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1.
Proc Biol Sci ; 280(1755): 20122901, 2013 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-23363635

RESUMO

Theory purports that animal foraging choices evolve to maximize returns, such as net energy intake. Empirical research in both human and non-human animals reveals that individuals often attend to the foraging choices of their competitors while making their own foraging choices. Owing to the complications of gathering field data or constructing experiments, however, broad facts relating theoretically optimal and empirically realized foraging choices are only now emerging. Here, we analyse foraging choices of a cohort of professional day traders who must choose between trading the same stock multiple times in a row--patch exploitation--or switching to a different stock--patch exploration--with potentially higher returns. We measure the difference between a trader's resource intake and the competitors' expected intake within a short period of time--a difference we call short-term comparative returns. We find that traders' choices can be explained by foraging heuristics that maximize their daily short-term comparative returns. However, we find no one-best relationship between different trading choices and net income intake. This suggests that traders' choices can be short-term win oriented and, paradoxically, maybe maladaptive for absolute market returns.


Assuntos
Comportamento de Escolha , Comportamento Competitivo , Comportamento Alimentar , Animais , Comércio , Humanos , Modelos Biológicos
2.
PLoS One ; 6(8): e23378, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21858093

RESUMO

Studying the interaction between a system's components and the temporal evolution of the system are two common ways to uncover and characterize its internal workings. Recently, several maps from a time series to a network have been proposed with the intent of using network metrics to characterize time series. Although these maps demonstrate that different time series result in networks with distinct topological properties, it remains unclear how these topological properties relate to the original time series. Here, we propose a map from a time series to a network with an approximate inverse operation, making it possible to use network statistics to characterize time series and time series statistics to characterize networks. As a proof of concept, we generate an ensemble of time series ranging from periodic to random and confirm that application of the proposed map retains much of the information encoded in the original time series (or networks) after application of the map (or its inverse). Our results suggest that network analysis can be used to distinguish different dynamic regimes in time series and, perhaps more importantly, time series analysis can provide a powerful set of tools that augment the traditional network analysis toolkit to quantify networks in new and useful ways.


Assuntos
Algoritmos , Modelos Biológicos , Transdução de Sinais/fisiologia , Arabidopsis/fisiologia , Simulação por Computador , Frequência Cardíaca/fisiologia , Humanos , Cinética , Fatores de Tempo
3.
Nature ; 465(7298): 622-6, 2010 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-20520715

RESUMO

The role of mentorship in protégé performance is a matter of importance to academic, business and governmental organizations. Although the benefits of mentorship for protégés, mentors and their organizations are apparent, the extent to which protégés mimic their mentors' career choices and acquire their mentorship skills is unclear. The importance of a science, technology, engineering and mathematics workforce to economic growth and the role of effective mentorship in maintaining a 'healthy' such workforce demand the study of the role of mentorship in academia. Here we investigate one aspect of mentor emulation by studying mentorship fecundity-the number of protégés a mentor trains-using data from the Mathematics Genealogy Project, which tracks the mentorship record of thousands of mathematicians over several centuries. We demonstrate that fecundity among academic mathematicians is correlated with other measures of academic success. We also find that the average fecundity of mentors remains stable over 60 years of recorded mentorship. We further discover three significant correlations in mentorship fecundity. First, mentors with low mentorship fecundities train protégés that go on to have mentorship fecundities 37% higher than expected. Second, in the first third of their careers, mentors with high fecundities train protégés that go on to have fecundities 29% higher than expected. Finally, in the last third of their careers, mentors with high fecundities train protégés that go on to have fecundities 31% lower than expected.


