This investigation reports on the generation of mono-Fab-Sb and Sb-IL2 monocytokine as models. They were expressed at high levels in NS/0 cells, purified on recombinant
protein A resin and were well-behaved in solution. When administered intravenously to mice, Sb pharmacokinetics exhibited the long serum half-life extensions typical of comparable Fc-containing immunofusion and IgG1 controls.”
“Introduction: Severe brain hypoxia in the territory of the occluded artery is a key feature of ischemic stroke. This region can be imaged using positron emission tomography (PET) and the standard hypoxia radiotracer F-18-fluoromisonidazole (F-18-FMISO). However, ICG-001 solubility dmso the utility of F-18-FMISO is limited by its slow accumulation in the lesion. Therefore, this study investigated three hypoxia-sensitive radiotracers, namely the nitroimidazole F-18-fluoroazomycin arabinoside (F-18-FAZA) and two Cu-64 bis(thiosemicarbazone) complexes (Cu-64-ATSM and Cu-64-ATSE), expected to have improved pharmacokinetic profiles relative to F-18-FMISO, in a rodent model of ischemic stroke.
Methods: In anaesthetised Wistar rats, the distal middle cerebral artery C188-9 was permanently
occluded by electrocoagulation, the radiotracers administered intravenously and animals PET scanned for up to 3 hours, followed by T2-weighted magnetic resonance imaging to map the infarct.
Results: As expected, late and prominent F-18-FMISO retention was observed despite lower tracer delivery into the affected region. Time-activity curves revealed that both Cu-64-ATSM and Cu-64-ATSE showed rapid entry and efflux from the brain, but did not show significant accumulation in the lesion. F-18-FAZA showed limited brain penetration, and accumulation in the lesion was inconsistent, low and as slow as F-18-FMISO.
Conclusions: This study suggests further development of these radiotracers as hypoxia markers for ischemic stroke may not be warranted. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.”
“The contribution of Th17 cells in acute graft-versus-host disease
(aGVHD) has been demonstrated in aGVHD mouse models. However, their contribution in human gastrointestinal aGVHD remains unclear. We evaluated Th17 cells Farnesyltransferase in a cohort of 23 patients at diagnosis of aGVHD. In this study, we have shown that the absolute number of Th17 cells using the CCR6 and CD161 markers were significantly higher in the intestinal mucosa of patients with aGVHD compared with intestinal mucosa of patients without aGVHD. Moreover, in keeping with the increase of CCR6+ and CD161+ T cells, ROR gamma t the key transcription factor that orchestrates the differentiation of Th17 cells, was significantly increased in the intestinal mucosa of patients with aGVHD compared with intestinal mucosa of patients without aGVHD (P=0.01). Since plasmacytoid dendritic cells (PDCs) have been reported to drive the differentiation of the Th17 subset, we quantified PDCs in these patients.