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At least 721 records · Page 40Linked to original sources
PubMed1990

Effects of zimeldine, a selective 5-HT reuptake inhibitor, combined with ritanserin, a selective 5-HT2 antagonist, on waking and sleep stages in rats.

Sleep and waking in rats were studied 8 h following administration of a selective 5-hydroxytryptamine (5-HT) reuptake inhibitor (zimeldine), a selective 5-HT2 antagonist (ritanserin) and a combination of ritanserin and zimeldine. Consistent with earlier findings, zimeldine gave a biphasic effect on sleep and waking. Waking was increased the first 3 h, followed by an increase in deep slow wave sleep (SWS-2), maximal in hours 4 and 5. Ritanserin gave an increase in SWS-2 that was spread out over the recording period. Ritanserin + zimeldine also gave a biphasic effect as zimeldine did, and the initial increase in waking and the following increase in SWS-2 tended to be stronger. Thus, ritanserin did not block the initial waking effect seen after zimeldine administration, indicating that this waking effect was not due to 5-HT2 stimulation. The increase in SWS-2 seemed to reflect an addition of the increases following the zimeldine and ritanserin alone conditions. This suggests that the increase in SWS-2 seen after 5-HT reuptake inhibition and 5-HT2 blockade are independent phenomena. Zimeldine alone, ritanserin alone and the combination all gave a clear reduction of rapid eye movement sleep.

Animals↗
PubMed1993

Influenza virus strains selectively recognize sialyloligosaccharides on human respiratory epithelium; the role of the host cell in selection of hemagglutinin receptor specificity.

The complement of sialyloligosaccharides present on the surface of human tracheal epithelium has been implicated as an important factor in the selection of hemagglutinin receptor specificity of human influenza A virus. Human strains of influenza A virus preferentially recognize host cell receptors bearing SA alpha 2,6Gal sequences, a sequence which is found on the surface of ciliated tracheal epithelium. A fluorescently-labelled H3 human virus strain bound avidly to the apical surface of human tracheal epithelium, while a fluorescently-labelled receptor variant strain, which preferentially binds SA alpha 2,3Gal sequences, showed little binding to the epithelial surface and localized primarily to intracellular mucin droplets. Extracts of human bronchial mucin, which is known to contain sialic acid primarily in the SA alpha 2,3Gal linkage, was a potent inhibitor of the binding of the receptor variant strain to trachea sections, while the binding of the parent strain was unaffected by the presence of mucin. Human bronchial mucin also inhibited the binding of the receptor variant strains, but not the parent virus strains, to human erythrocytes derivatized to contain SA alpha 2,6Gal sequences. These results suggest that a combination of selection pressures present in the respiratory tract environment have resulted in the evolution of a hemagglutinin receptor specificity in human influenza A virus strains which optimizes recognition of, binding to and infection of host cells.

Carbohydrate Sequence↗
PubMed1985

Selective attention and the brain: a hypothesis concerning the hippocampal--ventral striatal axis, the mediation of selective attention, and the pathogenesis of attentional disorders.

The mechanisms mediating selective attention are not currently known. Dysfunctional selective attention is a common and prominent finding in a variety of medical and psychiatric conditions. A hypothesis is developed that efferents from the hippocampal formation are the final common pathway of processes which determine the noteworthiness of both exteroceptive and interoceptive stimuli, and that dysfunction of these efferents is a common pathway for a variety of anatomical, electrophysiological, and neurochemical lesions. This hypothesis suggests that clinical syndromes of disordered attention may be caused by various lesions of efferent connections from hippocampal formation to nucleus accumbens. The hypothesis further addresses the possibility that the threshold of hippocampus to various classes of stimuli may change on a diurnal and phasic basis. Experimental evidence that bears on the hypothesis is reviewed and experimental implications of the hypothesis are explored.

Attention↗
PubMed1995

Non-selective digital subtraction angiography in comparison with selective conventional angiography in the diagnosis of carotid artery disease.

In the recent past, non-selective arterial digital subtraction angiography (NSDSA) seemed a less invasive alternative to conventional filmscreen angiography (CFA) in the diagnosis of carotid artery disease. NSDSA obviated the need for selective catheterization with its associated risks but yet took advantage of the DSA method. However, this technique has not found general application although there are no reports that formally assess the (dis)advantages of NSDSA. The aim of our study was to compare the reliability of NSDSA with CFA in evaluation of carotid bifurcations in patients with transient ischemic attacks or partial stroke by reviewing prospectively collected data. Over a 2-year period, 40 patients (upper age limit 65 years) underwent both NSDSA and CFA. Bilateral NSDSA was performed in all 40 patients (80 bifurcations). Bilateral CFA was performed in 27 patients whereas unilateral CFA was carried out in 13 patients (67 bifurcations). Inter- and intra-observer variability for the degree of stenosis was determined by calculation of kappa-values for a 4-point and a 2-point scale. The proportion of interpretable studies was significantly lower in NSDSA. The inter- and intra-observer agreement was on average better in CFA examinations, though the difference was only statistically significant for the inter-observer agreement. The results of our study indicate that images obtained with NSDSA give less reliable information about carotid artery disease than images obtained with CFA. This is in accordance with the fact that NSDSA now seems an abandoned technique.

