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2.
Medicine (Baltimore) ; 100(35): e27102, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477148

RESUMO

ABSTRACT: The turnover rate among kindergarten teachers in advanced countries is extremely high. As such, there is an urgent need to determine the reasons for this turnover and to identify ways to prevent it. The current study investigates the individual and environmental factors that impact kindergarten teachers' willingness to continue working.A total of 600 kindergarten teachers in Japan participated in this study. Participants responded to questionnaires regarding their willingness to continue working, mental health, work engagement, and the availability of social support. Multiple logistic regression analysis was used to analyze participants' data, with willingness to continue working for 5 or more years as the dependent variable. Additionally, Spearman rank correlation was used to examine the correlations between factors associated with willingness to continue working.Factors such as older age, living with a spouse, caring for younger children (up to 2 years old) at work, good mental health, and higher work engagement were significantly associated with teachers' higher willingness to continue working. Factors such as marriage, health and family problems, overtime work, issues with workplace childcare, and education policy, working time/day problems, human relations, and difficulties taking care of children were correlated with teachers' lack of willingness to continue working.The findings of this cross-sectional study suggest that welfare benefits and individual support systems could be key elements to encourage kindergarten teachers to continue working and could lead to their improved job satisfaction and mental health. Balanced work conditions and workers' high agreement with their workplace's overall childcare or educational policies may lead to lower turnover. Some programs - such as relationship counselling - could have a positive impact on teachers' mental health and job satisfaction.


Assuntos
Satisfação no Emprego , Professores Escolares/psicologia , Adulto , Distribuição de Qui-Quadrado , Estudos Transversais , Feminino , Humanos , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Reorganização de Recursos Humanos , Professores Escolares/estatística & dados numéricos , Inquéritos e Questionários , Carga de Trabalho/psicologia , Local de Trabalho/psicologia , Local de Trabalho/normas
3.
Neuropsychopharmacol Rep ; 41(3): 440-443, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34357702

RESUMO

Tardive dyskinesia (TD) is a common side effect of antipsychotics, and it remains a persistent and challenging problem. The blonanserin transdermal patch, developed in Japan and launched in September 2019, is the first antipsychotic transdermal treatment. Here, we describe a patient with schizophrenia who exhibited markedly improved orofacial dyskinesia after switching from blonanserin tablets to blonanserin transdermal patches. We speculate that the patch formulation might have led to more stable plasma blonanserin levels, thus reducing the side effects. Specifically, the patch formulation might have contributed to stable plasma levels via the continuous and direct absorption of blonanserin through the skin.

4.
Transl Psychiatry ; 11(1): 132, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602898

RESUMO

Genetic and epidemiological evidence has suggested that genetic factors are important in schizophrenia, although its pathophysiology is poorly understood. This study used whole-exome sequencing to investigate potential novel schizophrenia-causing genes in a Japanese family containing several members affected by severe or treatment-resistant schizophrenia. A missense variant, chr12:132064747C>T (rs200626129, P2805L), in the E1A-binding protein P400 (EP400) gene completely segregated with schizophrenia in this family. Furthermore, numerous other EP400 mutations were identified in the targeted sequencing of a schizophrenia patient cohort. We also created two lines of Ep400 gene-edited mice, which had anxiety-like behaviours and reduced axon diameters. Our findings suggest that rs200626129 in EP400 is likely to cause schizophrenia in this Japanese family, and may lead to a better understanding and treatment of schizophrenia.


