Penicillamin-induzierte Myasthenie bei chronischer Polyarthritis

Abstract

Bei zwölf Fr'uen im Durchschnittsalter von Si Jahren, die wegen einer chronischen Polyarthritis mit Penicillamin behandelt wurden, entwickelte sich nach einer durchschnittlichen Latenz von 7-8 Monaten eine myasthenische Reaktion. In der Mehrzahl der Fälle wurden rein okuläre Formen beobachtet, jedoch kam auch eine Generalisation verschiedener Schweregrade vor. Nach Absetzen des Penicillamins waren die myasthenischen Symptome meist voll reversibel, bei Wiederholung der Therapie traten sie stets erneut auf. Oft war eine vorübergehende symptomatische Therapie mit Cholinesterasehemmern notendig. Für die Induktion myasthenischer Symptome durch Penicillamin bei Patienten mit chronischer Polyarthritis kommt vermutlich ein ähnlicher oder gleicher Pathomechanismus in Betracht, wie er für die penicillamininduzierte Antibasalmembran-Neph ropathie nachgewiesen werden konnte.

Dynamics and energetics of solute permeation through the Plasmodium falciparum aquaglyceroporin

“…2 and 3(b)), contrary to what previous mutation experiments demonstrated. 9 The reduction in the water permeability due to the Glu125Ser mutation was attributed to the destabilization of the C loop and further disruption of the hydrogen bonds between Arg196 and Trp124. 9,10 However, the conformational change of the C loop may occur on a longer time scale than the simulated time (100 ns), impeding to be detected in our equilibrium simulations.…”

“…9 The reduction in the water permeability due to the Glu125Ser mutation was attributed to the destabilization of the C loop and further disruption of the hydrogen bonds between Arg196 and Trp124. 9,10 However, the conformational change of the C loop may occur on a longer time scale than the simulated time (100 ns), impeding to be detected in our equilibrium simulations. In fact, the C loop was observed to be rigidly anchored to the extracellular vestibule (with an average backbone rmsd of 0.97 Å with a standard deviation of 0.26 Å ) in the wild type simulation, and just slightly more flexible (with an average backbone rmsd of 1.06 Å and a standard deviation of 0.36 Å ) in the Glu125Ser simulation.…”

“…10 In addition, the C loop is anchored to the extracellular vestibule with Glu125 located in proximity to Arg196, highlighting on the importance of this region for the solute permeation, 10 as previously hypothesized from functional studies. 9 Despite the wealth of data available, a dynamical and energetic description at the single-molecule level of solute permeation through PfAQP is lacking so far. Furthermore, a systematic comparison of PfAQP with hAQP1 and GlpF (the most studied aquaporin and aquaglyceroporin, respectively), in terms of the solute permeation and their dynamical causes, is incomplete.…”

“…8 Furthermore, mutation studies demonstrated that a glutamate residue located at the C loop (Glu125) near the conserved Arg196 is critical for water permeation. 9 The structure of PfAQP was recently determined by X-ray crystallography at 2.05 A ˚resolution. 10 It revealed the 3D architecture of the channel and provided molecular insights into the efficient water and glycerol permeation.…”