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1.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-816615

RESUMO

BACKGROUND: Acromegaly is a rare disease primarily caused by growth hormone (GH)-secreting pituitary adenomas, and its treatment is costly. Moreover, some patients are unresponsive to treatment. Hence, there are increasing efforts to develop new drugs with improved effectiveness for this disease. BIM23B065 is a novel chimeric molecule that acts on both somatostatin and dopamine receptors. This study aimed to investigate the effects of BIM23B065 compared with those of a somatostatin receptor analog and a dopamine agonist.METHODS: The effects of BIM23B065 on the proliferation, GH and insulin-like growth factor-1 (IGF-1) levels, and extracellular signal-regulated kinase (ERK) 1/2 and cyclic AMP response element binding (CREB) phosphorylation of GH3 cells were investigated with MTS assay, enzyme-linked immunosorbent assay, and Western blotting, respectively. The dosage and treatment duration of BIM23B065 were tested in animal models of GH-secreting pituitary adenoma. The effect of BIM23B065 (3 mg/kg/day) on changes in IGF-1 levels before and after treatment was further investigated.RESULTS: In vitro, BIM23B065 treatment decreased GH release in the culture media and downregulated ERK 1/2 and CREB phosphorylation to 22% and 26%, respectively. In vivo, IGF-1 expression decreased to 50 % after 4 weeks of treatment with BIM23B065 using an osmotic pump implant. Moreover, magnetic resonance imaging results showed that the tumor size decreased significantly following treatment with BIM23B065 for 4 weeks.CONCLUSION: The novel chimeric molecule was effective in decreasing IGF-1 and GH levels and may serve as an effective therapeutic agent for acromegaly.


Assuntos
Acromegalia , Western Blotting , Meios de Cultura , AMP Cíclico , Agonistas de Dopamina , Dopamina , Ensaio de Imunoadsorção Enzimática , Hormônio do Crescimento , Adenoma Hipofisário Secretor de Hormônio do Crescimento , Humanos , Técnicas In Vitro , Fator de Crescimento Insulin-Like I , Imagem por Ressonância Magnética , Modelos Animais , Fosforilação , Fosfotransferases , Neoplasias Hipofisárias , Doenças Raras , Receptores Dopaminérgicos , Receptores de Somatostatina , Elementos de Resposta , Somatostatina
2.
Experimental Neurobiology ; : 289-299, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-739537

RESUMO

Transient receptor potential vanilloid subtype 1 (TRPV1) on astrocytes prevents ongoing degeneration of nigrostriatal dopamine (DA) neurons in MPP⁺-lesioned rats via ciliary neurotrophic factor (CNTF). The present study determined whether such a beneficial effect of astrocytic TRPV1 could be achieved after completion of injury of DA neurons, rather than ongoing injury, which seems more relevant to therapeutics. To test this, the MPP⁺-lesioned rat model utilized here exhibited approximately 70~80% degeneration of nigrostriatal DA neurons that was completed at 2 weeks post medial forebrain bundle injection of MPP⁺. TRPV1 agonist, capsaicin (CAP), was intraperitoneally administered. CNTF receptor alpha neutralizing antibody (CNTFRαNAb) was nigral injected to evaluate the role of CNTF endogenously produced by astrocyte through TRPV1 activation on DA neurons. Delayed treatment of CAP produced a significant reduction in amphetamine-induced rotational asymmetry. Accompanying this behavioral recovery, CAP treatment increased CNTF levels and tyrosine hydroxylase (TH) activity in the substantia nigra pars compacta (SNpc), and levels of DA and its metabolites in the striatum compared to controls. Interestingly, behavioral recovery and increases in biochemical indices were not reflected in trophic changes of the DA system. Instead, behavioral recovery was temporal and dependent on the continuous presence of CAP treatment. The results suggest that delayed treatment of CAP increases nigral TH enzyme activity and striatal levels of DA and its metabolites by CNTF endogenously derived from CAP-activated astrocytes through TRPV1, leading to functional recovery. Consequently, these findings may be useful in the treatment of DA imbalances associated with Parkinson's disease.