Assuntos
Escolha da Profissão , Matemática/normas , Mentores/estatística & dados numéricos , Competência Profissional/estatística & dados numéricos , Adulto , Fatores Etários , Algoritmos , Altruísmo , Bibliometria , Criança , Fertilidade , Humanos , Cadeias de Markov , Modelos Psicológicos , Método de Monte Carlo , Pais , Recursos Humanos
4.
Science ; 325(5948): 1696-700, 2009 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-19779200

RESUMO

The identification and modeling of patterns of human activity have important ramifications for applications ranging from predicting disease spread to optimizing resource allocation. Because of its relevance and availability, written correspondence provides a powerful proxy for studying human activity. One school of thought is that human correspondence is driven by responses to received correspondence, a view that requires a distinct response mechanism to explain e-mail and letter correspondence observations. We demonstrate that, like e-mail correspondence, the letter correspondence patterns of 16 writers, performers, politicians, and scientists are well described by the circadian cycle, task repetition, and changing communication needs. We confirm the universality of these mechanisms by rescaling letter and e-mail correspondence statistics to reveal their underlying similarity.


Assuntos
Comportamento , Comunicação , Correspondência como Assunto , Atividades Humanas , Ritmo Circadiano , Correio Eletrônico , Humanos , Modelos Estatísticos , Método de Monte Carlo , Distribuição Normal , Ocupações , Distribuição de Poisson , Política , Probabilidade , Ciência , Fatores de Tempo , Redação
5.
J Phys Chem A ; 113(17): 5176-94, 2009 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-19338326

RESUMO

Thermochemistry of radicals is not as extensively tabulated as that of stable molecular species, even when group additivity schemes are applied. When these radicals contain oxygen or nitrogen atoms, the availability of radical groups is even more limited. Many oxygen- and nitrogen-containing radicals and molecules are present in the atmosphere, and thermochemistry is a valuable component of the development of atmospheric models with predictive capabilities. This paper presents quantum chemical calculations using G3//B3LYP that have been performed to obtain heats of formation, entropies, and heat capacities as a function of the temperature of radicals and molecules from which group additivity values were obtained. Isodesmic and homodesmotic reactions were used to obtain improved estimates of the heats of formation. Thermodynamic property estimates were corrected to account for internal rotations. A total of 323 molecules were studied from which a total of 122 different groups, 21 gauche and cis corrections, and 5 secondary corrections were regressed.


Assuntos
Atmosfera/química , Simulação por Computador , Modelos Químicos , Teoria Quântica , Termodinâmica , Radicais Livres/química , Estrutura Molecular , Reprodutibilidade dos Testes
6.
Eur Phys J B ; 67(3): 369-375, 2009 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-24860255

RESUMO

We use agent-based modeling to investigate the effect of conservatism and partisanship on the efficiency with which large populations solve the density classification task - a paradigmatic problem for information aggregation and consensus building. We find that conservative agents enhance the populations' ability to efficiently solve the density classification task despite large levels of noise in the system. In contrast, we find that the presence of even a small fraction of partisans holding the minority position will result in deadlock or a consensus on an incorrect answer. Our results provide a possible explanation for the emergence of conservatism and suggest that even low levels of partisanship can lead to significant social costs.

7.
Proc Natl Acad Sci U S A ; 105(47): 18153-8, 2008 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-19017788

RESUMO

Patterns of deliberate human activity and behavior are of utmost importance in areas as diverse as disease spread, resource allocation, and emergency response. Because of its widespread availability and use, e-mail correspondence provides an attractive proxy for studying human activity. Recently, it was reported that the probability density for the inter-event time tau between consecutively sent e-mails decays asymptotically as tau(-alpha), with alpha approximately 1. The slower-than-exponential decay of the inter-event time distribution suggests that deliberate human activity is inherently non-Poissonian. Here, we demonstrate that the approximate power-law scaling of the inter-event time distribution is a consequence of circadian and weekly cycles of human activity. We propose a cascading nonhomogeneous Poisson process that explicitly integrates these periodic patterns in activity with an individual's tendency to continue participating in an activity. Using standard statistical techniques, we show that our model is consistent with the empirical data. Our findings may also provide insight into the origins of heavy-tailed distributions in other complex systems.