Assuntos
Esquizofrenia , Animais , Proteínas de Transporte , Exoma/genética , Humanos , Camundongos , Mutação de Sentido Incorreto , Linhagem , Esquizofrenia/genética , Sequenciamento Completo do Exoma
5.
Int J Neurosci ; : 1-8, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33225793

RESUMO

PURPOSE: Somatosensory processing problems are often reported in individuals with autism spectrum disorder (ASD), along with an abnormal multimodal integration of visual, tactile or proprioceptive information. However, the effects of visual stimulation and attention on somatosensory processing in ASD remain unknown. This study explores the effects of visual attention on somatosensory processing in ASD. MATERIALS AND METHODS: The neural activity in somatosensory areas and associated regions was investigated by measuring somatosensory evoked potentials (SEPs) elicited by median nerve stimulation, in three different conditions (closed eyes, open eyes and focused attention to a visual task). Nine individuals with ASD and nine typically developing (TD) individuals participated in the study. RESULTS: There were significant interactions between groups (ASD, TD) and conditions (closed eye, open eye, visual task requiring focused attention) for P100-N140 SEP amplitudes evaluated by 2-way analysis of variance. Post hoc analyses revealed that the P100-N140 amplitude with closed eyes recorded larger SEPs in the ASD group than in the TD group at C3' of the international 10-20 system. In the ASD group, the P100-N140 amplitude elicited smaller responses during visual tasks than with closed or open eyes. There were no significant differences in N20-P25 SEP components. CONCLUSIONS: These findings suggest that visual attention affects the later stages of somatosensory processing in individuals with ASD.

6.
J Neural Transm (Vienna) ; 127(11): 1517-1526, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32388794

RESUMO

Panic disorder (PD) is a common and debilitating neuropsychiatric disorder characterized by panic attacks coupled with excessive anxiety. Both genetic factors and environmental factors play an important role in PD pathogenesis and response to treatment. However, PD is clinically heterogeneous and genetically complex, and the exact genetic or environmental causes of this disorder remain unclear. Various approaches for detecting disease-causing genes have recently been made available. In particular, genome-wide association studies (GWAS) have attracted attention for the identification of disease-associated loci of multifactorial disorders. This review introduces GWAS of PD, followed by a discussion about the limitations of GWAS and the major challenges facing geneticists in the post-GWAS era. Alternative strategies to address these challenges are then proposed, such as epigenome-wide association studies (EWAS) and rare variant association studies (RVAS) using next-generation sequencing. To date, however, few reports have described these analyses, and the evidence remains insufficient to confidently identify or exclude rare variants or epigenetic changes in PD. Further analyses are therefore required, using sample sizes in the tens of thousands, extensive functional annotations, and highly targeted hypothesis testing.


Assuntos
Estudo de Associação Genômica Ampla , Transtorno de Pânico , Epigênese Genética , Predisposição Genética para Doença , Humanos , Transtorno de Pânico/genética
7.
J Neural Transm (Vienna) ; 127(11): 1501-1515, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32285255

RESUMO

Twin studies of psychiatric disorders such as schizophrenia and autism spectrum disorder have employed epidemiological approaches that determine heritability by comparing the concordance rate between monozygotic twins (MZs) and dizygotic twins. The basis for these studies is that MZs share 100% of their genetic information. Recently, biological studies based on molecular methods are now being increasingly applied to examine the differences between MZs discordance for psychiatric disorders to unravel their possible causes. Although recent advances in next-generation sequencing have increased the accuracy of this line of research, there has been greater emphasis placed on epigenetic changes versus DNA sequence changes as the probable cause of discordant psychiatric disorders in MZs. Since the epigenetic status differs in each tissue type, in addition to the DNA from the peripheral blood, studies using DNA from nerve cells induced from postmortem brains or induced pluripotent stem cells are being carried out. Although it was originally thought that epigenetic changes occurred as a result of environmental factors, and thus were not transmittable, it is now known that such changes might possibly be transmitted between generations. Therefore, the potential possible effects of intestinal flora inside the body are currently being investigated as a cause of discordance in MZs. As a result, twin studies of psychiatric disorders are greatly contributing to the elucidation of genetic and environmental factors in the etiology of psychiatric conditions.


