Progresión de los síntomas en niños con trastorno por déficit de atención e hiperactividad en tratamiento con metilfenidato / Progression of symptoms in children with attention deficit and hyperactivity disorder in treatment with methylphenidate

El trastorno por déficit de atención e hiperactividad (TDAH) es un trastorno neurobiológico frecuente en la infancia. Sus síntomas cardinales involucran a la atención y/o la impulsividad y/o la hiperactividad. Hay diferentes subtipos de TDAH según la expresividad clínica de esos tres síntomas. Hay distintas estrategias terapéuticas de alta efectividad. El metilfenidato, un estimulante que actúa en las vías dopaminérgicas y adrenérgicas, se utiliza con frecuencia en su tratamiento. El Cuestionario de Cualidades y Dificultades (SDQ) es un cuestionario de despistaje breve utilizado para la detección de problemas de salud mental en niños y adolescentes. Consta de 25 preguntas que se distribuyen en 5 escalas: sintomatología emocional, problemas de conducta, hiperactividad/inatención, problemas con los compañeros y conducta prosocial. Se recogió la puntuación del SDQ en una muestra de pacientes con TDAH con una edad situada entre los 7 y 12 años. Se comparó la puntuación obtenida antes de comenzar el tratamiento con metilfenidato y después de comenzar tratamiento, cada 3-6 meses y hasta un periodo de 2 años. Se realizó el procesamiento estadístico mediante R, que es un programa gratuito para análisis estadísticos y gráficos, y permite análisis temporales. Los resultados indican que la hiperactividad mejora a lo largo del primer año de tratamiento, la sintomatología emocional y los problemas de comportamiento mejoran durante los primeros 6 meses de tratamiento, la sintomatología prosocial mejora lentamente a lo largo de los 2 años y los problemas con compañeros no mejoran en el tiempo analizado.

Attention deficit and hyperactivity disorder (ADHD) is a neurobiological disorder frequent in childhood. The main symptoms are attention disorder and/or impulsivity and/or hyperactivity. There are different subtypes of ADHD according to the degree of presence of these three symptoms. There are different therapeutic approaches with high proved effectiveness. Methylphenidate, a stimulant that acts through the dopaminergic and adrenergic pathways, is commonly used for the treatment of ADHD. The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening instrument internationally used for the screening of mental health problems in children and adolescents. It consists in a 25 items questionnaire with 5 different scales: emotional symptoms, conduct problems, hyperactivity / inattention, peer relationship problems and prosocial behaviours. The SDQ score was collected in a sample of ADHD patients with an age between 7 and 12 years. The score obtained before starting treatment with methylphenidate was compared before and after starting treatment, every 3-6 months and up to a period of 2 years. Statistical processing was performed using R, which is a free program for statistical and graphical analysis, that allows temporary analysis. The results indicate that hyperactivity improves throughout the first year of treatment, emotional symptoms and behavioral problems improve during the first 6 months of treatment, pro-social symptoms slowly improve over 2 years. Problems with partners do not improve in the analyzed time.

Can the success of structured therapy for giggle incontinence be predicted?

ABSTRACT Introduction: To evaluate possible factors that can guide the clinician to predict potential cases refractoriness to medical treatment for giggle incontinence (GI) and to examine the effectiveness of different treatment modalities. Material and methods: The data of 48 children referred to pediatric urology outpatient clinic between 2000 and 2013 diagnosed as GI were reviewed. Mean age, follow-up, GI frequency, associated symptoms, medical and family history were noted. Incontinence frequency differed between several per day to less than once weekly. Children were evaluated with uroflowmetry-electromyography and post-void residual urine. Clinical success was characterized as a full or partial response, or nonresponse as defined by the International Children's Continence Society. Univariate analysis was used to find potential factors including age, sex, familial history, GI frequency, treatment modality and dysfunctional voiding to predict children who would possibly not respond to treatment. Results: Mean age of the patients was 8.4 years (range 5 to 16). Mean follow-up time and mean duration of asymptomatic period were noted as 6.7±1.4 years and 14.2±2.3 months respectively. While 12 patients were treated with only behavioral urotherapy (Group-1), 11 patients were treated with alpha-adrenergic blockers and behavioral urotherapy (Group-2) and 18 patients with methylphenidate and behavioral urotherapy (Group-3). Giggle incontinence was refractory to eight children in-group 1; six children in-group 2 and eight children in-group 3. Daily GI frequency and dysfunctional voiding diagnosed on uroflowmetry-EMG were found as outstanding predictive factors for resistance to treatment modalities. Conclusions: A variety of therapies for GI have more than 50% failure rate and a standard treatment for GI has not been established. The use of medications to treat these patients would not be recommended, as they appear to add no benefit to symptoms and may introduce severe adverse effects.