Adult↗
PubMed2005

3,4-disubstituted azetidinones as selective inhibitors of the cysteine protease cathepsin K. Exploring P3 elements for potency and selectivity.

The synthesis of a series of highly potent and selective inhibitors of cathepsin K based on the 3,4-disubstituted azetidin-2-one warhead is reported. A high degree of potency and selectivity was achieved by introducing a basic nitrogen into the distal part of the P3 element of the molecule. Data from kinetic and mass spectrometry experiments are consistent with the interpretation that compounds of this series transiently acylate the sulfhydrile of cathepsin K.

Azetidines↗
PubMed2006

Prior information of stimulus location: effects on ERP measures of visual selection and response selection.

This paper examines the effects of prior information of the location of an upcoming stimulus on event-related EEG potentials associated with the focusing of attention. Results of two tasks, reported in a previous publication (Praamstra, P., Boutsen, L., Humphreys, G.W., 2005. Frontoparietal control of spatial attention and motor intention in human EEG. J. Neurophysiol. 94, 764-774), were compared: one in which spatial attention was cued to the stimulus location and one in which the cue was non-informative. Only informative directional cues elicited directing-attention EEG potentials in the delay period between cue and target. Notwithstanding these electrophysiological signs of an attentional orientation prior to the occurrence of the target, there were no reaction time effects related to the presence of advance spatial information. By contrast, the advance information did have effects on EEG potentials following the target stimulus. The N2pc, reflecting an attentional selection mechanism in extrastriate cortex, was reduced in amplitude with advance spatial information. The N2cc, coinciding in time with the N2pc but measured over the motor cortex, was preempted by the advance spatial information. These results support that the N2cc is not due to overlap of the N2pc with movement execution-related activity. It is proposed that the neural activity underlying this EEG potential arises from the dorsal premotor cortex and serves an executive-attentional function that helps to ensure that the selection of a manual response is not biased by the direction of spatial attention.

Adult↗
PubMed2006

Protective effect of naproxen (non-selective COX-inhibitor) or rofecoxib (selective COX-2 inhibitor) on immobilization stress-induced behavioral and biochemical alterations in mice.

Chronic stress precipitates many neuropsychiatric disorders and alters the various oxidative stress parameters in brain. Cyclooxygenase (COX) is reported to play an important role in pathogenesis of various neurodegenerative disorders including stroke and seizures. In the present study, we examined the effect of naproxen (non-selective COX-inhibitor having much potency towards COX-I isoform) or rofecoxib (a selective COX-2 inhibitor) in subchronic immobilization stress. Mice were subjected to immobilized stress for 6 h daily for a period of seven days. Naproxen (7 mg/kg, i.p.) or rofecoxib (2 mg/kg, i.p.) was administered daily for 7 days before challenging them to immobilization stress. Behavioral analysis revealed the hyperlocomotor activity and increased anxiety response. Subchronic stress decreased percent retention of memory and also caused hyperalgesia in mice. Biochemical analysis revealed that chronic immobilization stress significantly increased lipid peroxidation and nitrite levels and decreased the reduced glutathione and adrenal ascorbic acid levels. Chronic treatment with naproxen or rofecoxib significantly attenuated the immobilization stress-induced behavioral and biochemical alterations. These results suggested that the use of COX-inhibitors (naproxen or rofecoxib) could be a useful neuroprotective strategy in the treatment of stress.

Adrenal Glands↗
PubMed2005

Usefulness of selective contrast echocardiography and selective scintigraphy for the evaluation of pulmonary arteriovenous fistula in a patient with systemic arterial supply to a normal lung.

To determine a surgical procedure for the correction of a systemic arterial supply to a normal lung, it is important to evaluate whether the patient has a pulmonary arteriovenous fistula. In this article, the authors report for the first time a patient in which selective contrast echocardiography and selective perfusion scintigraphy from an abnormal artery clearly demonstrated and quantified the pulmonary arteriovenous fistula. The authors believe that these methods are useful in determining the appropriate operative procedure for this condition.

