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PubMed1993

Presynaptic inhibition of excitatory synaptic transmission mediated by alpha adrenergic receptors in area CA3 of the rat hippocampus in vitro.

We have investigated the action of norepinephrine (NE) on excitatory synaptic transmission in the hippocampus by recording from CA3 pyramidal cells in organotypic slice cultures. NE (5 microM) was found to decrease the amplitude of pharmacologically isolated EPSPs elicited with stimulation of mossy fibers or recurrent axon collaterals (mean decrease in EPSP amplitude, 44%). Desensitization was observed with repetitive applications. NE did not affect the sensitivity of CA3 cells to iontophoretically applied AMPA, and did not affect the amplitude distribution of TTX-resistant, miniature excitatory synaptic currents. These data suggest that NE acts at presynaptic receptors to decrease glutamate release. This action of NE was blocked by the alpha receptor antagonist phentolamine and the specific alpha 1 receptor antagonist prazosine, but not by the beta receptor antagonist timolol or the alpha 2 receptor antagonist idazoxan. Inhibition of EPSPs by NE was prevented by pretreatment of cultures with pertussis toxin, indicating that G-proteins couple these receptors to their effectors. Stimulation of protein kinase C with phorbol ester blocked the action of NE on EPSPs. This effect, as well as the desensitization of NE responses, was reduced by application of the protein kinase inhibitor staurosporin. Presynaptic inhibition of excitatory synaptic transmission, mediated by alpha adrenergic receptors, represents a novel modulatory action of NE in the hippocampus.

Action Potentials↗
PubMed1995

Adenosine triphosphate stress echocardiography in the detection of myocardial ischemia.

The purpose of this study was to assess feasibility and safety in the diagnosis of coronary artery in the diagnosis of coronary artery disease and myocardial ischemia using adenosine triphosphate (ATP) stress echocardiography. ATP, a product of human myocardial tissue, is more potent than adenosine in increasing coronary blood flow. Like adenosine, ATP also has a short half-life (<10 s). Left ventricular echocardiograms were recorded during step-wise infusions of ATP in 86 patients who underwent coronary angiography and stress thallium 201 scintigraphy. No serious complications occurred with ATP infusion and most of the side effects were mild and transient. Significant coronary artery disease (>75% diameter stenosis) was present in 34 of 48 patients who had normal echocardiograms at rest. The sensitivity and specificity of ATP-induced wall motion abnormalities for coronary artery disease was 65% (22 of 34) and 100% (14 of 14), respectively. The sensitivity was 50% (10 of 20) in those with one-vessel disease and 86% (12 of 14) in those with multivessel disease (P < .05). In patients with normal echocardiograms at rest and without prior myocardial infarction, the sensitivity of ATP stress echocardiography for the detection of myocardial ischemia assessed by 201Tl single proton emission computed tomography was 58%, with a specificity of 76%, and a diagnostic accuracy of 66%. The sensitivity was 43% in those with one-vessel disease, and 86% in those with multivessel disease (P = .05). In patients with prior myocardial infarction, the sensitivity of ATP stress echocardiography for the detection of viable but jeopardized myocardium was 81%, with a specificity of 91%. The patients with well-developed collateral circulation had a higher incidence of developing wall motion abnormality than those without collaterals (70% v 40%, P < .01). ATP stress echocardiography is valuable for the assessment of coronary artery disease in patients with multivessel disease, coronary collaterals, and with prior myocardial infarction.

Adenosine Triphosphate↗
PubMed1991

Venous obstruction: an analysis of one hundred thirty-seven cases with hemodynamic, venographic, and clinical correlations.

