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Biomedical subjects

E Bacon

Publications and source records attributed to E Bacon.

18 recordsLinked to original sources

Effects of the amnesic drug lorazepam on complete and partial information retrieval and monitoring accuracy.

RATIONALE: In Koriat's accessibility model (Koriat, Psychol Rev, 100:609-639, 1993; Koriat, J Exp Psychol Gen, 124:311-333, 1995), when a person fails to recall a required target, he or she can nevertheless provide some partial information about the target. Moreover, individuals are able to provide feeling-of-knowing (FOK) judgments about the availability of the target in memory. The cues for the FOK evaluations reside in the products of the retrieval process itself. It was shown that the benzodiazepine lorazepam drug induces some impairment of memory. OBJECTIVES: The effects of the amnesic benzodiazepine lorazepam on the total and partial recall of recently learned material and on FOK ratings were investigated in healthy volunteers. METHODS: Twenty-eight healthy volunteers participated in the study: 14 of these received a capsule containing lorazepam (0.038 mg/kg) and 14 a placebo capsule. The material to be learned consisted of four-letter nonsense tetragrams with each letter providing partial information with regard to the four-letter target (Koriat, Psychol Rev, 100:609-639, 1993). RESULTS: The number of incorrect letters reported was higher for the lorazepam than for the placebo condition. The FOK magnitude was higher for the placebo participants than for the lorazepam participants. The predictive value of FOK for recognition was preserved by the drug. CONCLUSION: When studying four-letter nonsense letter strings, lorazepam participants present an impairment of episodic short-term memory and the drug has an effect on FOK estimates but not on the predictive accuracy of the FOK. The accessibility hypothesis of FOK was confirmed in this study and seems to retain some validity even under the effect of an amnesic drug.

Adult↗

Dimeric W3SO3 cluster complexes: synthesis, characterization, and potential applications as X-ray contrast agents.

Our continued research on the use of heavy metal cluster complexes as a new class of X-ray contrast agents in medical diagnostic imaging is described. A series of 2:3 cluster-ligand complexes, [(W(IV)3SO3)2L3]4- (L = linear polyaminopolycarboxylate ligands), were isolated from the reaction of aqua ion [W(IV)3SO3(H2O)9]4- (prepared in large quantities through an improved literature process) with respective ligands in refluxing DMF. The salts of [(W(IV)3SO3)2L3]4- complex anions were fully characterized using routine techniques such as elemental analysis, MS, HPLC, UV-vis, IR, and NMR. The solid structures of two complex anions, [(W(IV)3SO3)2(PDTA)3]4- and [(W(IV)3SO3)2(HO-PDTA)3]4-, were determined by X-ray crystallography. They are the first examples wherein two W(IV)3SO3 clusters are complexed and linked by three ligands that contain two terminal iminodiacetate (bis-IDA) groups. Complexation of the unstable aqua ion [W(IV)3SO3(H2O)9]4- with ligands has imparted desired biological compatibility to the tungsten metal cluster. These complexes are stable and highly soluble in H2O. The potential utility of such tungsten cluster complexes as X-ray contrast agents was evaluated in both in vitro and in vivo animal studies. In addition, the syntheses of several new linear polyaminopolycarboxylate ligands used in this study are reported.

Animals↗

Consciousness in schizophrenia: a metacognitive approach to semantic memory.

Recent studies have shown that schizophrenia may be a disease affecting the states of consciousness. The present study is aimed at investigating metamemory, i.e., the knowledge about one's own memory capabilities, in patients with schizophrenia. The accuracy of the Confidence level (CL) in the correctness of the answers provided during a recall phase, and the predictability of the Feeling of Knowing (FOK) when recall fails were measured using a task consisting of general information questions and assessing semantic memory. Nineteen outpatients were paired with 19 control subjects with respect to age, sex, and education. Results showed that patients with schizophrenia exhibited an impaired semantic memory. CL ratings as well as CL and FOK accuracy were not significantly different in the schizophrenic and the control groups. However, FOK ratings were significantly reduced for the patient group, and discordant FOK judgments were also observed more frequently. Such results suggest that FOK judgments are impaired in patients with schizophrenia, which confirms that schizophrenia is an illness characterized by an impaired conscious awareness of one's own knowledge.

Adult↗

Plasma membrane NADH oxidase of maize roots responds to gravity and imposed centrifugal forces.

NADH oxidase activities measured with excised roots of dark-grown maize (Zea mays) seedlings and with isolated plasma membrane vesicles from roots of dark-grown maize oscillated with a regular period length of 24 min and were inhibited by the synthetic auxin 2,4-dichlorophenoxyacetic [correction of dichorophenoxyacetic] acid. The activities also responded to orientation with respect to gravity and to imposed centrifugal forces. Turning the roots upside down resulted in stimulation of the activity with a lag of about 10 min. Returning the sections to the normal upright position resulted in a return to initial rates. The activity was stimulated reversibly to a maximum of about 2-fold with isolated plasma membrane vesicles, when subjected to centrifugal forces of 25 to 250 x g for 1 to 4 min duration. These findings are the first report of a gravity-responsive enzymatic activity of plant roots inhibited by auxin and potentially related to the gravity-induced growth response.