Assuntos
Correio Eletrônico , Distribuição de Poisson , Comportamento , Ritmo Circadiano , Humanos
8.
Psychiatry Res ; 105(1-2): 33-44, 2001 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-11740973

RESUMO

Platelet [14C]serotonin uptake, the density of serotonin transporters and 5HT(2) receptors, and 5HT(2) and alpha(2) receptor function in platelets were investigated in 29 outpatients (15 women and 14 men) diagnosed as having a major affective disorder (21 bipolar and 8 unipolar). The data were compared with data for 26 healthy volunteers matched for age, sex and season. No differences were found in the mean values for the uptake velocity (V(max)) and the affinity (K(m)) of the transport carrier for serotonin between patients and controls. However, female patients had lower V(max) compared to male patients and female control subjects. A positive correlation between plasma lithium and V(max) and a tendency toward a negative correlation between plasma lithium and K(m) was observed. Furthermore, there were no differences in platelet B(max) and K(d) for [3H]paroxetine binding and K(d) for [3H]LSD binding between patients and controls. However, there was an increased number of platelet 5-HT(2) receptors and a difference in serotonin-mediated potentiation of platelet ATP secretion between patients compared to controls, especially in women. The findings in the present study suggest that lithium has a net ameliorating impact on serotonin uptake which may render it resistant to change. They also postulate that the effect of lithium may be attained by a dual influence on postsynaptic serotonergic structures, as it increases both the density and the sensitivity of 5-HT(2) receptors.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Proteínas de Transporte/efeitos dos fármacos , Transtorno Depressivo Maior/tratamento farmacológico , Carbonato de Lítio/uso terapêutico , Glicoproteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Receptores Adrenérgicos alfa 2/efeitos dos fármacos , Receptores de Serotonina/efeitos dos fármacos , Adulto , Idoso , Transtorno Bipolar/sangue , Plaquetas/metabolismo , Transtorno Depressivo Maior/sangue , Feminino , Humanos , Carbonato de Lítio/farmacocinética , Dietilamida do Ácido Lisérgico/farmacocinética , Masculino , Pessoa de Meia-Idade , Paroxetina/farmacocinética , Ensaio Radioligante , Serotonina/sangue , Proteínas da Membrana Plasmática de Transporte de Serotonina , Resultado do Tratamento
9.
Int Clin Psychopharmacol ; 16(2): 93-101, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11236074

RESUMO

We investigated platelet [14C]serotonin (5-HT) uptake and lysergic acid diethylamide [N-methyl-3H] ([3H]LSD)- and phenyl-6'-paroxetine ([3H]paroxetine) binding in 30 patients with major depression at baseline and after 6 months of treatment with either paroxetine or sertraline. The study was of a double-blind design. Baseline data was compared with an age- and gender-matched group of healthy volunteers. Baseline Vmax was significantly lower in patients than in controls. Bmax for [3H]paroxetine binding were similar in patients and controls, but patients who suffered their first depression had significantly lower Bmax for [3H]paroxetine binding than patients who had suffered multiple depressions. Twenty-three patients (76%) (13 in the paroxetine group and 10 in the sertraline group) responded to treatment as judged by a 50% or more reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores after 6 months of treatment. There were no significant differences between the paroxetine and sertraline treated groups. Both paroxetine and sertraline caused a significant reduction in Vmax and a significant increase in Km. There was a strong correlation between Km and plasma drug concentration in patients who experienced their first depression but not in patients who had suffered multiple episodes. Bmax for [3H]paroxetine binding increased after paroxetine treatment while the opposite occurred after sertraline treatment. There was a significant interaction between the impact of drug and earlier depressions. All patients included in the study had been drug free for at least 2 months. Earlier antidepressant treatment may have long withstanding effects on the serotonin uptake machinery but it cannot be excluded that the sensitivity of the uptake mechanism may become more resistant to change in patients with recurrent depressive episodes.


