A benzodiazepine antagonist inhibits the cerebral metabolic and respiratory depressant effects of fentanyl

It is reported that benzodiazepines such as diazepam will stimulate the opiate receptor system and that B-carboline drugs, which are benzodiazepine antagonists, may interact with opiate receptors directly. The ability of 3-hydroxymethyl-B-carboline (3-HMC) to antagonize several parameters of fentanyl anesthesia was tested here in rats. Fentanyl (25 and 100 micrograms/kg iv) produced dose dependent depression of cerebral blood flow (CBF), measured by radioactive microspheres, and cerebral oxygen consumption (CMRO2). These effects were significantly inhibited by 10 mg/kg 3-HMC iv. To test for the specificity of this effect, 3-HMC was also given to rats ventilated with inspire concentrations of 2% halothane. Halothane depressed CMRO2 equally in 3-HMC and vehicle treated rats, indicating no significant effect of the benzodiazepine antagonist. Blood pressure was increased in 3-HMC compared to vehicle treated animals during both fentanyl and halothane anesthesia. CBF was increased in 3-HMC vs vehicle treated rats during halothane anesthesia but this could be accounted for by the elevated blood pressure and lack of cerebral autoregulation rather than a direct cerebrovascular effect. 3-HMC decreased the sleep time and respiratory depressant effects of fentanyl but enhanced the analgesic effects of the opiate, as measured by time to respond to a hot plate stimulus. These results indicate that 3-HMC has the ability to specifically antagonize fentanyl anesthesia. These effects may be produced by an action of 3-HMC at the benzodiazepine receptor and/or by an action of the B-carboline at opioid receptors.     

Multiple Molecular Forms of Enkephalins in the Guinea Pig Hippocampus

Abstract: The combined techniques of HPLC and radioimmunoassay were used to identify and quantitate enkephalin-related peptides in the guinea pig hippocampus. Both met- and leu-enkephalin were identified, in approximately a 2:1 ratio, as well as a third enkephalin-like molecule that is neither met- nor leu-enkephalin. The third enkephalin elutes earlier than met- or leu-enkephalin from a reversed-phase column, has a molecular weight similar to the other enkephalins, and is as active as these enkephalins are in inhibiting binding of labeled opiates to rat brain membranes. All regions of the hippocampus (dentate gyrus, CA1–2, CA3–4, and subiculum) contain all three immunoreactive peptides. Immunocytochemical techniques, using antisera raised against met-enkephalin, show with one antiserum immunoreactivity in the granule cell-mossy fiber system, and with the other scattered immunoreactive cells mostly in the CA2 region. Enkephalins are not confined to the mossy fiber system, as previously suggested, but may be a component of another hippocampal innervation.     

Detection of a specific isoform of alpha-actinin with antisera directed against dystrophin

We have characterized a protein immunologically related to dystrophin, the protein product of the Duchenne muscular dystrophy gene. We identify this related protein as a fast-twitch glycolytic isoform (mouse extensor digitorum longus-specific) of myofibrillar alpha-actinin. This specific isoform of alpha-actinin exhibits a more restricted pattern of expression in skeletal muscle than fast-twitch-specific isoforms of both myosin and Ca2+-ATPase. Our results provide evidence that dystrophin and myofibrillar alpha-actinin are related proteins, reinforcing the previous data concerning the sequence homologies noted between nonmuscle cytoskeletal alpha-actinin and dystrophin. In addition, we describe the first antisera directed against a specific myofibrillar skeletal muscle isoform of alpha-actinin.     

Quantitative trait locus analysis of susceptibility to diet-induced atherosclerosis in recombinant inbred mice

Quantitative trait locus (QTL) analysis is a statistical method that can be applied to identify loci making a significant impact on a phenotype. For the phenotype of susceptibility to diet-induced atherosclerosis in the mouse, we have studied four quantitative traits: area of aortic fatty streaks and serum concentrations of high-density lipoprotein-bound cholesterol (HDL-cholesterol), apolipoprotein A-I, and apolipoprotein A-II (apo A-II). QTL analysis revealed a significant locus on chromosome 1 distal impacting serum apo A-II concentration on a high-fat diet and serum HDL-cholesterol concentration on a chow diet. This locus is presumablyApoa-2, the structural gene for apo A-II. QTL analysis of aortic fatty streaks failed to reveal a significant locus.     