One hundred thirty-seven limbs with venous obstruction were analyzed. The arm/foot venous pressure differential and reactive hyperemia tests were found to be useful techniques to diagnose and grade venous obstruction. Traditional techniques including venography and ambulatory venous pressure are inferior in this regard. The newer techniques have provided newer insights in venous obstruction which are detailed herein. The hand-held Doppler was surprisingly very sensitive in grade I as well as in more severe forms of obstruction. Neither anatomic locale of obstruction nor its extent determined hemodynamic severity. Extensive proximal lesions could be hemodynamically mild, and conversely distal crural obstructions and single segment lesions could be hemodynamically severe. Phlebographic appearance was a poor index of collateralization. The paradoxical venous pressure response to the reactive hyperemia test in grade IV obstruction was found to be due to suppression or delay of the reactive hyperemia response itself in the presence of severe venous obstruction. The pain of venous claudication may be related to this phenomenon. Skin ulceration in the presence of venous obstruction was related to the associated reflux rather than the hemodynamic severity of the obstruction itself. The Linton procedure was found to be useful in treating such skin ulcerations. After perforator disruption, obstruction did not become hemodynamically worse, but reflux as measured by the Valsalva test improved with ulcer healing. The improvement in reflux related to Valsalva offers for the first time a hemodynamic rationale for the Linton procedure.

Arm↗
PubMed2007

Collateralization of the tectonigral projection with other major output pathways of superior colliculus in the rat.

Dopaminergic (DA) neurons exhibit a short-latency, phasic response to unexpected, biologically salient stimuli. The superior colliculus (SC) is also sensitive to such stimuli and sends a projection directly to DA-containing regions of the ventral midbrain. Recent evidence suggests that the SC is a critical relay for transmitting short-latency visual information to DA neurons. An important question is whether the ventral midbrain is an exclusive target of tectonigral neurons, or whether the tectonigral projection is a collateral branch of other tectofugal pathways. Double-label retrograde anatomical tracing techniques were used to address this issue. Injections of either Diamidino Yellow or Fluorogold into substantia nigra pars compacta (SNc) were combined with larger injections of True Blue into one of the following efferent projections of the SC: 1) target regions of the ipsilateral ascending projection to the thalamus; 2) the crossed descending tecto-reticulo-spinal pathway; 3) target structures of the ipsilateral descending projection; and 4) the contralateral superior colliculus. Moderate numbers of double-labeled neurons were observed following combined injections into substantia nigra and individual nuclei in the thalamus (ventromedial nucleus, 21.3%; central lateral, 18.4%; parafasicular nucleus 6.0%). Much less double-labeling was associated with injections into either of the descending projections (crossed, 1.0-3.2%; uncrossed, 0.2-2.7%) or the contralateral SC (0.7-1.9%). These results suggest: i) the SC may provide a coordinated input concerning the occurrence of unpredicted sensory events to both the substantia nigra and striatum (via the thalamus); and ii) few gaze-related motor signals are simultaneously relayed to DA-containing regions of the ventral midbrain.

Animals↗
PubMedDate not supplied

House dust mite sensitivity is a factor in chronic urticaria.

BACKGROUND: Chronic urticaria is one of the perplexing problems faced by clinicians. There are a few reports associating house dust mite sensitivity with chronic urticaria, based upon the patient's history as well as intradermal skin testing and in vitro analysis. AIMS: To investigate the possible association between house dust mite sensitivity and chronic urticaria. METHODS: In this case control study three groups of patients were enrolled. Group I: Chronic urticaria (73 subjects). Group II: Chronic urticaria with collateral allergic disorders (49 subjects). Group III: Normal subjects without chronic urticaria or other allergies (25 subjects). All the patients underwent skin prick testing with antigens of the house dust mite, Dermatophagoides pteronyssinus (DP) and Dermatophagoides farinae (DF), with positive and negative controls. RESULTS: Among the patients with chronic urticaria, 78/122 (64%) patients had skin sensitivity to house dust mites. Out of these, 39/73 (53%) had chronic urticaria alone and 39/49 (79%) had chronic urticaria with other associated allergies. Among the normal control subjects, 7/25(28%) reacted positively to house dust mites. CONCLUSION: This study suggests a possible association of house dust mite sensitivity with chronic urticaria.

Adult↗
PubMedDate not supplied

Myocardial ischemia in Kawasaki disease: evaluation with dipyridamole stress technetium 99m tetrofosmin scintigraphy.