Profile and pattern of crack consumption among inpatients in a Brazilian psychiatric hospital / Perfil e padrão de consumo de crack em pacientes internados em um hospital psiquiátrico brasileiro

Introduction: Crack cocaine use is associated with polydrug abuse, and inpatients dependent on crack exhibit profiles of serious consumption patterns. Use of alcohol and tobacco and other drugs is a risk factor for experimentation of additional drugs, including crack cocaine.Objectives:The present study describes the characteristics and crack consumption patterns among inpatients in treatment during 2011 and 2012 at the Hospital Psiquiátrico São Pedro (Porto Alegre, Brazil). An additional objective was to identify the sequence of alcohol and tobacco consumption prior to crack use.Methods: The participants were 53 male inpatients addicted to crack with a mean age of 27.5±7.3 years. A sociodemographic questionnaire; the Alcohol, Smoking and Substance Involvement Screening Test and the Mini Mental State Examination were all administered to participants. Inclusion criteria were crack cocaine dependency (based on the 10th edition of the International Classification of Diseases [ICD-10]) and being abstinent for 7 days. Patients with cognitive difficulties who were unable to understand and/or respond to the questionnaires were excluded from the sample.Results: The participants were young male adults with low educational level and low incomes and were polydrug users. The majority had made more than one attempt to quit. Use of legal drugs in early adolescence, prior to crack use, was identified.Conclusions: The profiles of the inpatients addicted to crack treated at this hospital indicate a serious usage pattern among those who seek specialized support. Crack use is frequent and is associated with use of other drugs and with difficulty sustaining abstinence. The pattern of progression from alcohol and tobacco use to crack cocaine dependency demands the attention of those responsible for prevention policies.

Introdução: O uso de crack continua associado ao abuso de múltiplas drogas, e o perfil do dependente de crack em tratamento tipo internação parece estar relacionado a um padrão grave de consumo. O consumo de álcool, tabaco e outras drogas é um fator de risco para a experimentação de novas drogas, como o crack.Objetivos: Descrever características e padrão de consumo do crack em pacientes em tratamento tipo internação no Hospital Psiquiátrico São Pedro (Porto Alegre, Brasil) nos anos de 2011 e 2012. Além disso, identificar a sequência de consumo de álcool e cigarro prévio ao crack.Método: Participaram do estudo 53 homens dependentes de crack, com média de idade de 27.5±7.3 anos. Os participantes responderam a um questionário sociodemográfico, ao Alcohol, Smoking and Substance Involvement Screening Test e ao Mini Exame do Estado Mental. Os critérios de inclusão foram: dependência de cocaine (crack) baseada na 10ª edição da Classificação Internacional de Doenças (CID-10) e estar há mais de 7 dias em abstinência. Pacientes que apresentavam prejuízos cognitivos ou dificuldades de compreensão para o entendimento dos questionários foram excluídos da amostra.Resultados: Os participantes eram adultos jovens, com baixa escolaridade e renda, poliusuários de drogas. A maioria dos participantes realizou mais de uma tentativa de parar o consumo. Uso de drogas lícitas no início da adolescência, antes da experimentação do crack, foi identificado.Conclusões: O perfil do dependente de crack tratado nesse hospital aponta para um grave padrão de consumo entre usuários que procuram assistência. O uso continua frequente, associado ao consumo de outras drogas e à dificuldade de manter-se em abstinência. O padrão de progressão do uso de álcool e tabaco para a dependência de crack requer atenção quanto a políticas de prevenção.

Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats / Tamoxifeno antagoniza os efeitos dos hormônios ovarianos que induzem comportamento similar a ansiedade e depressão em ratos

The effects of tamoxifen (TAM) on anxiety and depression-like behavior in ovariectomized (OVX) and naïve female rats were investigated. The animals were divided into Sham-TAM, OVX-TAM, Sham and OVX groups. Tamoxifen (1 mg/kg) was administered for 4 weeks. In the forced swimming test, the immobility times in the OVX and Sham-TAM groups were higher than in the Sham group. In the open field, the numbers of central crossings in the OVX and Sham-TAM groups were lower than the number in the Sham group, and the number of peripheral crossings in the OVX group was lower than the number in the Sham group. In the elevated plus maze, the numbers of entries to the open arm among the animals in the Sham-TAM and OVX groups were lower than the number in the Sham group, while the number of entries to the open arm in the OVX-TAM group was higher than the number in the OVX group. It was shown that deletion of ovarian hormones induced anxiety and depression-like behavior. Administration of tamoxifen in naïve rats led to anxiety and depression-like behavior that was comparable with the effects of ovarian hormone deletion. It can be suggested that tamoxifen antagonizes the effects of ovarian hormones. It also seems that tamoxifen has anxiolytic effects on ovariectomized rats.

Foram investigados os efeitos do tamoxifeno (TAM) no comportamento semelhante a ansiedade de depressão de ratas ooforectomizadas (OVX) e controles. Os animais foram divididos em Sham-TAM, OVX-TAM, Sham e OVX groups. Tamoxifeno (1 mg/kg) foi administrado por quatro semanas. No teste de natação forçada, os tempos de imobilidade nos grupos OVX e Sham-TAM foram maiores que aqueles do grupo Sham. No campo aberto, os números de cruzamento no centro nos grupos OVX e Sham-TAM foram menores que aquele do grupo Sham, e o número dos cruzamentos na periferia no grupo OVX foi menor que o número no grupo Sham. No labirinto elevado, os números de entradas com braços abertos entre os animais nos grupos Sham-TAM e OVX foram menores do que aqueles do grupo Sham, enquanto o número de entradas com os braços abertos no grupo OVX-TAM foi maior que aquele no grupo OVX. Foi observado que a deleção dos hormônios ovarianos induziu comportamento similar a ansiedade e depressão. A administração de tamoxifeno em ratos controle induziu a um comportamento que era comparável aos efeitos da deleção do hormônio ovariano. Pode ser sugerido que o tamoxifeno antagoniza os efeitos dos hormônios ovarianos. Parece também que o tamoxifeno tem efeito ansiolítico nas ratas ooforectomizadas.

Histone deacetylase activity and brain-derived neurotrophic factor (BDNF) levels in a pharmacological model of mania

Objective: In the present study, we aimed to examine the effects of repeated D-amphetamine (AMPH) exposure, a well-accepted animal model of acute mania in bipolar disorder (BD), and histone deacetylase (HDAC) inhibitors on locomotor behavior and HDAC activity in the prefrontal cortex (PFC) and peripheral blood mononuclear cells (PBMCs) of rats. Moreover, we aimed to assess brain-derived neurotrophic factor (BDNF) protein and mRNA levels in these samples. Methods: We treated adult male Wistar rats with 2 mg/kg AMPH or saline intraperitoneally for 14 days. Between the 8th and 14th days, rats also received 47.5 mg/kg lithium (Li), 200 mg/kg sodium valproate (VPT), 2 mg/kg sodium butyrate (SB), or saline. We evaluated locomotor activity in the open-field task and assessed HDAC activity in the PFC and PBMCs, and BDNF levels in the PFC and plasma. Results: AMPH significantly increased locomotor activity, which was reversed by all drugs. This hyperactivity was associated with increased HDAC activity in the PFC, which was partially reversed by Li, VPT, and SB. No differences were found in BDNF levels. Conclusion: Repeated AMPH administration increases HDAC activity in the PFC without altering BDNF levels. The partial reversal of HDAC increase by Li, VPT, and SB may account for their ability to reverse AMPH-induced hyperactivity. .

