Metabolic pathways of simvastatin (MK-733), a lactone prodrug of an inhibitor of HMG-CoA reductase, were elucidated in male rats, using the [14C]-labelled compound. Evidence has been obtained for hydrolysis of simvastatin and its metabolites at their 2,2-dimethylbutyryl moieties. Metabolites identified in plasma were 2,2-dimethylbutyric acid (DMB), 2,2-dimethyl-3-hydroxybutyric acid (DMHB) and an open chain hydroxy acid of simvastatin: metabolites identified in urine were DMHB, a glucuronide and the glycine conjugate of DMB. They were characterized by gas chromatography/electron impact and chemical ionization mass spectrometry as phenacyl or pertrimethylsilylated derivatives. The structures of the metabolites and the aglycone of the glucuronide were confirmed as phenacyl esters by comparison of their chromatographic data and mass spectra with those of the phenacyl derivatives of authentic compounds.

Animals↗

PubMedDate not supplied

Structure of the coding region and mRNA variants of the apyrase gene from pea (Pisum sativum).

Partial amino acid sequences of a 49 kDa apyrase (ATP diphosphohydrolase, EC 3.6.1.5) from the cytoskeletal fraction of etiolated pea stems were used to derive oligonucleotide DNA primers to generate a cDNA fragment of pea apyrase mRNA by RT-PCR and these primers were used to screen a pea stem cDNA library. Two almost identical cDNAs differing in just 6 nucleotides within the coding regions were found, and these cDNA sequences were used to clone genomic fragments by PCR. Two nearly identical gene fragments containing 8 exons and 7 introns were obtained. One of them (H-type) encoded the mRNA sequence described by Hsieh et al. (1996) (DDBJ/EMBL/GenBank Z32743), while the other (S-type) differed by the same 6 nucleotides as the mRNAs, suggesting that these genes may be alleles. The six nucleotide differences between these two alleles were found solely in the first exon, and these mutation sites had two types of consensus sequences. These mRNAs were found with varying lengths of 3' untranslated regions (3'-UTR). There are some similarities between the 3'-UTR of these mRNAs and those of actin and actin binding proteins in plants. The putative roles of the 3'-UTR and alternative polyadenylation sites are discussed in relation to their possible role in targeting the mRNAs to different subcellular compartments.

Actins↗

PubMedDate not supplied

Polymorphism of seminal gamma-glutamyl transpeptidase.

Electrophoretic analysis of seminal gamma-glutamyl transpeptidase (GGT) activity of 147 unrelated Japanese males revealed three types of band patterns. An anodal single band, a cathodal single band and heterozygous double bands termed 1, 2 and 2-1, respectively, were commonly identified in the samples. The frequencies of the three types were 1 = 0.22, 2 = 0.33 and 2-1 = 0.44. Seminal stains kept for more than 6 months revealed distinguishable band patterns as well as fresh samples.

Electrophoresis, Disc↗

PubMedDate not supplied

Gd-DTPA-enhanced MR imaging of injured spinal cord.

We retrospectively reviewed 15 gadolinium-enhanced magnetic resonance imaging examinations of the cervical spine in eight patients who had spinal cord injury. Enhancement was demonstrated at the periphery of the intramedullary lesion in three patients at 1 to 14 weeks after injury. The enhancement might reflect vascularized granulation in a reparative phase. Spinal cord injury should be considered in the differential diagnosis of enhanced intramedullary spinal cord lesions.

Adult↗