BACKGROUND: The coronary artery abnormalities in Kawasaki disease (KD) often cause myocardial ischemia. Previous publications have described the use of thallium 201 myocardial perfusion imaging to determine the extent of ischemia in patients with KD. The technetium perfusion agents offer better resolution and may offer additional information about ventricular function in these patients. This study was performed to evaluate myocardial perfusion in patients with KD through use of technetium 99m tetrofosmin (TF) in conjunction with dipyridamole vasodilator stress. METHODS AND RESULTS: Eighty-six patients with KD aged 11.5 +/- 6.4 years and 20 age-matched control patients without heart disease were studied. Among 86 patients with KD, significant coronary artery stenosis (>or=75%) was observed in 20, coronary aneurysm without stenosis in 37, and no coronary lesions in 29. After administration of high-dose dipyridamole infusion (0.70 mg/kg), 74 to 370 MBq TF was injected and 148 to 740 MBq TF was injected at rest 4 hours later. Single photon emission computed tomography images were obtained more than 30 minutes after TF injection. Regional myocardial hypoperfusion was observed in 18 patients who had coronary artery stenosis of 75% or greater (sensitivity, 90%, and specificity, 100%). Two patients did not demonstrate ischemic changes in coronary artery stenosis in group I; one had good collateral flow. There were no TF injection-related complications. CONCLUSIONS: Tetrofosmin myocardial perfusion imaging can detect regional hypoperfusion in children with KD.

Adolescent↗
PubMed1998

Semiquantitative reverse transcription-polymerase chain reaction analysis of mRNA for growth factors and growth factor receptors from normal and healing rabbit medial collateral ligament tissue.

Growth factors and their receptors play an essential role in the development, maturation, and response to injury of all tissues. A number of studies have explored the possibility of improving ligament healing with exogenous growth factors. However, limited data is available regarding the endogenous growth factor network in ligaments on which any exogenous growth factors must impact. The purpose of this study was to assess the endogenous growth factor network with molecular techniques. By the sensitive reverse transcription-polymerase chain reaction technique, transcripts for a number of growth factors and receptors were detected with RNA isolated from normal and healing rabbit medial collateral ligament tissues. These include transforming growth factor-beta1, insulin-like growth factors I and II, basic fibroblast growth factor, endothelin-1, and the receptors for insulin and insulin-like growth factor II. Semiquantitative reverse transcription-polymerase chain reaction analysis of RNA from normal and scar tissues from the medial collateral ligament revealed that the levels of several transcripts were elevated in the scar tissue. It was not possible to confirm biological activity because of the hypocellularity of the tissues; however, the results obtained indicate that the reverse transcription-polymerase chain reaction approach to defining the endogenous growth factor-receptor phenotype is feasible, and further definition should contribute to the development of rational approaches to exogenous therapy to improve healing.

Animals↗
PubMed1995

Pancreatic cancer staging. Endoscopic ultrasonography criteria for vascular invasion.

Endoscopic ultrasound (EUS) is the most sensitive imaging test available for examining the pancreas and associated structures. Small (< 2 cm) pancreatic malignancies can be detected with accuracy rates of more than 90%. Several EUS criteria have been proposed for their ability to diagnose malignant venous invasion. Although obstruction of a mesenteric vein and the resulting venous collaterals is a specific sign of unresectability, it is a rather insensitive parameter. As an alternative, signs of venous wall invasion, such as "irregular wall" have been proposed as being sensitive (67%-100%) and specific (100%) for malignant invasion of mesenteric veins. EUS appears to be particularly sensitive for detecting invasion of the portal and splenic veins. In contrast, the superior mesentera veins are more difficult to image with EUS and the results of staging of pancreatic masses demonstrate poor sensitivity (12%-17%) for detecting vascular invasion of the superior mesenteric vein.

Endoscopy↗
PubMed1994

Marked reduction in myocardial infarct size due to prolonged infusion of an antioxidant during reperfusion.