Assuntos
Animais , Anticorpos Neutralizantes , Astrócitos , Capsaicina , Fator Neurotrófico Ciliar , Dopamina , Neurônios Dopaminérgicos , Feixe Prosencefálico Mediano , Modelos Animais , Neurônios , Doença de Parkinson , Parte Compacta da Substância Negra , Ratos , Receptor do Fator Neutrófico Ciliar , Tirosina 3-Mono-Oxigenase
3.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-738872

RESUMO

The Korean Ministry of Food and Drug Safety has approved three anti-obesity drugs for long-term management in the past decade. In addition, since 2019, bariatric surgery has been financially supported by National Health Insurance Service in Korea. In this review, the mechanisms of action and the clinical implications of the recently approved anti-obesity drugs, lorcaserin, naltrexone/bupropion, and liraglutide are explained. Lorcaserin stimulates proopiomelanocortin (POMC)/cocaine- and amphetamine-regulated transcript (CART) neurons and inhibits neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons, which results in the activation of melanocortin 3/4 receptors. Naltrexone/bupropion stimulates POMC neurons through bupropion; this stimulation is augmented by blocking the autoinhibitory mechanism of POMC with naltrexone. The hypophagic effect of liraglutide is mediated through the direct activation of POMC/CART neurons and the indirect suppression of NPY/AgRP neurons through γ-aminobutyric acid-dependent signaling, with adjunctive suppression of the mesolimbic dopamine reward system. In addition to liraglutide, another glucagon-like peptide-1 receptor agonist, semaglutide, is expected to be added to the list of anti-obesity drugs in the near future. In patients with obesity and high cardiovascular risk, lorcaserin was considered neutral and liraglutide was considered favorable, whereas inconclusive results were obtained for naltrexone/bupropion.


Assuntos
Fármacos Antiobesidade , Cirurgia Bariátrica , Bupropiona , Dopamina , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Coreia (Geográfico) , Liraglutida , Naltrexona , Programas Nacionais de Saúde , Neurônios , Neuropeptídeo Y , Obesidade , Pró-Opiomelanocortina , Recompensa
4.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-787403

RESUMO

Depression is almost twice as prevalent in women than men. Atypical symptoms, somatic complaints, and comorbid anxiety disorders are more common in women, whereas suicide and comorbid substance use disorders are more common in men. Previous studies have also reported gender differences in the efficacy of and tolerability to specific classes of antidepressants. Various psychosocial and biological factors have been proposed to explain the gender differences in clinical characteristics of depression. The predominant theory of depression pathogenesis is the monoamine hypothesis, and consequently, monoamine neurotransmitters have been the primary target of antidepressants. In the first section of this review, study findings of clinical differences in depression by gender are summarized. Then, we provide an overview of the findings from human and rodent studies of gender differences in serotonin, norepinephrine, dopamine, and glutamate neurotransmitter systems. Total level, rate of synthesis, and receptor profiles of neurotransmitters seem to differ by gender in the euthymic state, depressed state, and in responses to stress or antidepressants. Furthermore, these neurotransmitters interact with gonadal hormones and the hypothalamic-pituitary-adrenal axis, systems that innately exhibit gender differences. Although most of the studies conducted so far are limited to animal models and results of the studies are heterogeneous, growing evidence suggests that gender differences exist in neurotransmitter systems, which possibly leads to gender differences in depression. More intensive studies in this field are needed to build gender-specific treatment strategies.


