New Pyrrolizidine Alkaloids and Glycosides from Anchusa strigosa

Six new pyrrolizidine alkaloids, a new carboxylic acid, a new phenolic and a new oleanane glycoside, together with the known compounds 7,7'-bis-(4-hydroxy-3,5-dimethoxyphenyl)-8,8'-dihydroxymethyltetrahydrofuran 4'-O-beta-D-glucopyranoside, rosmarinic acid, caffeic acid, tormentic acid 28-O-beta- D-glucopyranoside, euscaphic acid 28-O-beta-D-glucopyranoside, euscaphic acid, and allantoin were isolated from Anchusa strigosa roots. Their structures were established by high resolution NMR, MS, elemental analysis, and chemical reactions.     

Organochlorine pesticide and polychlorinated biphenyl residues in human milk from Rome (Italy) and surroundings

Bulletin of Environmental Contamination and Toxicology -     

Developments in insulin pumps and recommendations for best practices

Thanks to ongoing technological progress in the field of insulin pumps, recommendations for good practices are changing: contraindications are decreasing. Also, monitoring of the patient at home is carried out by the service provider in cooperation with the "initiating" treatment centre and its educational team, a sign of improvement in cooperation between healthcare professionals.     

Preventing the ubiquitin-proteasome-dependent degradation of frataxin, the protein defective in Friedreich's ataxia

Friedreich's ataxia (FRDA) is a devastating orphan disease, with no specific treatment. The disease is caused by reduced expression of the protein frataxin, which results in mitochondrial defects and oxidative damage. Levels of residual frataxin critically affect onset and progression of the disease. Understanding the molecular mechanisms that regulate frataxin stability and degradation may, therefore, be exploited for the design of effective therapeutics. Here we show that frataxin is degraded by the ubiquitin-proteasome system and that K(147) is the critical residue responsible for frataxin ubiquitination and degradation. Accordingly, a K(147)R substitution generates a more stable frataxin. We then disclose a set of lead compounds, computationally selected to target the molecular cleft harboring K(147), that can prevent frataxin ubiquitination and degradation, and increase frataxin levels in cells derived from FRDA patients. Moreover, treatment with these compounds induces substantial recovery of aconitase activity and adenosine-5'-triphosphate levels in FRDA cells. Thus, we provide evidence for the therapeutic potential of directly interfering with the frataxin degradation pathway.     

Sample preparation development and matrix effects evaluation for multianalyte determination in urine

The development of a generic analytical method remains difficult when a high number of compounds has to be simultaneously considered. This study proposes an innovative strategy for the development of a solid phase extraction (SPE) procedure before liquid chromatography-mass spectrometry analysis of 34 diuretics and beta-blockers in urine samples. These compounds have been selected since they are often encountered in anti-doping control. The principle is based on the selection of representative analytes during SPE protocol optimization, allowing a drastic reduction of generated data and development time. To select the representative compounds, all substances were classified based on their SPE behavior with a generic method and groups were formed with the help of a chemometric tool, namely hierarchical cluster analysis (HCA). One representative analyte per group was selected and used for subsequent SPE method development. Once the SPE method was developed, compounds were analyzed by LC-MS and matrix effects were evaluated to determine the influence of the matrix on the SPE process and MS signal alteration due to endogenous compounds. As a result, matrix effects evaluation must be performed on all analytes; representative compounds previously selected for SPE development were unable to predict matrix effects.