Cambios en la hemodinamia cerebral en consumidores crónicos de paco y cocaína: estudio de casos y controles / [Changes in cerebral hemodynamics in chronic users of \"PACO\" and cocaine: case-control study].

OBJECTIVE: To assess if there are changes in brain hemodynamics evaluated by means of transcranial doppler’s flow velocity, pulsatile index and cerebral perfusion pressure, between cocaine chronic abusers and healthy volunteers. METHOD: Prospective, case and control, observational study. Sex, age, user history, vital signs and transcranial doppler findings.Statistical analysis was performed by means of normality test, Wilcoxon’s test for non parametric samples and T Student test. RESULTS: Fifty-three abusers and 35 healthy volunteers were studied. Statistical differences were found for a diminish in age(p=0.008) and cerebral perfusion pressure in all cerebral arteries (p

Evidence-Based Korean Pharmacological Treatment Guideline for Depression, Revised Edition (II) : Antidepressant Efficacy Compared with Placebo, Difference in Efficacy of Antidepressants, and Appropriate Time of Efficacy Judgment in Antidepressant Therapy / 신경정신의학

OBJECTIVES: The purpose of this study was to suggest recommendations of antidepressant efficacy compared with placebo, difference in efficacy of antidepressants, and appropriate time of efficacy judgment in antidepressant therapy. METHODS: Using recommendations from 12 international and domestic clinical practice guidelines for depression, drawing of recommendation drafts, and peer review, the executive committee developed the guideline. RESULTS: Tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOI), selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRIs), norepinephrine and specific serotonergic antidepressants (NaSSAs), norepinephrine and dopamine reuptake inhibitors (NDRIs), and serotonin antagonist and reuptake inhibitors (SARIs) were strongly recommended as having antidepressant efficacy compared with placebo. Difference in efficacy of antidepressants was as follows. TCAs, MAOI, SSRI, SNRIs, and NaSSAs were strongly recommended, however, NDRIs, SARIs were weakly recommended. If there was no or minimal improvement with treatment, appropriate time of efficacy judgment in antidepressant therapy was estimated to be after two to four weeks. CONCLUSION: We hope that the results of this study will be helpful in encouraging the optimal treatment by understanding antidepressant efficacy compared with placebo, difference in efficacy of antidepressants, and appropriate time of efficacy judgment in antidepressant therapy.

Evidence-Based Korean Pharmacological Treatment Guideline for Depression, Revised Edition (III) : Dose Increment, Switching, Combination, and Augmentation Strategy in Antidepressant Therapy / 신경정신의학

OBJECTIVES: The aim of this study was to demonstrate the recommendations for antidepressant treatment strategy of dose increment, switching, combination, and augmentation therapy derived from Evidence-Based Korean Pharmacological Treatment Guideline for Depression, Revised Edition. METHODS: The guideline was developed through adaptation of 12 domestic and foreign clinical guidelines for depression, with key questions concerning pharmacotherapy of depression, and drawing of recommendations. RESULTS: The guideline strongly recommended dose increment, switching, and combination and augmentation therapy of antidepressant when patients with depression showed inadequate treatment outcomes from initial antidepressant treatment. The dose increment was strongly recommended when the patients had insufficient response from treatment with tricyclic antidepressants (TCAs), monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), and serotonin and norepinephrine reuptake inhibitors (SNRIs). Switching from SSRI to non-SSRI was also strongly recommended. The combination of initial medication and other classes of antidepressants could benefit from treatment with TCAs, SSRIs, SNRIs, and noradrenergic and specific serotonergic antidepressants. Combination with norepinephrine and dopamine reuptake inhibitors or serotonin-2 antagonist/reuptake inhibitors was weakly recommended. The guideline strongly recommended use of the augmentation strategy of adding lithium or benzodiazepine to initial antidepressants. Augmentation of lamotrigine, T3, methylphenidate, and modafinil was weakly recommended. CONCLUSION: If the initial outcomes of antidepressant therapy are unsatisfactory to the patients the next-step strategies of dose increment, switching, combination and augmentation of antidepressants should be considered after rechecking the patients' drug compliance, dose, and diagnosis.