Aorta, Thoracic↗
PubMed2005

BCG modulation of anaphylactic antibody response, airway inflammation and lung hyperreactivity in genetically selected mouse strains (Selection IV-A).

The effect of Bacillus Calmette-Guérin (BCG) treatment in allergic pulmonary reaction was studied in mice genetically selected accordingly to a High (H-IVA) or Low (L-IVA) antibody responsiveness. Mice were immunized with ovalbumin (OVA) or OVA plus BCG. Two days after nasal antigenic challenge, seric IgE and IgG1 anti-OVA, eosinophils in pulmonary tissue, inflammatory cells in bronchoalveolar lavage and the compliance and conductance of respiratory system were evaluated. H-IVA mice were found more susceptible than L-IVA, and BCG was able to inhibit simultaneously the production of IgE, the bronchopulmonary inflammation and bronchial hyperresponsiveness in these genetically selected mice.

Animals↗
PubMed2004

Cognitive and motor functioning in a patient with selective infarction of the left basal ganglia: evidence for decreased non-routine response selection and performance.

Focal damage to the basal ganglia is relatively rare, and little is known about the cognitive effects of damage to specific basal ganglia structures. A 28-year-old, highly educated male (patient RI) sustained a unilateral left ischemic infarction involving primarily the putamen and secondarily the head of the caudate and the anterior internal capsule. Two detailed neuropsychological assessments, at 3 and 16 months post-infarction, revealed that a majority of cognitive abilities were spared. RI's general intelligence, simple attention, concept formation, cognitive flexibility, and explicit memory were unaffected. Select cognitive abilities were affected, and these appeared to be related to direct involvement of the putamen and/or to indirect disruption of circuits between the basal ganglia and frontal lobes. Consistent with involvement of the left putamen, RI showed micrographia with his right hand. Interestingly, his micrographia was context-dependent, appearing only when verbal expression was involved (e.g., present when writing spontaneously, but not when copying sentences or when drawing). Evidence of disruption to frontal systems included variably decreased sustained attention, mildly decreased ability to generate words and to generate ideas, and significantly impaired abstraction ability in both verbal and visual modalities. Although there are several possible interpretations for these findings, this pattern of cognitive and motor functioning is consistent with neuroimaging research suggesting that the frontal/subcortical circuit between the putamen and frontal motor areas plays a role in non-routine response selection and performance.

Adult↗
PubMed2006

Selective antagonist at D3 receptors, but not non-selective partial agonists, influences the expression of cocaine-induced conditioned place preference in free-feeding rats.

The non-selective dopamine (DA) D(3) partial agonist BP 897 influenced rats' seeking behavior induced by cocaine-associated cues but there are contradictions about its ability to modulate cocaine-induced conditioned place preference (CPP), and mechanisms involved. We therefore re-evaluated its activity on both acquisition and expression of these behaviors, taking into consideration the actual brain concentrations of unchanged drug and its potential active metabolite 1-(2-methoxyphenyl)-piperazine (oOCH(3)PP), as well as its negative motivational properties. BP 897 induced conditioned place aversion (CPA) at 3 mg/kg, but not at 0.3 and 1 mg/kg. However, in this range of amply spaced doses BP 897 did not affect the acquisition and expression of cocaine (10 mg/kg i.p.) CPP in rats, although its brain concentrations were well above those affecting in vitro D(3) receptors. Concentrations of oOCH(3)PP were below the limits of quantification of the analytical procedure. As concerns the expression behavior, its structurally and pharmacologically related derivative N-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]benzo[b]furan-2-carboxamide (1 and 3 mg/kg, i.p.) also had no such effect. By contrast, the selective D(3) receptor antagonist SB-277011-A (3 mg/kg, i.p.) antagonized the expression of cocaine-induced CPP, supporting the suggestion that "full" antagonist activity at D(3) receptors is necessary to prevent 10 mg/kg cocaine-induced place conditioning in free-feeding rats.

Animals↗
PubMed2006

Tertiapin, a selective IKACh blocker, terminates atrial fibrillation with selective atrial effective refractory period prolongation.

