RESUMEN
B cell depletion by the anti-CD20 antibody ocrelizumab is effective in relapsing-remitting (RR) and primary progressive (PP) multiple sclerosis (MS). We investigated immunological changes in peripheral blood of a real-world MS cohort after 6 and 12 months of ocrelizumab. All RRMS and most PPMS patients (15/20) showed treatment response. Ocrelizumab not only reduced CD20+ B cells, but also numbers of CD20+ T cells. Absolute numbers of monocytes, dendritic cells and CD8+ T cells were increased, while CD56hi natural killer cells were reduced after ocrelizumab. The residual B cell population shifted towards transitional and activated, IgA+ switched memory B cells, double negative B cells, and antibody-secreting cells. Delaying the treatment interval by 2-3 months increased mean B cell frequencies and enhanced naive B cell repopulation. Ocrelizumab reduced plasma levels of interleukin(IL)-12p70 and interferon(IFN)-α2. These findings will contribute to understanding ineffective treatment responses, dealing with life-threatening infections and further unravelling MS pathogenesis.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Linfocitos T CD8-positivos , Factores Inmunológicos/uso terapéutico , Interleucina-12 , Sistema InmunológicoRESUMEN
A short route to peptide C-terminal thioesters was developed that does not require the use of special linkers or resins and is compatible with standard Fmoc chemistry. Following conventional solid-phase peptide synthesis, an excess of Me(2)AlCl and EtSH in dichloromethane cleaves peptides from Wang or Pam resins to give the corresponding thioesters directly in good yield and purity.
Asunto(s)
Oligopéptidos/síntesis química , Péptidos/síntesis química , Compuestos de Sulfhidrilo/síntesis química , Secuencia de Aminoácidos , Ésteres/síntesis química , Ésteres/química , Indicadores y Reactivos , Datos de Secuencia Molecular , Oligopéptidos/química , Péptidos/química , Compuestos de Sulfhidrilo/químicaRESUMEN
PURPOSE: Functional improvement after stroke has been related to the intensity of treatment. The present study was set up to observe how stroke patients spend their time in a rehabilitation unit. METHOD: Behavioural mapping was performed throughout a full working day in a Belgian and Swiss stroke unit. RESULTS: Patients were most frequently involved in therapeutic activities, 28% of the day in Belgium and 45% in Switzerland. Physiotherapy accounted for the majority of the therapy time. The Belgian patients spent 27% of the day in their own room and Swiss patients 49% of the day. The most striking finding was that the Swiss patients spent nearly 1.5 hours per day more in therapy. CONCLUSIONS: Differences between the two settings could only partially be explained by more favourable patient-staff ratios in the Swiss setting. Autonomous practice, group therapy sessions and family involvement have to also be considered.