Assuntos
Antidepressivos , Transtornos de Ansiedade , Fatores Biológicos , Depressão , Dopamina , Feminino , Ácido Glutâmico , Hormônios Gonadais , Humanos , Masculino , Modelos Animais , Neurotransmissores , Norepinefrina , Roedores , Serotonina , Transtornos Relacionados ao Uso de Substâncias , Suicídio
5.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-765862

RESUMO

OBJECTIVE: Impulse control disorders (ICDs) in Parkinson's disease (PD) are mostly related to dopamine replacement therapy (DRT); however, drug-naïve PD patients have also frequently experienced impulsivity. This phenomenon makes clinicians hesitate treating patients with DRT. In this study, we assessed the effect of impulsivity on quality of life (QOL) in drug-naïve PD patients. METHODS: Two hundred three newly diagnosed, nonmedicated PD patients were enrolled, and they received structured clinical interviews, physical examinations and validated questionnaires to evaluate motor and nonmotor symptoms and QOL. Impulsivity was evaluated using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS). RESULTS: Thirty-eight patients (18.7%) had impulsivity with QUIP-RS scores ≥ 1 and 4 patients (2.0%) were diagnosed with combined ICDs. Motor and nonmotor symptoms were significantly correlated with the Parkinson's Disease Questionnaire-39 summary index. Female sex and QUIP-RS scores were also correlated with QOL in drug-naïve PD patients. CONCLUSION: The results of the present study showed that impulsivity negatively influences QOL in early drug-naïve PD patients. In addition, more severe motor and nonmotor symptoms were also associated with lower QOL. Such findings complicate treatment but provide valuable information for managing early PD.


Assuntos
Transtornos Disruptivos, de Controle do Impulso e da Conduta , Dopamina , Feminino , Humanos , Comportamento Impulsivo , Doença de Parkinson , Exame Físico , Qualidade de Vida
6.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-765851

RESUMO

OBJECTIVE: It is unclear whether the decline in dopamine transporters (DAT) differs among idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with different levels of olfactory impairment. This study aimed to characterize DAT changes in relation to nonmotor features in iRBD patients by olfactory loss. METHODS: This prospective cohort study consisted of three age-matched groups: 30 polysomnography-confirmed iRBD patients, 30 drug-naïve Parkinson's disease patients, and 19 healthy controls without olfactory impairment. The iRBD group was divided into two groups based on olfactory testing results. Participants were evaluated for reported prodromal markers and then underwent 18F-FP-CIT positron emission tomography and 3T MRI. Tracer uptakes were analyzed in the caudate, anterior and posterior putamen, substantia nigra, and raphe nuclei. RESULTS: Olfactory impairment was defined in 38.5% of iRBD patients. Mild parkinsonian signs and cognitive functions were not different between the two iRBD subgroups; however, additional prodromal features, constipation, and urinary and sexual dysfunctions were found in iRBD patients with olfactory impairment but not in those without. Tracer uptake showed significant group differences in all brain regions, except the raphe nuclei. The iRBD patients with olfactory impairment had uptake reductions in the anterior and posterior putamen, caudate, and substantia nigra (p < 0.016 in all, adjusted for age), which ranged from 0.6 to 0.8 of age-normative values. In contrast, those without olfactory impairment had insignificant changes in all regions ranging above 0.8. CONCLUSION: There was a clear distinction in DAT loss and nonmotor profiles by olfactory status in iRBD.


Assuntos
Encéfalo , Cognição , Estudos de Coortes , Constipação Intestinal , Proteínas da Membrana Plasmática de Transporte de Dopamina , Dopamina , Humanos , Imagem por Ressonância Magnética , Doença de Parkinson , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Putamen , Núcleos da Rafe , Transtorno do Comportamento do Sono REM , Sono REM , Olfato , Substância Negra
7.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-765850