Food intake and serum levels of iron in children and adolescents with attention-deficit/hyperactivity disorder / Ingestão alimentar e níveis séricos de ferro em crianças e adolescentes com transtorno de déficit de atenção/hiperatividade

Objective: To investigate hematologic variables related to iron deficiency and food intake in attention-deficit/hyperactivity disorder. Method: The sample comprised 62 children and adolescents (6-15 years old) divided into three groups: Group 1: 19 (30.6 percent) patients with attention-deficit/hyperactivity disorder using methylphenidate for 3 months; Group 2: 22 (35.5 percent) patients with attention-deficit/hyperactivity disorder who were methylphenidate naïve and Group 3: 21 (33.9 percent) patients without attention-deficit/hyperactivity disorder. Serum iron, ferritin, transferrin, hemoglobin, mean corpuscular volume, red cell distribution width, mean corpuscular hemoglobin concentration, nutritional diagnostic parameters - Body Mass Index Coefficient, food surveys were evaluated among the groups. Results: The attention-deficit/hyperactivity disorder group drug naïve for methylphenidate presented the highest red cell distribution width among the three groups (p = 0.03). For all other hematologic and food survey variables, no significant differences were found among the groups. No significant correlation between dimensional measures of attention-deficit/hyperactivity disorder symptoms and ferritin levels was found in any of the three groups. Conclusion: Peripheral markers of iron status and food intake of iron do not seem to be modified in children with attention-deficit/hyperactivity disorder, but further studies assessing brain iron levels are needed to fully understand the role of iron in attention-deficit/hyperactivity disorder pathophysiology.

Objetivo: Investigar as variáveis hematológicas relacionadas à deficiência de ferro e à ingestão alimentar no transtorno de déficit de atenção/hiperatividade. Método: Sessenta e duas crianças e adolescentes (6-15 anos) divididos em três grupos: Grupo 1: 19 (30,6 por cento) pacientes com transtorno de déficit de atenção/hiperatividade com uso de metilfenidato durante três meses; Grupo 2: 22 (35,5 por cento) pacientes com transtorno de déficit de atenção/hiperatividade sem uso de medicamento; e Grupo 3: 21 (33,9 por cento) pacientes sem transtorno de déficit de atenção/hiperatividade. Ferro sérico, ferritina, transferrina, hemoglobina, volume corpuscular médio, amplitude de distribuição dos eritrócitos, concentração da hemoglobina corpuscular média, parâmetros de diagnóstico nutricional - Coeficiente de Índice de Massa Corporal, inquérito alimentar e a correlação entre os sintomas do transtorno e os níveis de ferritina foram avaliados. Resultados: O grupo com transtorno de déficit de atenção/hiperatividade não medicado com metilfenidato apresentou maior amplitude de distribuição dos eritrócitos dentre os três grupos (p = 0,03). Nas outras variáveis hematológicas e inquéritos alimentares não encontramos diferença significativa entre os grupos. Não observamos correlação entre os sintomas do transtorno de déficit de atenção/hiperatividade e ferritina. Conclusão: Marcadores periféricos do estado nutricional de ferro e a ingestão alimentar de ferro não parecem estar modificados em crianças com transtorno de déficit de atenção/hiperatividade, mas mais estudos avaliando os níveis de ferro no cérebro são necessários para compreensão plena do papel do ferro na fisiopatologia do transtorno de déficit de atenção/hiperatividade.

