Transport of Glial Cell Line-Derived Neurotrophic Factor into Liposomes across the Blood-Brain Barrier: In Vitro and in Vivo Studies

Glial cell line-derived neurotrophic factor (GDNF) was encapsulated into liposomes in order to protect it from enzyme degradation in vivo and promote its permeability across the blood-brain barrier (BBB). In this study, GDNF conventional liposomes (GDNF-L) and GDNF target sterically stabilized liposomes (GDNF-SSL-T) were prepared. The average size of liposomes was below 90 nm. A primary model of BBB was established and evaluated by transendothelial electrical resistance (TEER) and permeability. This BBB model was employed to study the permeability of GDNF liposomes in vitro. The results indicated that the liposomes could enhance transport of GDNF across the BBB and GDNF-SSL-T had achieved the best transport efficacy. The distribution of GDNF liposomes was studied in vivo. Free GDNF and GDNF-L were eliminated rapidly in the circulation. GDNF-SSL-T has a prolonged circulation time in the blood and favorable brain delivery. The values of the area under the curve (AUC(0–1 h)) in the brain of GDNF-SSL-T was 8.1 times and 6.8 times more than that of free GDNF and GDNF-L, respectively. These results showed that GDNF-SSL-T realized the aim of targeted delivery of therapeutic proteins to central nervous system

Cross-cultural adaptation, reliability, and validity of the Chinese version of the STarT Back Screening Tool in patients with low back pain.

Study Design. Translation and psychometric testing.Objective. The study aims to investigate the reliability and validity of the Chinese version of the STarT Back Screening Tool (STarT) in Chinese-speaking patients with low back pain (LBP) after translation and cultural adaptation.Summary of Background Data. To date, no previous studies exist on the translation process and validation of the Chinese version of the STarT.Methods. The procedure of translation, which included 6 stages, was performed according to the current recommended guidelines. Psychometric testing included face validity, test-retest reliability, and discriminant validity. A total of 307 patients completed a questionnaire booklet containing the Chinese version of the STarT, Roland-Morris Disability Questionnaire, Coping Strategies Questionnaire, Tampa Scale for Kinesiophobia-17, and Hospital Anxiety and Depression Scale. Seventy-four randomly selected patients were asked to finish the STarT a second time within 24 to 48 hours. The demographic characteristics and outcomes of psychometric testing were compared with the original English cohort.Results. No items of the final version had reported ambiguity after the face validation and no floor or ceiling effects were noted. The intraclass correlation coefficient was 0.933 (95% confidence interval, 0.896–0.957), demonstrating very good reliability. Discriminant validity was established, with area under curve results in the range from 0.751 to 0.893 (95% confidence interval, 0.697–0.930) in the Chinese cohort compared with 0.840 to 0.925 (95% confidence interval, 0.772–0.948) in the original English cohort.Conclusion. The results confirm the successful translation and adaptation of the STarT into Chinese, with appropriate reliability and validity. Therefore, this version can be recommended for clinical and research use for Chinese patients with LBP

Running Exercise Alleviates Pain and Promotes Cell Proliferation in a Rat Model of Intervertebral Disc Degeneration

Chronic low back pain accompanied by intervertebral disk degeneration is a common musculoskeletal disorder. Physical exercise, which is clinically recommended by international guidelines, has proven to be effective for degenerative disc disease (DDD) patients. However, the mechanism underlying the analgesic effects of physical exercise on DDD remains largely unclear. The results of the present study showed that mechanical withdrawal thresholds of bilateral hindpaw were significantly decreased beginning on day three after intradiscal complete Freund’s adjuvant (CFA) injection and daily running exercise remarkably reduced allodynia in the CFA exercise group beginning at day 28 compared to the spontaneous recovery group (controls). The hindpaw withdrawal thresholds of the exercise group returned nearly to baseline at the end of experiment, but severe pain persisted in the control group. Histological examinations performed on day 70 revealed that running exercise restored the degenerative discs and increased the cell densities of the annulus fibrosus (AF) and nucleus pulposus (NP). Furthermore, immunofluorescence labeling revealed significantly higher numbers of 5-bromo-2-deoxyuridine (BrdU)-positive cells in the exercise group on days 28, 42, 56 and 70, which indicated more rapid proliferation compared to the control at the corresponding time points. Taken together, these results suggest that running exercise might alleviate the mechanical allodynia induced by intradiscal CFA injection via disc repair and cell proliferation, which provides new evidence for future clinical use