BACKGROUND: There has been controversy about whether early reperfusion of myocardial infarcts causes further necrosis mediated by reactive oxygen species or other mechanisms. Unequivocal evidence that therapeutic agents given only during reperfusion can prevent, rather than delay or modify, injury has been sparse. Failure to account for variables, such as collateral blood flow, that influence infarct size independently and attempts to measure infarct size too early in reperfusion may have limited the sensitivity and specificity of some previous studies. METHODS AND RESULTS: After 90 minutes of coronary occlusion and 48 hours of reperfusion in a canine model, we examined the effect on infarct size of intravenous infusion of N-(2-mercaptopropionyl)-glycine (MPG), a diffusible antioxidant. Infarct size and region at risk were measured by post-mortem dual perfusion with triphenyl tetrazolium chloride and Evans blue dyes, and regional myocardial blood flow was measured with radioactive microspheres. Infusion of MPG 100 mg.kg-1.h-1, beginning either 15 minutes before the onset of reperfusion or 30 minutes after the onset of reperfusion and continued until 4 hours of reperfusion and followed by an intramuscular dose, reduced infarct size, normalized for both region at risk and the level of collateral blood flow, by 60% and 45%, respectively. When infusion of MPG was limited to the last 15 minutes of ischemia and the first hour of reperfusion only, the normalized infarct size was reduced by 26%. Heart rate, blood pressure, and their product did not differ among the four groups studied. The plasma half-time of MPG was < 10 minutes. In in vitro experiments MPG was a scavenger of hydrogen peroxide but not of superoxide radical. CONCLUSIONS: After 90 minutes of coronary ligation, infusion of the diffusible hydrogen peroxide scavenger, MPG, for several hours, beginning as late as 30 minutes after the onset of reperfusion, substantially reduced infarct size measured 48 hours later. In this model, necrosis caused by processes during reperfusion may be more extensive than necrosis caused by ischemia alone. Since infusion of this agent for only the first hour of reperfusion was considerably less effective, it appears that most of the oxidant injury leading to necrosis occurred after the first 60 minutes but within the first 4 hours of reperfusion.

Animals↗
PubMed1999

Afferent projections of infrared-sensitive sensilla in the beetle Melanophila acuminata (Coleoptera: Buprestidae).

Beetles of the genus Melanophila are able to detect infrared radiation by using specialized sensilla in their metathoracic pit organs. We describe the afferent projections of the infrared-sensitive neurons in the central nervous system. The axons primarily terminate in the central neuropil of the fused second thoracic ganglia where they establish putative contacts with ascending interneurons. Only a few collaterals appear to be involved in local (uniganglionic) circuits. About half of the neurons send their axons further anterior to the prothoracic ganglion. A subset of these ascend to the subesophageal ganglion, and about 10% project to the brain. Anatomical similarities suggest that the infrared-sensitive neurons are derived from neurons supplying mechanosensory sensilla. The arborization pattern of the infrared afferents suggests that infrared information is processed and integrated upstream from the thoracic ganglia.

Afferent Pathways↗
PubMed1987

Recognising stroke prone patients with a poor collateral circulation.

The prognosis in carotid disease is extremely variable and is influenced by the availability of collateral circulation. This study investigates the possibility of recognising patients with a poor collateral potential by using non-invasive tests. Preoperative OPG and EEG were compared with intraoperative EEG during test clamping in 208 carotid endarterectomies. Clamping ischaemia occurred in 29 patients (14%). Preoperative EEG had a sensitivity of 62% and a specificity of 82%. OPG showed a sensitivity of 96% and a specificity of 54%. Combined OPG and EEG resulted in a sensitivity of 93% and a specificity of 73%. Both tests are safe and easy to perform and interpret. These techniques can be used to identify those patients with carotid stenosis who have an increased risk of stroke due to a poor collateral circulation and may help to refine the indications for carotid endarterectomy.

Brain Ischemia↗
PubMed2001

Mechanisms of citric acid-induced bronchoconstriction.

