SEARCH · PubMed Health

Results for “Collateral sensitivity”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,405 records · Page 78Linked to original sources

PubMed1999

Metacarpophalangeal arthroscopy.

Although small joint arthroscopy has become commonplace over the past decade, relatively little attention has been paid to the investigation and clinical utility of metacarpophalangeal (MP) joint arthroscopy. The literature is scant in this area and consists of only a handful of case reports. In addition, the arthroscopic anatomy of the MP joint has not as yet been reported. Six cadaveric hands (24 joints) were rigorously studied in the laboratory using standard 2.5-mm small joint arthroscopic instrumentation and 5 lb of overhead traction. Radial and ulnar portals were used with care not to injure the extensor tendons. Arthroscopic anatomic landmarks include: (1) A consistent tripartite configuration of the main radial and ulnar collateral ligaments with characteristic changes in relative fiber orientation as the digit goes from extension to flexion, (2) nonvisualization of the accessory collateral ligament from inside the joint, (3) transitional amorphous capsular fibers connecting the collateral ligaments to the volar plate and dorsal capsule, (4) four synovial recesses (radial, ulnar, volar, and dorsal-proximal), (5) metacarpal head and proximal phalanx, (6) a consistent circumferential meniscal equivalent around the margin of the proximal phalanx articular surface, and (7) the sesamoid-metacarpal articulation in the thumb MPjoint. There are published case reports on the utility of MP joint arthroscopy for synovectomy in rheumatoid arthritis and hemachromatosis and realigning Stener lesions in gamekeepers' thumbs. The current clinical series reveals preliminary experience with the technique. MP joint arthroscopy was useful in relieving a locked MP joint from a loose osteochondral body and sagittal tear in the volar plate that enfolded into the joint surface. Intra-articular release of post-traumatic volar plate and dorsal capsular contracture were readily accomplished using this technique. Juxta-articular bone lesions such as osteoid osteomas can be removed with careful preoperative planning. Gamekeeper's thumbs that are unstable on stress radiographs can undergo arthroscopy with excellent sensitivity to determine the presence of a Stener lesion before an open or arthroscopic repair. The advantages of arthroscopic versus open techniques are similar to those experienced in larger joints. With time, more indications will emerge.

Arthroscopy↗

PubMed1994

Dry air- and hypertonic aerosol-induced bronchoconstriction and cellular responses in the canine lung periphery.

Dry air and hypertonic saline both create an osmotic stress to the airways, whilst dry air alone induces transient cooling of the airway mucosa. It is unclear whether these two stimuli lead to bronchoconstriction via the same mechanisms. We compared airflow- and hypertonic aerosol-induced bronchoconstriction (AIB and HIB, respectively) in the canine lung periphery, using a wedged bronchoscope to measure collateral system resistance (Rcs). Bronchoalveolar lavage (BAL) was used to examine changes in cells and mediators during AIB and HIB. We found that: 1) peripheral airways are not refractory to either dry air or hypertonic aerosols, and do not exhibit cross-refractoriness to these stimuli; 2) differences in strength of stimulus can alter the magnitude but not the time course of HIB; 3) within an individual, AIB and HIB are significantly correlated; 4) epithelial cells recovered in BAL fluid (BALF) are significantly elevated after AIB, and are similarly increased after HIB; 5) when compared to control, mediators recovered in BALF are significantly elevated after AIB but not HIB; 6) HIB is not altered by cyclo-oxygenase inhibition; and 7) lavage with hypertonic fluid does not affect the number of epithelial cells recovered, although the concentrations of some mediators are increased. We speculate that differences in cell and mediator profiles reflect differences in the time course of AIB and HIB that result from the modulation of temperature sensitive pathways that occurs during dry air, but not during hypertonic aerosol challenge.

Aerosols↗

PubMed2001

A purine-sensitive mechanism regulates the molecular program for axon growth.

