Effect of food on the pharmacokinetics and pharmacodynamics of R1663, an oral factor Xa inhibitor, in healthy male volunteers.

Aims: To explore the effect of food intake on the relative bioavailability of R1663 and on its pharmacodynamic effects (prothrombin time (PT) and activated partial thromboplastin time (aPTT)) after a single oral dose of 200 mg.

Methods: This was a prospective, open-label, randomized, two-way crossover study. Eight healthy male volunteers received R1663 on two occasions, after a high fat/high calorie breakfast and after an overnight fast of 10 h, with a 7-day washout between doses.

Safety, pharmacokinetics and pharmacodynamics of multiple ascending doses of R1663, an oral factor Xa inhibitor, in healthy young subjects coupled with exploration of influence of gender and age.

This study investigated the safety, pharmacokinetics and pharmacodynamics of multiple oral doses of R1663, a factor Xa inhibitor, and explored the influence of age and gender on pharmacokinetics and pharmacodynamics of R1663. This was a single-blind, randomised, placebo-controlled, dose escalation study in 48 healthy male volunteers aged 18 to 44 years. R1663 doses up to 300 mg twice daily or 400 mg once daily were administered for seven days.

Crossover dose escalation study to assess safety, pharmacokinetics, and pharmacodynamics of single doses of R1663, an oral factor Xa inhibitor, in healthy male volunteers.

This study investigated the safety, pharmacokinetics, and pharmacodynamics of single oral doses of R1663, a factor Xa inhibitor, in healthy volunteers. It was a single-blind, randomized, crossover, placebo-controlled, dose escalation study in 33 healthy male volunteers aged 18 to 45 years. Each volunteer was dosed on 3 occasions with R1663 or placebo.

Drug-drug interaction study of ketoconazole and ritonavir-boosted saquinavir.

Saquinavir, a potent human immunodeficiency virus protease inhibitor, is extensively metabolized by CYP3A4. Saquinavir is coadministered with ritonavir, a strong CYP3A4 inhibitor, to boost its exposure. Ketoconazole is a potent CYP3A inhibitor.

Absence of an interaction between iron and mycophenolate mofetil absorption.

Aim: To determine whether concomitant iron affects the absorption of mycophenolate mofetil.

Methods: An open-label, single centre, randomized, crossover trial was conducted in 16 healthy males. Fasting subjects received mycophenolate mofetil alone (treatment A) or co-administered with iron (treatment B).

Large-scale protein expression for proteome research.

Access to pure and soluble recombinant proteins is essential for numerous applications in proteome research, such as the production of antibodies, structural characterization of proteins, and protein microarrays. Through the German cDNA Consortium we have access to more than 1500 ORFs encoding uncharacterized proteins. Preparing a large number of recombinant proteins calls for the careful refinement and re-evaluation of protein purification tools.

Structure and assembly of the RNA binding domain of bluetongue virus non-structural protein 2.

Bluetongue virus non-structural protein 2 belongs to a class of highly conserved proteins found in orbiviruses of the Reoviridae family. Non-structural protein 2 forms large multimeric complexes and localizes to cytoplasmic inclusions in infected cells. It is able to bind single-stranded RNA non-specifically, and it has been suggested that the protein is involved in the selection and condensation of the Bluetongue virus RNA segments prior to genome encapsidation.

A novel quaternary structure of the dimeric alpha-crystallin domain with chaperone-like activity.

alphaB-crystallin, a member of the small heat-shock protein family and a major eye lens protein, is a high molecular mass assembly and can act as a molecular chaperone. We report a synchrotron radiation x-ray solution scattering study of a truncation mutant from the human alphaB-crystallin (alphaB57-157), a dimeric protein that comprises the alpha-crystallin domain of the alphaB-crystallin and retains a significant chaperone-like activity. According to the sequence analysis (more than 23% identity), the monomeric fold of the alpha-crystallin domain should be close to that of the small heat-shock protein from Methanococcus jannaschii (MjHSP16.

Dimeric structure of the coxsackievirus and adenovirus receptor D1 domain at 1.7 A resolution.

