin generation, was augmented by the addition of exogenous C1I to plasma in vitro. In the present study, tPA, M5 or placebo +/− C1I were administered in two rat stroke models. In Part-I, permanent MCA occlusion was used to evaluate intracranial hemorrhage (ICH) by the thrombolytic regimens. In Part II, thromboembolic occlusion was used with thrombolysis administered 2 h later. Infarct and edema volumes, and ICH were determined at 24 h, and neuroscore pre (2 h) and post (24 h) treatment. In Part I, fatal ICH occurred in 57% of tPA and 75% of M5 rats. Adjunctive C1I reduced this to 25% and 17% respectively. Similarly, semiquantitation of ICH by neuropathological examination showed significantly less ICH in rats given adjunctive C1I compared with tPA or M5 alone. In Part-II, tPA, M5, and M5+C1I induced comparable ischemic volume reductions (>55%) compared with the saline or C1I controls, indicating the three treatments had a similar fibrinolytic effect. ICH was seen in 40% of tPA and 50% of M5 rats, with 1 death in the latter. Only 17% of the M5+C1I rats showed ICH, and the bleeding score in this group was significantly less than that in either the tPA or M5 group. The M5+C1I group had the best Benefit Index, calculated by dividing percent brain salvaged by the ICH visual score in each group. In conclusion, adjunctive C1I inhibited bleeding by M5, induced significant neuroscore improvement and had the best Benefit Index. The C1I did not compromise fibrinolysis by M5 in contrast with tPA, consistent with previous in vitro findings
Impact of Load-Related Neural Processes on Feature Binding in Visuospatial Working Memory
BACKGROUND: The capacity of visual working memory (WM) is substantially limited and only a fraction of what we see is maintained as a temporary trace. The process of binding visual features has been proposed as an adaptive means of minimising information demands on WM. However the neural mechanisms underlying this process, and its modulation by task and load effects, are not well understood. OBJECTIVE: To investigate the neural correlates of feature binding and its modulation by WM load during the sequential phases of encoding, maintenance and retrieval. METHODS AND FINDINGS: 18 young healthy participants performed a visuospatial WM task with independent factors of load and feature conjunction (object identity and position) in an event-related functional MRI study. During stimulus encoding, load-invariant conjunction-related activity was observed in left prefrontal cortex and left hippocampus. During maintenance, greater activity for task demands of feature conjunction versus single features, and for increased load was observed in left-sided regions of the superior occipital cortex, precuneus and superior frontal cortex. Where these effects were expressed in overlapping cortical regions, their combined effect was additive. During retrieval, however, an interaction of load and feature conjunction was observed. This modulation of feature conjunction activity under increased load was expressed through greater deactivation in medial structures identified as part of the default mode network. CONCLUSIONS AND SIGNIFICANCE: The relationship between memory load and feature binding qualitatively differed through each phase of the WM task. Of particular interest was the interaction of these factors observed within regions of the default mode network during retrieval which we interpret as suggesting that at low loads, binding processes may be 'automatic' but at higher loads it becomes a resource-intensive process leading to disengagement of activity in this network. These findings provide new insights into how feature binding operates within the capacity-limited WM system
Promotion of plasma membrane repair by vitamin E
Severe vitamin E deficiency results in lethal myopathy in animal models. Membrane repair is an important myocyte response to plasma membrane disruption injury as when repair fails, myocytes die and muscular dystrophy ensues. Here we show that supplementation of cultured cells with α-tocopherol, the most common form of vitamin E, promotes plasma membrane repair. Conversely, in the absence of α-tocopherol supplementation, exposure of cultured cells to an oxidant challenge strikingly inhibits repair. Comparative measurements reveal that, to promote repair, an anti-oxidant must associate with membranes, as α-tocopherol does, or be capable of α-tocopherol regeneration. Finally, we show that myocytes in intact muscle cannot repair membranes when exposed to an oxidant challenge, but show enhanced repair when supplemented with vitamin E. Our work suggests a novel biological function for vitamin E in promoting myocyte plasma membrane repair. We propose that this function is essential for maintenance of skeletal muscle homeostasis
Atividade física em trabalhadores de Centros de Atenção Psicossocial do Sul do Brasil: tendências temporais
Comparison of Amino-acid Sequences of Hypothalamic Peptide, Brain-specific Histone and Myelin Basic Protein
Active Synthesis of Mouse Polymeric Immunoglobulin Receptor in the Epithelial Cells of the Distal Urinary Tubule in Kidney
Condições de trabalho e automedicação em profissionais da rede básica de saúde da zona urbana de Pelotas, RS
Remote sensing of Arctic atmospheric aerosols
In this chapter remote sensing techniques as applied to studies of Arctic aerosol are surveyed. They include the analysis of ground and shipborne observations of atmospheric aerosol using sunphotometers and also airborne/satellite observations using optical instrumentation (lidars, imagers, radiometers)