Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

Multiple sclerosis registries in Europe – An updated mapping survey

Highlights Nineteen questionnaires from European MS registries were analysed. Aim and focus as well as number of patients and inclusion criteria vary considerably. Most of the MS registries collect data within common general categories. There are more pronounced differences regarding specific subcategories

An optimization and refinement of the whole-gut transit assay in mice

BackgroundGastrointestinal motility measurements in mice are currently performed under suboptimal conditions, as these nocturnal animals are measured during light conditions. In addition, other stressors, like individual housing, placement in a new cage during observation, and lack of bedding and cage enrichment cause animal discomfort and might contribute to higher variability. Here we aimed to develop a refined method of the widely-used whole-gut transit assay. MethodsWildtype mice (N = 24) were subjected to the standard or refined whole-gut transit assay, either with or without a standardized slowing in gastrointestinal motility induced by loperamide. The standard assay consisted of a gavage with carmine red, observation during the light period and individual housing in a new cage without cage enrichment. For the refined whole-gut transit assay, mice were gavaged with UV-fluorescent DETEX (R), observed during the dark period, while pairwise housed in their home cage with cage enrichment. Time until excretion of the first colored fecal pellet was assessed, and pellets were collected to assess number, weight, and water content. Key ResultsThe DETEX (R)-containing pellets were UV-detectable, allowing to measure the mice in their active period in the dark. The refined method caused less variation (20.8% and 16.0%) compared to the standard method (29.0% and 21.7%). Fecal pellet number, weight, and water content was significantly different between the standard and refined method. Conclusions & InferencesThis refined whole-gut transit assay provides a reliable approach to measure whole-gut transit time in mice in a more physiological context, with reduced variability compared to the standard method

Increased EEG delta frequency corresponds to chorioamnionitis-related brain injury

We evaluated the impact of chorioamnionitis on the intrapartal EEG delta frequency in the non-anesthetized preterm sheep. 10 mg intra-amniotic LPS or saline were given 2 or 14 days before preterm birth at gestational day 125. Lambs were delivered by Caesarean section under local anesthesia. A 5-minute EEG depicted delta activity and amplitude, and the relationship between EEG delta activity and both the white matter (WM) and cortical microglial activation and apoptosis was analyzed. EEG delta activity was increased significantly in the 14-day LPS preterm fetuses compared to both preterm control and 2-day LPS animals (p less than 0.05). No differences were seen between controls and the 2-day LPS fetuses. A direct association was demonstrated between EEG delta activity and both cortical microglial activation (r = 0,645, p = 0,024) and apoptosis (r = 0,580, p = 0,048), and between delta and WM activated microglia (r = 0,742, p = 0,006) and apoptosis (r = 0,777, p = 0,003). This study is the first to show a relationship between brain dysfunction and chorioamnionitis-related injury at birth

Autologous transplantation of ischemically injured kidneys in pigs.

BACKGROUND: Expansion of the organ donor pool can be obtained through novel interventions attenuating ischemic acute kidney injury, which will enable the use of kidneys that suffered prolonged ischemia. In basic science, new therapeutic targets are identified that should be tested in a relevant large animal model before use in human kidney transplantation. MATERIALS AND METHODS: The current paper provides a detailed description of the technique of autologous transplantation of ischemically injured kidneys in pigs with special emphasis on perioperative care. Results. The animal model was validated by showing that renal function after transplantation was proportional to the duration of warm ischemia before organ recovery. The extent of renal dysfunction was reproducible following kidney transplantations with the same warm ischemia time. CONCLUSIONS: Our experience may reduce the learning curves of other research groups taking an interest in the model and improve preclinical testing of novel interventions that modulate renal ischemia and reperfusion injury in kidney transplantation

Evaluating the effect of enhanced physical activity and energy management on fatigue in patients suffering from multiple sclerosis: the MS TeleCoach study

status: publishe