A specific, accurate, precise, and reproducible High-performance liquid chromatographic-Ultraviolet (HPLC-UV) method was developed for the simultaneous quantitation of BMS-181101 (I), a new antidepressant, and its putative metabolites, 6'-hydroxy (II) and 7'-hydroxy (III) of BMS-181101 in rat and monkey plasma. The assay procedure involved solid-phase extraction of the three analytes and the internal standard (IS; BMY-42568) on 1 mL Bond Elut CN cartridge using an automated solid phase extraction controller (ASPEC) system. The final elution of the analytes was performed using 0.25% triethylamine in methanol. The eluate mixture was evaporated to dryness, the residue was reconstituted in the mobile phase and injected onto a Zorbax Phenyl column (4.6 x 250 mm; 5 microns) at a flow-rate of 1.2 mL/min. The mobile phase consisted of 20% acetonitrile, 10% methanol, 69% water and 1% 1.0 M ammonium phosphate and 1.0 M tetramethylammonium hydroxide mixture adjusted to pH 3 by phosphoric acid. An ultraviolet absorbance detector set at 287 nm was used to detect the analytes. The nominal retention times were 5, 8, 15, and 18 min for II, III, I, and IS, respectively. The standard curves for the three analytes were linear in the concentration range of 50-1000 ng/mL. The lower limit of quantitation was 50 ng/mL for each analyte. The analyses of quality control (QC) samples indicated that the nominal values could be predicted with an accuracy of (+/-) 10.5% for all three analytes in rat and monkey plasma. The precision values of the QC samples for all three analytes were within 12.7% RSD for rat and monkey plasma. All three analytes and the IS were stable in the autosampler for at least 38 h; freeze/thaw stability of the 3 analytes was established for three cycles. Stability of BMS-181101 was established for one month at -20 degrees C. The application of the assay to a pharmacokinetic study in monkey is described.

Animals↗

PubMedDate not supplied

Herpes simplex virus: discovering the link between heparan sulphate and hereditary bone tumours.

To gain entry into the host, viruses use host cell surface molecules that normally serve as receptors for other ligands. Herpes simplex virus type 1 (HSV-1) uses heparan sulphate (HS) glycosaminoglycans (GAGs) as receptors for initial attachment to the host cell surface. HS GAGs are both ubiquitous and structurally diverse, and normally serve as critical mediators of interactions between the cell and the extracellular environment. We have used the HS binding ability of HSV-1 to identify the function of a cellular gene, EXT1, which is involved in HS polymerisation. Cellular factors that affect virus growth and replication are often key regulators of the cell cycle and EXT1 is no different-humans with inherited mutations in EXT1 have developmental defects that lead to bone tumours (hereditary multiple exostoses, HME) and sometimes chondrosarcomas. Thus, as a result of using HSV-1 as a molecular probe, a functionally orphaned disease gene now has a defined function. These findings highlight the utility of viruses for investigating important cellular processes.

Cell Line↗

PubMedDate not supplied

Human phylogenetic relationships according to the D1S80 locus.

By analyzing the allelic frequencies at the D1S80 locus in 43 human populations, we show that the locus is polymorphic globally and that it can be used to discriminate between major racial groups and subpopulations through phylogenetic analysis. Although the use of informative multiple loci generally provides more accurate phylogenetic relationships, in instances where time and/or target DNA availability is limited, D1S80 could provide useful data to discriminate between human groups. Also, knowledge of which loci independently provide accurate phylogenetic relationships, such as the D1S80, can be used to design more accurate multi-locus combinations. In addition, allele frequencies at the locus are reported, for the first time, for Bahamian individuals of African origin and for Chimila, Bari, and Navajo (Cañoncito Valley) native Americans. Allelic data was obtained using standard polymerase chain reaction (PCR) techniques. In the four new populations, 65 genotypes and 20 segregating alleles were observed. All populations conformed to Hardy-Weinberg expectations except the Chimila.

Genetics, Population↗

PubMedDate not supplied

Human cataract formation.

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Cataract↗