Do boys with MAOA_LPR*2R allele present cognitive and learning impairments? / Meninos com o alelo maoa_lpr*2r apresentam prejuízos cognitivos e de aprendizagem?

ABSTRACT. Monoamine oxidase A (MAOA) polymorphisms have been associated with antisocial disorders. Less attention has been paid to the cognitive functioning of individuals with different MAOA alleles. No study has described the cognitive phenotype associated with the less frequent, low enzyme activity allele, MAOA_LPR*2R. Objective: We describe the cognitive correlates of boys having MAOA_LPR*2R allele, ascertained in a sample of school children with normal intelligence, not referred for behavioral disorders. Methods: Participants were eight boys, attending from the second to fifth grades in state-run schools. They were identified among 712 children with typical general cognitive ability, genotyped for MAOA_LPR polymorphism. Participants were assessed with general intelligence, mathematics and spelling achievement, and verbal and visuospatial working memory tests. Neuropsychological performance was compared to published standards, using 1 SD below the mean as a cutoff value for low performance. Results: Intelligence of boys with MAOA_LPR*2R allele varied from above average (N=2) to low average in the other children. Five out of eight boys with the MAOA_LPR*2R allele had low mathematics achievement, and three presented additional difficulties with spelling. Four out of eight children had low short-term and working memory performance. Discussion: This is the first study describing cognitive correlates and school performance in boys having the MAOA_LPR*2R allele. Having this allele, and therefore, probably low MAO-A activity, does not necessarily imply low intelligence or low school performance. However, learning difficulties, particularly in math, and low working memory performance were observed in boys having this allele. This suggests a role of MAOA in learning difficulties.

RESUMO. Polimorfismos da monoaminoxidase A (MAOA) são associados a transtornos antissociais. Menos atenção tem sido dada ao funcionamento cognitivo de indivíduos com diferentes alelos de MAOA. Nenhum estudo descreveu o fenótipo cognitivo associado ao alelo menos frequente, de baixa atividade enzimática, MAOA_LPR*2R. Objetivo: Descrevemos os correlatos cognitivos de meninos com o alelo MAOA_LPR*2R, identificados em uma amostra de escolares com inteligência normal, não encaminhados por transtornos de comportamento. Métodos: Oito meninos com o alelo MAOA_LPR*2R foram identificados entre 712 crianças genotipadas, com inteligência típica, que cursavam do 2º ao 5º ano em escolas públicas. Foram avaliados: inteligência, desempenho em matemática e ortografia, memória de trabalho verbal e visuoespacial. O desempenho foi comparado a normas publicadas, utilizando-se 1 desvio padrão (DP) abaixo da média como ponto de corte para desempenho rebaixado. Resultados: A inteligência dos meninos com alelo MAOA_LPR*2R variou de acima da média (N=2) a médio-inferior nas demais crianças. Cinco dos oito meninos com alelo MAOA_LPR*2R apresentaram desempenho rebaixado em matemática e três apresentaram dificuldades adicionais em ortografia. Quatro dos oito meninos apresentaram baixo desempenho de memória de curto prazo e de trabalho. Discussão: Este é o primeiro estudo a descrever os correlatos cognitivos e o desempenho escolar em meninos com alelo MAOA_LPR*2R. Ter esse alelo não significa necessariamente baixa inteligência ou baixo desempenho escolar. No entanto, dificuldades de aprendizagem, principalmente em matemática, e desempenho rebaixado da memória de trabalho foram observados em mais da metade dos meninos com esse alelo. Isso sugere um papel do MAOA nas dificuldades de aprendizagem.

Source, metabolism and function of dopamine in digestive tract / 生理学报

Dopamine (DA), as a catecholamine neurotransmitter widely distributed in the central nervous system and the peripheral tissues, has attracted a lot of attention. Especially in recent years, DA has been found to regulate the function of the immune system, and the involvement of DA in the intestinal mucosal inflammation-related diseases has become a hot research topic. The digestive tract is an important source of peripheral DA, and DA is not only produced in the enteric nervous system and gastrointestinal epithelium, but also produced by intestinal microorganisms. In addition to the synthetases of DA, the DA contents in body tissues are also affected by the two kinds of metabolic enzymes, monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). This article reviewed the sources, metabolism, and functions of DA in digestive tract, especially focusing on the distribution and function of MAO and COMT, the enzymes degrading DA.