Axon growth is characterized by a distinctive program of gene expression. We present evidence here that this program is regulated through a purine-sensitive mechanism, and that it can be re-activated in mature CNS neurons to induce extensive axon growth in vitro and in vivo. In dissociated goldfish retinal ganglion cells, the purine nucleoside inosine acts intracellularly to stimulate axon outgrowth by inducing the expression of GAP-43, Talpha-1 tubulin, and other growth-associated proteins. The purine analog 6-thioguanine (6-TG) acts in the opposite fashion, blocking axon growth and the underlying program of molecular changes. Prior studies in PC12 cells have shown that 6-TG selectively inhibits the activity of N-kinase, a 47-49 kDa serine-threonine kinase. Inosine acts as a competitor of 6-TG, suggesting that it acts as an N-kinase agonist, and that this kinase is part of a modular signal transduction pathway controlling axon growth. Following unilateral transections of the corticospinal tract in mature rats, inosine applied to the intact sensorimotor cortex stimulated layer 5 pyramidal cells to upregulate GAP-43 expression and to sprout axon collaterals that crossed the midline and reinnervated regions of the cervical spinal cord which had lost their normal afferents. It will now be important to identify the molecular changes that lie upstream and downstream of N-kinase, and to explore the clinical potential of activating this pathway in patients who have sustained CNS injury.

Animals↗

PubMed1995

Dihydrofolate reductase binding and cellular uptake of nonpolyglutamatable antifolates: correlates of cytotoxicity toward methotrexate-sensitive and -resistant human head and neck squamous carcinoma cells.

Several mechanisms have been demonstrated to be independently involved in methotrexate (MTX) resistance, including increased dihydrofolate reductase (DHFR) activity, decreased membrane transport, and decreased conversion to noneffluxing polyglutamates by folylpolyglutamate synthetase. We conducted the present study to test the hypothesis that nonpolyglutamatable antifolates with an N delta-hemiphthaloyl-L-ornithine side chain could be more potent than MTX against MTX-sensitive and -resistant human carcinoma cells via tighter DHFR binding, more efficient cellular uptake, the ability to bypass defective polyglutamation, or a combination. Two nonpolyglutamatable antifolates, N alpha-(4-amino-4-deoxypteroyl)-N delta-hemiphthaloyl-L-ornithine (PT523) and the new B-ring analogue N alpha-[4-[N-(2,4-diamino-5-chloroquinazolin-6-yl)methyl]amino] benzoyl-N delta-hemiphthaloyl-L-ornithine (PT619), were tested as inhibitors of purified recombinant human DHFR and were found to bind somewhat better to the enzyme than MTX as determined by competitive radioligand binding assay. PT523 and PT619 were 9- and 14-fold, respectively, more active than MTX as inhibitors of parental SCC25 human and neck squamous carcinoma cell growth in 72-hr cultures. Moreover, there was an even greater increase in relative potency against two previously described MTX-resistant cell lines with an increased DHFR content and a decreased ability to convert MTX to polyglutamates: SCC25/R1 (selected with MTX) and SCC25/CP (selected with cisplatin but collaterally resistant to MTX). Both PT523 and PT619 very efficiently inhibited [3H]MTX uptake by SCC25 cells in a 1-hr assay, with PT523 being 11-fold more potent and PT619 being 17-fold more potent than MTX. Greater inhibition of [3H]MTX uptake with PT523 and PT619 than with MTX was also observed in SCC25/R1 and SCC/CP cells. However, the increase in activity of PT523 and PT619 relative to MTX in uptake experiments was less than that in growth-inhibition assays, especially for SCC25/CP cells. This suggested that additional cytotoxicity determinants may exist in these resistant cells.

Antimetabolites, Antineoplastic↗

PubMed1982

A sensitive period for ganglion cell degeneration and the formation of aberrant retino-fugal connections following tectal lesions in rats.

