Chemical warfare agents, such as soman, and pesticides, such as chlorpyrifos, dichlorvos or malathion, are toxic organophosphorous compounds (OPCs) that are readily absorbed by the skin. Decontamination using solvents or surfactants may modify the cornified layer – the skin's main barrier against xenobiotic penetration. Thus, effective skin decontamination with fewer side effects is desired. We determined the membrane absorption, decontamination

RET encodes a receptor tyrosine kinase that is essential for spermatogenesis, development of the sensory, sympathetic, parasympathetic, and enteric nervous systems and the kidneys, as well as for maintenance of adult midbrain dopaminergic neurons. RET is alternatively spliced to encode multiple isoforms that differ in their C-terminal amino acids. The RET9 and RET51 isoforms display unique levels of autophosphorylation and have differential interactions

Multiple endocrine neoplasia type 2 is an inherited cancer syndrome characterized by tumors of thyroid and adrenal tissues. Germline mutations of the REarranged during Transfection (RET) proto-oncogene, leading to its unregulated activation, are the underlying cause of this disease. Multiple endocrine neoplasia type 2 has been a model in clinical cancer genetics, demonstrating how knowledge of the genetic basis can shape the diagnosis and treatment

Organic nitrates and nitrites are used in cardiovascular therapy as vasodilators. They are supposedly biotransformed to nitric oxide (NO), which activates soluble guanylyl cyclase (sGC) - the enzyme responsible for their biological activity. Organic nitrites are potential intermediates in the transformation of nitrates to NO. NO appears to have both cytoprotective and cytotoxic properties. In the brain, NO might be cytoprotective by increasing the

The activation of calcium-dependent cysteine proteases (calpains) due to an uncontrolled increase in the cellular calcium influx can lead to aberrant degradation of cellular proteins and cell death. The inhibitory effect of doxycycline on other proteases, but not calpains, has been reported. We discovered that doxycycline significantly inhibits murine calpain 2 at concentrations ≥ 30 μM. An increase in the calcium ion concentration did not affect

Matrix metalloproteinase-2 (MMP-2) has emerged as a key protease in various pathologies associated with oxidative stress, including myocardial ischemia-reperfusion, heart failure or inflammation. Peroxynitrite (ONOO(-)), an important effector of oxidative stress, was reported to activate some full length MMP zymogens, particularly in the presence of glutathione (GSH), but whether this occurs for MMP-2 is unknown. Treating MMP-2 zymogen with ONOO(-)