Assuntos
Transtorno do Espectro Autista , Esquizofrenia , Transtorno do Espectro Autista/genética , Epigênese Genética , Humanos , Esquizofrenia/genética , Gêmeos Dizigóticos , Gêmeos Monozigóticos/genética
8.
Nat Commun ; 11(1): 1837, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32296055

RESUMO

Guanosine 5'-monophosphate reductase (GMPR) is involved in the purine salvage pathway and is conserved throughout evolution. Nonetheless, the GMPR of Trypanosoma brucei (TbGMPR) includes a unique structure known as the cystathionine-ß-synthase (CBS) domain, though the role of this domain is not fully understood. Here, we show that guanine and adenine nucleotides exert positive and negative effects, respectively, on TbGMPR activity by binding allosterically to the CBS domain. The present structural analyses revealed that TbGMPR forms an octamer that shows a transition between relaxed and twisted conformations in the absence and presence of guanine nucleotides, respectively, whereas the TbGMPR octamer dissociates into two tetramers when ATP is available instead of guanine nucleotides. These findings demonstrate that the CBS domain plays a key role in the allosteric regulation of TbGMPR by facilitating the transition of its oligomeric state depending on ligand nucleotide availability.


Assuntos
Cistationina beta-Sintase/química , Cistationina beta-Sintase/metabolismo , GMP Redutase/química , GMP Redutase/metabolismo , Trypanosoma brucei brucei/enzimologia , Regulação Alostérica , Cristalografia por Raios X , Cinética , Domínios Proteicos , Multimerização Proteica , Estrutura Secundária de Proteína
9.
Neurology ; 92(20): e2364-e2374, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31004071

RESUMO

OBJECTIVE: To identify genes related to normal-pressure hydrocephalus (NPH) in one Japanese family with several members with NPH. METHODS: We performed whole-exome sequencing (WES) on a Japanese family with multiple individuals with NPH and identified a candidate gene. Then we generated knockout mouse using CRISPR/Cas9 to confirm the effect of the candidate gene on the pathogenesis of hydrocephalus. RESULTS: In WES, we identified a loss-of-function variant in CFAP43 that segregated with the disease. CFAP43 encoding cilia- and flagella-associated protein is preferentially expressed in the testis. Recent studies have revealed that mutations in this gene cause male infertility owing to morphologic abnormalities of sperm flagella. We knocked out mouse ortholog Cfap43 using CRISPR/Cas9 technology, resulting in Cfap43-deficient mice that exhibited a hydrocephalus phenotype with morphologic abnormality of motile cilia. CONCLUSION: Our results strongly suggest that CFAP43 is responsible for morphologic or movement abnormalities of cilia in the brain that result in NPH.


Assuntos
Cílios/ultraestrutura , Proteínas do Citoesqueleto/genética , Hidrocefalia de Pressão Normal/genética , Proteínas dos Microtúbulos/genética , Animais , Grupo com Ancestrais do Continente Asiático , Códon sem Sentido , Família , Feminino , Humanos , Hidrocefalia de Pressão Normal/patologia , Mutação com Perda de Função , Masculino , Camundongos , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Linhagem , Sequenciamento Completo do Exoma
10.
Medicine (Baltimore) ; 97(49): e13530, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30544456

RESUMO

In industrialized countries, the turnover rate of preschool workers is extremely high and now represents a social problem. Consequently, it has become important to promote stable early care and educational environments for this population. Several factors related to working environments are known to affect turnover intention; however, the specific factors related to turnover intention among preschool workers have not yet been identified. Considering this, the objective of the present study was to determine factors associated with preschool workers' willingness to continue working.The participants of this study were 1137 preschool workers based in Nagasaki Prefecture, Japan. Multivariate logistic regression analysis was used to analyze the participants' data, with willingness to continue working for 5 years or more set as the dependent variable.Analysis of the results for all subjects clearly showed that male sex, older age, good mental health, high number of social supports, and good work engagement have a positive effect on willingness to continue working. Further, stratifying the participants in terms of age revealed that for preschool workers under 39 years, male sex, good mental health, high number of social supports, and good work engagement act positively in regard to willingness to continue working. Meanwhile, for those over 40 years, it was found that permanent employment and good work engagement act positively in this regard. Thus, work engagement was the only common factor between preschool workers under 39 and over 40.The findings of this cross-sectional study demonstrate that the factors associated with willingness to continue working among preschool workers differ between younger and older professionals. These findings underline the importance of considering age categories when attempting to maximize such professionals' willingness to continue working.