Assuntos
Transtorno Depressivo/tratamento farmacológico , Dietilamida do Ácido Lisérgico/farmacocinética , Paroxetina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Antagonistas da Serotonina/farmacocinética , Serotonina/farmacocinética , Sertralina/uso terapêutico , Administração Oral , Adulto , Transtorno Depressivo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento
10.
Int J Neuropsychopharmacol ; 4(4): 329-36, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11806858

RESUMO

Central serotonergic function abnormalities are thought to be associated with the pathogenesis of affective disorder. Reduced serotonergic function, induced by tryptophan depletion, has in several studies transiently reversed the antidepressant effect of SSRIs in depressed patients in remission. Serotonergic pathways are suggested to be of importance in the mechanisms of the action of lithium. The purpose of this study was to investigate whether the stabilizing effect of lithium is dependent on short-term availability of serotonin. Tryptophan depletion was induced in thirty patients with affective disorder (20 bipolar and 10 unipolar), all stabilized on lithium treatment for at least one year. The study was performed using a randomized, double-blind, controlled design. Plasma tryptophan was reduced by 80% in the experimental group and 16% in the control group. However, no clinically relevant mood changes were observed. Transient reduction in serotonergic function does not seem to affect mood in affective-disorder patients stabilized on lithium treatment.


Assuntos
Antimaníacos/uso terapêutico , Lítio/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/psicologia , Serotonina/fisiologia , Triptofano/fisiologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Afeto/efeitos dos fármacos , Idoso , Aminoácidos/sangue , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/metabolismo , Transtorno Bipolar/psicologia , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/metabolismo , Prolactina/sangue , Triptofano/deficiência , Triptofano/metabolismo
11.
Int Clin Psychopharmacol ; 15(2): 83-91, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10759339

RESUMO

We investigated the effect of the selective serotonin reuptake inhibitor (SSRI) citalopram after 6-8 weeks and 6 months of treatment on clinical and peripheral indexes for central serotonergic function: platelet [14C]serotonin uptake and [3H]paroxetine- and [3H]LSD-binding to platelets membranes in 33 patients with panic disorder. Basal data from patients were compared with data from a control material consisting of 33 healthy volunteers. Bmax for platelet [3H]paroxetine binding was significantly lower in patients than in controls. There were no differences in serotonin uptake or [3H]LSD-binding between patients and controls. The degree of anxiety and depression was assessed using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory self-assessment scales, and the Clinical Anxiety Scale and the Montgomery Asberg Depression Rating Scale for clinical evaluation. Complete remission was found in one third of the patients after 6-8 weeks and in two-thirds after 6 months of treatment. The reduction in assessment scores was parallelled with similar reductions in platelet 5-HT2-receptor density, [3H]LSD affinity variable (Kd) and Vmax for platelet [14C]5-HT uptake. Citalopram treatment did not alter Bmax and Kd for platelet [3H]paroxetine-binding. A positive correlation was found between Vmax for the platelet [14C]5-HT uptake and BAI after 6 months citalopram treatment. The present study shows that citalopram has a therapeutic effect in panic disorders. A prerequisite of responding to treatment might be plasticity in the serotonergic system.


Assuntos
Citalopram/farmacologia , Transtorno de Pânico/tratamento farmacológico , Receptores de Serotonina/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Adulto , Ansiedade , Plaquetas , Citalopram/uso terapêutico , Depressão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Serotonina/fisiologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico
12.
Thromb Res ; 95(5): 235-43, 1999 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-10515288

RESUMO

We have previously found that the naturally occurring amine p-aminobenzoic acid (PABA) inhibits the thrombin-induced thromboxane B2 production in human platelets. In this report we show that PABA and its acetylated metabolite p-acetamidobenzoic acid (PACBA) inhibit platelet aggregation induced by agonists such as adenosine diphosphate (ADP) and arachidonic acid (AA). Both substances were equipotent to acetylsalicylic acid regarding inhibition of ADP-induced aggregation and approximately 50% as potent as acetylsalicylic acid regarding arachidonic acid-induced aggregation. Although not significantly inhibiting collagen aggregation, PABA and PACBA reduced the concomitant adenosine triphosphate (ATP) secretion by approximately 30 and 20%, respectively. The antiaggregatory effect does not seem to be mediated through cyclic adenosine monophosphate (cAMP) increase because in our experiments PABA and PACBA did not significantly affect cAMP levels. However, we have found that PABA and PACBA inhibit the intracellular aequorin indicated Ca2+ transient upon arachidonic acid stimulation. Our results describe a hitherto unknown effect of PABA and PACBA on platelet aggregation.