Background: The coxsackievirus and adenovirus receptor (CAR) comprises two extracellular immunoglobulin domains, a transmembrane helix and a C-terminal intracellular domain. The amino-terminal immunoglobulin domain (D1) of CAR is necessary and sufficient for adenovirus binding, whereas the site of coxsackievirus attachment has not yet been localized. The normal cellular role of CAR is currently unknown, although CAR was recently proposed to function as a homophilic cell adhesion molecule.

The 60-residue C-terminal region of the single-stranded DNA binding protein of herpes simplex virus type 1 is required for cooperative DNA binding.

ICP8 is the major single-stranded DNA (ssDNA) binding protein of the herpes simplex virus type 1 and is required for the onset and maintenance of viral genomic replication. To identify regions responsible for the cooperative binding to ssDNA, several mutants of ICP8 have been characterized. Total reflection X-ray fluorescence experiments on the constructs confirmed the presence of one zinc atom per molecule.

Recommendations for extraction of chronically implanted transvenous pacing and defibrillator leads: indications, facilities, training. North American Society of Pacing and Electrophysiology Lead Extraction Conference Faculty.

The procedure of lead removal has recently matured into a definable, teachable art with its own specific tools and techniques. It is now time to recognize and formalize the practice of lead removal according to the current methods of medicine and the health care industry. In addition, since at this time the only prospective scientific study of lead extraction is the PLEXES trial, we suggest that studies relating to the techniques of and indications for lead extraction be designed.

Intravascular extraction of problematic or infected permanent pacemaker leads: 1994-1996. U.S. Extraction Database, MED Institute.

Of the 400,000-500,000 permanent pacemaker leads implanted worldwide each year, around 10% may eventually fail or become infected, becoming potential candidates for removal. Intravascular techniques for removing problematic or infected leads evolved over a 5-year period (1989-1993). This article analyzes results from January 1994 through April 1996, a period during which techniques were fairly stable.

The glutamine-rich domain of the Drosophila GAGA factor is necessary for amyloid fibre formation in vitro, but not for chromatin remodelling.

The Drosophila GAGA factor binds specifically to the sequence GAGAG, and synergises with nucleosome remodelling factor to remodel chromatin in vitro. It consists of an N-terminal domain (POZ/BTB) which mediates protein-protein interactions, a central region which contains the DNA-binding domain, and a C-terminal glutamine-rich region. It is shown that the glutamine-rich region is responsible for the formation of fibres in vitro which, on the basis of their tinctorial properties and CD spectra, may be classified as amyloid fibres.

Lead extraction in young patients with and without congenital heart disease using the subclavian approach.

Pacemaker lead removal using interlocking stylets and dilator sheaths has greatly reduced the need for major surgical intervention when lead extraction is required. Previous reports have shown the utility of this method in older patients, most of whom have anatomically normal hearts. The purpose of this study is to report the results of this technique in young patients with and without congenital heart disease.

Leaf quality and insect herbivory in model tropical plant communities after long-term exposure to elevated atmospheric CO.

Results from laboratory feeding experiments have shown that elevated atmospheric carbon dioxide can affect interactions between plants and insect herbivores, primarily through changes in leaf nutritional quality occurring at elevated CO. Very few data are available on insect herbivory in plant communities where insects can choose among species and positions in the canopy in which to feed. Our objectives were to determine the extent to which CO-induced changes in plant communities and leaf nutritional quality may affect herbivory at the level of the entire canopy.

Crystallization and preliminary X-ray crystallographic studies on the adenovirus ssDNA binding protein in complex with ssDNA.

Crystals of the C-terminal domain of the adenovirus single-stranded DNA binding protein (DBP) in complex with the single-stranded oligonucleotide (dT)16 have been obtained by a batch method from material obtained by chymotryptic digest of full-length DBP. The colorless crystals grow as hexagonal prisms to a maximal size of approximately 0.85 x 0.

A comparison of three sampling techniques to estimate the population size of caterpillars in trees.

Three sampling techniques commonly used to estimate the population size of caterpillars and sawfly larvae in trees (branch samples, frass production, water basins), were compared with respect to sampling error and economic costs. At the level of tree populations (e.g.

Tunicamycin-inhibited carrot somatic embryogenesis can be restored by secreted cationic peroxidase isoenzymes.

Somatic embryogenesis of carrot (Daucus carota L.) is inhibited by the glycosylation inhibitor tunicamycin. This inhibition is reversible by the addition of correctly glycosylated glycoproteins which have been secreted into the culture medium.