2,4-Dichlorophenoxyacetic Acid↗

Defective relationship between subjective experience and behavior in schizophrenia.

OBJECTIVE: The relationship between subjective experience and behavior abnormalities in schizophrenia was investigated. METHOD: Eighteen patients with schizophrenia and 18 normal comparison subjects completed a general knowledge task with two incentive conditions to measure monitoring effectiveness, control sensitivity, and response criterion setting. RESULTS: The patients' levels of monitoring effectiveness and control sensitivity were lower than those of the comparison subjects. The effect of incentives on response criterion values was similar in the two groups. CONCLUSIONS: Patients were impaired in subjectively assessing the correctness of their knowledge, and their behavior was less determined by subjective experience than that of normal subjects. The patients' intact sensitivity to incentives has implications for cognitive remediation.

Adult↗

Confidence level and feeling of knowing for episodic and semantic memory: an investigation of lorazepam effects on metamemory.

The effects of lorazepam (0.026 or 0.038 mg/kg), a benzodiazepine, and of a placebo on metamemory, i.e. knowledge about one's own memory capabilities, were investigated in 36 healthy volunteers. Accuracy of confidence levels (CL) in the correctness of recalled answers and accuracy of feeling of knowing (FOK) the answers when recall fails were measured using a sentence memory task assessing episodic memory and a task consisting of general information questions and assessing semantic memory. Lorazepam impaired episodic memory. Unexpectedly, it also impaired performance in both the recall and recognition phases of the task assessing semantic memory, suggesting that it decreased the ability to distinguish between correct and incorrect information. In episodic memory, lorazepam 0.038 mg/kg-treated subjects exhibited an impaired CL accuracy, compared to placebo-treated subjects, and their FOK accuracy was at chance. In semantic memory, their overall CL and FOK accuracy was apparently spared. However, these subjects selectively overestimated their CL judgements for incorrect answers; moreover, secondary analyses showed that FOK accuracy for a subset of low-accuracy items was virtually nil. These results suggest that lorazepam impairs metamemory for both episodic and semantic memory.

Adult↗

[Memory and benzodiazepines].

Benzodiazepines (BZs) affect acquisition of new information, while retrieval of already learned information is unimpaired. The variability of this effect is important and depends on the nature of the BZ, its dose, the route of administration and the susceptibility of the subject taking the drug. This last factor depends itself on the anxiety level, the age, and a less known idiosyncratic susceptibility of the patient. Finally, there is probably a partial tolerance for the amnestic action of BZs, which explains the fact that the most dramatic amnesias have been described after administration of a single dose of BZ, taken by a patient unaccustomed to BZs. The value of pharmacocinetic and pharmacodynamic characteristics in predicting cognitive impairment remains misunderstood, even though in clinical practice the greatest amnestic effects have been described with short-acting BZs. The interest of studying BZs induced amnesia rely upon several arguments: first, it can be an harmful side-effect, which could be avoided or at least predicted by a better knowledge of BZs and the synthesis of new and more specific drugs; secondly it is an interesting model of organic amnesia, which could allow a better understanding of normal memory.

Adult↗

Cyclic GMP potentiation by WIN 58237, a novel cyclic nucleotide phosphodiesterase inhibitor.

The objectives of this study were to determine the potency and selectivity of the structurally novel cyclic nucleotide phosphodiesterase (PDE) inhibitor, WIN 58237 (1-cyclopentyl-3-methyl-6-(4- pyridyl)pyrazolo[3,4-d]pyrimidin-4-(5H)-one), and to determine if this compound possesses cyclic GMP (cGMP) PDE inhibitory activity in vitro and in vivo. WIN 58237 is a competitive inhibitor of cGMP PDE V from canine aorta, with a Ki value of 170 nM. It is a relatively less potent inhibitor of calmodulin-sensitive PDE I and cGMP-inhibitable cyclic AMP PDE III; but does inhibit cyclic AMP PDE IV with an IC50 value of approximately 300 nM. In vitro, WIN 58237 is a functional cGMP PDE inhibitor at submicromolar concentrations as evident by potentiation of both sodium nitroprusside- and atrial natriuretic factor-mediated vasorelaxation of contracted, endothelial-denuded rat aortic rings. Moreover, WIN 58237 possesses vasorelaxant activity in the presence of an intact endothelium or nitric oxide. Similar results are evident in vivo, as WIN 58237 (0.3-3.0 mg/kg i.v.) decreases mean arterial pressure in conscious spontaneously hypertensive rats with an associated increase in vascular (aortic) cGMP content in vivo. Both the decrease in mean arterial blood pressure and increase in aortic cGMP content are attenuated by the nitric oxide synthase inhibitor, N omega-nitro-l-arginine. However, WIN 58237 may possess an additional depressor mechanism of action. WIN 58237 restores vasorelaxation responsiveness to nitroglycerin in vitro and in vivo in models of vascular tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases↗

[3H]muscimol and [3H]flunitrazepam binding sites in the developing cerebellum of mice treated with methylazoxymethanol at different postnatal ages.

