S100 protein-immunoreactive primary sensory neurons in the trigeminal and dorsal root ganglia of the rat

The cell body size (cross-sectional area) of S100-immunoreactive (-ir) primary neurons was measured in the trigeminal (TG) and lumbar dorsal root ganglia (DRG). About a half of neurons exhibited S100-immunoreactivity (-ir) in the DRG (44.0%) and TG (59.0%). DRG neurons with cell bodies >1200 μm² mostly exhibited S100-ir (96.5%), whereas S100-ir DRG neurons <600 μm² were rare (8.0%). 36.6% of DRG neurons in the cell size range 600–1200 μm² showed the ir. TG neurons >800 μm² mostly exhibited S100-ir (93.1%), whereas those <400 μm² were devoid of it (positive cells 10.5%). 58.3% of TG cells in the range 400–800 μm² contained S100-ir. Double-immunofluorescence method revealed the co-expression of S100 and other calcium-binding proteins. Parvalbumin-ir neurons mostly exhibited S100-ir in the DRG (97.4%) and TG (97.0%). The co-expression of S100 and calbindin D-28k was very rare in the DRG, because the DRG contained few calbindin D-28k-ir neurons. Unlike in the DRG, numerous neurons co-expressed S100- and calbindin D-28k-ir in the TG. Most calbindin D-28k-ir TG neurons were also immunoreactive for S100 (90.7%). Sub-populations of calretinin (CR)-ir neurons co-expressed S100-ir in both the DRG (68%) and TG (50.0%). Virtually all CR-ir neurons >1400 μm² co-expressed S100-ir in the DRG (100%) and TG (95.9%). CR-ir neurons <800 μm² were rarely exhibited S100-ir (DRG 18.0%, TG 21.9%). 71.3 and 60.5% of CR-ir neurons in the range 800–1400 μm² co-expressed S100-ir in the DRG and TG, respectively. The present study indicates that S100 is closely correlated to the primary neuronal cell size in the DRG and TG.     

Distribution of calbindin D-28K and parvalbumin immunoreactivities in the nucleus olfactorius anterior of the rat

The distributions of calbindin D-28K (CaBP) and parvalbumin (PV) in the rat nucleus olfactorius anterior (NOA) were described using monoclonal antibodies and the avidin-biotin-peroxidase method. The NOA showed a high immunoreactivity for CaBP, with a rostrocaudal increase in the positive neurons and fibres. Pars externa (NOAe) was the only subdivision which showed a low CaBP immunostaining. PV-positive elements were less abundant than those CaBP immunostained. The main difference in the distributions for both proteins was observed in the pars medialis which was practically PV negative. PV- and CaBP-stained neurons showed similar morphologies in the subdivisions where they were present. In NOAe, we observed a characteristic PV- and CaBP-positive neuronal type, with an oriented dendritic pattern. Transition areas were clearly observable in both CaBP- and PV-labelled sections.     

Neurophysiological investigation of effects of the D-1 agonist SKF 38393 on tonic activity of substantia nigra dopamine neurons

The effects of the D-1 agonist SKF 38393 on tonic activity of rat substantia nigra pars compacta dopamine neurons were studied using extracellular, single-unit recording techniques. Unlike nonselective D-1/D-2 dopamine agonists or the D-2 agonist quinpirole, SKF 38393 did not inhibit dopamine neuronal activity when applied iontophoretically or when administered intravenously in doses up to 20 mg/kg to chloral hydrate-anesthetized rats. Moreover, pretreatment with SKF 38393 did not alter the inhibitory response of these neurons to apomorphine or the D-2 agonist quinpirole. However, in locally anesthetized, gallamine-treated, artificially respired rats, dopamine cell activity was significantly altered by i.v. administration of SKF 38393; firing rate increases and decreases were observed. Administration of the inactive enantiomer of SKF 38393, S-SKF 38393, did not induce similar changes in parallel experiments. These results support the idea that unlike D-2 autoreceptor stimulation, D-1 receptor stimulation does not exert a direct local effect on dopamine neurons in the substantia nigra pars compacta and suggest that D-1 receptor stimulation at sites postsynaptic to the dopamine cells may indirectly affect the activity of some dopamine neurons through long-loop feedback mechanisms.     

In vivo receptor binding,neurochemical and functional studies with the dopamine D-1 receptor antagonist SCH 23390

Summary A series of in vivo experiments were undertaken, relating functional (motor activity, body temperature), dopamine (DA) receptor binding and neurochemical (catecholamine synthesis and utilization, DA release) aspects of the pharmacology of SCH 23390 in the rat.The compound inhibited the locomotor hyperactivity, but not the hypothermia, induced by the potent DA stimulant DP-5,6-ADTN. Interstingly, SCH 23390 simultaneously failed to displace DP-5,6-ADTN from its binding sites in the rat striatum—used as a direct in vivo biochemical index of DA (D-2) receptor interaction. The spontaneous locomotion in non-pretreated rats was likewise inhibited by SCH 23390. The locomotor-suppressive action, but not the DP-5,6-ADTN-displacing capcity of the D-2 blocker haloperidol was significantly enhanced by SCH 23390, suggesting that motility can be suppressed by either enhanced D-1 or D-2 (postsynaptic) receptor blockade, but also that the D-1 and D-2 sites involved may be physically distinct.SCH 23390 only slightly altered in vivo neurochemical of DA synthesis, release and nerve-impulse flow, indicating that, while similar in suppressing dopaminergic behaviour, the D-1 antagonist is less effective than traditional neuroleptics as an activator of DA neuronal feedback mechanisms. The weak increases of DA synthesis and release nonetheless obtained were equal in magnitude (30–40%) in the limbic vs. striatal brain areas; also in this respect, SCH 23390 thus differs from classical neuroleptics, which generally display more marked effects in the striatum than in limbic tissue.No major changes in the in vivo indices of NA synthesis and utilization (or in 5-HT synthesis) were found after SCH 23390 administration, by and large supporting the DA receptor specificity of the compound.In summary, the studies demonstrated that SCH 23390 can offset and accentuate, respectively, behavioural consequences of D-2 receptor stimulation and blockade. Importantly, at the same time no direct interaction at the level of D-2 DA receptor sites in the striatum was detected. Only slight, D-2 antagonist-like, changes in neurochemical indices of dopaminergic activity were observed after D-1 receptor blockade by means of SCH 23390. With regard to DA agonist hypothermia, SCH 23390 was without effect per se, but (at a high dose) attenuated the action of the D-2 antagonist haloperidol. The observations may indicate that the complex interactions between central D-1 and D-2 receptor-controlled mechanisms that influence behaviour, neurochemistry, and possibly autonomic nervous expression, are not identical.     

