33 research outputs found

    CNS Penetration of Intrathecal-Lumbar Idursulfase in the Monkey, Dog and Mouse: Implications for Neurological Outcomes of Lysosomal Storage Disorder

    Get PDF
    A major challenge for the treatment of many central nervous system (CNS) disorders is the lack of convenient and effective methods for delivering biological agents to the brain. Mucopolysaccharidosis II (Hunter syndrome) is a rare inherited lysosomal storage disorder resulting from a deficiency of iduronate-2-sulfatase (I2S). I2S is a large, highly glycosylated enzyme. Intravenous administration is not likely to be an effective therapy for disease-related neurological outcomes that require enzyme access to the brain cells, in particular neurons and oligodendrocytes. We demonstrate that intracerebroventricular and lumbar intrathecal administration of recombinant I2S in dogs and nonhuman primates resulted in widespread enzyme distribution in the brain parenchyma, including remarkable deposition in the lysosomes of both neurons and oligodendrocytes. Lumbar intrathecal administration also resulted in enzyme delivery to the spinal cord, whereas little enzyme was detected there after intraventricular administration. Mucopolysaccharidosis II model is available in mice. Lumbar administration of recombinant I2S to enzyme deficient animals reduced the storage of glycosaminoglycans in both superficial and deep brain tissues, with concurrent morphological improvements. The observed patterns of enzyme transport from cerebrospinal fluid to the CNS tissues and the resultant biological activity (a) warrant further investigation of intrathecal delivery of I2S via lumbar catheter as an experimental treatment for the neurological symptoms of Hunter syndrome and (b) may have broader implications for CNS treatment with biopharmaceuticals

    Comparing post-release survival and habitat use by captive-bred Cabot’s Tragopan (Tragopan caboti) in an experimental test of soft-release reintroduction strategies

    Get PDF
    Background: Restoring a viable population by reintroduction is the ultimate goal of a large number of ex situ conservation projects for endangered animals. However, many reintroductions fail to establish a population in the wild, partly because released animals cannot acclimate to the native environment of the release site, resulting in very low survival rates. Acclimation training is a technique to resolve this problem, although it does not have positive results in all species. We tested whether acclimation training and soft-release could improve the reintroduction success for captive-bred Cabot’s Tragopan (Tragopan caboti), an endangered pheasant in southern China. Methods: Reintroduction of captive-bred Cabot’s Tragopan was carried out in the Taoyuandong National Nature Reserve, China from 2010 to 2011. We built a soft-release enclosure for acclimation training in the typical montane habitat of this pheasant. Nine birds were acclimated to the environment of this release site in this cage for more than 50 days before release (“trained birds”), while 11 birds remained only in the cage for 3 days prior to release (“untrained birds”). Released birds were tagged with a collar radio-transmitter. Results: Post-release monitoring revealed that the survival rate of trained birds was higher than that of untrained birds after 50 days (trained: 85.7%; untrained: 20.0%). Cox regression analysis showed that there was a significant difference in the mortality rates between the trained and untrained birds. In addition, a survey of the habitat of the experimental and the control groups showed significant differences in habitat selection between the groups. Conclusion: Our study suggests that pre-release acclimatization training is an important factor that can lead to improved survival and habitat selection of captive-bred reintroduced tragopans

    CD64 as a potential biomarker in septic arthritis

    Get PDF
    Background Traditional inflammatory markers are generally unhelpful in discerning septic arthritis from inflammatory joint disease due to their lack of specificity. We wished to explore the discriminatory power of the novel inflammatory marker, Fc-gamma-receptor type 1, CD64, in patients presenting with acute arthritis. Methods Patients were recruited prospectively in the time period June 2009 to December 2011. Thirty-six patients presenting with an acute flare of chronic rheumatic arthritis, 31 with crystal-induced arthritis and 23 with septic arthritis were included. Traditional inflammatory markers, CD64 and procalcitonin (PCT) were measured and their diagnostic abilities were compared. Results CD64 and PCT both demonstrated a specificity of 98%, but poor sensitivities of 59% and 52%, respectively. White blood cell count (WBC), and erythrocyte sedimentation rate (ESR) did not have significant discriminatory power, while C-reactive protein (CRP) proved to have the best diagnostic accuracy as measured by area under the ROC curve (AUC 0.92, 95% confidence-interval 0.87-0.98). Subgroup analysis excluding patients with septic arthritis without concurrent bacteremia, and likewise exclusion of the patients with septic arthritis caused by coagulase negative staphylococci, both improved the diagnostic accuracy of CD64 and PCT, but not of WBC and CRP.</p< Conclusions CD64 and PCT are highly specific for infectious disease, but they predominantly measure bacteremia. Their use in hospital practice has yet to be defined, and especially so in localized infections
    corecore