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A strong and reproducible effect of an external electric field (EEF) on liquid films confined within a nanogap between a highly polished steel ball and a smooth glass disk is described. Induced by the EEF, microbubbles were observed at the edge of the contact region. This phenomenon is more obvious in polar liquid films than that in nonpolar ones. A stronger EEF causes a decrease in the film thickness in the contact region initially, and then the variation becomes much smaller. When the ball is applied with a positive EEF, the emergence of microbubbles is stable over time, while it becomes much less as time progresses. Different mechanisms of these experimental phenomena have been discussed. [ABSTRACT FROM AUTHOR]

Gas extraction is an effective measure for reducing gas accidents in the colliery; however, extracting gas in coal with low permeability is difficult. To obtain the influential law of mining-induced stress on the permeability of coal and improve the effect of gas extraction, this study took the 17218 face of Zhangji Coal Mine under Huainan Mine Industry Group as the engineering background to set the measurement station at both the return airway and haulage roadway of the face, establish the FLAC3D numerical calculation model, and comprehensively analyze the evolution laws of mining-induced stress, gas flow, gas extraction amount, and coal mass failure characteristic during the actual mining process at the face. Research results showed that during the actual mining process at the face, gas flow and mining-induced stress showed the same changing law, and the permeability of coal mass was controlled by mining-induced stress. The peak of coal stress at the side of the return airway, the degree of stress concentration, and its scope of influence were all large. The coal failure scope and degree at the side of the return airway were all large and the permeability of coal mass was high. The permeability of coal mass in the zone in which the stress was reduced at the face was the highest. The gas concentration could be significantly reduced if on-site technicians extract the gas in the stress reduction zone. The research findings enrich the theoretical research on coal permeability and provide the basis for effective gas extraction. [ABSTRACT FROM AUTHOR]

Raw coal was used as the study object in this paper to identify the evolution characteristics of acoustic emission (AE) during the dilation process of gas-containing coal. The coal specimens were stored in gas seal devices filled with gas at different pressures (0, 0.5, 1.0, and 1.5 MPa) for 24 h prior to testing. Then, the specimens were tested in a rock-testing machine, and the deformation and crack fracture patterns were recorded by using strain gauges and an AE system. The axial and volumetric strains-stress curves were analyzed in relation to the AE and the failure mode. Results show that as gas pressure increases, the uniaxial compression strength and elasticity modulus of gas-containing coal decreases, whereas the Poisson's ratio increases. In all the coal specimens, the dilation initiation stress decreases, and the dilation degree increases. During the dilation process, before the loaded coal specimens reach peak stress, and as the load increases, the changes in the specimens and in the AE energy parameter of specimens can be divided into four phases: crack closure deformation, elastic deformation, stable crack propagation, and unstable crack propagation (dilation process). Across the four phases, the AE energy increases evidently during crack closure and elastic deformation but decreases during stable crack propagation. As the gas pressure increases, the AE signal frequency increases from 4.5 KHz to 8.1 KHz during the dilation process. Thus, the gas presence in coal specimens exerts a significant influence on the closure of sample cracks and dilation damage. [ABSTRACT FROM AUTHOR]

The alternative splicing pattern of cyclic AMP response element-binding protein (CREB) in the central nervous system (CNS) of the rat has been investigated by an exon-flanking polymerase chain reaction (PCR) strategy. A series of RT-PCR studies with primer pairs flanking all possible alternative splicing sites (corresponding to a genomic region with at least one full exon and two flanking introns) has revealed multiple splice patterns in nine regions of the rat CNS. These include some novel transcripts that lack the phosphorylation site and a segment of the leucine zipper region which is crucial for dimerization and DNA binding. Some isoforms previously reported as testis-specific were also detected in the rat CNS. The findings from this study, which include differential splicing patterns among CNS regions, suggest a complex expression and functional regulation of CREB in the CNS., (Copyright 1999 Elsevier Science B.V.)