Effects of fluoxetine and imipramine in rat fetuses treated during a critical gestational period: a macro and microscopic study / Efeitos da fluoxetina e imipramina em fetos de ratas tratadas durante o período crítico da gestação: estudo macro e microscópico

OBJECTIVE: To evaluate morphological alterations in rat fetuses treated with fluoxetine and imipramine during the "critical" period of gestation. METHOD: Fifteen female rats were separated into three groups (n = 5) and treated with 10 mg/kg/day of test substances on the ninth, tenth and eleventh day of pregnancy: G1, fluoxetine; G2, imipramine hydrochloride; G3 (control), saline. On day 21, cesarean sections were performed to release the fetuses, whose bodies were weighed and macroscopically analyzed. The placenta was also weighed. The fetuses were then fixed and their encephala removed and weighed. Sections of the frontal lobe were taken for histological neuron counting. RESULTS: G1 and G2 showed the highest fetal body weight. Placental weight showed statistical differences (p < 0.01): G1 weighed more than G2 and G3. Otherwise, G2 exhibited the highest encephalon weight, statistically differing from G3 (control) and fluoxetine-treated G1 (p < 0.01). However, G1 did not statistically (p > 0.01) differ from the control group. G3 showed the highest number of neurons per area when compared to G1 and G2 (p < 0.01). CONCLUSION: The use of antidepressants in rats caused an increase in fetal weight and a decrease in the number of fetal frontal lobe neurons, thus suggesting that the use of antidepressants by pregnant women can induce depression in fetuses due to alterations in their neural development.

OBJETIVO: Avaliar as possíveis alterações ocorridas em nível macroscópico e microscópico de fetos de ratas submetidas ao tratamento com fluoxetina e imipramina durante o período "crítico" da gestação. MÉTODO: Quinze ratas, posteriormente ao acasalamento, foram divididas em três grupos experimentais (n = 5): G1, tratadas com 10mg/kg/dia de fluoxetina; G2, tratadas com 10mg/kg/dia de cloridrato de imipramina, e G3 (controle), tratadas com 10mg/kg/dia de solução fisiológica a 0,9 por cento, no 9º, 10º e 11º dias de prenhez das ratas. Posteriormente à cesária, no 21º dia de prenhez, analisou-se macroscopicamente o peso fetal e placentário. Os fetos foram fixados e houve a remoção do encéfalo para pesagem e preparação das lâminas do tecido neuronal para contagem de neurônios do lobo frontal. RESULTADOS: O G1 e G2 apresentaram maior peso fetal. O G1 apresentou maior peso placentário, diferindo do G2 e G3 (p < 0,01). De forma diferente, o G2 possuiu maior peso encefálico, diferindo do G3 e G1 (p < 0,01). G1 não diferiu estatisticamente do grupo controle (p > 0,01). O G3 exibiu maior número de neurônios, por área, do lobo frontal em relação a G1 e G2 (p < 0,01). CONCLUSÃO: A adoção dos antidepressivos causou, nos fetos, aumento de peso e redução da contagem de neurônios do lobo frontal, sugerindo que a indicação de antidepressivos às gestantes pode induzir a depressão nos fetos por alterações em seu neurodesenvolvimento.

Nicotine dependence and smoking cessation / 中南大学学报(医学版)

Tobacco use is the single most preventable cause of death, disability and disease in the world and is projected to be the leading cause of death and disability across all developed and developing countries by 2020. Nicotine, the primary active ingredient of cigarettes that contributes to physical dependence, acts on nicotine receptors in the central nervous system and leads to the release of neurotransmitters (such as dopamine). Like other drugs of abuse, nicotine is thought to produce reinforcing effect by activating the mesocorticolimbic dopamine system. A wide variety of cessation treatments of nicotine dependence is commercially available, yet only 2 general approaches have received empirical validation: behavioral intervention (including 5 As brief intervention) and pharmacotherapy. The evidences show that 5 As brief intervention is one of the most cost-effective treatments in clinical work for busy physicians. Three types of medications have been available in market for smoking cessation treatment: nicotine replacement treatment (NRT, i.e., transdermal patch, gum, inhaler, nasal spray, and lozenge), sustained release bupropion and varenicline. Varenicline, a novel alpha4beta2 nicotinic receptor partial agonist, is effective for tobacco dependence. Phase III trials suggest that it is more effective than NRT and bupropion SR. The safety profile of varenicline is excellent, with the most commonly occurring adverse events, nausea, typically mild and well tolerated. However, new safety warnings are added to the varenicline label because of post-marketing report including agitation, depression and suicidality. A causal connection between varenicline use and these symptoms has not been established.

Effects of dextromethorphan on dopamine dependent behaviours in rats.