Sex-Related Effects of Prenatal Stress on Region-Specific Expression of Monoamine Oxidase A and β Adrenergic Receptors in Rat Hearts / Efeitos Sexo-Específicos de Estresse Pré-Natal na Expressão Região-Específica de Monoamina Oxidase A e Receptores Adrenérgicos Β no Coração de Ratos

Abstract Background: Prenatal stress may increase risk of developing cardiovascular disorders in adulthood. The cardiotoxic effects of catecholamines are mediated via prolonged adrenergic receptor stimulation and increased oxidative stress upon their degradation by monoamine oxidase A (MAO-A). Objectives: We investigated long-term effects of prenatal stress on β (1, 2, 3) adrenergic receptors and MAO-A gene expression in the hearts of adult rat offspring. Methods: Pregnant rats were exposed to unpredictable mild stress during the third week of gestation. RNA was isolated from left ventricular apex and base of adult offspring. Quantitative PCR was used to measure gene expression in collected ventricular tissue samples. The level of significance was set to p < 0.05. Results: β3 adrenergic receptor mRNA was undetectable in rat left ventricle. β1 adrenergic receptor was the predominantly expressed subtype at the apical and basal left ventricular myocardium in the control females. Male offspring from unstressed mothers displayed higher apical cardiac β1 than β2 adrenergic receptor mRNA levels. However, β1 and β2 adrenergic receptor mRNAs were similarly expressed at the ventricular basal myocardium in males. Unlike males, prenatally stressed females exhibited decreased β1 adrenergic receptor mRNA expression at the apical myocardium. Prenatal stress did not affect cardiac MAO-A gene expression. Conclusions: Collectively, our results show that prenatal stress may have exerted region- and sex-specific β1 and β2 adrenergic receptor expression patterns within the left ventricle.

Resumo Fundamento: Estresse pré-natal pode aumentar os riscos de desenvolver doenças cardiovasculares na idade adulta. Os efeitos cardiotóxicos de catecolaminas são mediados pela estimulação prolongada dos receptores adrenérgicos e pelo aumento do estresse oxidativo após sua degradação pela monoamina oxidase A (MAO-A). Objetivos: Investigamos os efeitos a longo prazo de estresse pré-natal nos receptores β (1, 2, 3) adrenérgicos e na expressão do gene MAO-A nos corações da prole adulta de ratos. Método: Ratas prenhes foram expostas a estresse crônico moderado imprevisível durante a terceira semana de gestação. O RNA foi isolado do ápice e da base do ventrículo esquerdo da prole adulta. Utilizou-se PCR quantitativa em tempo real para medir a expressão gênica nas amostras de tecido ventricular coletadas. O nível de significância foi estabelecido em p < 0,05. Resultados: Foi indetectável o mRNA do receptor adrenérgico β3 no ventrículo esquerdo dos ratos. O receptor adrenérgico β1 foi o subtipo mais expresso no miocárdio ventricular esquerdo apical e basal nas fêmeas controle. A prole masculina das mães não estressadas apresentou níveis cardíacos apicais de mRNA do receptor adrenérgico β1 mais altos do que os de β2. Porém, mRNAs dos receptores adrenérgicos β1 e β2 foram expressos de forma semelhante no miocárdio basal ventricular na prole masculina em geral. Ao contrário da prole masculina, a prole feminina exposta ao estresse pré-natal exibiu uma expressão diminuída do mRNA do receptor adrenérgico β1 no miocárdio apical. O estresse pré-natal não afetou a expressão gênica de MAO-A cardíaca. Conclusões: Coletivamente, nossos resultados mostram que estresse pré-natal pode ter exercido padrões de expressão região- e sexo-específica dos receptores adrenérgicos β1 e β2 no ventrículo esquerdo.