RESUMO

OBJECTIVE: Ample evidence has suggested that age at onset of Parkinson's disease (PD) is associated with heterogeneous clinical features in individuals. We hypothesized that this may be attributed to different patterns of nigrostriatal dopamine loss. METHODS: A total of 205 consecutive patients with de novo PD who underwent 18F-FP-CIT PET scans (mean follow-up duration, 6.31 years) were divided into three tertile groups according to their age at onset of parkinsonian motor symptoms. Striatal dopamine transporter (DAT) availability was compared between the old- (n = 73) and young-onset (n = 66) groups. In addition, the risk of developing freezing of gait (FOG) and longitudinal requirements for dopaminergic medications were examined. RESULTS: The old-onset PD group (mean age at onset, 72.66 years) exhibited more severe parkinsonian motor signs than the young-onset group (52.58 years), despite comparable DAT availability in the posterior putamen; moreover, the old-onset group exhibited more severely decreased DAT availability in the caudate than the young-onset group. A Cox regression model revealed that the old-onset PD group had a higher risk for developing FOG than the young-onset group [hazard ratio 2.523, 95% confidence interval (1.239–5.140)]. The old-onset group required higher doses of dopaminergic medications for symptom control than the young-onset group over time. CONCLUSION: The present study demonstrated that the old-onset PD group exhibited more severe dopamine loss in the caudate and were more likely to develop gait freezing, suggesting that age at onset may be one of the major determinants of the pattern of striatal dopamine depletion and progression of gait disturbance in PD.


Assuntos
Idade de Início , Proteínas da Membrana Plasmática de Transporte de Dopamina , Dopamina , Seguimentos , Congelamento , Marcha , Humanos , Doença de Parkinson , Tomografia por Emissão de Pósitrons , Putamen , Tempo (Meteorologia)
8.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-765189

RESUMO

Symptomatic relapse is observed frequently and often associated with social and/or occupational decline that can be difficult to reverse in patients with schizophrenia. Several atypical antipsychotics, including risperidone, olanzapine, paliperidone, and aripiprazole, have become available as long-acting injectable antipsychotics (LAIs), and new evidence has been accumulating. LAIs appear to have a significant role in at least a group of schizophrenia patients. Improving the adherence, continuous availability, managing changes in receptor sensitivity, and lowering the requirement of cumulative doses are some of the major advantages of LAIs. Patients with first episode psychosis, dopamine super-sensitivity syndromes, and comorbid substance abuse might particularly benefit. Delaying the initiation of LAI until the establishment of non-adherence is not recommended. The results of clinical trials comparing LAIs with oral antipsychotics (OAPs) are inconsistent because they are influenced considerably by the study design. On the other hand, several barriers to LAIs use in current practice include clinical lack of knowledge, and negative attitudes about LAIs. This article tries to help clinicians better characterize the role of LAIs in the treatment of schizophrenia.


Assuntos
Antipsicóticos , Aripiprazol , Dopamina , Mãos , Humanos , Adesão à Medicação , Palmitato de Paliperidona , Transtornos Psicóticos , Recidiva , Risperidona , Esquizofrenia , Transtornos Relacionados ao Uso de Substâncias
9.
Experimental Neurobiology ; : 602-611, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763786

RESUMO

Synaptic dopamine (DA) is mainly regulated by the presynaptic DA transporter (DAT). Single-photon emission computerized tomography (SPECT) with the DAT radiotracer [¹²³I]FP-CIT assesses changes in synaptic DA availability when endogenous DA displaces [¹²³I]FP-CIT or competes for DAT. Here, we investigated the effects of haloperidol (HAL) and clozapine (CLZ) on [¹²³I]FP-CIT binding in the rat striatum and midbrain to assess the utility of [¹²³I]FP-CIT SPECT to quantify changes in synaptic DA availability. Rats underwent [¹²³I]FP-CIT SPECT after intraperitoneal administration of normal saline (vehicle), HAL (1 and 7 mg/kg), CLZ (10 and 54 mg/kg) and bupropion (BUP, a DAT blocker, 20 and 100 mg/kg). In the striatum and midbrain, percent differences in the nondisplaceable binding potential (BP(ND)) of [¹²³I]FP-CIT compared to the vehicle were calculated for the various drugs and doses. In another experiment, changes in endogenous striatal DA concentration were measured by in vivo microdialysis under the conditions used in the SPECT study. BUP dose-dependently occupied DAT at considerable levels. Compared to the vehicle, HAL decreased [¹²³I]FP-CIT BP(ND) in the striatum (−25.29% and −2.27% for 1 and 7 mg/kg, respectively) and to a greater degree in the midbrain (−58.74% and −49.64% for 1 and 7 mg/kg, respectively), whereas the CLZ-treated group showed a decrease in the midbrain (−38.60% and −40.38% for 10 and 54 mg/kg, respectively) but an increase in the striatum (18.85% and 38.64% for 10 and 54 mg/kg, respectively). Antipsychotic-induced changes in endogenous striatal DA concentrations varied across drugs and doses. The data demonstrate that [¹²³I]FP-CIT SPECT may be a useful preclinical technique for detecting increases in synaptic DA availability in the midbrain and striatum in response to HAL, with results comparable to those of in vivo microdialysis.


