Moreover, we also revealed that this activation of ERK1/2 occurred through transient receptor potential (TRP) A1, a member of the TRP family of ion channels. In contrast, it is known that the activation of p38 MAPK (p38) contributes to the development and maintenance of inflammatory and neuropathic pain. On the basis of these results, the aim of this study was to investigate the involvement of p38 and TRPA1 in acute visceral pain. Male Sprague-Dawley rats were used.
Electromyographic responses to gastric distension (GD) were recorded from the acromiotrapezius muscle. We then examined the phosphorylated-p38 (p-p38) labeling in the dorsal root ganglion (DRG) after GD using immunohistochemistry. Selleck LY2835219 Noxious GD induced p-p38 in DRG neurons with a peak at 2 min after GD. We also found a stimulus intensity-dependent increase in the number of p-p38-immunoreactive neurons in the DRG. Intrathecal administration of the p38 inhibitor, SB203580, attenuated the electromyographic response to noxious GD. Furthermore, intrathecal administration of TRPA1 antisense oligodeoxynucleotide decreased the p38 activation in DRG neurons. The activation of p38 pathways in DRG neurons by noxious GD may be correlated with the activation state of the primary afferent neurons through TRPA1, and further, involved in the development of visceral
pain. NeuroReport 24:68-72 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. NeuroReport 2013, 24:68-72″
“Improved survival of patients with acute SRT1720 mw lymphoblastic leukemia (ALL) has emerged from identifying new prognostic markers; however, 20% of children still suffer recurrence. Previously, the altered expression of Fat1 cadherin has been implicated in a number of solid tumors. In this report, in vitro analysis shows
that Fat1 protein is expressed by a range of leukemia cell lines, but not by normal peripheral blood (PB) and bone marrow (BM) cells from healthy donors. In silico analysis of expression of array data from clinical leukemias found significant levels of Fat1 transcript in 11% of acute myeloid AZD5582 solubility dmso leukemia, 29% and 63% of ALL of B and T lineages, respectively, and little or no transcript present in normal PB or BM. Furthermore, in two independent studies of matched diagnosis – relapse of precursor B-cell (preB) ALL pediatric samples (n = 32 and n = 27), the level of Fat1 mRNA expression was prognostic at the time of diagnosis. High Fat1 mRNA expression was predictive of shorter relapse-free and overall survival, independent of other traditional prognostic markers, including white blood cell count, sex and age. The data presented demonstrate that Fat1 expression in preB-ALL has a role in the emergence of relapse and could provide a suitable therapeutic target in high-risk preB-ALL.