Assuntos
Ácido 4-Aminobenzoico/farmacologia , Ácido Araquidônico/farmacologia , Plaquetas/metabolismo , Cálcio/metabolismo , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , para-Aminobenzoatos , Difosfato de Adenosina/farmacologia , Plaquetas/patologia , Humanos
13.
Psychiatry Res ; 85(2): 189-98, 1999 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-10220009

RESUMO

The uptake of [14C]5-HT, [3H]paroxetine and [3H]LSD binding was determined in platelets from 30 untreated patients with major depression and compared with corresponding variables from 30 healthy age-, sex- and season-matched control subjects. The maximum velocity (Vmax) for the 5-HT uptake was significantly decreased in patients (P = 0.014) compared to control subjects. Depressed women had significantly lower Vmax than female control subjects. In men, Vmax did not differ between patients and control subjects. Vmax was significantly lower in male inpatients compared with male outpatients (P = 0.05). The density (Bmax) of 5-HT uptake sites was found to be significantly increased in patients (P < 0.05) compared to control subjects and male patients had significantly higher Bmax than male control subjects, but there was no difference between female control subjects and female patients. No significant difference was found in Bmax of 5-HT2-receptors between patients and control subjects. A positive correlation was found between Bmax of 5-HT2-uptake sites and the degree of anxiety and between Bmax of 5-HT2 receptors and MADRS scores. Bmax of 5-HT2-receptors was positively correlated with the degree of suicidality. The results in the present study indicate that there may be a gender difference in serotonergic dysfunction in depression.


Assuntos
Plaquetas/fisiologia , Transtorno Depressivo Maior/fisiopatologia , Serotonina/sangue , Adulto , Idoso , Análise de Variância , Ansiedade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Receptores de Serotonina/fisiologia , Análise de Regressão , Serotonina/deficiência , Índice de Gravidade de Doença , Fatores Sexuais , Suicídio
14.
Scand Cardiovasc J ; 32(5): 289-95, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9835004

RESUMO

Of 35 acetylsalicylic acid (ASA)-treated patients undergoing coronary artery bypass surgery, 10 received a high dose of aprotinin (mean 5.2 x 10(6) KIU) during cardiopulmonary bypass (CPB); in 15 cases low-dose aprotinin (2 x 10(6) KIU) was added to the CPB priming solution, and 10 patients made up a control group without aprotinin. Median total blood loss was 52% less in aprotinin-treated patients, irrespective of dose, than in the controls. Fibrin-D dimer levels remained low in patients treated with high-dose aprotinin, but increased significantly in the control group. Platelet adhesion and platelet adenosine triphosphate secretion were reduced after CPB in all patients. Whole-blood aggregation after bypass was enhanced in aprotinin-treated patients. Aprotinin inhibited fibrinolysis and seemingly preserved platelet function despite ASA treatment. In view of the possible risks and relatively high cost of aprotinin, use of a high dose seems unnecessary, since a low dose was equally effective in reducing blood loss in ASA-treated patients.