Background and Objectives: Sumatriptan is a novel drug for migraine headache pain, which, on the basis of its mechanism of action, may have therapeutic potential in other pain states. Sumatriptan inhibits neurogenic inflammation in dural vessels by activating the 5-HTIB and 5-HTID inhibitory serotonin (5-hydroxytryptamine [5-HT]) receptor subtypes on terminals of trigeminal neurons. This study was designed to determine the role of sumatriptan in peripheral pain mechanisms by detecting whether 5-HTIB and 5-HTID receptors and the recently cloned excitatory 5-HT7 receptor, for which sumatriptan displays moderate binding affinity, are present in peripheral sensory neurons, and by determining the effect of sumatriptan on peripheral neurogenic inflammation., Methods: A polymerase chain reaction (PCR) technique was used to detect mRNA for 5-HT receptors in rat lumbar dorsal root ganglia. Rat knee joint plasma extravasation was used to determine the effect of sumatriptan on peripheral neurogenic inflammation., Results: The mRNA for the sumatriptan-activated receptors 5-HTIB, 5-HTID, and 5-HT7, was detected in lumbar dorsal root ganglia. In rat knee joint, capsaicin-activated C-fibers stimulated plasma extravasation to 273 +/- 62% of baseline. Low-concentration sumatriptan (50 nM) significantly inhibited capsaicin-induced plasma extravasation to 106 +/- 6% of baseline. High-concentration sumatriptan (1 microM) significantly enhanced capsaicin-induced plasma extravasation to 572 +/- 55% of baseline., Conclusions: Sumatriptan inhibits peripheral neurogenic inflammation, probably via 5-HT1B/1D receptors, and may be a novel therapy for inflammatory pain states. However, high concentrations (> 200 nM) may enhance neurogenic inflammation, possibly by activation of 5-HT7 receptors, which may explain lack of migraine relief and excessive injection site pain in 20-30% of patients treated with sumatriptan.

Over the course of 1 to 2 years, the field has moved swiftly to investigate the functional and structural properties of the newly cloned opioid receptors. Achieving a better understanding of these macromolecules is likely to have profound implications for drug design aimed at the production of better analgesic drugs, for a more fundamental understanding of mechanisms of action of drugs of abuse, and for a more comprehensive knowledge base regarding the biology of opioid peptides in particular, and neuroactive peptides in general.

Three full-length cDNA clones encoding the guinea pig A1 adenosine receptor have been isolated by polymerase chain reaction (PCR) and low-stringency hybridization screening of a guinea pig brain cDNA library. These three cDNAs, though differing in their 5' untranslated regions, contain the same open reading frame encoding a 326 amino acid residue protein with seven hydrophobic alpha-helices long enough to form the transmembrane domains, suggesting that it belongs to the G protein-coupled receptor superfamily. This protein is highly homologous to the A1 adenosine receptors previously cloned from other species. Pharmacological characterization of this receptor transiently expressed in mammalian cells demonstrates that, despite its high homology to A1 adenosine receptors of other species, the guinea pig A1 adenosine receptor displays a unique pharmacological profile: high affinity for the A1-selective antagonist CPX, yet very low affinity for some A1-selective agonists such as CCPA, CHA and R-PIA. Northern blotting for different guinea pig tissues and in situ hybridization for guinea pig brain sections reveal an abundant and broad distribution of mRNA of this A1 subtype receptor in the brain.

