Lung surfactant protein C (SP-C) is a lipopeptide that contains two fatty acyl (palmitoyl) chains bound via intrinsically labile thioester bonds. SP-C can transform from a monomeric K K-helix into L L-sheet aggregates, reminiscent of structural changes that are supposed to occur in amyloid fibril formation. SP-C is here shown to form amyloid upon incubation in solution. Furthermore, one patient with pulmonary alveolar proteinosis (PAP, a rare disease where lung surfactant proteins and lipids accumulate in the airspaces) and six healthy controls have been studied regarding presence and composition of amyloid fibrils in the cell-free fraction of bronchoalveolar lavage (BAL) fluid. Abundant amyloid fibrils were found in BAL fluid from the patient with PAP and, in low amounts, in three of the six healthy controls. SDS-insoluble fibrillar material associated with PAP mainly consists of SP-C, in contrast to the fibrils found in controls. Fibrillated SP-C has to a significant extent lost the palmitoyl groups, and removal of the palmitoyl groups in vitro increases the rate of fibril formation.z 1999 Federation of European Biochemical Societies.

No abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The only existing study of CYP2C19*17-associated alterations in drug pharmacokinetics was retrospective and compared probe drug metabolic ratios.• The CYP2C19*17 allele had been associated with a two-and fourfold decrease in omeprazole and S/R-mephenytoin metabolic ratios. WHAT THIS STUDY ADDS• This study characterized the single-dose pharmacokinetics of omeprazole, along with the 5-hydroxy and sulphone metabolites, in CYP2C19*17/*17 and CYP2C19*1/*1 subjects.• The observed differences in omeprazole AUC• suggest that the CYP2C19*17 allele is an important explanatory factor behind individual cases of therapeutic failure. AIMSTo investigate the influence of the CYP2C19*17 allele on the pharmacokinetics of omeprazole, a commonly used CYP2C19 probe drug, in healthy volunteers. METHODSIn a single-dose pharmacokinetic study, 17 healthy White volunteers genotyped as either CYP2C19*17/*17 or CYP2C19*1/*1 received an oral dose of 40 mg of omeprazole. Plasma was sampled for up to 10 h postdose, followed by quantification of omeprazole, 5-hydroxy omeprazole and omeprazole sulphone by high-performance liquid chromatography. RESULTSThe mean omeprazole AUC• of 1973 h nmol l -1 in CYP2C19*17/*17 subjects was 2.1-fold lower [95% confidence interval (CI) 1.1, 3.3] than in CYP2C19*1/*1 subjects (4151 h nmol l

No abstract