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“Background: Voltage-gated sodium channels dysregulation is important for hyperexcitability

leading to pain persistence. Sodium channel blockers currently used to treat neuropathic pain are poorly tolerated. Getting new molecules to clinical use selleck compound is laborious. We here propose a drug already marketed as anticonvulsant, rufinamide.\n\nMethods: We compared the behavioral effect of rufinamide to amitriptyline using the Spared Nerve Injury neuropathic pain model in mice. We compared the effect of rufinamide on sodium currents using in vitro patch clamp in cells expressing the voltage-gated sodium channel Nav1.7 isoform and on dissociated dorsal root ganglion neurons to amitriptyline and mexiletine.\n\nResults: In naive mice, amitriptyline (20 mg/kg) increased withdrawal threshold to mechanical stimulation from 1.3 (0.6-1.9) (median [95% CI]) to 2.3 g (2.2-2.5) and latency of withdrawal to heat stimulation

from 13.1 (10.4-15.5) to 30.0 s (21.8-31.9), whereas rufinamide had no effect. Rufinamide and amitriptyline alleviated injury-induced mechanical allodynia for 4 h (maximal effect: 0.10 +/- 0.03 g (mean +/- SD) to 1.99 +/- 0.26 g for rufinamide and 0.25 +/- 0.22 g to 1.92 +/- 0.85 g for amitriptyline). All drugs reduced peak current and stabilized the inactivated state of voltage-gated sodium channel Nav1.7, with similar effects in dorsal root ganglion neurons.\n\nConclusions: At doses alleviating neuropathic pain, amitriptyline showed alteration of behavioral response possibly LEE011 purchase related to either alteration of basal pain sensitivity or sedative effect or both. Side-effects and drug tolerance/compliance are major problems with drugs such as amitriptyline. Rufinamide seems to have a better tolerability profile and could be a new alternative to explore for the treatment of neuropathic pain.”
“IL-7 is an important cytokine for lymphocyte differentiation. Similar to what occurs in vivo, human CD19(+)

cells developing in LY411575 inhibitor human/murine xenogeneic cultures show differential expression of the IL-7 receptor alpha (IL-7R alpha) chain (CD127). We now describe the relationship between CD127 expression/signaling and Ig gene rearrangement. In the present study, < 10% of CD19(+) CD127(+) and CD19(+) CD127(+) populations had complete VDJ(H) rearrangements. IGH locus conformation measurements by 3D FISH revealed that CD127(+) and CD127(+) cells were less contracted than pediatric BM pro-B cells that actively rearrange the IGH locus. Complete IGH rearrangements in CD127(+) and CD127(+) cells had smaller CDR3 lengths and fewer N-nucleotide insertions than pediatric BM B-lineage cells. Despite the paucity of VDJH rearrangements, microarray analysis indicated that CD127(+) cells resembled large pre-B cells, which is consistent with their low level of Ig light-chain rearrangements.