Rats of 0, 3, 5, 10 and 30 days of age received unilateral tectal lesions. After surviving for 150 days the retinal ganglion cell layer of the contralateral eye was examined for evidence of a ganglion cell loss. The retino-fugal projections of the eye contralateral to the lesion were studied in autoradiographs. In the animals operated at 0 days of age, 33% of the ganglion cells had degenerated but in animals operated at 5 days of age, 67% of the ganglion cells had degenerated. The animals operated at 30 days of age show no significant cell loss. An aberrant retinal projection to the lateral posterior nucleus of the thalamus was found only in animals operated at 0 and 3 days of age. The retinal projection to the thalamus was investigated in normal rats of 0, 3, 5 and 10 days of age using the anterograde transport of horseradish peroxidase. There was a conspicuous projection to the lateral posterior nucleus in animals of 0 and 3 days of age, but in the 5-day-old rat the retinal projection to the lateral posterior nucleus was very small and similar to the adult pattern. We conclude that transecting the tectal terminals of retinal ganglion cells causes the ganglion cells to degenerate, unless they are old enough to have formed sustaining collaterals. In addition, the tectal lesion removes a major tectal input to the lateral posterior nucleus and, if carried out within the first few days, leads to the preservation of the normally transient retinal projection to the lateral posterior nucleus, presumably by reducing competition between axon terminals.

Animals↗

PubMed1998

Detection of coronary stenoses on source and projection images using three-dimensional MR angiography with retrospective respiratory gating: preliminary experience.

OBJECTIVE: Our objective was to study the ability of three-dimensional MR angiography with retrospective respiratory gating to reveal stenoses in proximal coronary arteries on source and projection images. CONCLUSION: Proximal coronary artery stenoses can be identified using three-dimensional MR angiography with retrospective respiratory gating, both with projection images and on source images alone. Reasons for missed lesions included collateral vessels and retrograde flow distal to complete occlusion and volume averaging of vessels with adjacent structures. Causes of false-positive interpretations included small foci of decreased signal intensity distal to complete occlusion, partial volume effects on individual partitions, and regions of distal vessels leaving the imaging plane.

Aged↗

PubMed2003

Development of the Key Behaviors Change Inventory: a traumatic brain injury behavioral outcome assessment instrument.

OBJECTIVE: To describe the development and initial validation of a neurobehavioral outcome measure, the Key Behaviors Change Inventory (KBCI), for individuals with traumatic brain injury (TBI). DESIGN: Scale construction and development, and validity study. SETTING: Large state university and postal survey. PARTICIPANTS: Seventy-five volunteer undergraduate students and 25 volunteer collateral informants of individuals with TBI participated in the item-analysis phase. Thirty members of the Brain Injury Association and 20 members of the National Multiple Sclerosis Society rated both an identified patient and an age- and gender-equated control in the validation phase. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Content validity was examined through expert panel item sorts. Scale internal consistencies were examined with the Cronbach alpha. Construct validity was examined by comparing scale elevations between controls and 2 neurologic groups. RESULTS: Item-analysis procedures resulted in 8 scales of 8 items each: inattention, impulsivity, unawareness of problems, apathy, interpersonal difficulties, communication problems, somatic difficulties, and emotional adjustment. Internal consistency reliability coefficients ranged from.82 to.91. Multivariate analysis of variance revealed significant (P</=.001) differences in scale elevations among TBI, multiple sclerosis (MS), and control groups. The TBI and MS groups scored significantly higher than the control group on all scales; a subset of KBCI scales discriminated between the 2 neurologic groups. CONCLUSION: The KBCI was both sensitive and specific to typical behavioral changes after TBI, thus supporting its usefulness in rehabilitation settings. Cross-validation and development of a normative database are future steps necessary in its development.

Adaptation, Psychological↗

PubMed1995

Potassium currents in isolated CA1 neurons of the rat after kindling epileptogenesis.

