22 research outputs found
The use of high performance liquid chromotography in the study of enzyme mechanism and evolution: active site labelling of D-amino acid oxidase; homology between lipoamide dehydrogenase and glutathione reductase
Absence of Foxp3(+) regulatory T cells during allergen provocation does not exacerbate murine allergic airway inflammation
Regulatory T cells (Tregs) play a non-redundant role in maintenance of immune homeostasis. This is achieved by suppressing both, priming of naıšve cells and effector cell functions. Although Tregs have been implicated in modulating allergic immune responses, their influence on distinct phases of development of allergies remains unclear. In this study, by using bacterial artificial chromosome (BAC)-transgenic Foxp3-DTR (DEREG) mice we demonstrate that the absence of Foxp3+ Tregs during the allergen challenge surprisingly does not exacerbate allergic airway inflammation in BALB/c mice. As genetic disposition due to strain specificity may contribute significantly to development of allergies, we performed similar experiment in C57BL/6 mice, which are less susceptible to allergy in the model of sensitization used in this study. We report that the genetic background does not influence the consequence of this depletion regimen. These results signify the temporal regulation exerted by Foxp3+ Tregs in limiting allergic airway inflammation and may influence their application as potential therapeutics
Brain delivery research in public-private partnerships: The IMI-JU COMPACT consortium as an example
Validation of a selfâcompleted Dystonia NonâMotor Symptoms Questionnaire
OBJECTIVES: To develop and validate a novel 14âitem selfâcompleted questionnaire (in English and German) enquiring about the presence of nonâmotor symptoms (NMS) during the past month in patients with craniocervical dystonia in an international multicenter study. METHODS: The Dystonia NonâMotor Symptoms Questionnaire (DNMSQuest) covers seven domains including sleep, autonomic symptoms, fatigue, emotional wellâbeing, stigma, activities of daily living, sensory symptoms. The feasibility and clinimetric attributes were analyzed. RESULTS: Data from 194 patients with CD (65.6% female, mean age 58.96 ± 12.17 years, duration of disease 11.95 ± 9.40 years) and 102 ageâ and sexâmatched healthy controls (66.7% female, mean age 55.67 ± 17.62 years) were collected from centres in Germany and the UK. The median total NMS score in CD patients was 5 (interquartile range 3â7), significantly higher than in healthy controls with 1 (interquartile range 0.75â2.25) (P < 0.001, MannâWhitney Uâtest). Evidence for intercorrelation and convergent validity is shown by moderate to high correlations of total DNMSQuest score with motor symptom severity (TWSTRS: r_{s} = 0.61), clinical global impression (r_{s} = 0.40), and healthârelated quality of life measures: CDQâ24 (r_{s} = 0.74), EQâ5D index (r_{s} = â0.59), and scale (r_{s} = â0.49) (all P < 0.001). Data quality and acceptability was very satisfactory. INTERPRETATION: The DNMSQuest, a patient selfâcompleted questionnaire for NMS assessment in CD patients, appears robust, reproducible, and valid in clinical practice showing a tangible impact of NMS on quality of life in CD. As there is no specific, comprehensive, validated tool to assess the burden of NMS in dystonia, the DNMSQuest can bridge this gap and could easily be integrated into clinical practice
Inhibition of human glutathione reductase by the nitrosourea drugs 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-(2-hydroxyethyl)-1-nitrosourea. A crystallographic analysis
Generation of Brain Microvascular Endothelial-Like Cells from Human Induced Pluripotent Stem Cells by Co-Culture with C6 Glioma Cells
Glutathione reductase from yeast. Differential reactivity of the nascent thiols in two-electron reduced enzyme and properties of a monoalkylated derivative
p-Hydroxybenzoate Hydroxylase from Pseudomonas fluorescens. 2. Fitting of the Amino-Acid Sequence to the Tertiary Structure
Magnetic circular dichroism studies on the active-site flavin of lipoamide dehydrogenase
A randomized double-blind clinical trial on safety and efficacy of tauroursodeoxycholic acid (TUDCA) as add-on treatment in patients affected by amyotrophic lateral sclerosis (ALS): the statistical analysis plan of TUDCA-ALS trial
Background
Amyotrophic lateral sclerosis (ALS) is a highly debilitating neurodegenerative condition. Despite recent advancements in understanding the molecular mechanisms underlying ALS, there have been no significant improvements in therapeutic options for ALS patients in recent years. Currently, there is no cure for ALS, and the only approved treatment in Europe is riluzole, which has been shown to slow the disease progression and prolong survival by approximately 3 months. Recently, tauroursodeoxycholic acid (TUDCA) has emerged as a promising and effective treatment for neurodegenerative diseases due to its neuroprotective activities.
Methods
The ongoing TUDCA-ALS study is a double-blinded, parallel arms, placebo-controlled, randomized multicenter phase III trial with the aim to assess the efficacy and safety of TUDCA as add-on therapy to riluzole in patients with ALS. The primary outcome measure is the treatment response defined as a minimum of 20% improvement in the ALS Functional Rating Scale-Revised (ALSFRS-R) slope during the randomized treatment period (18 months) compared to the lead-in period (3 months). Randomization will be stratified by country. Primary analysis will be conducted based on the intention-to-treat principle through an unadjusted logistic regression model. Patient recruitment commenced on February 22, 2019, and was closed on December 23, 2021. The database will be locked in September 2023.
Discussion
This paper provides a comprehensive description of the statistical analysis plan in order to ensure the reproducibility of the analysis and avoid selective reporting of outcomes and data-driven analysis. Sensitivity analyses have been included in the protocol to assess the impact of intercurrent events related to the coronavirus disease 2019. By focusing on clinically meaningful and robust outcomes, this trial aims to determine whether TUDCA can be effective in slowing the disease progression in patients with ALS.
Trial registration
ClinicalTrials.gov NCT03800524. Registered on January 11, 2019