Two models of perturbed cerebellar ontogenesis were obtained by a single administration of methylazoxymethanol (MAM), a potent antimitotic agent, to mouse pups either on the day of birth (MAM0 mice) or at postnatal day 5 (MAM5 mice). The alterations of the cerebellar GABAergic system were studied by measuring glutamic acid decarboxylase activity, [3H]muscimol binding sites, which are known to be concentrated in the GABAA receptors in the internal granular layer, and [3H]flunitrazepam binding sites, which are more abundant in the molecular layer. The primary target of the antimitotic agent are the precursors of the glutamatergic and GABAceptive granule cells. In both models GABAergic structures, as revealed by GAD activity measurements, appear to be relatively spared, and recovery of granule cell numbers occurs during development in MAM5 mice. In MAM treated mice the number of [3H]muscimol binding sites (on a per cerebellum basis) decrease as the number of granule cells decrease, although some recovery occurred in MAM5 mice, but not in MAM0 mice. In MAM5 mice, [3H]flunitrazepam binding sites (on a per cerebellum basis) were relatively unaffected, while they were decreased significantly, but to a lesser extent than [3H]muscimol binding sites, in MAM0 animals. The more significant reduction of granule cell numbers and the cytoarchitectural disruption resultant from the more precocious application of the antimitotic appear responsible for the significant alteration and lack of recovery in MAM0 mice.

Animals↗

Differential ontogenesis of type I and II benzodiazepine receptors in mouse cerebellum.

The ontogeny of type I and type II benzodiazepine binding sites was studied in mouse cerebellum by displacement of [3H]flunitrazepam binding by zolpidem, a ligand specific for the type I sites. Type I binding sites predominate throughout development and in the adult while type II sites account for 25% of total cerebellar benzodiazepine binding sites at birth and, during development, decrease to 10% or less in the adult. On a per cerebellum basis type II sites increase during the first postnatal week and then remain at a steady level while type I sites increase until adulthood. These results may indicate a specific localization of the type II sites (and of the corresponding alpha-protein subunits in the GABA/benzodiazepine receptor complex) in structures already present at birth and developing during a short early postnatal period. The affinity of zolpidem for its high affinity (type I) binding sites increases during cerebellar ontogeny, this increase possibly indicates an epigenetic (post-translational) 'maturation' process of the corresponding receptor molecule. Hill numbers indicate the existence of an additional binding site heterogeneity greater during development but still present in the adult; probably this is to be related to the simultaneous presence of different 'maturation' stages during development and with a certain variety of the final products.

Aging↗

Stoichiometry of muscimol and benzodiazepine binding sites in developing mouse cerebellum.

The ontogeny of high affinity GABAA and central benzodiazepine receptors in the mouse cerebellum was investigated by measuring [3H]muscimol and [3H]flunitrazepam binding to membrane preparations during postnatal development. In the P2 fraction, [3H]muscimol binding was much more abundant than [3H]flunitrazepam binding at all ages. [3H]muscimol Bmax exhibited a peak around postnatal day 25 while [3H]flunitrazepam binding did not follow a parallel course. These results can be explained by the preferential presence in cerebellum of certain variants of the different subunits of the GABAA receptor complex and with different topographical distributions of the different receptor subtypes. Development dependent changes of organelle distribution during subcellular fractionation also contributed to the described developmental pattern.

Animals↗

Alteration of benzodiazepine receptors in mouse cerebellum following methylazoxymethanol treatment during development.

The specific binding of [3H]flunitrazepam was studied to biochemically specify the morphological alterations induced in mouse cerebellum by a single injection of an antimitotic agent, methylazoxymethanol (MAM) performed at the beginning of the postnatal life. The MAM injection causes a general reduction of the benzodiazepine receptors in the adult mice which is particularly severe in mice having been injected the 1st day of postnatal life (so-called MAM0 mice) as compared to animals injected the 5th day (MAM5 mice): in MAM0 mice the benzodiazepine receptor is reduced to half of the control value. The affinity of the benzodiazepine towards its receptor was not affected and the topographic and biochemical action of MAM in the central nervous system was ascertained. Correlations could be made between the biochemical modifications and the morphological alterations otherwise described.

Aging↗