Postpartum depression: association with genetic polymorphisms of noradrenaline metabolic enzymes and the risk factors / 南方医科大学学报

OBJECTIVE@#To investigate the association of genetic polymorphisms of norepinephrine metabolizing enzymes with postpartum depression and analyze the risk factors for postpartum depression in women following cesarean section.@*METHODS@#A total of 591 Chinese woman of Han Nationality undergoing caesarean section were enrolled in this study. The diagnosis of postpartum depression was established for an Edinburgh Postnatal Depression Scale (EPDS) score ≥9. For all the women without antepartum depression, the genotypes of catechol-O-methyltransferase (COMT; at 5 sites including rs2020917 and rs737865) and monoamine oxidase A (rs6323) were determined using Sequenom Mass Array single nucleotide polymorphism (SNP) analysis. We analyzed the contribution of the genetic factors (SNPs, linkage disequilibrium and haplotype) to postpartum depression and performed logistic regression analysis to identify all the potential risk factors for postpartum depression and define the interactions between the genetic and environmental factors.@*RESULTS@#The incidence of postpartum depression was 18.1% in this cohort. Univariate analysis suggested that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype) were significantly correlated with the occurrence of postpartum depression ( < 0.05). Logistic regression analysis showed that COMT polymorphism at rs2020917 (TT genotype) and rs737865 (GG genotype), severe stress during pregnancy, and domestic violence were the risk factors for postpartum depression ( < 0.05); no obvious interaction was found between the genetic polymorphisms and the environmental factors in the occurrence of postpartum depression.@*CONCLUSIONS@#The rs2020917TT and rs737865GG genotypes of COMT, stress in pregnancy, and domestic violence are the risk factors for postpartum depression.

Differences in dietary intakes, body compositions, and biochemical indices between metabolically healthy and metabolically abnormal obese Korean women

BACKGROUND/OBJECTIVES: There are various factors that affect metabolic abnormalities related to obesity. The purpose of this study is to analyze the differences in dietary intakes and body compositions of obese women according to metabolic risks and to classify them as metabolically healthy obese (MHO) or metabolically abnormal obese (MAO). SUBJECTS/METHODS: This study was conducted on 59 obese Korean women aged 19 to 60 years. NCEP-ATPIII criteria were applied and the women classified as MHO (n = 45) or MAO (n = 14). Body composition of each subject was measured by using dual-energy x-ray absorptiometry (DEXA). Three-day food records were used to analyze dietary intake. Eating habits and health-related behaviors were determined through questionnaires. Indirect calorimetry was used to measure resting metabolic rate and respiratory rate. RESULTS: The average age of the subjects was 43.7 years. The analysis of body composition according to phenotype revealed significantly higher body fat mass (P < 0.05), arm fat mass (P < 0.05), and android fat mass (P < 0.05), as measured by DEXA, in the MAO group than in the MHO group. There was no significant difference in the dietary intake of the two groups. However, eating behaviors differed. Compared to the MHO group, the MAO women had a shorter meal time (less than 10 minutes), a preference of oily foods, and a tendency to eat until full. Therefore, the eating habits of MHO women were more positive than those of MAO women. CONCLUSIONS: The results suggest that fat distribution in each body region affects various metabolic abnormalities. A high level of arm fat mass in obese Korean women may increase metabolic risk. In addition, eating habits of obese Korean women are considered to be environmental factors affecting the metabolic phenotype of obese Korean women.

Fatty Acid Increases cAMP-dependent Lactate and MAO-B-dependent GABA Production in Mouse Astrocytes by Activating a G(αs) Protein-coupled Receptor

Medium-chain fatty acids (MCFAs) are mostly generated from dietary triglycerides and can penetrate the blood-brain barrier. Astrocytes in the brain use MCFAs as an alternative energy source. In addition, MCFAs have various regulatory and signaling functions in astrocytes. However, it is unclear how astrocytes sense and take up MCFAs. This study demonstrates that decanoic acid (DA; C10), a saturated MCFA and a ligand of G(αs) protein-coupled receptors (G(αs)-GPCRs), is a signaling molecule in energy metabolism in primary astrocytes. cAMP synthesis and lactate release were increased via a putative G(αs)-GPCR and transmembrane adenylyl cyclase upon short-term treatment with DA. By contrast, monoamine oxidase B-dependent gamma-aminobutyric acid (GABA) synthesis was increased in primary cortical and hypothalamic astrocytes upon long-term treatment with DA. Thus, astrocytes respond to DA by synthesizing cAMP and releasing lactate upon short-term treatment, and by synthesizing and releasing GABA upon long-term treatment, similar to reactive astrocytes. Our data suggest that astrocytes in the brain play crucial roles in lipid-sensing via GPCRs and modulate neuronal metabolism or activity by releasing lactate via astrocyte-neuron lactate shuttle or GABA to influence neighboring neurons.