Assuntos
Aprotinina/administração & dosagem , Perda Sanguínea Cirúrgica/prevenção & controle , Ponte Cardiopulmonar , Hemostáticos/administração & dosagem , Trifosfato de Adenosina/metabolismo , Adulto , Idoso , Angina Instável/tratamento farmacológico , Angina Instável/cirurgia , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Transfusão de Sangue , Intervalos de Confiança , Relação Dose-Resposta a Droga , Feminino , Fibrina/análise , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Adesividade Plaquetária/efeitos dos fármacos , Contagem de Plaquetas/efeitos dos fármacos , Cuidados Pré-Operatórios , Valores de Referência , Resultado do Tratamento
15.
Psychiatry Res ; 78(3): 163-72, 1998 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-9657420

RESUMO

We investigated platelet 14C-serotonin uptake and platelet [3H]LSD and [3H]paroxetine binding in 11 patients with seasonal affective disorder (SAD). Patients were reinvestigated after light therapy, applied at 07.00-09.00 h for 10 consecutive days. The degree of depression was rated before and after light therapy using the Comprehensive Psychopathological Rating Scale (CPRS). Baseline data in patients were compared with data from a control group consisting of 11 age- and sex-matched healthy volunteers. Seven patients responded to light therapy with a > 50% reduction in CPRS scores. In non-responders, the reduction in CPRS was 24.7 +/- 5.5%. There was a significant inverse correlation (P = 0.014) between Km for platelet 14C-serotonin uptake and CPRS scores. Patients had significantly higher Bmax for platelet [3H]LSD binding (P = 0.04) and significantly lower Bmax for platelet [3H]paroxetine binding (P = 0.016). There was a strong, multiple correlation between Bmax for [3H]LSD, as the dependent variable, and Km, Vmax and Bmax for [3H]paroxetine binding in patients (P < 0.0001) but not in controls. Responders to light therapy had significantly higher Km (P = 0.023) and significantly lower Bmax for [3H]paroxetine binding (P = 0.028) than non-responders. Bmax for [3H]paroxetine binding increased significantly to normal levels after light therapy. The results indicate that SAD is associated with aberrations in the serotonin uptake mechanism. The enhanced 5-HT2-receptor density may reflect a consequential up-regulation.


Assuntos
Plaquetas/metabolismo , Fototerapia , Transtorno Afetivo Sazonal/terapia , Serotonina/metabolismo , Adulto , Idoso , Feminino , Humanos , Dietilamida do Ácido Lisérgico/metabolismo , Masculino , Pessoa de Meia-Idade , Paroxetina/metabolismo , Receptores de Serotonina/metabolismo , Transtorno Afetivo Sazonal/sangue , Transtorno Afetivo Sazonal/fisiopatologia , Inibidores Seletivos de Recaptação de Serotonina/metabolismo
16.
J ECT ; 14(1): 15-24, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9661089

RESUMO

We investigated the effect of electroconvulsive treatment (ECT) on platelet 14C-serotonin uptake, 3H-paroxetine binding and 5-HT2 receptors in 12 patients (10 women and 2 men) unresponsive to pharmacological treatment. The mean numbers of ECTs given was 6.1 +/- 1.5. Mean treatment days was 14.6 +/- 3.8. Mean percent reduction in MADRS scores was 80.7 +/- 19.7 (p < 0.002). The number of 5-HT2 receptors increased significantly and uniformly after ECT (p = 0.011). There was no correlation between the degree of increase in 5-HT2 receptor densities and the reduction in MADRS scores after ECT. There was no difference in mean Bmax for platelet 3H-paroxetine binding before and after ECT. Bmax increased in six patients and decreased in six patients. The study shows an increase in platelet 5-HT2-receptor densities in depression after repeated ECT. Recognizing the similarities between 5-HT2 receptors in platelets and cerebral cortex, it seems reasonable to assume that a similar upregulation of cortical 5-HT2 receptors occurs after ECT.