Assuntos
Emprego/psicologia , Professores Escolares/psicologia , Adulto , Fatores Etários , Estudos Transversais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Reorganização de Recursos Humanos
11.
ACS Cent Sci ; 4(6): 664-665, 2018 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-29974060
12.
J Neural Transm (Vienna) ; 125(9): 1395-1400, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29926268

RESUMO

Several studies report that patients with attention-deficit hyperactivity disorder (ADHD) have a low plasma concentration of polyunsaturated fatty acids (PUFAs). Since fish intake varies among countries and is high in Japan, those results may not apply to Japanese patients with ADHD. However, there is currently not enough evidence to support this. We compared the plasma PUFAs levels of patients with ADHD with the standard reference levels for healthy subjects, and examined the relationship between those PUFAs levels and the subject's psychological evaluation. The subjects were 24 patients (age < 20 years) previously diagnosed with ADHD (according to the DSM-IV-TR criteria) at the psychiatric department of the Nagasaki University Hospital, between November 2010 and November 2015. The plasma concentrations of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) were measured using gas chromatography. Data pertaining to global assessment of functioning (GAF), clinical global impressions, ADHD Rating Scale-IV, and the drug used for treatment (atomoxetine or methylphenidate) were obtained from the medical records. The plasma concentrations of DHA, EPA, and EPA/AA were significantly lower than the normal reference range, indicating that ADHD patients present an imbalance in PUFAs levels. This trend is similar to ADHD patients in other countries and replacement therapy in Japanese ADHD patients may be useful.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/sangue , Ácidos Graxos Ômega-3/sangue , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Ácidos Graxos Ômega-3/deficiência , Ácidos Graxos Insaturados/sangue , Feminino , Humanos , Japão , Masculino , Índice de Gravidade de Doença , Adulto Jovem
13.
Transl Psychiatry ; 8(1): 41, 2018 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-29391400

RESUMO

Panic disorder (PD) is characterized by recurrent and unexpected panic attacks, subsequent anticipatory anxiety, and phobic avoidance. Recent epidemiological and genetic studies have revealed that genetic factors contribute to the pathogenesis of PD. We performed whole-exome sequencing on one Japanese family, including multiple patients with panic disorder, which identified seven rare protein-altering variants. We then screened these genes in a Japanese PD case-control group (384 sporadic PD patients and 571 controls), resulting in the detection of three novel single nucleotide variants as potential candidates for PD (chr15: 42631993, T>C in GANC; chr15: 42342861, G>T in PLA2G4E; chr20: 3641457, G>C in GFRA4). Statistical analyses of these three genes showed that PLA2G4E yielded the lowest p value in gene-based rare variant association tests by Efficient and Parallelizable Association Container Toolbox algorithms; however, the p value did not reach the significance threshold in the Japanese. Likewise, in a German case-control study (96 sporadic PD patients and 96 controls), PLA2G4E showed the lowest p value but again did not reach the significance threshold. In conclusion, we failed to find any significant variants or genes responsible for the development of PD. Nonetheless, our results still leave open the possibility that rare protein-altering variants in PLA2G4E contribute to the risk of PD, considering the function of this gene.


Assuntos
Estudos de Associação Genética/métodos , Fosfolipases A2 do Grupo IV/genética , Transtorno de Pânico/genética , Sequenciamento Completo do Exoma/métodos , Adulto , Estudos de Casos e Controles , Feminino , Alemanha , Humanos , Japão , Masculino , Linhagem , Risco
14.
Hum Genome Var ; 4: 17032, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28765789

RESUMO

Monozygotic (MZ) twins have been thought to be genetically identical. However, recent studies have shown discordant variants between them. We performed whole-exome sequencing (WES) in five MZ twin pairs with discordant neurodevelopmental disorders and one healthy control MZ twin to detect discordant variants. We identified three discordant variants confirmed by deep sequencing after analysis by personalized next-generation sequencing (NGS). Three mutations in FBXO38 (chr5:147774428;T>G), SMOC2 (chr6:169051385;A>G) and TDRP (chr8:442616;A>G), were detected with low allele frequency of mutant alleles on deep sequencing, suggesting that these loci are mosaic due to somatic mutations in a developmental stage. Our results suggest that deep sequencing analysis would be an adequate method to detect discordant mutations in candidate genes responsible for heritable diseases.