Effects and Mechanisms of Radiofrequency Ablation of Renal Sympathetic Nerve on Anti-Hypertension in Canine / Efeitos e Mecanismos da Denervação Simpática Renal por Radiofrequência na Anti-Hipertensão em Cães

Abstract Background: Radiofrequency ablation of renal sympathetic nerve (RDN) shows effective BP reduction in hypertensive patients while the specific mechanisms remain unclear. Objective: We hypothesized that abnormal levels of norepinephrine (NE) and changes in NE-related enzymes and angiotensinconverting enzyme 2 (ACE2), angiotensin (Ang)-(1-7) and Mas receptor mediate the anti-hypertensive effects of RDN. Methods: Mean values of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were assessed at baseline and follow-up. Plasma and renal norepinephrine (NE) concentrations were determined using highperformance liquid chromatography with electrochemical detection, and levels of NE-related enzyme and ACE2-Ang(1-7)- Mas were measured using real time PCR, Western blot and immunohistochemistry or Elisa in a hypertensive canine model fed with high-fat diet and treated with RDN. The parameters were also determined in a sham group treated with renal arteriography and a control group fed with normal diet. Results: RDN decreased SBP, DBP, MAP, plasma and renal NE. Compared with the sham group, renal tyrosine hydroxylase (TH) expression was lower and renalase expression was higher in the RDN group. Compared with the control group, renal TH and catechol-o-methyl transferase (COMT) were higher and renalase was lower in the sham group. Moreover, renal ACE2, Ang-(1-7) and Mas levels of the RDN group were higher than those of the sham group, which were lower than those of the control group. Conclusion: RDN shows anti-hypertensive effect with reduced NE and activation of ACE2-Ang(1-7)-Mas, indicating that it may contribute to the anti-hypertensive effect of RDN.

Resumo Fundamentos: A denervação simpática renal por radiofrequência (DSR) mostra redução eficaz da pressão arterial (PA) de pacientes hipertensos, ainda que os mecanismos específicos permaneçam obscuros. Objetivo: Fizemos a hipótese de que níveis alterados de noradrenalina (NA) e mudanças nas enzimas relacionadas à NA e enzima conversora de angiotensina 2 (ECA-2), angiotensina (Ang)-(1-7) e receptor Mas são mediadores dos efeitos antihipertensivos da DSR. Métodos: Foram avaliados os valores médios de pressão arterial sistólica (PAS), pressão arterial diastólica (PAD) e pressão arterial média (PAM) no início e durante o seguimento. Foram medidas as concentrações plasmática e renal de noradrenalina (NA) por cromatografia líquida de alta eficiência com detecção eletroquímica, e os níveis de enzima relacionada à NA e ECA2-Ang-(1-7)-Mas através de PCR em tempo real, Western blot e imunohistoquímica ou Elisa em um modelo canino de hipertensão que recebeu ração rica em gordura e foi tratado com DSR. Os parâmetros também foram determinados em um grupo de cirurgia simulada submetido à arteriografia renal e em um grupo controle que recebeu dieta normal. Resultados: DSR causou diminuição da PAS, PAD, PAM e das concentrações plasmática e renal de NA. Em comparação ao grupo placebo, a expressão da tirosina hidroxilase (TH) renal foi menor e a da renalase foi maior no grupo DSR. Em comparação ao grupo controle, os níveis de TH renal e de catecol-o-metil-transferase (COMT) foram maiores e os de renalase foram menores no grupo cirurgia simulada. Além disso, os níveis renais de ECA2, Ang-(1-7) e Mas foram maiores no grupo DSR do que no grupo cirurgia simulada, que, por sua vez, foram menores do que no grupo controle. Conclusões: A DSR mostra efeitos anti-hipertensivos com redução da NA e ativação da ECA2-Ang-(1-7)-Mas, o que indica que pode contribuir com o efeito anti-hipertensivo da DSR.