A full-length complementary DNA (cDNA) clone encoding the guinea pig brain A2 adenosine receptor has been isolated by polymerase chain reaction (PCR) and low-stringency-hybridization screening of a guinea pig brain cDNA library. This cDNA contains a long open reading frame encoding a 409-amino acid-residue protein which is highly homologous to the A2 adenosine receptors previously cloned from other species. Hydrophobicity analysis of the deduced protein sequence reveals seven hydrophobic regions, characteristic of a member of the G-protein-coupled receptor superfamily. Radioligand binding assay and functional (GTPase and cAMP) assays of the receptor, transiently expressed in mammalian cells, demonstrate typical characteristics of the A2 type adenosine receptor. The messenger RNA (mRNA) of this A2 receptor is found in the brain, heart, kidney and spleen. Receptor autoradiography with [3H]CGS21680, a specific A2 agonist, and in situ hybridization with A2 cRNA probe in guinea pig brain indicate that the receptor is expressed exclusively in the caudate nucleus. The pharmacological profile and anatomical distribution of this receptor indicate that it is of the A2a subtype. This work represents the first cloning of an A2a receptor in a rodent species, offers a complete pharmacological characterization of the receptor and provides an anatomical comparison between binding profile and gene expression of the receptor.

To examine the processing of products of the dynorphin gene in the central nervous system, immunoreactive (ir) dynorphin (Dyn) A, Dyn B, Dyn A-(1-8), alpha- and beta-neo-endorphin (alpha- and beta-Neo) in rat brain and spinal cord were measured, using specific antisera after gel filtration and high-performance liquid chromatography (HPLC). Three peaks of Mr about 8, 4, and 2 kDa for ir-Dyn A and ir-Dyn B, and one peak of Mr less than 2 kDa for ir-Dyn A-(1-8), ir-alpha-, and ir-beta-Neo were found both in the brain and in the spinal cord. The 8 kDa peak was recognized by Dyn A and Dyn B antisera and, after hydrolysis by proline-specific endopeptidase, by beta-Neo antiserum. The 8 kDa peak was recognized by a monoclonal antibody against the amino terminal sequence Tyr-Gly-Gly-Phe of all opioid peptides and by an antiserum directed toward the carboxyl terminus of Dyn B, indicating that it contains, from the amino terminal tyrosine of neo-endorphin to the carboxyl-terminal threonine of Dyn B, all 3 opioid peptide regions in the prodynorphin. By means of proline-specific endopeptidase hydrolysis, we also found a big dynorphin precursor (Mr approximately equal to 26 kDa) in both brain and spinal cord.

A dose-dependent analgesic effect of intrathecally injected dynorphin B was observed in rats using the tail flick as nociceptive test. Intrathecal injection of 20 nmol of dynorphin B increased the tail flick latency by 90 +/- 23%, an effect that lasted about 90 min. For the same degree of analgesia, dynorphin B was 50% more potent than morphine on a molar basis. The analgesic effect of this dose of dynorphin B was partially blocked by 10 mg/kg, but not by 1 mg/kg, of subcutaneous naloxone, showing a relative resistance to naloxone reversal as compared with morphine analgesia. The analgesia produced by dynorphin B was unchanged in morphine-tolerant rats but was significantly decreased in rats tolerant to ethylketazocine. These results suggest that dynorphin B produces its potent analgesic effect by activation of kappa rather than mu opioid receptors in the rat spinal cord.

Injection of protein-A purified antibodies against Met-enkephalin and beta-endorphin into the periaqueductal gray matter (PAG) was shown to decrease the analgesic effect of electroacupuncture (EA) in rabbits. Met-enkephalin antibodies were more potent than the beta-endorphin antibodies in causing a statistically-significant effect on electroacupuncture analgesia. Antibodies to Met-enkephalin were also active at the spinal level, whereas antibodies against beta-endorphin were without effect: this is in agreement with a rich enkephalinergic innervation and absence of beta-endorphin-containing fibres in the spinal cord. Substance P, the other neuropeptide of this study, also seems to be important in mediating effects of electroacupuncture. Injection of antibodies into the periaqueductal gray caused decrease of the effect of electroacupuncture whereas intrathecal administration of Fab-fragment substance P antibodies caused a marked potentiation. The demonstration of site specificity of the neuropeptides in mediating analgesia induced by electroacupuncture supports the validity of this experimental approach.