Role of myeloperoxidase-derived oxidants in the induction of vascular smooth muscle cell damage.

Myeloperoxidase (MPO) is released by activated immune cells and forms the oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) from the competing substrates chloride and thiocyanate. MPO and the overproduction of HOCl are strongly linked with vascular cell dysfunction and inflammation in atherosclerosis. HOCl is highly reactive and causes marked cell dysfunction and death, whereas data with HOSCN are conflicting, and highly dependent on the nature of the cell type.

Modulation of hypochlorous acid (HOCl) induced damage to vascular smooth muscle cells by thiocyanate and selenium analogues.

The production of hypochlorous acid (HOCl) by myeloperoxidase (MPO) plays a key role in immune defense, but also induces host tissue damage, particularly in chronic inflammatory pathologies, including atherosclerosis. This has sparked interest in the development of therapeutic approaches that decrease HOCl formation during chronic inflammation, including the use of alternative MPO substrates. Thiocyanate (SCN) supplementation decreases HOCl production by favouring formation of hypothiocyanous acid (HOSCN), which is more selectively toxic to bacterial cells.

Selenomethionine supplementation reduces lesion burden, improves vessel function and modulates the inflammatory response within the setting of atherosclerosis.

Atherosclerosis is a chronic inflammatory disease of the vasculature characterised by the infiltration of activated neutrophils and macrophages at sites of damage within the vessel wall, which contributes to lesion formation and plaque progression. Selenomethionine (SeMet) is an organic form of selenium (Se), an essential trace element that functions in the regulation of the immune response by both bolstering the endogenous thioredoxin and glutathione antioxidant defence systems and by directly scavenging damaging oxidant species. This study evaluated the effect of dietary SeMet supplementation within a high fat diet fed apolipoprotein E deficient (ApoE) mouse model of atherosclerosis.

Effects of a novel selenium substituted-sugar (1,4-anhydro-4-seleno-d-talitol, SeTal) on human coronary artery cell lines and mouse aortic rings.

Chronic low-grade inflammation and oxidative damage are strongly associated with pathologies including cardiovascular disease. As a consequence, there is considerable interest in agents that mitigate damage. Selenium compounds can act as potent protective agents against oxidation due to the high reactivity and nucleophilicity of the selenium atom.

Quantification of low molecular weight selenium metabolites in human plasma after treatment with selenite in pharmacological doses by LC-ICP-MS.

The paper presents an analytical method for quantification of low molecular weight (LMW) selenium compounds in human plasma based on liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS) and post column isotope dilution-based quantification. Prior to analysis, samples were ultrafiltrated using a cut-off value of 3000 Da. The method was validated in aqueous solution as well as plasma using standards of selenomethionine (SeMet), Se-methylselenocysteine (MeSeCys), selenite, and the selenosugar Se-methylseleno-N-acetylgalactosamine (SeGal) for linearity, precision, recoveries, and limits of detection and quantitation with satisfactory results.

The influence of pressure on the intrinsic dissolution rate of amorphous indomethacin.

New drug candidates increasingly tend to be poorly water soluble. One approach to increase their solubility is to convert the crystalline form of a drug into the amorphous form. Intrinsic dissolution testing is an efficient standard method to determine the intrinsic dissolution rate (IDR) of a drug and to test the potential dissolution advantage of the amorphous form.