Association between GABA3 Gene Polymorphisms and Attention Deficit Hyperactivity Disorder in Korean Children

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is common disorder of the school-age population. ADHD is familial and genetic studies estimate heritability at 80–90%. The aim of the present study was to investigate the association between the genetic type and alleles for gamma-aminobutyric acid receptor subunit beta-3 (GABA3) gene in Korean children with ADHD. METHODS: The sample consisted of 180 ADHD children and 159 control children. We diagnosed ADHD according to DSM-IV. ADHD symptoms were evaluated with Conners' Parent Rating Scales and Dupaul Parent ADHD Rating Scales. Blood samples were taken from the 339 subjects, DNA was extracted from blood lymphocytes, and PCR was performed for GABA3 rs2081648, rs1426217 and rs981778 Polymorphism. Alleles and genotype frequencies were compared using the chi-square test. We compared the allele and genotype frequencies of GABA3 gene polymorphism in the ADHD and control groups. RESULTS: This study showed that there was a significant correlation among the frequencies of the rs2081648 (OR=0.71, 95% CI=0.51–0.98, p=0.040) of alleles of MAO, but the final conclusions are not definite. Follow up studies with larger patient or pure subgroups are expected. CONCLUSION: These results suggested that GABA3 might be related to ADHD symptoms.

Monoamine Oxidase-A Genetic Variants and Childhood Abuse Predict Impulsiveness in Borderline Personality Disorder

OBJECTIVE: Impulsivity is a core feature of borderline personality disorder (BPD) and antisocial personality disorder (ASPD) that likely arises from combined genetic and environmental influences. The interaction of the low activity variant of the monoamine oxidase-A (MAOA-L) gene and early childhood adversity has been shown to predict aggression in clinical and non-clinical populations. Although impulsivity is a risk factor for aggression in BPD and ASPD, little research has investigated potential gene-environment (G×E) influences impacting its expression in these conditions. Moreover, G×E interactions may differ by diagnosis. METHODS: Full factorial analysis of variance was employed to investigate the influence of monoamine oxidase-A (MAO-A) genotype, childhood abuse, and diagnosis on Barratt Impulsiveness Scale-11 (BIS-11) scores in 61 individuals: 20 subjects with BPD, 18 subjects with ASPD, and 23 healthy controls. RESULTS: A group×genotype×abuse interaction was present (F(2,49)=4.4, p=0.018), such that the interaction of MAOA-L and childhood abuse predicted greater BIS-11 motor impulsiveness in BPD. Additionally, BPD subjects reported higher BIS-11 attentional impulsiveness versus ASPD participants (t(1,36)=2.3, p=0.025). CONCLUSION: These preliminary results suggest that MAOA-L may modulate the impact of childhood abuse on impulsivity in BPD. Results additionally indicate that impulsiveness may be expressed differently in BPD and ASPD.

Susceptibility to methamphetamine dependence associated with high transcriptional activity alleles of VNTR polymorphism in the promoter region of monoamine oxidase A [MAOA]

Background and purpose: Monoamine oxidase A [MAOA, Xp11.3; OMIM: 309850] can modulate the level of neurotransmitters in the central nervous system. A 30 bp variable number of tandem repeat [VNTR] genetic polymorphism on the promoter region of the MAOA can modulate the transcriptional activity of the gene. Association between this polymorphism and dependency to methamphetamine was investigated

Subjects and methods: A total of 65 methamphetamine abusers [52 males and 13 females] and 635 healthy controls [525 males and 110 females] were included in the present case-control study. Genotypic analysis for the MAOA VNTR polymorphism was determined by conventional PCR. Based on transcriptional activity of the VNTR alleles, the alleles were categorized into two classes: L allele [2R and 3R alleles] and H allele [3.5R, 4R and 5R alleles], which have low and high transcriptional activities, respectively

Results: Our data show that the H allele significantly increases the risk of methamphetamine dependence in males [OR = 2.03, 95% CI: 1.04-3.67, P = 0.037]. The H allele seems positively associated with the risk of dependency to methamphetamine among females, but the observed OR did not reach the significance level, probability due to small sample size of the patients

Conclusion: The present study supports the role of the VNTR polymorphism on the promoter region of the MAOA on methamphetamine dependence

Estudo da relação entre o polimorfismo VNTR MAOA-u e o tabagismo em trabalhadores da Diretoria de Administração do Campus (Dirac), unidade da Fundação Oswaldo Cruz / Study of the relationship between VNTR polymorphism MAP-u and smoking workers of the Board of Directors of the Campus (Dirac) unit of the Oswaldo Cruz Foundation