Daily tetanic stimulation of the Schaffer collaterals generates an epileptogenic focus in area CA1 of the rat hippocampus, ultimately leading to generalized tonic-clonic convulsions (kindling). Potassium currents were measured under voltage-clamp conditions in pyramidal neurons, acutely dissociated from the focus of fully kindled rats, one day and six weeks after the last generalized seizure. Their amplitude, kinetics, voltage dependence and calcium dependence were compared with controls. With Ca2+ influx blocked by 0.5 mM Ni2+, the sustained current (delayed rectifier) and the transient current (A-current) were not different after kindling. Calcium influx evoked an additional fast transient current component. This transient calcium-dependent current component was increased by 154%, but only immediately after the seizure. A second, slow calcium-dependent potassium current component was dependent on the intracellular calcium level, set by the pipette as well as on calcium influx. The peak amplitude of this slow calcium-dependent current was under optimal calcium conditions not different after kindling, but we found indications that either calcium homeostasis or the calcium sensitivity of the potassium channels was affected by the kindling process. In contrast to the previously described enhancement of calcium current, kindling epileptogenesis did not change the total potassium current amplitude. The minor changes that were observed can be related either to changes in calcium current or to changes in intracellular calcium homeostasis.

Animals↗

PubMed1983

Structure - function relationships for gamma-substituted glutamate analogues on dentate granule cells.

We previously demonstrated in the Schaffer collateral-CA1 region of the hippocampus that bath-applied agonists could be distinguished from antagonists among a group of acidic amino acid analogues by extracellular recording techniques. Here we report the use of the extracellular signs of agonist activity for discerning agonists and antagonists among several gamma-substituted glutamate analogues tested in the perforant path. The two-pathway composition of the perforant path offers the advantage over CA1 in that pathway-specificity, a postulated characteristic of antagonists, may be tested. By extracellular recording, D- and L-homocysteic acid, L-serine-O-sulfate, and L-2-amino-4-(5-tetrazolyl)-butanoic acid [L-glutamate tetrazole] were identified as agonists, and all 4 analogues were more potent than L-glutamate for inhibiting synaptic field potentials. Two previously identified antagonists, L-2-amino-4-phosphonobutyric acid and L-O-phosphoserine, exhibited the pathway-specificity and inhibitory kinetics consistent with properties expected for antagonists; both compounds detected 3 perforant path components with the same rank in sensitivity, suggesting that they are acting on the same set of receptors.

Aminobutyrates↗

PubMed2004

Unstable cerebral hemodynamics in carotid artery occlusion and large hemispheric stroke: a cerebral blood flow volume study.

PURPOSE: In chronic internal carotid artery (ICA) occlusion, cerebral hemodynamics are likely to be stable due to collateral flow. The authors evaluated cerebral hemodynamics in ICA occlusion using the sonographic method of cerebral blood flow volume (CBVF) measurement to find differences that might identify patients with large hemispheric stroke in ICA occlusion. METHOD AND RESULTS: The ultrasound method of CBVF measurement was used, which represents the sum of flow volumes of both internal carotid and both vertebal arteries. CBVF was measured in 29 patients with ICA occlusion including patients with (1) chronic ICA occlusion without acute minor stroke, (2) chronic ICA occlusion with acute minor stroke, (3) acute minor stroke due to acute ICA occlusion, and (4) ICA occlusion and large hemispheric stroke. In ICA occlusion, overall CBVF is lower compared to healthy volunteers, due to a significant reduction of CBVF in groups 3 and 4. Comparing groups, there were no differences in CBVF between groups 1, 2, and 3. CBVF in group 4 is reduced compared to all other groups. By receiver-operating characteristic analysis, a CBVF cutoff value for large hemispheric stroke was computed with a sensitivity of 100% and a specificity of 95.8%. CONCLUSION: Stroke due to acute ICA occlusion is associated with decreased CBVF compared to chronic ICA occlusion. Moreover, ICA occlusion and large hemispheric stroke are associated with decreased CBVF compared to all other groups, indicating instability of cerebral hemodynamics. CBVF measurement thus may be a useful tool in predicting large middle cerebral artery stroke early in ICA occlusion.

Aged↗

PubMed1991

Injuries to the posterior cruciate ligament of the knee.