It is well known that vagal nerve tone plays a crucial role in atrial fibrillation (AF). Acetylcholine-activated potassium current (IKACh) mediates much of the cardiac response to vagal nerve stimulation (VNS), but the contribution of IKACh to AF remains unknown. We investigated the role of the IKACh channel in canine AF models using tertiapin, a selective IKACh blocker. Tertiapin (4-41 nmol kg(-1), i.v.) terminated AF in the canine VNS-induced and aconitine-induced AF models. The muscarinic M-receptor antagonist AF-DX-116 terminated AF in these models, but the adenosine receptor antagonist DPCPX had no effect. Thus it is likely that IKACh activation via the M-receptor has a crucial role in both models. Tertiapin (12 nmol kg(-1), i.v.) preferentially prolonged the atrial effective refractory period (ERP) but not the ventricular ERP under the VNS condition. This peptide (4-41 nmol kg(-1), i.v.) did not affect PQ, QRS and corrected QT intervals in isoflurane-anaesthetised dogs. These results suggest that a selective IKACh blocker is effective in canine AF models without affecting ventricular repolarisation, and might be useful for the treatment of patients with AF.

Animals↗
PubMed1997

Potassium transport in opossum kidney cells: effects of Na-selective and K-selective ionizable cryptands, and of valinomycin, FCCP and nystatin.

The effects of two ionizable cryptands, the Na-selective (221)C10 and the K-selective (222)C10, and of valinomycin, FCCP and nystatin on K+ fluxes in opossum kidney (OK) cells have been quantified. The Na,K-ATPase (ouabain-sensitive 86Rb influx) was stimulated by nystatin (> or = 20%), and inhibited by the other ionophores (50-80%), by barium (K-channel blocker) (61%) and by amiloride (Na entry blocker) (34%). The Vmax of the Na,K-ATPase phosphatase activity was unmodified by the ionophores, indicating the absence of direct interaction with the enzyme. The ATPi content was unmodified by the inhibitors and nystatin, but was lowered by (221)C10 (47%), (222)C10 (75%), valinomycin (72%) and FCCP (88%). Amiloride was found to partially remove the inhibition caused by (222)C10 (51%) and valinomycin (49%). Rb efflux was stimulated by nystatin (32%), unmodified by valinomycin, and was inhibited by (221)C10 (19%), (222)C10 (19%) and FCCP (10%). Barium (39%) and amiloride (32%) inhibited this efflux and, in their presence, the nystatin effect persisted, whereas that of the other ionophores vanished. At pH 6.4, the Rb efflux decreased by 14% of its value at pH 7.4, with no additional inhibition by cryptands. Cryptands are shown to inhibit the pH-sensitive K+-conductance, probably by inducing a K+-H+ exchange at the plasma membrane, and by uncoupling oxidative phosphorylation by inducing the entry of K+ and H+ (and possibly Ca2+) ions into the mitochondria.

Adenosine Triphosphate↗
PubMed1964

THE ELECTROOSMOTIC EFFECTS ARISING FROM THE INTERACTION OF THE SELECTIVELY ANION AND SELECTIVELY CATION PERMEABLE PARTS OF MOSAIC MEMBRANES.

It has been previously shown, theoretically and in model system experiments, that mosaic membranes composed of anion-selective (electropositive) and cation-selective (electronegative) parts interposed between electrolytic solutions of different concentrations give rise to local electrical circuits. In this work with model systems it is shown that these currents produce electroosmosis. In systems with permselective electronegative membranes and KCl solutions, the electroosmotic water transport was 16 moles/faraday. With the permselective electronegative membrane replaced by more porous electronegative membranes, the electroosmotic effects were about twice as high. With Li salts, the water transport was considerably larger. A system with a permselective electropositive membrane of 50 cm(2) effective area and an electronegative membrane of 120 cm(2) gave internally generated currents up to 20 ma. In extrapolating from the results with macromodels to effects with true mosaics, i.e. microsystems, it is stressed that current depends on the linear distance over which membranes interact. In true mosaic membranes, the current pathways will be of the same order as the dimensions of individual membrane microelements; the sum of all local microcurrents will be correspondingly larger than the current in the macromodel, and the electroosmotic effects will be proportionately greater. Electroosmotic effects with true charge-mosaic membranes may be of the same order or larger than the liquid transport by normal and anomalous osmosis which might occur across the individual parts of the charge-mosaic.

Biophysical Phenomena↗
PubMed1996

Analysis of the effects of cyclooxygenase (COX)-1 and COX-2 in spinal nociceptive transmission using indomethacin, a non-selective COX inhibitor, and NS-398, a COX-2 selective inhibitor.

