Pharmacologic Characterization of LTGO-33, a Selective Small Molecule Inhibitor of the Voltage-Gated Sodium Channel Na1.8 with a Unique Mechanism of Action.

Discovery and development of new molecules directed against validated pain targets is required to advance the treatment of pain disorders. Voltage-gated sodium channels (Nas) are responsible for action potential initiation and transmission of pain signals. Na1.

TMEM16A controls EGF-induced calcium signaling implicated in pancreatic cancer prognosis.

Pancreatic cancer typically spreads rapidly and has poor survival rates. Here, we report that the calcium-activated chloride channel TMEM16A is a biomarker for pancreatic cancer with a poor prognosis. TMEM16A is up-regulated in 75% of cases of pancreatic cancer and high levels of TMEM16A expression are correlated with low patient survival probability.

The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel.

Calcium-activated chloride channels (CaCCs) formed by TMEM16A or TMEM16B are broadly expressed in the nervous system, smooth muscles, exocrine glands, and other tissues. With two calcium-binding sites and a pore within each monomer, the dimeric CaCC exhibits voltage-dependent calcium sensitivity. Channel activity also depends on the identity of permeant anions.

Differential effect of Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) on leukocyte infiltration during contact hypersensitivity responses.

Background: 2'-4' Dinitrofluorobenzene (DNFB) induced contact hypersensitivity is an established model of contact sensitivity and leukocyte migration. Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) deficient mice were used to examine the role of PECAM-1 in the migration capacity of several different leukocyte populations after primary and secondary application.

Results: γδ T lymphocytes, granulocytes, and Natural Killer cells were most affected by PECAM-1 deficiency at the primary site of application.

Microhemorrhage is an early event in the pulmonary fibrotic disease of PECAM-1 deficient FVB/n mice.

Platelet Endothelial Cell Adhesion Molecule 1 (PECAM-1) deficient mice in the FVB/n strain exhibit fatal chronic pulmonary fibrotic disease. The illness occurs in the absence of a detectable pro-inflammatory event. PECAM-1 is vital to the stability of vascular permeability, leukocyte extravasation, clotting of platelets, and clearance of apoptotic cells.

Non-invasive diagnosis of early pulmonary disease in PECAM-deficient mice using infrared pulse oximetry.

Pulse oximetry is a common tool for detecting reduced pulmonary function in human interstitial lung diseases. It has not previously been used in a mouse model of interstitial lung disease. Further, platelet endothelial cell adhesion molecule deficient mice rarely show symptoms until disease is advanced.

Flexible low-cost system for small animal aerosol inhalation exposure to drugs, proteins, inflammatory agents, and infectious agents.

The design for a simple, low-cost aerosol generation system for rodent inhalation studies is described here. This system is appropriate for low biohazard-level agents. In this study, two biosafety level 2 agents, Pasturella pneumotropica and Pseudomonas aeruginosa, were tested successfully.