Alleviation of symptoms associated with inflammatory disease states
a technology for inflammatory diseases and symptoms, applied in the field of alleviation of symptoms associated with inflammatory disease states, can solve the problems of affecting the effect of inflammatory reaction, affecting the normal course of disease, and affecting the effect of immune response, so as to inhibit plasma leakage, the effect of confirming the effect of the therapy, and reducing the risk of inflammatory reaction
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example 1
Induction of EAE
Eighteen male monkeys Macaca fasciculatis weighing 2-3 kg were sensitized to myelin basic protein (BP) by the intra dermal injection of 0.1 ml of an emulsion containing 5.0 mg of monkey BP and 0.5 mg of heat-killed M. tuberculosis. Each animal was obtained and housed by the Regional Primate Research Center at the University of Washington, Seattle. The Primate Center conforms to the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Ten days after sensitization to BP, each animal was outfitted with a femoral catheter and tether to facilitate blood sampling and the administration of treatments or anesthetics for magnetic resonance imaging (MRI). The animals were maintained on intravenous heparin (18 units / hour) to prevent blood clots from forming in the intra venous lines.
The animals were randomly admitted to specific treatment groups before they were sensitized to BP. This was done to schedule MRI and to prevent the severity of clinic...
example 2
Treatment By Antibody Infusion
At the onset of definite clinical signs (± to +) six EAE animals received a bolus injection of mAb 60.3 (2 mg / kg) and dexamethasone (4 mg / kg). Dexamethasone was administered to reduce the incidence of severe acute EAE which is rapidly fatal within 48 hours unless treated immediately. Sever acute EAE occurs in approximately 25% of animals induced to develop EAE and is caused by edema in areas involving or impinging upon the brain stem or cerebral cortex. Following injection of the bolus, these six animals were treated by continuous infusion of mAb 60.3 (2 mg / kg / day) for seven days. Over the seven day treatment period, the dose of dexamethasone, which started at 4 mg / kg, was halved every two days until only 1 mg had been in effect for three days. Six control EAE animals were treated only with dexamethasone, following the same protocol outlined above, and six additional controls were treated with continuous infusion of saline.
Animals that improved and...
example 3
Evaluation of Disease Progression
Disease progression was monitored by a combination of clinical evaluation, blood analysis and magnetic resonance imaging. Clinical evaluations were performed twice daily.
As indicated in Table 2 below, all of the animals in this study developed clinical signs of EAE 13-26 days after sensitization to myelin basic protein.
In Table 2, listing of animal numbers in boldface identified animals scanned by MRI; the Onset / Grade column reflects the day of onset after sensitization and the severity of clinical signs (see Table 1) at onset; the Survival / Grade column reflects days of survival post-onset and severity of clinical signs at time of sacrifice.
TABLE 2THERAPEUTIC RESULTSAnimalsOnset / GradeTreatmentSurvival / Grade8907017 days / +60.3 + dex 2 days / D8907521 days / +60.3 + dex42 days / ±8908021 days / +60.3 + dex42 days / ±8906918 days / ±60.3 + dex42 days / ±8907118 days / ±60.3 + dex21 days / ++8907422 days / +60.3 + dex13 days / +8714321 days / ±dex alone17 days / ++8712524...
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