In asthma patients, microaspiration of acid into the lower airways (ie, airway acidification) causes such respiratory responses as cough and bronchoconstriction. The mechanism of bronchoconstriction induced by airway acidification is unknown, although evidence is emerging that increasing proton concentrations in airway tissues can activate a subpopulation of primary sensory neurons, so-called capsaicin-sensitive primary sensory neurons, that contain such neuropeptides as the tachykinins substance P (SP) and neurokinin A (NKA). Protons activate a capsaicin-operated channel/receptor, located in the afferents of capsaicin-sensitive neurons, with the subsequent opening of ion channels that are permeable to sodium, potassium, and calcium ions. This event initiates a propagated action potential that antidromically depolarizes collateral fibers and triggers neuropeptide release from nerve fiber varicosities. The tachykinins SP and NKA, released from terminals of primary sensory neurons in peripheral tissues, cause all the major signs of inflammation (neurogenic inflammation) by means of activation of NK(1) and NK(2) receptors. Exposure of the airways to acidic solutions stimulates sensory nerve endings of capsaicin-sensitive sensory neurons and causes different airway responses, including bronchoconstriction. Recently, the NK(2), and to a lesser extent the NK(1), receptors have been shown to be involved with citric acid-induced bronchoconstriction in the guinea pig, which is in part mediated by endogenously released bradykinin. Tachykinins and bradykinin, released by airway acidification, could also modulate citric acid-induced bronchoconstriction by their ability to subsequently release the epithelially derived bronchoprotective nitric oxide (NO). Further study with selective tachykinin NK(1) and NK(2) agonists demonstrated that only the septide-insensitive tachykinin NK(1) receptor releases NO. Thus, bronchoconstriction induced by citric acid inhalation in the guinea pig, mainly caused by the tachykinin NK(2) receptor, is counteracted by bronchoprotective NO after activation of bradykinin B(2) and tachykinin NK(1) receptors in airway epithelium. If a similar mechanism is involved in the pathogenesis of bronchial asthma associated with gastroesophageal reflux in the respiratory tract, new therapeutic strategies should be investigated.

Airway Resistance↗
PubMed1986

Morphology and physiology of abducens motoneurons and internuclear neurons intracellularly injected with horseradish peroxidase in alert squirrel monkeys.

Axons of abducens motoneurons and internuclear neurons were penetrated with HRP-filled glass microelectrodes in alert squirrel monkeys. The firing rate of these axons and spontaneous eye movements were recorded and the axons were then injected with HRP for subsequent visualization of the recorded cells. Soma-dendritic and axon and axonal terminal morphology were studied for possible correlation with firing frequency. The physiology of squirrel monkey abducens neurons is qualitatively similar to their counterparts in the rhesus monkey and the cat, being primarily correlated with the position and velocity of the eyes. The locations of moto- and internuclear neurons are similar in the squirrel monkey and cat as are the axonal projections and terminals. However, squirrel monkey abducens cells are smaller than their feline counterparts and have dendrites that are confined to the cellular borders of the abducens nucleus. The size of the soma and proximal dendrites of moto- and internuclear neurons are poorly correlated with either their threshold for recruitment or their tonic eye position sensitivity. However, cells with smaller dendritic trees tended to have higher saccadic eye velocity sensitivity than those with larger trees. Three types of internuclear neurons were distinguishable upon the basis of their axon collaterals. All cells terminated within the medial rectus subdivision of the oculomotor nucleus. One class of cells did not give rise to collaterals before projecting to the oculomotor nucleus and the other classes gave rise to collaterals that terminated in the intermediate and/or caudal interstitial nuclei of the median longitudinal fasciculus. Within the IIIrd nucleus internuclear terminations were usually confined to a single subgroup of medial rectus motoneurons.

Abducens Nerve↗
PubMed1995

Heterogeneity of contraction-induced effects in neurons of the cat dorsal spinocerebellar tract.