Assuntos
Plaquetas/metabolismo , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Receptores de Serotonina/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Transporte/fisiologia , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Masculino , Glicoproteínas de Membrana/fisiologia , Pessoa de Meia-Idade , Paroxetina/farmacocinética , Ensaio Radioligante , Serotonina/sangue , Proteínas da Membrana Plasmática de Transporte de Serotonina , Inibidores Seletivos de Recaptação de Serotonina/farmacocinética , Resultado do Tratamento
17.
Acta Psychiatr Scand ; 97(5): 374-80, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9611088

RESUMO

A double-blind study of the tryptophan depletion (TD) challenge was performed on a sample consisting of 20 patients with a major depressive disorder in clinical remission after citalopram treatment. TD was induced by the intake of 43 g of an amino acid mixture containing the five large neutral amino acids. The control group received the same mixture, to which 2.3 g tryptophan had been added. Five of the 12 challenged patients showed a worsening of depressive symptoms during the day of the test. In contrast, there was no mood alteration in the eight control patients. Baseline cortisol levels were significantly higher in responders to TD compared to those in non-responders and controls. Platelet serotonin-receptor function and plasma prolactin levels were correlated. There was a significant positive correlation in the baseline data between rated mood state and plasma cortisol and a significant inverse correlation between related mood state and plasma tryptophan concentration. Thus low mood appeared to be associated with low serotonin precursor availability as well as with high cortisol levels.


Assuntos
Citalopram/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Receptores de Serotonina/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Triptofano/deficiência , Adulto , Idoso , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Citalopram/efeitos adversos , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Inventário de Personalidade , Prolactina/sangue , Receptores de Serotonina/sangue , Serotonina/fisiologia , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Triptofano/fisiologia
18.
Thromb Res ; 86(2): 127-40, 1997 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-9175234

RESUMO

We have previously shown that p-aminobenzoic acid (PABA) is acetylated by several cell lines and most peripheral blood cells, including platelets, to p-acetamidobenzoic acid (PACBA). The structural similarity of PABA and PACBA to local anesthetics and some non steroidal anti inflammatory drugs urged us to perform the present investigation. When human platelets were stimulated with thrombin to liberate AA, we found that PABA inhibited the production of thromboxane (TxB2) as measured with enzyme-linked immunosorbent assay. The inhibition was reversible and observed at PABA concentrations ranging between 55 and 1000 microM. At 328 microM PABA the production of TxB2 diminished by 87% (p = 0.013). PACBA in the same doses did not affect the production of TxB2. When platelets were incubated with [1-14C]AA, in the presence of PABA, the production of [1-14C]TxB2 was only slightly inhibited, according to analysis by high pressure liquid chromatography. Obviously PABA is not mainly acting as a prostaglandin H (cyclooxygenase) or Tx synthase inhibitor. It is rather affecting a step prior to thromboxane production, most likely the liberation of the precursor AA. In conclusion, our results demonstrate for the first time that PABA, a substance occurring in nature, inhibits endogenous TxB2 synthesis in human platelets and might thus exert profound effects on platelet AA metabolism.


Assuntos
Ácido 4-Aminobenzoico/farmacologia , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Tromboxano B2/biossíntese , para-Aminobenzoatos , Ácido 4-Aminobenzoico/metabolismo , Ácido 4-Aminobenzoico/farmacocinética , Acetilação , Anti-Inflamatórios não Esteroides/farmacologia , Ácido Araquidônico/sangue , Ácido Araquidônico/metabolismo , Transporte Biológico Ativo , Sequestradores de Radicais Livres/farmacologia , Humanos , Técnicas In Vitro , Masculino , Trombina/antagonistas & inibidores , Trombina/farmacologia , Tromboxano B2/sangue
19.
Pharmacol Toxicol ; 79(6): 312-7, 1996 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9000258