The posterior cruciate ligament (PCL) is the strongest ligament about the knee and is approximately twice as strong as the anterior cruciate ligament. Its main function is to prevent the posterior dislocation of the tibia in relation to the femur, providing 95% of the strength to resist the tibial posterior displacement. Along with the anterior cruciate ligament (ACL) the PCL controls the passive 'screw home' mechanism of the knee in terminal knee extension. It also provides mechanical support for the collateral ligaments during valgus or varus stress of the knee. PCL ruptures are uncommon apparently due to its strong fibre structure. The most frequent injury mechanism in isolated PCL tears is a direct blow on the anterior tibia with the knee flexed thus driving the tibia posteriorly. Automobile accidents (in which the knee hits the dashboard) and soccer injuries (in which an athlete receives a blow to the anterior surface of the tibia during knee flexion) characteristically produce this type of injury. In other PCL injury mechanisms (hyperextension, hyperflexion or rotational injuries with associated valgum/varum stress), other knee structures are also often damaged. The most characteristic diagnostic finding in a knee with a PCL rupture is the 'posterior sag sign' meaning the apparent disappearance of the tibial tubercle in lateral inspection when the knee is flexed 90 degrees. This is due to gravity-assisted posterior displacement of the tibia in relation to the femur. A positive posterior drawer test performed at 90 degrees of flexion and a knee hyperextension sign are sensitive but nonspecific tests. False negative findings are frequent, especially in acute cases. If necessary, the clinical diagnosis of the PCL tear can be verified by magnetic resonance imaging, examination under anaesthesia, arthroscopy, or a combination of these modalities. If a PCL avulsion fragment has been dislocated, surgical treatment is recommended. In isolated, complete midsubstance tears of the PCL the majority of the recent studies recommend conservative treatment, since abnormal residual posterior laxity1 in most of these knees is consistent with functional stability and minimal symptoms. This has been the case even in athletes. In isolated PCL tears, the outcome seems to depend more on the muscular (quadriceps) status of the knee than on the amount of residual posterior laxity. Therefore, the conservative treatment protocol emphasises intensive quadriceps exercises, and only a short (under 2 weeks) immobilisation period followed by early controlled activities and early weightbearing.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1997

Characterization of the anoxia-induced long-term synaptic potentiation in area CA1 of the rat hippocampus.

1. The purpose of the present study was to characterize the mechanisms underlying the anoxia-induced long-term potentiation (LTP) of glutamatergic synaptic transmission in the CA1 region of rat hippocampus by use of intracellular recordings in vitro. 2. In response to superfusion of an anoxic medium equilibrated with 95% N2 - 5% CO2, the initial slope (measured within 3 ms from the onset of the synaptic response) of the excitatory postsynaptic potential (e.p.s.p.) generated in the hippocampal CA1 neurones by stimulation of Schaffer collateral-commissural afferent pathway was significantly decreased by 91.3 +/- 4.9% (n = 10) within 10 min of the anoxic episode. The reduction of the initial slope of the e.p.s.p. was accompanied by a transient membrane hyperpolarization followed by a sustained depolarization (10.8 +/- 1.7 mV, n = 10), along with a reduction in membrane input resistance (69.3 +/- 4.8% of control, n = 10). On return to reoxygenated medium, the e.p.s.p. slope returned to the control value within 8-10 min and was subsequently and progessively potentiated to reach a plateau (195.6 +/- 14.7% of control, n = 10) 15-20 min after return to control ACSF. This anoxic episode-induced persistent potentiation of synaptic transmission lasted for more than 1 h and was termed anoxic LTP. 3. The anoxic episode induced a persistent potentiation of the initial slopes of both pharmacologically isolated alpha-amino-3-hydroxy-5-methyl-4-isoxazola-propionate (AMPA) receptor-mediated e.p.s.p. (e.p.s.p.AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated e.p.s.p. (e.p.s.p.NMDA) with a similar time course and magnitude. The sensitivity of postsynaptic neurones to NMDA (10 microM), but not to AMPA (10 microM) was also persistently potentiated following the anoxic episode. In addition, the anoxia-induced LTP of the initial slope of e.p.s.p.AMPA was accompanied by a decrease in the magnitude of paired-pulse facilitation (PPF; from 106.8 +/- 17.6 to 46.6 +/- 18.4%, n = 6), a phenomenon which was associated with presynaptic transmitter release mechanisms. 4. The induction of the anoxic LTP is dependent on the extracellular Ca2+ concentration. The induction of the anoxic LTP was completely abolished when the external Ca2+ was removed and substituted with equimolar Mg2+. Moreover, the anoxic LTP was completely abolished in neurones intracellularly recorded with Ca2+ chelator bis-(O-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA, 500 mM). 5. Occlusion experiments were performed to examine whether the sustained enhancement of the initial slope of the e.p.s.p. produced by tetanic stimulation and the anoxic episode share common cellular mechanisms. Three episodes of tetanic stimulation were delivered to saturate the LTP, following which a long period (15 min) of anoxia failed to cause a further potentiation of the initial slope of the e.p.s.p. Similarly, prior induction of anoxic LTP also significantly attenuated the subsequent synaptic potentiation induced by a high-frequency tetanic stimulation (100 Hz for 1 s duration). These data imply that these two forms of synaptic plasticity may share a common cellular mechanism. 6. These results provide strong evidence that the generation of the anoxia-induced LTP of glutamatergic synaptic transmission in the CA1 region of rat hippocampus probably involves both of the presynaptic and postsynaptic loci. The mechanisms underlying the persistent potentiation are likely to be attributable to an enhancement of presynaptic glutamate release and a selective upregulation of postsynaptic NMDA receptor-mediated synaptic response through the Ca2+-dependent processes.

