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ReN1869 (NNC 05-1869) is a novel, selective H1 receptor antagonist that has been developed for analgesic purposes. In a first human dose administration study, the safety and pharmacokinetics of seven single oral doses in the range of 3.5 to 95 mg ReN1869 were studied. The study was a randomized, double-blind, placebo-controlled, dose-escalating study in 56 healthy subjects. No serious or severe adverse events were reported. After active doses, an average of 0.6 adverse events (AEs) was reported per subject in comparison to 0.5 AEs per subject after placebo, and the frequency of subjects reporting AEs was not related to dose level. The most frequently reported adverse events were dizziness, fatigue, and somnolence, and their occurrence was not proportional to dose. Vital signs, ECG recordings, and clinical laboratory results showed no changes of clinical relevance. During telemetric monitoring at all dose levels until 4 hours after dosing, no clinically relevant abnormalities were observed. A maximally tolerated dose was not identified. ReN1869 was rapidly absorbed after dosing. The overall mean value of t1/2 and oral clearance was 4.7 hours and 11.7 L/h, respectively. The parameters Cmax and AUC increased proportionally with dose level, whereas all other pharmacokinetic parameters were independent of the dose. In conclusion, single-dose administration of ReN1869 in doses up to 95 mg exhibited very few adverse events and no clinically relevant effects on any of the observed safety parameters. The pharmacokinetics points to simple first-order pharmacokinetics for ReN1869. All together, it makes ReN1869 a potential new drug candidate for the treatment of chronic pain and inflammatory conditions of neurogenic origin. [ABSTRACT FROM AUTHOR]

Helicobacter pylori isolates show greater genetic diversity than other bacterial species studied, but the basis for this phenomenon is unknown. Whether detectable genomic mutation appears within an H. pylori population during persistent colonization was investigated. Paired H. pylori populations obtained across 7- to 10-year intervals from 13 patients were characterized by use of methods including polymerase chain reaction (PCR) genotyping for cagA, vacA, iceA, recA, and IS605; random arbitrarily primed DNA (RAPD)-PCR and amplified fragment length polymorphism (AFLP) analysis; and ELISA, to determine Lewis phenotypes. Genotyping, including recA sequence analysis, revealed that initial and follow-up populations represented the same population in 11 patients (85%). Nevertheless, distinct dissimilarities were shown within each of these 11 pairs by both RAPD-PCR and AFLP analyses. During follow-up, Lewis-y levels, but not Lewis-x levels, decreased significantly. The changes detected by RAPD-PCR and AFLP indicate that genetic drift occurs within H. pylori populations over the course of years of colonization of a single host. [ABSTRACT FROM AUTHOR]

Presents findings of a study which assessed the effects of uncoupling protein 3 (UCP3) overexpression at physiological levels and UCP3 ablation on key transport proteins and enzymes. Correlation between serum nonesterified fatty acids and fatty acid uptake with UCP3 overexpression; Impact of UCP3 overexpression on muscle fatty acid transport protein content; Effect of UCP3 overexpression on the activity of key mithocondrial enzymes.

Individual Fe atoms on a Cu2N/Cu(100) surface exhibit strong magnetic anisotropy due to the crystal field. We show that we can controllably enhance or reduce this anisotropy by adjusting the relative position of a second nearby Fe atom, with atomic precision, in a low-temperature scanning tunneling microscope. Local inelastic electron tunneling spectroscopy, combined with a qualitative first-principles model, reveal that the change in uniaxial anisotropy is driven by local strain due to the presence of the second Fe atom. [ABSTRACT FROM AUTHOR]