15.
Sci Rep ; 7(1): 2887, 2017 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-28588275

RESUMO

Here we report de novo non-synonymous single-nucleotide variants (SNVs) by conducting whole exome sequencing of 18 trios consisting of Japanese patients with sporadic schizophrenia and their parents. Among nine SNVs, we explored the functional impact of the de novo mutation in TBL1XR1 [c.30 C > G (p.Phe10Leu)], a gene previously found to be associated with autism spectrum disorder and epilepsy. Protein structural analysis revealed that Phe10Leu mutation may decrease the structural stability of the TBL1XR1 protein. We demonstrate that Phe10Leu mutation alters the interaction of TBL1XR1 with N-CoR and ß-catenin, which play critical roles in regulation of Wnt-mediated transcriptional activity. Consistently, TBL1XR1-mediated activation of Wnt signaling was up-regulated by Phe10Leu mutation. These results suggest that a de novo TBL1XR1 point mutation could alter Wnt/ß-catenin signaling activity. Further studies are required to clarify the involvement of TBL1XR1 mutations in neuropsychiatric conditions.


Assuntos
Mutação , Proteínas Nucleares/genética , Receptores Citoplasmáticos e Nucleares/genética , Proteínas Repressoras/genética , Via de Sinalização Wnt , Alelos , Substituição de Aminoácidos , Exoma , Predisposição Genética para Doença , Humanos , Modelos Moleculares , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Polimorfismo de Nucleotídeo Único , Conformação Proteica , Receptores Citoplasmáticos e Nucleares/química , Receptores Citoplasmáticos e Nucleares/metabolismo , Proteínas Repressoras/química , Proteínas Repressoras/metabolismo , Esquizofrenia/genética , Sequenciamento Completo do Exoma
16.
PLoS Negl Trop Dis ; 10(1): e0004339, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26731263

RESUMO

The metabolic pathway of purine nucleotides in parasitic protozoa is a potent drug target for treatment of parasitemia. Guanosine 5'-monophosphate reductase (GMPR), which catalyzes the deamination of guanosine 5'-monophosphate (GMP) to inosine 5'-monophosphate (IMP), plays an important role in the interconversion of purine nucleotides to maintain the intracellular balance of their concentration. However, only a few studies on protozoan GMPR have been reported at present. Herein, we identified the GMPR in Trypanosoma brucei, a causative protozoan parasite of African trypanosomiasis, and found that the GMPR proteins were consistently localized to glycosomes in T. brucei bloodstream forms. We characterized its recombinant protein to investigate the enzymatic differences between GMPRs of T. brucei and its host animals. T. brucei GMPR was distinct in having an insertion of a tandem repeat of the cystathionine ß-synthase (CBS) domain, which was absent in mammalian and bacterial GMPRs. The recombinant protein of T. brucei GMPR catalyzed the conversion of GMP to IMP in the presence of NADPH, and showed apparent affinities for both GMP and NADPH different from those of its mammalian counterparts. Interestingly, the addition of monovalent cations such as K+ and NH4+ to the enzymatic reaction increased the GMPR activity of T. brucei, whereas none of the mammalian GMPR's was affected by these cations. The monophosphate form of the purine nucleoside analog ribavirin inhibited T. brucei GMPR activity, though mammalian GMPRs showed no or only a little inhibition by it. These results suggest that the mechanism of the GMPR reaction in T. brucei is distinct from that in the host organisms. Finally, we demonstrated the inhibitory effect of ribavirin on the proliferation of trypanosomes in a dose-dependent manner, suggesting the availability of ribavirin to develop a new therapeutic agent against African trypanosomiasis.