Animals↗

PubMed2002

Selective muscarinic regulation of functional glutamatergic Schaffer collateral synapses in rat CA1 pyramidal neurons.

Analysis of the cholinergic regulation of glutamatergic neurotransmission is an essential step in understanding the hippocampus because it can influence forms of synaptic plasticity that are thought to underlie learning and memory. We studied in vitro the cholinergic regulation of excitatory postsynaptic currents (EPSCs) evoked in rat CA1 pyramidal neurons by Schaffer collateral (SC) stimulation. Using "minimal" stimulation, which activates one or very few synapses, the cholinergic agonist carbamylcholine (CCh) increased the failure rate of functional more (36 %) than of silent synapses (7 %), without changes in the EPSC amplitude. These effects of CCh were insensitive to manipulations that increased the probability of release, such as paired pulse facilitation, increases in temperature and increases in the extracellular Ca(2+) : Mg(2+) ratio. Using "conventional" stimulation, which activates a large number of synapses, CCh inhibited more the pharmacologically isolated non-NMDA (86 %) than the NMDA (47 %) EPSC. The changes in failure rate, EPSC variance and the increased paired pulse facilitation that paralleled the inhibition imply that CCh decreased release probability. Muscarine had similar effects. The inhibition by both CCh and by muscarine was prevented by atropine. We conclude that CCh reduces the non-NMDA component of SC EPSCs by selectively inhibiting transmitter release at functional synapses via activation of muscarinic receptors. The results suggest that SCs have two types of terminals, one in functional synapses, selectively sensitive to regulation through activation of muscarinic receptors, and the other in silent synapses less sensitive to that regulation. The specific inhibition of functional synapses would favour activity-dependent plastic phenomena through NMDA receptors at silent synapses without the activation of non-NMDA receptors and functional synapses.

Adenosine↗

PubMed2006

Differential roles of NR2A and NR2B-containing NMDA receptors in LTP and LTD in the CA1 region of two-week old rat hippocampus.