The effect of pulsed microwaves on passive electrical properties and interspike intervals of snail neurons

The effects of pulsed microwaves (2.45 GHz, 10 μs, 100 pps, SAR: 81.5 kW/kg peak, 81.5 W/kg average) on membrane input resistance and action potential (AP) interval statistics were studied in spontaneously active ganglion neurons of land snails (Helix aspersa), at strictly constant temperature (20.8±.07°C worst case). Statistical comparison with sham-irradiated neurons revealed a significant increase in the mean input resistance of neurons exposed to pulsed microwaves (P ? .05 ). Pulsed microwaves had no visible effect on mean AP firing rate; this observation was confirmed by analysis of interspike intervals (ISIs). Using an integrator model for spontaneously active neurons, we found the net input current to be more variable in neurons exposed to pulsed microwaves. The mean input current was not affected. The standard deviation of ISIs and the autocorrelation of the input current were marginally affected, but these changes were not consistent across neurons. Although the observed effects were less obvious than those reported in other studies, they represent evidence of a direct interaction between neurons and pulsed microwaves, in the absence of macroscopic temperature changes. The data do not suggest a single, specific mechanism for such interaction. © 1993 Wiley-Liss, Inc.     

Habitat selection and space use overlap between feral horses,pronghorn, and greater sage-grouse in cold arid steppe

Populations of feral horses (Equus ferus caballus) in the western United States have increased during the past decade, consequently affecting co-occurring wildlife habitat. Feral horses may influence 2 native wildlife species, greater sage-grouse (Centrocercus urophasianus; sage-grouse) and pronghorn (Antilocapra americana) through mechanisms of habitat alteration and competition. Wyoming, USA, contains the largest populations of pronghorn and sage-grouse of any state and also has the highest degree of range overlap between feral horses and these species. Consequently, the effects that horses may have on pronghorn and sage-grouse populations in Wyoming have implications at local, state, and population-wide levels. Managers need information concerning habitat selection and space use overlap among these species to develop appropriate management strategies; yet this information is absent for most feral horse management areas. To address this knowledge need, we attached global positioning system (GPS) transmitters to horses, pronghorn, and sage-grouse within the greater Bureau of Land Management–Adobe Town Herd Management Area in southern Wyoming and northern Colorado, USA, between 2017 and 2021 to evaluate habitat selection and space use of all species during 3 biologically relevant seasons: spring (Apr–Jun; sage-grouse breeding, nesting, and early-brood rearing; pronghorn late gestation and early parturition), summer (Jul–Oct; sage-grouse summer and late-brood rearing; pronghorn late parturition and breeding), and winter (Nov–Mar; non-breeding season). Feral horses selected flatter slopes and shorter mean shrub height across all seasons and were closer to water in spring and summer. Pronghorn habitat selection was similar to horses, but they also avoided oil and gas well pads year-round. During spring, sage-grouse selected greater herbaceous cover, flatter slopes, and areas farther from well pads. In summer, sage-grouse selected greater mean shrub height, flatter slopes, and were closer to water. In winter, sage-grouse selected flatter slopes and areas with greater vegetation production during the preceding summer. Our results indicate strong year-round overlap in space use between horses and pronghorn, whereas overlap between horses and sage-grouse is greatest during the summer in this region. Consequently, managers should recognize the potential for horses to influence habitat quality of pronghorn and sage-grouse in the region.     

SYSTEMATIC ANALYSIS OF SPHAEROPLEA (CHLOROPHYCEAE)1

A systematic investigation of the genus Sphaeroplea was conducted using cladistic analyses of both structural and isozyme characters for the same set of taxa. The structural data were not able to fully resolve some of the taxa while the isozyme data did produce a tree in which all nodes were supported by data. The structural characters were relatively consistent with one another, whereas the isozyme characters were much less internally consistent. Results from independent, cladistic analyses of both data sets support the concept that among those Sphaeroplea species investigated, S. fragilis Buchheim et Hoffman had an early divergence. The two data sets differed primarily in that the structural data support monophyly of the genus Sphaeroplea and the isozyme data do not. The greater relative consistency of the structural data suggests better support for trees inferred from its analysis. Furthermore, searches for character congruence between the two data sets revealed isozyme data which support monophyly of the genus Sphaeroplea, but had been overwhelmed by conflicting isozyme characters.