4,864 research outputs found
Protective effects of lycium barbarum polysaccharides on cerebral edema and blood-brain barrier disruption after ischemic stroke
Young Investigators Symposium I (Y3) - Di YangBACKGROUND: Ischemic stroke is a destructive cerebrovascular disease and one of the leading causes of death worldwide. The long term disability after stroke induces heavy burden both to the patients and the society. Yet, no effective neuroprotective agents are available. The polysaccharides extracted from the fruits of wolfberry, Lycium barbarum (LBP), showed neuroprotective and immune-modulative functions. We aim to evaluate the protective effects of LBP in experimental stroke using a focal cerebral ischemia/reperfusion (I/R) model. METHODS: C57BL/6N mice were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by 22 h of reperfusion. Prior to ischemia induction, animals were treated with either vehicle (PBS) or LBP daily for 7 days. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement and immunohistochemical analysis as well as Western blot experiments. Evans blue (EB) extravasation experiment was performed to determine blood-brain barrier (BBB) disruption after MCAO. RESULTS: LBP treatment significantly improved neurological scores and decreased infarct size, hemispheric swelling and water content as well as reduced EB extravasation. In addition, fewer apoptotic cells were identified in the LBP-treated brains by TUNEL assay. Immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were also significantly decreased in LBP-treated brains. We further observed a reduction of nuclear factor-κB translocation and IκB expression after LBP treatment. CONCLUSION: Seven-day LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin water channel up-regulation and glial activation. The protective effects of LBP might partially act through its anti-inflammatory effects. The present study suggests that LBP may be used as a preventive neuroprotectant for ischemic stroke.postprin
Optimizing antimicrobial treatment schedules: some fundamental analytical results
This work studies fundamental questions regarding the optimal design of
antimicrobial treatment protocols, using standard pharmacodynamic and
pharmacokinetic mathematical models. We consider the problem of designing an
antimicrobial treatment schedule to achieve eradication of a microbial
infection, while minimizing the area under the time-concentration curve (AUC).
We first solve this problem under the assumption that an arbitrary
antimicrobial concentration profile may be chosen, and prove that the 'ideal'
concentration profile consists of a constant concentration over a finite time
duration, where explicit expressions for the optimal concentration and the time
duration are given in terms of the pharmacodynamic parameters. Since
antimicrobial concentration profiles are induced by a dosing schedule and the
antimicrobial pharmacokinetics, the ideal concentration profile is not strictly
feasible. We therefore also investigate the possibility of achieving outcomes
which are close to those provided by the ideal concentration profile,using a
bolus+continuous dosing schedule, which consists of a loading dose followed by
infusion of the antimicrobial at a constant rate. We explicitly find the
optimal bolus+continuous dosing schedule, and show that, for realistic
parameter ranges, this schedule achieves results which are nearly as efficient
as those attained by the ideal concentration profile. The optimality results
obtained here provide a baseline and reference point for comparison and
evaluation of antimicrobial treatment plans
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