O tabagismo representa um problema de Saúde Publica e é considerado a principal causa de morte evitável no mundo. A nicotina presente no tabaco estimula a liberação de dopamina, que é o neurotransmissor chave na dependência tabágica, por seu papel nos mecanismos de recompensa cerebral. Desta forma, genes que regulam a concentração da dopamina podem ter influência no comportamento do tabagismo, como o gene que codifica a enzima MAO, responsável pela degradação de dopamina. No presente estudo,foi verificada a relação entre o polimorfismo na região promotora do gene MAOA (VNTR MAOA-u) e o tabagismo. Este estudo foi do tipo transversal com a participação de 121 homens, trabalhadores da Diretoria de Administração do Campus (Dirac), unidade da Fundação Oswaldo Cruz (74 nunca fumantes, 26 ex-fumantes e 21 fumantes atuais). O polimorfismo foi determinado na amostra populacional pela técnica da Reação em Cadeia da Polimerase (PCR). As análises estatísticas não revelaram associação significativa entre o polimorfismo VNTR MAOA-u e o status tabágico, bem como relação com as características do comportamento do tabagismo (tempo de fumo, idade de início, número de recaídas, idade que parou de fumar, grau de dependência nicotínica – FNTD e número de cigarros consumidos por dia). Dada a importância do tema, considera-se importante a realização de futuros estudos com maior tamanho amostral para confirmação dos resultados encontrados e maior esclarecimento sobre os mecanismos genéticos que podem contribuir com a susceptibilidade à dependência ao tabaco.

Smoking is a public health problem and is considered the leading cause of preventable death in the world. The nicotine present in tobacco stimulates the release of dopamine, thekey neurotransmitter in nicotine dependence, by role in the brain's reward mechanisms. Thus, genes that regulate the concentration of dopamine can influence the smoking behavior, as the gene encoding the MAO enzyme responsible for the dopamine degradation. In the present study, we detected the relationship between a polymorphism inthe promoter region of the MAOA gene (MAOA VNTR-u) and smoking. This study wascross-sectional with the participation of 121 men, workers of Diretoria de Administraçãodo Campus (Dirac), unidade da Função Oswaldo Cruz (74 never smokers, 26 former smokers and 21 current smokers). The polymorphism was determined in the sample population by the technique of Polymerase Chain Reaction (PCR). Statistical analysis revealed no significant association between the polymorphism MAOA-u VNTR and thes moking status as well as relationship with the smoking behavior characteristics (duration of smoking, age at smoking iniciation, number of relapses, age stopped smoking, degree of nicotine dependence - FNTD and the number of cigarettes smoked per day). Given thei mportance of the issue, it is considered important to conduct further studies with larger sample size to confirm the results found and more information about the genetic mechanisms that may contribute to susceptibility to tobacco addiction.

A Biocompatibility Evaluation of Hydroxyapaite·Titania Surface for Dental Implant / 치위생과학회지

The objective of this study was to fabricate hydroxyapatite (HA) containing titania layer by HA blasting and anodization method to obtain advantages of both methods and evaluated biocompatibility. To fabricate the HA containing titania layer on titanium, HA blasting treatment was performed followed by microarc oxidation (MAO) using the electrolyte solution of 0.04 M β-glycerol phosphate disodium salt n-hydrate and 0.4 M calcium acetate n-hydrate on the condition of various applied voltages (100, 150, 200, 250 V) for 3 minutes. The experimental group was divided according to the surface treatment procedure: SM (simple machined polishing treatment), HA, MAO, HA+MAO 100, HA+MAO 150, HA+MAO 200, HA+ MAO 250. The wettability of surface was observed by contact angle measurement. Biocompatibility was evaluated by cell adhesion, and cell differentiation including alkaline phosphatase activity and calcium concentration with MC3T3-E1 cells. The porous titanium oxide containing HA was formed at 150 and 200 V. These surfaces had a more hydrophilic characteristic. Biocompatibility was demonstrated that HA·titania composite layer on titanium showed enhanced cell adhesion, and cell differentiation. Therefore, these results suggested that HA containing titania layer on titanium was improved biological properties that could be applied as material for dental implant system.

