l-Buthionine Sulfoximine Detection and Quantification in Polyurea Dendrimer Nanoformulations.

l-Buthionine sulfoximine (l-BSO) is an adjuvant drug that is reported to increase the sensitivity of cancer cells to neoplastic agents. Dendrimers are exceptional drug delivery systems and l-BSO nanoformulations are envisaged as potential chemotherapeutics. The absorption of l-BSO at a low wavelength limits its detection by conventional analytical tools. A simple and sensitive method for l-BSO detection and quantification is now reported. In this study, l-BSO was encapsulated in a folate-targeted generation four polyurea dendrimer (PUREG4-FA2) and its release profile was followed for 24 h at pH 7.4 and 37 °C. The protocol uses in situ l-BSO derivatization, by the formation of a catechol-derived orto-quinone, followed by visible detection of the derivative at 503 nm. The structure of the studied l-BSO derivative was assessed by NMR spectroscopy.

Did consumption of flour bleached by the agene process contribute to the incidence of neurological disease?

The present report proposes the hypothesis that increased levels of neurodegenerative disorders in humans may have arisen due to inclusion in the diet of methionine sulfoximine (MSO), a byproduct of the bleaching of flour by nitrogen trichloride. This method of bleaching, the 'agene process' was in use from early in the century and continued until at least 1949/1950. Estimates indicate that, at least in the UK, as much as 80% of all flour during this period was produced by this process. MSO acts directly to inhibit the production of two crucial molecules, glutathione (GSH) and glutamine. Decreases in GSH, a key antioxidant and free radical scavenger, diminish the body's antioxidant defenses and may lead to increased oxidative stress. Decreases in glutamine synthesis may act to increase free glutamate and give rise to increased levels of ammonia. Cells in the nervous system are particularly sensitive to a decline in either GSH or glutamine. The combined effects of decreases in these molecules, particularly with long-term exposure to MSO in bleached flour, may have had quite drastic effects on neuronal health and survival. The present hypothesis may provide clues to the etiology of neurological disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), suggesting that such disorders may arise in part due to toxic actions of some compounds in processed human foods.