Impact of the blood sampling site on time–concentration drug profiles following intravenous or buccal drug administration

The aim of this study was to examine the effect of the sampling site on the drug concentration–time profile, following intravenous or buccal (often called ‘oral transmucosal’) drug administration. Buprenorphine (20 μg/kg) was administered IV or buccally to six cats. Blood samples were collected from the carotid artery and the jugular and medial saphenous veins for 24 h following buprenorphine administration. Buprenorphine concentration–time data were examined using noncompartmental analysis. Pharmacokinetic parameters were compared using the Wilcoxon signed rank test, applying the Bonferroni correction. Significance was set at P < 0.05. Following IV administration, no difference among the sampling sites was found. Following buccal administration, maximum concentration [jugular: 6.3 (2.9–9.8), carotid: 3.4 (1.9–4.9), medial saphenous: 2.5 (1.7–4.1) ng/mL], area under the curve [jugular: 395 (335–747), carotid: 278 (214–693), medial saphenous: 255 (188–608) ng·min/mL], and bioavailability [jugular: 47 (34–67), carotid: 32 (20–52), medial saphenous: 23 (16–55)%] were higher in the jugular vein than in the carotid artery and medial saphenous vein. Jugular venous blood sampling is not an acceptable substitute for arterial blood sampling following buccal drug administration.     

Magnetism on the angrite parent body and the early differentiation of planetesimals

Angrites are among the oldest known pristine basaltic meteorites and record the earliest stages of planet formation and differentiation. Our paleomagnetic analysis of three angrites found that they record a past magnetic field of approximately 10 microteslas on the angrite parent body extending from 4564 to at least 4558 million years ago. Because the angrite paleomagnetic record extends beyond the expected lifetime of the early circumstellar disk, these paleofields were probably generated internally on the angrite parent body, possibly by an early dynamo in a rapidly formed metallic core.     

A double mass extinction at the end of the paleozoic era

Three tests based on fossil data indicate that high rates of extinction recorded in the penultimate (Guadalupian) stage of the Paleozoic era are not artifacts of a poor fossil record. Instead, they represent an abrupt mass extinction that was one of the largest to occur in the past half billion years. The final mass extinction of the era, which took place about 5 million years after the Guadalupian event, remains the most severe biotic crisis of all time. Taxonomic losses in the Late Permian were partitioned among the two crises and the intervening interval, however, and the terminal Permian crisis eliminated only about 80 percent of marine species, not 95 or 96 percent as earlier estimates have suggested.     

Mental symptoms in Huntington's disease and a possible primary aminergic neuron lesion

Monoamine oxidase activity was higher in the cerebral cortex and basal ganglia of patients dying from Huntington's disease than in controls. Enzyme kinetics and multiple substrate studies indicated that the increased activity was due to elevated concentrations of monoamine oxidase type B. Concentrations of homovanillic acid were increased in the cerebral cortex but not in the basal ganglia of brains of patients with Huntington's disease. These changes may represent a primary aminergic lesion that could underlie some of the mental symptoms of this disease.     

Hydrocephalus in mice inoculated neonatally by the oronasal route with reovirus type 1

Mice inoculated neonatally by the oronasal route with reovirus type 1 or 2 developed typical acute disease. Fifteen percent of the mice recovered from the acute infection. No further disease was noted in mice infected with reovirus 2, but 9 percent of the survivors of reovirus I infections developed hydrocephalus at a mean time of 109 days after inoculation. Infectious virus could not be isolated from hydrocephalic mice.     

SOS response induction by beta-lactams and bacterial defense against antibiotic lethality

The SOS response aids bacterial propagation by inhibiting cell division during repair of DNA damage. We report that inactivation of the ftsI gene product, penicillin binding protein 3, by either beta-lactam antibiotics or genetic mutation induces SOS in Escherichia coli through the DpiBA two-component signal transduction system. This event, which requires the SOS-promoting recA and lexA genes as well as dpiA, transiently halts bacterial cell division, enabling survival to otherwise lethal antibiotic exposure. Our findings reveal defective cell wall synthesis as an unexpected initiator of the bacterial SOS response, indicate that beta-lactam antibiotics are extracellular stimuli of this response, and demonstrate a novel mechanism for mitigation of antimicrobial lethality.     

Maplike representation of celestial E-vector orientations in the brain of an insect

For many insects, the polarization pattern of the blue sky serves as a compass cue for spatial navigation. E-vector orientations are detected by photoreceptors in a dorsal rim area of the eye. Polarized-light signals from both eyes are finally integrated in the central complex, a brain area consisting of two subunits, the protocerebral bridge and the central body. Here we show that a topographic representation of zenithal E-vector orientations underlies the columnar organization of the protocerebral bridge in a locust. The maplike arrangement is highly suited to signal head orientation under the open sky.