Assuntos
GMP Redutase/metabolismo , Trypanosoma brucei brucei/enzimologia , Sequência de Aminoácidos , Animais , Antimetabólitos/farmacologia , GMP Redutase/genética , Regulação Enzimológica da Expressão Gênica , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Proteínas Recombinantes , Ribavirina/farmacologia , Especificidade da Espécie , Temperatura , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/metabolismo
17.
J Chem Phys ; 142(10): 104111, 2015 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-25770530

RESUMO

An Elongation-counterpoise (ELG-CP) method was developed for performing accurate and efficient interaction energy analysis and correcting the basis set superposition error (BSSE) in biosystems. The method was achieved by combining our developed ab initio O(N) elongation method with the conventional counterpoise method proposed for solving the BSSE problem. As a test, the ELG-CP method was applied to the analysis of the DNAs' inter-strands interaction energies with respect to the alkylation-induced base pair mismatch phenomenon that causes a transition from G⋯C to A⋯T. It was found that the ELG-CP method showed high efficiency (nearly linear-scaling) and high accuracy with a negligibly small energy error in the total energy calculations (in the order of 10(-7)-10(-8) hartree/atom) as compared with the conventional method during the counterpoise treatment. Furthermore, the magnitude of the BSSE was found to be ca. -290 kcal/mol for the calculation of a DNA model with 21 base pairs. This emphasizes the importance of BSSE correction when a limited size basis set is used to study the DNA models and compare small energy differences between them. In this work, we quantitatively estimated the inter-strands interaction energy for each possible step in the transition process from G⋯C to A⋯T by the ELG-CP method. It was found that the base pair replacement in the process only affects the interaction energy for a limited area around the mismatch position with a few adjacent base pairs. From the interaction energy point of view, our results showed that a base pair sliding mechanism possibly occurs after the alkylation of guanine to gain the maximum possible number of hydrogen bonds between the bases. In addition, the steps leading to the A⋯T replacement accompanied with replications were found to be unfavorable processes corresponding to ca. 10 kcal/mol loss in stabilization energy. The present study indicated that the ELG-CP method is promising for performing effective interaction energy analyses in biosystems.


Assuntos
Técnicas de Química Analítica , Modelos Biológicos , Teoria Quântica
18.
Leuk Res ; 37(9): 1132-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23806233

RESUMO

We examined the effects of diet nutrients on xenotransplanted leukemia cells, THP-1 or NB4. THP-1 tumors showed more growth when fed with high fat diet, while NB4 tumors grew more with high carbohydrate diet. Then, administration of 2-deoxyglucose (a glycolysis inhibitor) showed a significant antitumor effect on both tumors: NB4 tumor showed large necrotic areas, while THP-1 tumor did not, but had augmented expression of enzymes for fatty acid oxidation. 2-Deoxyglucose inhibited the growth of NB4 by cell death because main energy producing pathway (glycolysis) was abolished, while 2-deoxyglucose slowed the growth of THP-1 by shifting energy metabolism to fatty acid ß-oxidation.


Assuntos
Antimetabólitos/farmacologia , Proliferação de Células , Desoxiglucose/farmacologia , Dieta , Suplementos Nutricionais , Leucemia Experimental/tratamento farmacológico , Animais , Western Blotting , Metabolismo Energético/efeitos dos fármacos , Feminino , Glicólise/efeitos dos fármacos , Humanos , Técnicas Imunoenzimáticas , Leucemia Experimental/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Neoplasias , Transplante Heterólogo , Células Tumorais Cultivadas
19.
Psychiatry Clin Neurosci ; 67(4): 203-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23683150