RESUMO

Activated neutrophils are assumed to be one plausible cause of tissue injury in the ischaemic and reperfused myocardium. We studied the inhibitory effects of the calcium antagonists felodipine, nimodipine and verapamil on human neutrophil activation in order to elucidate the mechanisms underlying their myocardioprotective effects and to determine whether calcium antagonists with different chemical structures vary in their effect on neutrophil activation. Neutrophils were stimulated with formyl-Met-Leu-Phe (0.1 microM) or by phorbol myristate acetate (0.16 microM), and the rise in cytosolic calcium and the H2O2 production were determined. For felodipine, the inhibitory effect on granulocyte elastase release was also studied. The calcium antagonists reduced formyl-Met-Leu-Phe and phorbol myristate acetate-induced neutrophil activation in a concentration-dependent manner, the order of potency being: felodipine > nimodipine > verapamil. For felodipine, the IC50 (concentration causing 50% reduction) values were 3 x 10(-6) and 2 x 10(-6) M for the formyl-Met-Leu-Phe-induced cytosolic calcium increase and H2O2 production, respectively. The IC50-value for the phorbol myristate acetate-induced cytosolic calcium increase was 6 x 10(-6) and for H2O2 production 4 x 10(-6) M. For formyl-Met-Leu-Phe-induced granulocyte elastase release, the IC50-value was 5 x 10(-6) M. The inhibitory effect of felodipine on the phorbol myristate acetate-induced granulocyte elastase release did not exceed 50%. Nimodipine was a less potent inhibitor than felodipine for both formyl-Met-Leu-Phe- and phorbol myristate acetate-induced cell activities. Verapamil was even less potent than the other two agents. The present study demonstrates that felodipine potentially suppresses neutrophil activation at micromolar concentrations. However, this observation should not be directly extrapolated to explain the tissue protection by the compounds without evidence of profound local accumulation.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Cálcio/metabolismo , Peróxido de Hidrogênio/metabolismo , Elastase de Leucócito/metabolismo , Neutrófilos/efeitos dos fármacos , Citosol/efeitos dos fármacos , Felodipino/farmacologia , Humanos , Ativação de Neutrófilo/efeitos dos fármacos , Neutrófilos/metabolismo , Nimodipina/farmacologia , Verapamil/farmacologia
20.
JAMA ; 273(17): 1360-5, 1995 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-7715061

RESUMO

OBJECTIVE: To characterize on-the-road, behind-the-wheel driving abilities and related laboratory performances of subjects with mild Alzheimer's disease (AD) and vascular dementia. DESIGN: Prospective, experimental study involving two mild dementia and three age and health control groups. Road test reliability and validity were assessed. SETTING: Greater western Los Angeles. Subjects were enrolled from the community by referral and from the Veterans Affairs dementia and diabetes clinics. PARTICIPANTS: Eighty-seven driving subjects were enrolled; 83 completed the study. A sample of eligible dementia clinic subjects consisting of 15 mild AD patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association probable AD criteria, while 12 met Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and Hachinski diagnostic criteria for multi-infarct dementia (vascular dementia). Clinic control subjects consisted of 15 age-matched patients with diabetes and without a history of stroke or dementia. Community controls consisted of 26 healthy, age-matched, older subjects (> 60 years) and 16 young subjects (20 to 35 years). MAIN OUTCOME MEASURES: Drive score from the Sepulveda (Calif) road test and laboratory measures of attention, perception, and memory. RESULTS: The drive scores in the mild AD group (mean, 22.1; SD, 3.8) and in the vascular dementia group (mean, 24.0; SD, 7.8) differed significantly (P < .001 studentized range test) from the drive scores in the diabetic control group (mean, 31.5; SD, 3.9), the older control group (mean, 32.6; SD, 2.8), and the young control group (mean, 33.6; SD, 3.2). Drive score among the three control groups did not vary significantly. Short-term memory (Sternberg), visual tracking, and Folstein Mini-Mental State Examination scores correlated best with drive score, with a cumulative R2 of 0.68. Drive score and number of collisions and moving violations per 1000 miles driven were negatively correlated (r = -0.38; P < .02). CONCLUSIONS: Based on this study, type and degree of cognitive impairment are better predictors of driving skills than age or medical diagnosis per se. Specific testing protocols for drivers with potential cognitive impairment may detect unsafe drivers more effectively than using age or medical diagnosis alone as criteria for license restriction or revocation.


Assuntos
Doença de Alzheimer , Condução de Veículo , Demência Vascular , Adulto , Idoso , Análise de Variância , Cognição , Análise Discriminante , Humanos , Modelos Lineares , Análise por Pareamento , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Reprodutibilidade dos Testes
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