1,720,992 research outputs found
The atypical antipsychotic quetiapine increases both noradrenaline and dopamine release in the rat prefrontal cortex
No full textQuetiapine is a novel atypical antipsychotic drug with multi-receptorial affinity. Using in vivo microdialysis, we investigated if quetiapine modulates extracellular noradrenaline and dopamine in brain areas generally believed to be involved in the pathophysiology of schizophrenia and in the action of antipsychotic drugs. Quetiapine (5, 10 and 20 mg/kg, i.p.) increased levels of noradrenaline in both the prefrontal cortex and the caudate nucleus, while it increased dopamine levels mainly in the prefrontal cortex. It is argued that the marked increase of dopaminergic transmission in the prefrontal cortex induced by quetiapine might be relevant to its therapeutical action. © 2004 Elsevier B.V. All rights reserved
Genotyping of CYP2D6 polymorphisms by MALDI–TOF mass spectrometry in Sardinian people
No full textThe CYP2D6 enzyme is involved in the metabolism of many commonly prescribed drugs. The presence of CYP2D6 gene SNPs can alter CYP2D6 enzymatic activity with effects ranging considerably within a population. Objectives: In this study we have developed a genotyping platform able to determine the alleles related to interindividual variability in CYP2D6 gene. Design and methods: We used a Long PCR strategy coupled to MALDI–TOF mass spectrometry (Sequenom®) to develop a SNPs genotyping method. Furthermore, an amplification allele–specific was carried out to infer the correct allelic phase. Results: We tested the multiplex platform in 250 DNA Sardinian samples and found it to be 100% concordant with the sequencing results of our previous work. Conclusions: The MALDI–TOF–based multiplexing system allowed simultaneous and efficient genotyping of a set of CYP2D6 SNPs, evidencing its potential use in diagnostic test development to predict drug responses and clinical outcome
Alpha2-adrenoceptor mediated co-release of dopamine and noradrenaline from noradrenergic neurons in the cerebral cortex
No full textPrevious results suggest that extracellular dopamine (DA) in
the rat cerebral cortex originates from dopaminergic and
noradrenergic terminals. To further clarify this issue, dialysate
DA, dihydroxyphenylacetic acid (DOPAC) and noradrenaline
(NA) were measured both in the medial prefrontal cortex
(mPFC) and in the occipital cortex (OCC), with dense and
scarce dopaminergic projections, respectively. Moreover, the
effect of the a2-adrenoceptor antagonist RS 79948 and the
D2-receptor antagonist haloperidol on extracellular DA, DOPAC
and NA was investigated. Extracellular DA and DOPAC
concentrations in the OCC were 43% and 9%, respectively,
those in the mPFC. Haloperidol (0.1 mg/kg i.p.) increased DA
and DOPAC (by 35% and 150%, respectively) in the mPFC,
but was ineffective in the OCC. In contrast, RS 79948
(1.5 mg/kg i.p.) increased NA, DA and DOPAC, both in the
mPFC (by approximately 50%, 60% and 130%, respectively)
and the OCC (by approximately 50%, 80% and 200%,
respectively). Locally perfused, the DA transporter blocker
GBR 12909 (10 lM) was ineffective in either cortex, whereas
desipramine (DMI, 100 lM) markedly increased extracellular
NA and DA in both cortices. The weak haloperidol effect on
DA efflux was not enhanced after DA- and NA-transporter
blockade, whereas after DMI, RS 79948 markedly increased
extracellular NA, and especially DA and DOPAC in both cortices.
The results support the hypothesis that most extracellular
DA in the cortex is co-released with NA from
noradrenergic terminals, such co-release being primarily
controlled by a2-adrenoceptors
Homo sapiens haplotype 4 cytochrome P450 2D6 variant (CYP2D6) gene, CYP2D6*2M/CYP2D6*41 hybrid allele, complete cds.
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Analysis of CYP2D6 allele frequencies and identification of novel SNPs and sequence variations in Sardinians
No full textThe CYP2D6 enzyme is involved in the metabolism of many commonly prescribed drugs. The presence of polymorphisms in the CYP2D6 gene may modulate enzyme level and activity affecting individual responses to pharmacological treatment in drug level, response and adverse reactions. Aims: This study aimed to analyze the determination of allele frequencies in Sardinians and the comparison to frequencies found in the Caucasian Population. Methods and Materials: We used a Long PCR strategy coupled to direct genomic DNA sequencing analysis. An amplification allele–specific was carried out to infer the correct allelic phase. The TaqMan® Gene Copy Number Assay (Applied BiosystemsTM) was used to verify the presence of gene deletions/multiplications. Results and Conclusions: Our results indicated that CYP2D6 allele frequencies in Sardinians differed from those previously detected in the Caucasian Population. Moreover, three new SNPs and four novel haplotypes were identifie
Mirtazapine-induced corelease of dopamine and noradrenaline from noradrenergic neurons in the medial prefrontal and occipital cortex
No full textThe novel antidepressant mirtazapine has been shown to increase extracellular noradrenaline and dopamine in the medial prefrontal
cortex. Our previous studies indicate that extracellular dopamine in the cerebral cortex originates largely from noradrenergic terminals, such
release being controlled by a2-adrenoceptors. Because mirtazapine inhibits a2-adrenoceptors, the possibility that it might corelease dopamine
and noradrenaline was investigated. By means of microdialysis, the effect of mirtazapine on extracellular dopamine, 3,4-dihydroxyphenylacetic
acid (DOPAC) and noradrenaline in the medial prefrontal cortex, densely innervated by dopaminergic and noradrenergic neurons, and
in the occipital cortex, receiving equal noradrenergic but scarce dopaminergic projections, was compared. Basal extracellular concentration of
noradrenaline was similar in both cortices, while dopamine in the occipital cortex was only about 50% lower than in the medial prefrontal
cortex, reflecting noradrenergic rather than dopaminergic projections. The intraperitoneal (i.p.) administration of mirtazapine (5 and 10 mg/
kg) increased extracellular dopamine, DOPAC and noradrenaline to approximately the same extent in both cortices, an effect totally
suppressed by the a2-adrenoceptors agonist clonidine (0.15 mg/kg, i.p.). To exclude the possibility that mirtazapine-induced increase in
dopamine might result from reduced dopamine removal from extracellular space, noradrenaline and dopamine uptake mechanisms were
blocked by perfusing 100 AM desipramine into either cortex. The combined i.p. administration of mirtazapine (5 mg/kg) and the local
perfusion of desipramine produced an additional increase in extracellular dopamine, DOPAC and noradrenaline in the medial prefrontal
cortex and occipital cortex compared with the increase produced by either drug given alone. The results suggest that mirtazapine by inhibiting
a2-adrenoceptors produces a corelease of noradrenaline and dopamine from noradrenergic terminals in the cerebral cortex.
D 2004 Elsevier B.V. All rights reserved
Homo sapiens haplotype 1 cytochrome P450 2D6 variant (CYP2D6) gene, CYP2D6*2M allele, complete cds.
No full textVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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