1. Clarke's column neurons of the dorsal spinocerebellar tract (DSCT) were recorded intracellularly in anaesthetized cats during weak sustained contractions of triceps surae (TS) produced by direct electrical stimulation of the muscle. 2. Of 145 DSCT neurons, 77 (53%) were contraction sensitive suggesting that information about weak contraction of a limited number of muscles is widely distributed among DSCT neurons. Four types of effects were observed in individual neurons during TS contractions. 3. In the first group of 11 DSCT neurons (14% of the contraction-sensitive cells), the effect was excitation persisting throughout the duration of contractions. These responses were ascribed to actions of afferents from contraction-activated tendon organs. 4. In a second group of 15 neurons (20% of the contraction-sensitive cells), quickly declining excitatory potentials were recorded during sustained TS contractions. By analogy with previous observations of contraction-induced effects in motoneurons, the decline of excitation might be explained by contraction-induced presynaptic inhibition of group I afferents in Clarke's column. 5. Declining inhibitions, resembling those previously observed in homonymous and synergic motoneurons, were recorded in 49% of contraction-sensitive DSCT neurons. This appears in keeping with the fact that interneurons mediating Ib inhibition to motoneurons project axon collaterals to DSCT neurons. Presynaptic inhibition of Ib fibres might therefore cause parallel reductions of inhibitory potentials in motoneurons and in DSCT neurons. 6. In a final group of 13 neurons, mixed excitatory and inhibitory effects were observed during TS contractions. Such DSCT neurons might monitor the excitability of Ib interneurons by integration of information about input to and output from these neurons. 7. The non-uniform patterns of DSCT responses to TS contractions suggest complex processing of information on ankle extensor activity in cerebellum. Phasic signalling of contraction onset is observed in many DSCT neurons while others carry messages about duration and strength of contraction.

Animals↗
PubMed1994

Mechanism of early anoxia-induced suppression of the GABAA-mediated inhibitory postsynaptic current.

1. We investigated the mechanism of hypoxia-induced depression of gamma-aminobutyric acid-A (GABAA)-mediated inhibitory postsynaptic currents (IPSCs) in CA1 neurons of hippocampal slices from 21- to 28-day-old rats. Cells were examined by whole-cell patch-clamp recording and hypoxia was induced by switching perfusion of the slice from oxygenated artificial cerebral spinal fluid (ACSF) to ACSF saturated with 95% N2-5% CO2. 2. Synaptic responses evoked by stimulation of the Schaffer collateral-commissural projection at a fixed holding potential (VH = -60 mV) during anoxia revealed that the IPSC appeared more sensitive than the excitatory postsynaptic current to anoxia-induced depression. All subsequent studies examined the GABAA-mediated IPSC synaptic responses in isolation by direct stimulation of GABA interneurons in the stratum radiatum in the presence of extracellular 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP) (20 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (50 microM) to block glutamatergic currents and intracellular QX-314 (lidocaine N-ethyl bromide, 1 mM) to block GABAB-mediated currents. When studied in this manner (VH = -60 mV) the GABAA-mediated IPSC appeared to change from an outward to inward current after exposure to anoxia. 3. The current-voltage relationship of GABAA-mediated IPSCs revealed that these changes resulted from a positive shift in the IPSC reversal potential without a significant change in the conductance. Thus under patch clamp apparent IPSC inhibition may result from a decrease in the extracellular concentration of chloride ions. Similar findings were observed with micropipettes that contained high intracellular chloride concentrations. 4. Miniature spontaneous IPSCs were examined in the presence of tetrodotoxin (1 microM) with micropipettes containing high intracellular chloride concentrations. The miniature IPSCs (mIPSCs) appeared as spontaneous transient inward currents. Consistent with an anoxia-induced decrease in extracellular chloride, the mean amplitude of the mIPSCs increased after the onset of anoxia. A significant decrease in rise and decay time was also noted during anoxia. The frequency of the mIPSCs also increased by approximately 300%. 5. The resting input resistance of the cells was examined by measuring the current resulting from a 20-mV hyperpolarizing pulse. A significant reduction in resistance was observed 2 min after the onset of anoxia. This still occurred, although to a lesser degree, in the presence of glutamatergic blockers (20 microM CPP plus 50 microM CNQX). In the presence of both GABAergic (picrotoxin, 100 microM) and glutamatergic blockers no significant reduction in resting input resistance was apparent after 2 min of anoxia.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed2006

[What electroneuromyographic criteria are required for the diagnosis of amyotrophic lateral sclerosis?].