Prostaglandins are now thought to play an important role in nociceptive information transmission in the spinal cord. Prostaglandins are known to be produced by cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid. Two forms of COX have been identified: COX-1, which is constitutively expressed in most tissues and organs, and COX-2, which is an inducible enzyme and is localized primarily in inflammatory cells and tissues. COX-2 mRNA has been reported to be expressed in the brain in normal rats. We investigated the role of COX-1 and COX-2 in the spinal nociceptive transmission during the rat formalin test and the hot plate test using indomethacin, a non-selective COX-1 and COX-2 inhibitor, and NS398, a selective COX-2 inhibitor. In the formalin test, drugs were administered intrathecally or intraperitoneally 10 min before (pre-treatment study) or 7 min after (post-treatment study) the formalin injection. Both intrathecally administered indomethacin and NS398 inhibited the formalin induced flinching behavior in a dose-dependent manner in the pre-treatment study, but not in the post-treatment study. Both indomethacin and NS398 had no effect on the hot plate test at a dose which depressed the formalin induced flinching behavior. These data suggested that COX-2 is expressed in the central nervous system, including the spinal cord, and that COX-2 plays an important role in the spinal nociceptive transmission during the formalin test, but not during the hot plate test.

Analysis of Variance↗
PubMed1999

Quantification of glutaric acid by isotope dilution mass spectrometry for patients with glutaric acidemia type I: selected ion monitoring vs. selected ion storage.

An isotope dilution mass spectrometric assay for the quantification of glutaric acid in urine and serum samples was developed. The performance of a quadrupole mass filter (QMF) gas chromatography-mass spectrometry (GC-MS) instrument, operated in the selected ion monitoring mode, and a quadrupole ion trap (QIT) GC/MS instrument, operated in the selected ion storage mode, was compared. Both instruments gave linear standard curves with glutaric acid concentrations between 0.19 and 3.8 microM. The average coefficients of correlation were 0.9998 and 0.9993 for the QMF and the QIT system, respectively. There was good agreement between the glutaric acid concentrations measured with the two instruments. The run-to-run precision was between 1.2 and 3.7% and between 6.2 and 8.6%, the average recovery of glutaric acid in urine and serum samples was 96 and 103% with the QMF and QIT instrument, respectively. We conclude that although the QMF has a slightly better performance, both instruments can be used to reliably measure glutaric acid concentrations from urine and serum patient samples.

Child↗
PubMed1997

Actions of isoform-selective and non-selective nitric oxide synthase inhibitors on endotoxin-induced vascular leakage in rat colon.

The effects of the nitric oxide (NO) synthase inhibitor, N-(3-(aminomethyl)benzyl)-acetamidine (1400W) which is selective for the inducible isoform of NO synthase, on rat colonic microvascular injury provoked by Escherichia coli endotoxin (3 mg/kg i.v.) has been compared to those of aminoguanidine (25-50 mg/kg, s.c.), NG-iminoethyl-L-ornithine (L-NIO, 15-30 mg/kg, s.c.) and NG-nitro-L-arginine methyl ester (L-NAME, 2-5 mg/kg, s.c.). Administration of aminoguanidine, L-NIO or L-NAME concurrently with endotoxin provoked microvascular albumin leakage 1 h later, presumably by inhibiting constitutive NO synthase, whereas 1400W (0.1-10 mg/kg, s.c.) had no such effect. Administration of all these agents during the expression of inducible NO synthase (i.e. 3 h after endotoxin challenge) attenuated the subsequent endotoxin-provoked albumin leakage 1 h later. Moreover, concurrent administration of 1400W (0.2-5 mg/kg, s.c.; doses that did not affect systemic arterial blood pressure) with endotoxin suppressed the subsequent rise in albumin leakage after 5 h. These findings indicate that 1400W is a potent inhibitor of colonic microvascular injury associated with induction of NO synthase in vivo. 1400W will thus be useful to investigate in vivo the therapeutic potential of a selective inducible NO synthase inhibitor in inflammation.

Amidines↗
PubMed1999

Evidence for a small anion-selective channel in the cell wall of Mycobacterium bovis BCG besides a wide cation-selective pore.

Two channels were observed in extracts of whole Mycobacterium bovis BCG cells using organic solvents and detergents. The channels derived from organic solvent treatment had a single-channel conductance of about 4.0 nS in 1 M KCl in lipid bilayer membranes with properties similar to those of the channels discovered previously in Mycobacterium smegmatis and Mycobacterium chelonae. The channel was in its open configuration only at low transmembrane potentials. At higher voltages it switched to closed states that were almost impermeable for ions. Lipid bilayer experiments in the presence of detergent extracts of whole cells revealed another channel with a single-channel conductance of only 780 pS in 1 M KCl. Our results indicate that the mycolic acid layer of M. bovis BCG contains two channels, one is cation-selective and its permeability properties can be finely controlled by cell wall asymmetry or potentials. The other one is anion-selective, has a rather small single-channel conductance and is voltage-insensitive. The concentration of channel-forming proteins in the cell wall seems to be small, which is in agreement with the low cell wall permeability for hydrophilic solutes.

Anions↗