The unchanged expression of Na(v)1.6 contrasts to our previous finding that showed an increased expression of Na(v)1.7 at both typical and atypical nodal sites within painful samples. Together, these findings suggest there is not a simple replacement of one isoform with another, but rather an increased co-expression of multiple isoforms at both intact and remodeling/demyelinating (atypical) nodal sites within the painful dental pulp. The resultant heterogeneous population of isoforms may produce unique axonal excitability properties that could contribute
to spontaneous pain sensations that are common in toothache. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Objective: The matrix metalloproteinases (MMPs) have been implicated in the aggressive course of non-small cell lung cancer (NSCLC). However, there are a large number of MMP subtypes PDK inhibitor with diverse
proteolytic substrates and different induction pathways. This study tested the hypothesis that a differential MMP profile would exist between NSCLC and normal lung and that MMP patterns AZD5363 solubility dmso would differ between NSCLC histologic types.
Methods: NSCLC samples and remote normal samples were obtained from patients with stage I or II NSCLC with either squamous cell (n = 22) or adenocarcinoma (n = 19) histologic characteristics. Absolute concentrations for each of the MMP subclasses were determined by a calibrated and validated multiplex suspension array: collagenases (MMP-1, -8, and -13), gelatinases (MMP-2 and -9), lysins (MMP-2 and -7), and elastase (MMP-12).
Results: Overall, MMP levels were significantly increased in NSCLC compared with normal. For example, MMP-1 and PD173074 in vivo MMP-7 increased by approximately 10-fold in NSCLC (P < .05). Moreover, a different MMP portfolio was observed between NSCLC histologic types. For example MMP-1, -8, -9, and -12 increased by more than 4-fold in squamous cell versus adenocarcinoma
(P < .05). In those patients who had recurrence within 3 years of resection, 3-fold higher levels of MMP-8 and -9 were observed (P < .05).
Conclusion: Increased levels of a number of MMP types occur with NSCLC, but the MMP profile was distinctly different between histologic types and in those patients with recurrence. These different MMP profiles may be important in the mechanistic basis for the natural history of different NSCLC types, as well as identifying potential prognostic and therapeutic targets. (J Thorac Cardiovasc Surg 2010; 139: 984-90)”
“Glutamate neurotransmission is highly regulated, largely by glutamate transporters. In the spinal cord, the glutamate transporter GLT-1 is primarily responsible for glutamate clearance. Downregulation of GLT-1 can occur in activated astrocytes, and is associated with increased extracellular glutamate and neuroexcitation. Among other conditions, astrocyte activation occurs following repeated opioids and in models of chronic pain.