Dextromethorphan, a noncompetitive blocker of N-methyl-D- aspartate (NMDA) type of glutamate receptor, at 7.5-75 mg/kg, ip did not induce oral stereotypies or catalepsy and did not antagonize apomorphine stereotypy in rats. These results indicate that dextromethorphan at 7.5-75 mg/kg does not stimulate or block postsynaptic striatal D2 and D1 dopamine (DA) receptors. Pretreatment with 15 and 30 mg/kg dextromethorphan potentiated dexamphetamine stereotypy and antagonised haloperidol catalepsy. Pretreatment with 45, 60 and 75 mg/kg dextromethorphan, which release 5-hydroxytryptamine (5-HT), however, antagonised dexamphetamine stereotypy and potentiated haloperidol catalepsy. Apomorphine stereotypy was not potentiated or antagonised by pretreatment with 7.5-75 mg/kg dextromethorphan. This respectively indicates that at 7.5-75 mg/kg dextromethorphan does not exert facilitatory or inhibitory effect at or beyond the postsynaptic striatal D2 and D1 DA receptors. The results are explained on the basis of dextromethorphan (15-75 mg/kg)-induced blockade of NMDA receptors in striatum and substantia nigra pars compacta. Dextromethorphan at 15 and 30 mg/kg, by blocking NMDA receptors, activates nigrostriatal dopaminergic neurons and thereby potentiates dexampetamine stereotypy and antagonizes haloperidol catalepsy. Dextromethorphan at 45, 60 and 75 mg/kg, by blocking NMDA receptors, releases 5-HT and through the released 5-HT exerts an inhibitory influence on the nigrostriatal dopaminergic neurons with resultant antagonism of dexampetamine stereotypy and potentiation of haloperidol catalepsy.

Bleeding gums: duloxetine may be the cause.

Duloxetine is a newly introduced drug. It is being prescribed for the management of diabetic neuropathic pain and major depressive disorder. The most frequently observed adverse events with duloxetine are nausea, dry mouth and somnolence, constipation, diarrhea, decreased appetite, weight loss, feeling of fatigue, dizziness, somnolence, hypohidrosis, decreased libido and erectile dysfunction. One of the patients being prescribed the drug developed bleeding gums on being started with the drug which resolved on stopping it. We hereby report this case.

Fármacos antidepresivos / Antidepressant drugs

En el presente artículo se describen las diferentes drogas utilizadas para el tratamiento de la depresión, sus modos de acción, sus efectos adversos y las diversas precauciones y advertencias

Tabagismo, abandono do fumo e os otorrinolaringologistas do estado de São Paulo / Smoking, smoking cessation and otorhinolaryngologists in the state of Sao Paulo, Brazil

Os otorrinolaringologistas estão diretamente envolvidos no diagnóstico e tratamento de doenças provocadas pelo cigarro, incluindo o câncer das vias aéreas superiores. É importante que os especialistas estejam capacitados a tratar o tabagismo e a dependência da nicotina. Também se sabe que há fumantes entre os próprios médicos. OBJETIVO: Pesquisar as opiniões e condutas de otorrinolaringologistas do Estado de São Paulo frente ao tabagismo e à dependência química da nicotina, e avaliar o hábito tabagístico dos especialistas. FORMA DE ESTUDO: Corte transversal. MATERIAL E MÉTODOS: Foram selecionados aleatoriamente 600 otorrinolaringologistas do Estado de São Paulo. A esses especialistas foi enviado, em março de 2005, por correio, um questionário padrão. Foram analisadas as respostas recebidas no período de março a maio de 2005. RESULTADOS: Foram recebidas 209 respostas. Nestas, 97 profissionais (46,4 por cento) avaliaram sua familiaridade com os meios de tratamento da dependência de nicotina como regular e 60 (28,7 por cento) como insatisfatória. Dos participantes do estudo, 144 (68,9 por cento) nunca fumaram, 50 (23,9 por cento) são ex-fumantes, nove (4,3 por cento) são fumantes ocasionais e seis (2,9 por cento) são fumantes. CONCLUSÃO: A prevalência de tabagistas na amostra de 209 otorrinolaringologistas do Estado de São Paulo foi de 7,1 por cento.

