Human umbilical cord blood-derived mononuclear cell transplantation: case series of 30 subjects with hereditary ataxia.

BACKGROUND: The differential diagnosis for hereditary ataxia encompasses a variety of diseases characterized by both autosomal dominant and recessive inheritance. There are no curative treatments available for these neurodegenerative conditions. This open label treatment study used human umbilical cord blood-derived mononuclear cells (CBMC) combined with rehabilitation training as potential disease modulators. METHODS: 30 patients suffering from hereditary ataxia were treated with CBMCs administered systemically by intravenous infusion and intrathecally by either cervical or lumbar puncture. Primary endpoint measures were the Berg Balance Scale (BBS), serum markers of immunoglobulin and T-cell subsets, measured at baseline and pre-determined times post-treatment. RESULTS: A reduction of pathological symptoms and signs was shown following treatment. The BBS scores, IgG, IgA, total T cells and CD3+CD4 T cells all improved significantly compared to pre-treatment values (P < 0.01~0.001). There were no adverse events. CONCLUSION: The combination of CBMC infusion and rehabilitation training may be a safe and effective treatment for ataxia, which dramatically improves patients' functional symptoms. These data support expanded double blind, placebo-controlled studies for these treatment modalities.

Ulinastatin: A Potential Alternative to Glucocorticoid in the Treatment of Severe Decompression Sickness.

Inflammatory reaction is the crux in various clinical critical diseases including decompression sickness (DCS). Ulinastatin (UTI), a potent anti-inflammatory agent, has been used clinically, including as a substitution for steroids. This study aimed to explore the potential effects of UTI upon DCS in a rabbit model. Eighty-eight rabbits were subjected to simulated diving to 6 atmospheres absolute (ATA) for 60 min with 2.5-minute decompression. Three doses of UTI (15/7.5/3.75 × 105 U/kg) or saline were intravenously administered immediately following decompression. Circulating bubbles were monitored for 3 h following decompression and DCS signs were evaluated for 24 h. Blood was sampled 8 times during 72 h after decompression for inflammatory, endothelial, oxidative and routine blood indices. Lung tissues were also sampled for evaluating endothelial function. Another six rabbits were used as Normal controls. In the high dose UTI group the mortality, general morbidity and incidence of severe DCS was decreased from 31.25 to 9.38% (P = 0.030), 84.38 to 62.50% (P = 0.048) and 46.88 to 21.88% (P = 0.035), respectively. The high dose of UTI significantly postponed the occurrence of DCS (P = 0.030) and prolonged survival time (P = 0.009) compared with the Saline group, and significantly ameliorated inflammation responses, endothelial injuries and oxidative damage. The results strongly suggest the benefit of UTI on DCS, especially for severe cases. Large doses are needed to achieve significant effects. UTI may be a potential ideal pharmacological candidate for the treatment of severe DCS.

Off-label use of tacrolimus in children with Henoch-Schönlein purpura nephritis: a pilot study.

BACKGROUND: Tacrolimus is used off-label in the treatment of Henoch-Schönlein purpura nephritis (HSPN) in children, with limited evidence-based data. Based on clinical empirical experience and mechanism of action, tacrolimus might be promoted as treatment for childhood HSPN. The objectives of this pilot study were to assess its effectiveness and safety, and to explore the potential impact of CYP3A5 genotype. METHODS: Children with HSPN receiving tacrolimus as empirical treatment were included in this prospective, observational study. Effectiveness was classified as complete remission, partial remission or non-response. General safety data analyses during and after study drug exposure included adverse events, reasons for discontinuation, deaths, laboratory data and vital signs. Trough concentration was determined using high-performance liquid chromatography with tandem mass spectrometry. Pharmacogenetic analysis was performed on the CYP3A5 gene. RESULTS: A total of 20 patients with a mean age of 7.5 (SD 2.1) years participated in the whole process of the study. Twelve patients reached complete remission and eight patients reached partial remission at the end of 6-month treatment. No patients discontinued tacrolimus treatment due to adverse events, and no drug-related adverse events were shown to have a causal association with tacrolimus therapy. Dose-adjusted trough concentration was significantly higher in children with CYP3A5*1 allele as compared with patients with CYP3A5*3/*3 genotype (170.7±100.9 vs 79.8±47.4 (ng/mL)/(mg/kg)). CONCLUSION: This pilot study showed that tacrolimus might be an effective and well-tolerated drug for the treatment of HSPN in children. CYP3A5 polymorphism had a significant impact on tacrolimus concentration.