Asociación entre los polimorfismos 5HTTLPR, uMAOA y depresión en una cohorte de pacientes de atención primaria / Association between serotonin transporter and monoamine oxidase A gene polymorphisms and depression

Background: Serotonin plays a central role regulating mood and on the development of depressive disorders. Aim: To study whether 5HTTLPR functional polymorphisms in the serotonin transporter gene or the Monoamine oxidase A gene (uMAOA) were risk markers for depression. Material and Methods: The Composite International Diagnostic Interview (CIDI) was applied to 1,062 consultants in primary health care centers aged between 18 and 75 years to establish the diagnosis of depression. A sample of saliva was obtained for DNA extraction and genetic analyses. Results: No association between the presence of depressive disorders and 5HTTLPR (ss) or uMAOA (3/3) risk genotypes was found. Psychological abuse and the presence of two or more life events were found to be predictors of depression in the studied sample. Conclusions: In this study, 5HTTLPR and uMAOA polymorphisms were not risk factors for depression. However, psychological abuse and the presence of two or more life events were risk factors for depressive disorders.

Effects of Lonicera Japonica flavone on immunomodulation in mice / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study immunomodulating activity of Lonicera Japonica flavone by investigating immune enzymatic activity of serum and antoxidized activity of lymphoid organs in mice.</p><p><b>METHODS</b>Fifty KM mice were randomly divided into control group, model group, low dose group, middle dose group and high dose group(n = 10), respectively. And low dose group, middle dose group and high dose group were given Lonicera Japonica flavone with 100 mg/kg, 200 mg/kg and 400 mg/kg every day, respectively, while control group and model group were administered with NS. After continuously giving drug 7 weeks, other groups were injected with Dexamethasome (Dex: 25 mg /kg) for 3 days by subcutaneous injection, but the control group were treated with NS. And after giving Lonicera Japonica flavone 1 week simultaneously, organ indexes , the activity of acid phosphatase (ACP), alkaline phosphatase (AKP) and lysozyme (LSZ) in serum , and the content of monoamine oxidase (MAO), total antioxidant capacity (T-AOC), total superoxide dismutase (SOD) and malondialdehyde (MDA) in lymphoid organs in mice were tested, respectively.</p><p><b>RESULTS</b>Lonicera Japonica flavone could significantly improve the organ indexes, and significantly improve the activity of ACP, AKP and LSZ in serum, and significantly improve the contents of T-AOC and SOD, but reduce that of MAO and MDA in lymphoid organs in immunosuppressed mice.</p><p><b>CONCLUSION</b>Ionicera Japonica flavone can significantly improve the activity of immune enzyme in serum and the antioxidized activity of lymphoid organs in mice. It suggests that Ionicera Japonica flavone has a good immunomodulatory effects.</p>

Polymorphisms of catechol-O-methyltransferase and monoamine oxidase B genes among Chinese patients with Parkinson's disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study polymorphisms of catechol-O-methyltransferase (COMT) and monoamine oxidase B (MAO-B) genes among Chinese patients with Parkinson's disease.</p><p><b>METHODS</b>Genotypes of the COMT and MAO-B genes of 1408 patients with Parkinson's disease was sequenced using Sanger method. And these patients were recruited by Chinese Parkinson Study Group from 29 research centers throughout the country.</p><p><b>RESULTS</b>The genotypic frequencies of COMT rs4680 AA, AG, GG were 8.9%, 42.0% and 49.1%. Those of rs4818 CC, CG, GG were 42.5%, 45.6% and 11.9%, respectively. The genotype frequencies of MAO-B rs1799836 A/AA, AG, G/GG were 74.4%, 14.1% and 11.5%, respectively. The haplotype formed by COMT rs4680 (GG) and MAO-B rs1799836 (A/AA) genotype has a frequency of 36.86%.</p><p><b>CONCLUSION</b>Polymorphisms of COMT and MAO-B genes has a unique characteristics among Chinese patients with Parkinson's disease. They may be related with differences in drug response in such patients.</p>

Anticonvulsant profile of 2-ethylthio-7-methyl-4-(4-methylphenyl)pyrazolo[1, 5-a][1, 3, 5]triazine

This work evaluates the central nervous effects in ICR strain mice of 2-ethylthio-7-methyl-4-(4-methylphenyl)pyrazolo[1,5-a][1,3,5]triazine (MH4b1), a compound obtained by an efficient one-step reaction of S,S-diethyl 4-methylbenzoylimidodithiocarbonate with 5-amino-3-methyl-1H-pyrazole, in order to assess its neuro-pharmacological profile. The tests applied were: maximal electroshock seizure (MES), pentylenetetrazole (PTZ) seizures, forced swimming, plus maze, marble burying, sleeping time, rota-rod and catalepsy. In addition, MH4b1 binding to the benzodiazepine site of the GABA-A receptor and MH4b1 inhibition of monoamine oxidase (MAO) subtypes A and B were evaluated. MH4b1 showed anticonvulsant effects in a dose dependent manner (30-300 mg/kg, p.o.) against MES and inhibition of MAO-B (IC50: 24.5 µM) without activity at the benzodiazepine site. These data suggest that MH4b1 has anticonvulsant properties related to MAO-B inhibition.