RESUMO

AIMS: The purpose of this study was to examine the usefulness of near-infrared spectroscopy (NIRS) for identifying abnormalities in prefrontal brain activity in children with autism spectrum disorders (ASD) as they inferred the mental states of others. METHODS: The subjects were 16 children with ASD aged between 8 and 14 years and 16 age-matched healthy control children. Oxygenated hemoglobin concentration was measured in the subject's prefrontal brain region on NIRS during tasks expressing a person's mental state (MS task) and expressing an object's characteristics (OC task). RESULTS: There was a significant main effect of group (ASD vs control), with the control group having more activity than the ASD group. But there was no significant main effect of task (MS task vs OC task) or hemisphere (right vs left). Significant interactions of task and group were found, with the control group showing more activity than the ASD group during the MS task relative to the OC task. CONCLUSIONS: NIRS showed that there was lower activity in the prefrontal brain area when children with ASD performed MS tasks. Therefore, clinicians might be able to use NIRS and these tasks for conveniently detecting brain dysfunction in children with ASD related to inferring mental states, in the clinical setting.


Assuntos
Encéfalo/fisiopatologia , Transtornos Globais do Desenvolvimento Infantil/fisiopatologia , Empatia/fisiologia , Percepção Social , Teoria da Mente/fisiologia , Adolescente , Mapeamento Encefálico/métodos , Criança , Expressão Facial , Feminino , Humanos , Relações Interpessoais , Masculino , Estimulação Luminosa , Espectroscopia de Luz Próxima ao Infravermelho
20.
Oncol Rep ; 29(5): 2053-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23440281

RESUMO

The shift in energy metabolism from oxidative phosphorylation to glycolysis can serve as a target for the inhibition of cancer growth. Here, we examined the metabolic changes induced by 2-deoxyglucose (2-DG), a glycolysis inhibitor, in leukemia cells by metabolome analysis. NB4 cells mainly utilized glucose as an energy source by glycolysis and oxidative phosphorylation in mitochondria, since metabolites in the glycolytic pathway and in the tricarboxylic acid (TCA) cycle were significantly decreased by 2-DG. In THP-1 cells, metabolites in the TCA cycle were not decreased to the same extent by 2-DG as in NB4 cells, which indicates that THP-1 utilizes energy sources other than glucose. TCA cycle metabolites in THP-1 cells may be derived from acetyl-CoA by fatty acid ß-oxidation, which was supported by abundant detection of carnitine and acetylcarnitine in THP-1 cells. 2-DG treatment increased the levels of pentose phosphate pathway (PPP) metabolites and augmented the generation of NADPH by glucose-6-phosphate dehydrogenase. An increase in NADPH and upregulation of glutathione synthetase expression resulted in the increase in the reduced form of glutathione by 2-DG in NB4 cells. We demonstrated that a combination of 2-DG and inhibition of PPP by dehydroepiandrosterone (DHEA) effectively suppressed the growth of NB4 cells. The replenishment of the TCA cycle by fatty acid oxidation by carnitine palmitoyltransferase in THP-1 cells, treated by 2-DG, might be regulated by AMPK, as the combination of 2-DG and inhibition of AMPK by compound C potently suppressed the growth of THP-1 cells. Although 2-DG has been effective in preclinical and clinical studies, this treatment has not been fully explored due to concerns related to potential toxicities such as brain toxicity at high doses. We demonstrated that a combination of 2-DG and DHEA or compound C at a relatively low concentration effectively inhibits the growth of NB4 and THP-1 cells, respectively. These observations may aid in the identification of appropriate combinations of metabolic inhibitors at low concentrations which do not cause toxicities.


Assuntos
Desoxiglucose/farmacologia , Metabolismo Energético/efeitos dos fármacos , Leucemia/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Acetilcoenzima A/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Linhagem Celular Tumoral , Ciclo do Ácido Cítrico/efeitos dos fármacos , Desidroepiandrosterona/farmacologia , Ácidos Graxos/metabolismo , Glucose/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Glutationa/metabolismo , Glicólise/efeitos dos fármacos , Humanos , Metaboloma/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , NADP/metabolismo , Oxirredução/efeitos dos fármacos , Fosforilação Oxidativa/efeitos dos fármacos , Via de Pentose Fosfato/efeitos dos fármacos , Via de Pentose Fosfato/fisiologia , Pirazóis/farmacologia , Pirimidinas/farmacologia
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