Otorhinolaryngologists are directly involved in the diagnosis and management of smoking related diseases, including upper airway malignancy. It is important that the specialists have skills to treat smoking and nicotine dependence. It is also known that there are smokers amongst doctors. AIM: To assess the opinions and practices of the otorhinolaryngologists of the state of Sao Paulo, Brazil, concerning smoking and nicotine dependence, and evaluation of smoking habits of the specialists. STUDY DESIGN: Cross-sectional. MATERIAL AND METHODS: We randomly selected 600 otorhinolaryngologists of Sao Paulo State, Brazil. A survey was mailed to the specialists in March 2005. We gathered data received from March to May 2005. RESULTS: There were 209 respondents. Forty-seven specialists (46.4 percent) rated themselves as moderately familiar with the methods for treatment of nicotine dependence, and 60 (28.7 percent) as unsatisfactorily familiar. One hundred and forty-four respondents (68.9 percent) have never smoked, 50 (23.9 percent) were former-smokers, nine (4.3 percent) were occasional smokers and six (2.9 percent) were regular smokers. CONCLUSION: The prevalence of smoking in the sample of 209 otorhinolaryngologists of Sao Paulo State, Brazil, was 7.1 percent.

Dopamine receptors oppositely regulate cocaine-induced transcription factor CREB activation / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the role of dopamine receptors in the regulation of the activity of transcription factor cAMP response element-binding protein (CREB) after cocaine treatment.</p><p><b>METHODS</b>By using dopamine receptor antagonists SCH23390 and nafadotride, the activation of CREB by D1 and D3 dopamine receptors after cocaine treatment and role of extracellular signal-regulated kinase (ERK) in cocaine-induced CREB activation were examined by Western blotting, which was also employed for determination of the effect of SCH23390 and nafadotride on CREB activation.</p><p><b>RESULTS</b>D1 receptor antagonist could inhibit cocaine-induced CREB activation, while D3 receptor antagonist enhanced cocaine-induced CREB activation. Dopamine receptor antagonists SCH23390 and nafadotride did not induce CREB activation. SL327, a MEK inhibitor, inhibited cocaine-induced CREB activation.</p><p><b>CONCLUSION</b>D1 and D3 dopamine receptors can oppositely regulate CREB activation after cocaine treatment and this regulation depends on ERK signaling pathway.</p>

Psicofarmacoterapia antidepresiva / Antidepressant pharmacotherapy

Considering the prevalence of major unipolar depression, the economical costs of its management and the different medications available for its treatment, it is imperative to have a good knowledge of the basic principles used to classify anti depressive medications. A good acquaintance on their mechanisms of action on neurotransmission and receptors, wil allow a better understanding of their therapeutic action and secondary effects. Tricyclics, non selective MAO inhibitors, reversible MAO inhibitors, selective serotonin reuptake inhibitors, dopamine and noradrenalin reuptake inhibitors, 5-HT2 blockers with serotonin reuptake blocking effect, serotonin, noradrenalin and dopamine reuptake inhibitors, alfa 2 receptor blockers and 5-HT/2-3 inhibitors are the eight available types of antidepressants

El Síndrome de interrupción de los inhibidores selectivos de la recaptación de serotonina / The discontinuation syndrome of selective serotonin reuptake inhibitors

Los pacientes que suspenden las medicaciones (antidepresivos, estabilizadores del afecto o antipsicóticos) presentam con frecuencia síntomas y cognoscitivos que pueden, en algunos casos, como sucede con los IMAOS clásicos, requerir tratamiento intrahospitalario. La sintomatología es inespecífica y difiere de los síntomas secundarios indeseables del fármaco o del síndrome de abstinencia que se apresenta con hipnóticos, barbitúricos, benzodiacepinas, alcohol o sub tancias adictivas. En el presente trabajo se hace una revisión de la literarura sobre los aspectos clínicos, epidemiológicos y terapéuticos del Síndrome de Interrupción del tratamiento con los inhibidores selectivos de la recaptación de serotonina (SRS)