The role of NMDA receptors in the induction of long-term potentiation (LTP) and long-term depression (LTD) is well established but which particular NR2 subunits are involved in these plasticity processes is still a matter of controversy. We have studied the effects of subtype selective NMDA receptor antagonists on LTP induced by high frequency stimulation (100 Hz for 1s) and LTD induced by low frequency stimulation (1 Hz for 15 min) in the CA1 region of hippocampal slices from 14 day old Wistar rats. Against recombinant receptors in HEK293 cells NVP-AAM077 (NVP) was approximately 14-fold selective for NR2A vs NR2B receptors, whilst Ro 25-6981 (Ro) was highly selective for NR2B receptors. On NMDA receptor-mediated EPSCs from Schaffer collaterals in CA1 neurones, NVP and Ro both reduced the amplitude but differentially affected the time constant of decay. The data are compatible with the selective effect of NVP (0.1 microM) and Ro (4 microM) on native NR2A and NBR2B receptors, respectively. NVP reduced both LTP and LTD whereas Ro reduced only LTP. Thus, LTP was reduced by 63% at 0.1 microM NVP and almost completely at 0.4 microM whereas 5 microM Ro reduced LTP by 45%. These data are consistent with a role for both NR2A and NR2B in the induction of LTP, under our experimental conditions. In comparison, LTD was unaffected by Ro (5 microM) even in the presence of a glutamate uptake inhibitor threo-beta-benzylaspartic acid (TBOA) to increase the concentration of glutamate at NR2B containing receptors. NVP (0.2-0.4 microM), however, produced a concentration dependent inhibition of LTD which was complete at 0.4 microM. The lack of effect of 0.1 microM NVP on LTD contrasts with its marked effect on LTP and raises the possibility that different NVP-sensitive NR2 subunit-containing NMDA receptors are required for LTP and LTD in this preparation.

Animals↗

PubMed1995

Modulation of glutamate and aspartate release from slices of hippocampal area CA1 by inhibitors of arachidonic acid metabolism.

Slices of hippocampal area CA1 were used to test inhibitors of arachidonic acid metabolism for their effects on glutamate/aspartate release from the CA3-derived Schaffer collateral, commissural, and ipsilateral associational terminals. Test compounds [3 microM nordihydroguaiaretic acid (NDGA) and 1 microM 3-[3-(4-chlorobenzyl)-3-tert-butylthio-5- isopropylindol-2-yl]-2,2-dimethyl-propanoic acid (MK-886)] that reduced the production and release of 5-lipoxygenase metabolites also selectively reduced the K(+)-evoked release of aspartate. In contrast, the cyclooxygenase inhibitor indomethacin (100 microM) selectively enhanced the release of glutamate. At a concentration (100 microM) that nonselectively depressed the release of arachidonic acid and its metabolites, NDGA markedly depressed the release of aspartate, glutamate, and GABA. An inhibitor of the 12-lipoxygenase and an inhibitor of nitric oxide synthase did not affect the K(+)-evoked release of any transmitter amino acid. These results suggest that a 5-lipoxygenase product selectively enhances aspartate release and a cyclooxygenase product selectively depresses glutamate release. They are also consistent with previous evidence that arachidonic acid and/or platelet-activating factor enhances the release and depresses the uptake of glutamate and aspartate. The K(+)-evoked release of excitatory amino acids is much more sensitive to modulation by lipid mediators than is GABA release. Activation of NMDA receptors may enhance the K(+)-evoked release of glutamate and aspartate from CA1 slices by stimulating the production and release of lipid modulators.

Animals↗

PubMed1995

Effect of a calcium-sensitizing positive inotropic agent MCI-154 and its combined use with enalapril on postischemic contractile dysfunction of dog hearts.

We wished to elucidate the effects of the calcium-sensitizing positive inotropic agent MCI-154 and its combined use with an angiotensin-converting enzyme (ACE) inhibitor enalapril on postischemic contractile dysfunction. Anesthetized dogs underwent a 30-min occlusion of the left anterior descending coronary artery (LAD) followed by 2 h of reperfusion. Regional myocardial segment shortening in the ischemic LAD area was assessed by sonomicrometry. Myocardial segment shortening decreased in response to the LAD occlusion and remained decreased during 2-h reperfusion. The intravenous infusion of MCI-154 (0.1 or 0.3 micrograms/kg/min) initiated 10 min after occlusion and throughout reperfusion significantly improved the recovery of segment shortening. The alleviation of the postischemic contractile dysfunction by MCI-154 was augmented when the animals were treated with a bous injection of enalapril (0.3 mg/kg) 15 min before ischemia followed by an infusion of the drug (0.003 mg/kg/min). The pretreatment with enalapril alone (0.3 mg/kg plus 0.003 mg/kg/min or 1 mg/kg plus 0.01 mg/kg/min) did not alleviate the postichemic dysfunction, however, although it decreased systemic blood pressure (BP). Ischemic bed size, myocardial necrosis (by triphenyltetrazolium chloride staining), and collateral blood flow (by colored microspheres) were similar in all experimental groups. These results indicate that MCI-154 improves the postischemic contractile function of dog heart, whereas enalapril fails to improve it. ACE inhibitors may also augment the efficacy of cardiotonics on postischemic dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1989