Synaptic potentials and effects of amino acid antagonists in the auditory cortex

Neurons of in vitro guinea pig and rat auditory cortex receive a complex synaptic pattern of afferent information. As many as four synaptic responses to a single-stimulus pulse to the gray or white matter can occur; an early-EPSP followed, sequentially, by an early-IPSP, late-EPSP, and late-IPSP. Paired pulse stimulation and pharmacological studies show that the early-IPSP can modify information transmission that occurs by way of the early-EPSP. Each of these four synaptic responses differed in estimated reversal potential, and each was differentially sensitive to antagonism by pharmacological agents. DNQX (6,7-dinitroquinoxaline-2,3-dione), a quisqualate/kainate receptor antagonist, blocked the early-EPSP, and the late-EPSP was blocked by the NMDA receptor antagonist APV (D-2-amino-5-phosphonovalerate). The early-IPSP was blocked by the GABA-a receptor antagonist bicuculline, and the late-IPSP by the GABA-b receptor antagonists 2-OH saclofen or phaclofen. Presentation of stimulus trains, even at relatively low intensities, could produce a long-lasting APV-sensitive membrane depolarization. Also discussed is the possible role of these synaptic potentials in auditory cortical function and plasticity.     

急性心肌梗塞溶栓治疗后D-二聚体动态变化的意义

在22例符合溶栓条件的急性心肌梗塞患者，应用尿激酶溶栓治疗前后，用乳胶颗粒凝集法检测了血清D-二聚体的动态变化和对照组比较，D-二聚体含量在梗塞相关动脉（IRA）再通者明显升高（P＜0．01），而IRA未再通者仅稍有升高（P＞0．05）。结果表明，D-二聚体水平和IRA再通与否之间有良好的相关性，且方法简便，易于推广。     

High-Performance Liquid Chromatographic (HPLC) Assay Using Fluorescence Detection for the Simultaneous Determination of Gallopamil and Norgallopamil in Human Plasma

Gallopamil is a calcium-channel antagonist with reported activity in experimental animals three to five times higher than that of verapamil. An automated high-performance liquid chromatographic (HPLC) method with fluorescence detection is described for the simultaneous determination of gallopamil and its metabolite norgallopamil in plasma. Gallopamil was well resolved from norgallopamil and other metabolites, allowing simultaneous quantitation of both drugs. The detection limit for both gallopamil and norgallopamil was 0.9 ng/ml. This method has been successfully used for the determination of gallopamil and norgallopamil following the administration of 25-, 37.5-, and 50-mg oral doses of drug.     

Chronic administration of a selective dopamine D-2 agonist: factors determining behavioral tolerance and sensitization

The locomotor stimulant effects of sustained administration of a potent and selective dopamine (DA) D-2 receptor agonist, [+]-4-propyl-9-hydroxynaphthoxazine (PHNO), in rats were assessed 24 h a day during 12 h light-dark cycles. PHNO was administered continuously with subcutaneous implants of Alzet osmotic minipumps (5 g/h), for 12 h a day with modified osmotic minipumps (5 g/h), or by daily injections (15 g, SC). Tolerance was observed to occur only with 24 h continuous infusions and only during the light period. The other treatment regimens produced sensitization of the locomotor response. Daytime tolerance to continuous infusions of PHNO was reversed following reversal of the light-dark cycle. A normally arousing stimulus also reversed (temporarily) daytime tolerance. The present results indicate that the temporal pattern of administration of DA agonists, the phase of the circadian cycle and environmental stimuli associated with arousal are important determinants of the behavioral consequences of long-term treatment.     

Subtyping of MRSA isolates belonging to a widely disseminated clonal group by polymorphism of the dru sequences in mec-associated DNA

During the past 7 years the "Berlin epidemic MRSA" has spread throughout whole Germany. SmaI macrorestriction patterns of this clonal group are rather stable as are the length polymorphisms at the 3' end of the coagulase gene and the x-region of spa. However, the dru region (direct repeat units) of mec-associated DNA exhibits a length polymorphism due to deletion of one or more direct repeat units. Five different subclones could be discriminated by dru region length polymorphism. Location of deletions and of a few point mutations allow a delineation of these subclones.     

Inhibition in carotid body chemoreceptors mediated by D-2 dopaminoceptors: Antagonism by benzamides

Inhibition of chemosensory nerve impulses in the cat is evoked by dopamine (DA) applied to carotid body chemoreceptors. Pharmacological characterization of the dopaminoceptors involved in this action was determined through their blockade with benzamides, selective antagonists of D-2 receptors. Both metoclopramide and sulpiride were effective blockers of DA-induced chemosensory inhibition. Furthermore, both drugs induced an immediate increase in the frequency of carotid nerve chemosensory impulses, suggesting the presence of previous tonic inhibition of chemoreceptor discharges by endogenous DA released from glomus cells.