Este trabalho avalia o efeito do 2-etiltio-7-metil-4-(4-metilfenil)pirazol[1,5-a][1,3,5]triazina (MH4b1) no sistema nervoso central de camundongos ICR. O MH4b1 foi obtido por a reação de 4-metilbenzoilimidoditiocarbonato de S,S-dietil e 5-amino-3-metil-1H-pirazol em uma única etapa. O perfil neurofarmacológico foi realizado por testes de convulsão induzida por eletrochoque (MES) e pentilenotetrazol (PTZ) e por testes de nado forçado, labirinto em cruz, esconder as esferas, sono barbitúrico, rota-rod e catalepsia. Também foi avaliada a união do MH4b1 ao o local de ligação de benzodiazepínicos do receptor GABA-A e a capacidade inibitória do MH4b1 sobre a monoaminoxidase (MAO) A e B. O MH4b1 mostrou efeito anticonvulsivante dependente da dose (30-300 mg) no teste do MES e apresentou atividade inibitória da MAO-B (CI50: 24.5 µM) sem interagir com o local de ligação de benzodiazepínicos do receptor. Os resultados sugerem que o MH4b1 tem atividade anticonvulsivante relacionada com a inibição da MAO-B.

Behavioural and neuroendocrine effects of aqueous extract of Boerhaavia diffusa Linn. in mice using tail suspension and forced swim tests – A preliminary study.

The present study was done to evaluate the effect of aqueous extract of B. diffusa on depression in mice using behavioral models such as tail suspension test (TST) and forced swim test (FST). The extract (50, 100 and 200 mg/kg, po) was administered for 14 successive days to Swiss young albino mice. On 14th day, 60 min after administration, mice were subjected to TST and FST. The administration of aqueous extract of B. diffusa (50, 100 and 200 mg/kg, po) significantly decreased immobility period in both TST and FST, indicating significant antidepressant-like activity. The lowest dose (50 mg/kg) of the extract decreased the immobility period most significantly in FST, showing most potent antidepressant-like action. The efficacy of the extract (50 mg/kg) was comparable to fluoxetine (20 mg/kg). The extract did not show any significant effect on locomotor activity. The extract showed significant monoamine oxidase -A inhibitory activity. There was no significant effect of the extract on plasma corticosterone levels. Prazosin (α1-adrenoceptor antagonist), sulpiride (selective D2-receptor antagonist), baclofen (GABAB agonist), and p-CPA (tryptophan hydroxylase inhibitor) significantly attenuated the extract-induced antidepressant-like effect, when tested in TST. The extract might produce antidepressant-like effect by interaction with α1-adrenoceptors, dopamine-D2 receptors, serotonergic, and GABAB receptors. Thus, aqueous extract of B. diffusa showed significant antidepressant-like activity in mice probably through involvement of monoaminergic and GABAergic systems.

Increasing activity of a monoamine oxidase by random mutation / 生物工程学报

The monoamine oxidase mutant A-1 (F210V/L213C) from Aspergillus niger showed some catalytic activity on mexiletine. To futher improve its activity, the mutant was subjected to directed evolution with MegaWHOP PCR (Megaprimer PCR of Whole Plasmid) and selection employing a high-throughput agar plate-based colorimetric screen. This approach led to the identification of a mutant ep-1, which specific activity was 189% of that for A-1. The ep-1 also showed significantly improved enantioselectivity, with the E value increased from 101 to 282; its kinetic k(cat)/K(m) value increased from 0.001 51 mmol/(L x s) to 0.002 89 mmol/(L x s), suggesting that catalytic efficiency of ep-1 had been improved. The mutant showed obviously higher specific activities on 7 of all tested 11 amines substrates, and the others were comparable. Sequence analysis revealed that there was a new mutation T162A on ep-1. The molecular dynamics simulation indicated that T162A may affect the secondary structure of the substrate channel and expand the binding pocket.