Electroneuromyography is essential for the diagnostic of amyotrophic lateral sclerosis. The aim of conventional needle examen is to detect peripheral motoneuron involvement by the identification of active and chronic diffuse neurogenic activities. This brings up the problem of the selection of the muscle to test to enhance the sensitivity of the exam. Recent techniques permit to study the reorganization of the motor units more precisely. Motoneuron loss is appraised by several methods for macro-EMG estimates of the number of motor units. The collateral reinnervation can be evaluated by single fibre EMG. The other main objective is to detect conduction abnormalities. These lead to differential diagnoses of pure motor neuropathy with conduction blocks. The different prognostic value of these different conditions required defining both sensitive and specific electrophysiological diagnostic criteria.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Cholinergic function in the hippocampus of juvenile rats chronically deprived of NGF.

Intracellular and extracellular recordings were used to assess the cholinergic function in hippocampal slices from juvenile rats chronically deprived of NGF. NGF was neutralised by implanting into the lateral ventricle of postnatal (P) day 2 rats, alphaD11 hybridoma cells (secreting monoclonal antibodies specific for NGF). Parental myeloma cells (P3U) were used as controls. At P15-P18, slow cholinergic EPSPs could be elicited in cells from both alphaD11- and P3U-treated rats. However, slices from alphaD11-implanted rats exhibited a 50% reduction in acetylcholine release following stimulation of cholinergic fibres. This effect was associated to a significant increase in the sensitivity of pyramidal cells to carbachol, as suggested by the shift to the left of the dose/response curve. This may reflect a compensatory mechanism for the reduced efficacy of cholinergic innervation in NGF-deprived rats. In both alphaD11- and P3U-treated rats, carbachol was able to induce a similar concentration-dependent depression of the field EPSPs, evoked by Schaffer collateral stimulation, suggesting that presynaptic muscarinic receptors were not altered. In rats implanted with alphaD11 cells at P15 and sacrificed at P21-P24, no changes in the sensitivity to carbachol were found. At this developmental stage, no differences in acetylcholine release were observed between P3U- and alphaD11-treated animals. These results provide physiological evidence for a regulatory role of NGF in the cholinergic function of the hippocampus during postnatal development.

Acetylcholine↗
PubMed2000

Talk is cheap: measuring drinking outcomes in clinical trials.

OBJECTIVE: To evaluate the correspondence among measures of self-reported drinking, standard biological indicators and the reports of collateral informants, and to identify patient characteristics associated with observed discrepancies among these three sources of research data. METHOD: Using data collected from a large-scale clinical trial of treatment matching with alcoholics (N = 1,726), these three alternative outcome measures were compared at the time of admission to treatment and at 12 months after the end of treatment. RESULTS: Patient self-reports and collateral reports agreed most (97.1%) at treatment admission when heavy drinking was unlikely to be denied. In contrast, liver function tests were relatively insensitive, with positive serum gamma-glutamyl transpeptidase (GGTP) values obtained from only 39.7% of those who admitted to heavy drinking. At 15-month follow-up the correspondence between client self-report and collateral report decreased to 84.7%, but agreement with blood chemistry values increased to 51.6%. When discrepancies occurred, they still indicated that the client' s self-report is more sensitive to the amount of drinking than the biochemical measures. Patients who presented discrepant results tended to have more severe drinking problems, more previous treatments, higher levels of pretreatment drinking and significantly greater levels of cognitive impairment, all of which could potentially interfere with accurate recall. CONCLUSIONS: In clinical trials using self-selected research volunteers, biochemical tests and collateral informant reports do not add sufficiently to self-report measurement accuracy to warrant their routine use. Resources devoted to collecting these alternative sources of outcome data might be better invested in interview procedures designed to increase the validity of self-report information.

Adult↗