Long-term expansion and sensitization of mechanosensory receptive fields in Aplysia support an activity-dependent model of whole-cell sensory plasticity.

Long-term changes in peripheral receptive field properties of mechanosensory/nociceptive neurons were investigated 1-3 weeks after noxious stimulation. Noxious stimuli consisted of a deep penetrating cut through the middle of the tail, strong electric shock applied to the tail surface, or a combination of deep and superficial tail stimulation. Action potentials evoked in the tail were monitored with intracellular electrodes in central somata of tail sensory neurons. Three long-term changes in receptive field properties were produced in the region of noxious stimulation: (1) mechanosensory thresholds decreased, (2) receptive field areas increased, and (3) the percentage of cells showing receptive field extension across the tail midline increased. Sizes and shapes of individual receptive fields did not vary during extensive testing of tails perfused with artificial seawater or during testing in cobalt solutions that block synaptic transmission. This stability of receptive field geometry, coupled with the observation that increased peripheral excitability in these cells does not increase receptive field size, suggests that long-term receptive field alterations involve growth of peripheral sensory processes. A model is proposed in which the signaling strength of the entire sensory cell increases in response to trauma of its receptive field. In this model long-term enhancement of central and peripheral sensory responsiveness is selectively triggered by activity dependent extrinsic modulation of the centrally located soma, which accelerates synthesis of growth-associated proteins used in collateral and regenerative sprouting of traumatized peripheral processes.

Adaptation, Physiological↗

PubMed2004

Cocaine- and amphetamine-regulated transcript peptide (CART) is a selective marker of rat granule cells and of human mossy cells in the hippocampal dentate gyrus.

Cocaine- and amphetamine-regulated transcript (CART) peptide immunocytochemistry was used to reveal cellular localization in the dentate gyrus and in Ammon's horn of the rat and human hippocampal formations. In the rat dentate gyrus, only granule cells were labeled, whereas in humans, only mossy cells of the hilar region expressed CART peptide immunoreactivity. In the rat, CART-positive granule cells were located at the molecular layer border of the granule cell layer and had no features that would distinguish them from other granule cells. The mossy fiber bundle was labeled in the hilus as well as along the entire CA3 area of Ammon's horn. In the human, CART-immunoreactive mossy cells displayed the characteristic thorny excrescences both on their somata and their main dendrites. Axon collaterals of mossy cells could be seen in the hilus and the main axons formed a dense band in the inner molecular layer of the dentate gyrus, suggesting that mossy cells are the principal source of the associational pathway. Granule cells of the dentate gyrus and pyramidal neurons of the human hippocampal formation were devoid of CART peptide immunoreactivity. A few labeled non-pyramidal cells and a large group of strongly immunostained axons of unknown origin were present in all layers of CA1-3. Granule cells are the main excitatory cell population of the dentate gyrus while mossy cells are in a key position in controlling activity of granule cells. The specific location of CART peptide in the dentate granule cells of rodents and in the mossy cells of the human hippocampus may indicate involvement of neuronal circuitry of the dentate gyrus in the memory-related effects of cocaine and amphetamine. Independently of its functional role, CART peptide can be used as a specific marker of human mossy cells and of the dentate associational pathway. The sensitivity of CART peptide to postmortem autolysis may restrict the use of this marker in surgically removed hippocampi or in human brains removed and fixed shortly after death.

Adult↗