Assuntos
Animais , Bupropiona , Clozapina , Dopamina , Haloperidol , Mesencéfalo , Microdiálise , Ratos , Tomografia Computadorizada de Emissão de Fóton Único
10.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763564

RESUMO

Aripiprazole is an atypical antipsychotic that acts as a partial agonist of dopamine type 2 receptors as well as 5-HT1A receptors. It is used in the treatment of schizophrenia and in type 1 bipolar disorder for mania. Because aripiprazole is well tolerated with few side effects it is used off-label in other psychotic disorders. The prevalence of abnormal liver function tests with antipsychotic use is 32%, with clinically significant effects in 4% of cases. No cases of aripiprazole-induced liver injury have been published. We report a 28-year-old female who presented with non-affective first-episode psychosis and who was treated with aripiprazole. Initially she was medicated with 10 mg per day, with an increase to 20 mg per day on the 12th day of hospitalization. Nine days after she became icteric, with nausea and had a vomiting episode. Laboratory analysis revealed a very high level of alanine aminotransferase, and minor to moderately high levels of aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin. Aripiprazole was tapered and paliperidone was started with the improvement of clinical and laboratory findings.


Assuntos
Adulto , Alanina Transaminase , Fosfatase Alcalina , Aripiprazol , Aspartato Aminotransferases , Bilirrubina , Transtorno Bipolar , Dopamina , Feminino , Hepatite , Hospitalização , Humanos , Fígado , Testes de Função Hepática , Náusea , Palmitato de Paliperidona , Prevalência , Transtornos Psicóticos , Receptor 5-HT1A de Serotonina , Esquizofrenia , Transaminases , Transferases , Vômito
11.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763562

RESUMO

Schizophrenic patients resistant to antipsychotics are diagnosed as having treatment-refractory schizophrenia, and they are treated with clozapine. However, clozapine is sometimes combined with electroconvulsive therapy (ECT) if clozapine monotherapy fails. In this report, a severe treatment-refractory schizophrenic patient who did not respond to clozapine even with ECT, but who recovered with asenapine monotherapy, is presented. Asenapine, considered a serotonin spectrum dopamine modulator, is a new atypical antipsychotic with unique pharmacological features that is used not only for schizophrenia, but also for bipolar disorder. The unique features of asenapine may be effective for some treatment-refractory schizophrenic patients.


Assuntos
Antipsicóticos , Transtorno Bipolar , Clozapina , Dopamina , Eletroconvulsoterapia , Humanos , Recidiva , Esquizofrenia , Serotonina , Suicídio
12.
Artigo | WPRIM (Pacífico Ocidental) | ID: wprim-763553

RESUMO

OBJECTIVE: This study aimed to investigate the long-term effects of aripiprazole treatment during adolescence on behavior, cognitive function, and dopamine D2 receptor (D2R) expression in adult rats. METHODS: Adolescent male Sprague-Dawley rats were injected intraperitoneally with aripiprazole, risperidone, or vehicle control for 3 weeks (postnatal day 36–56). After a 2-week washout period, locomotion, anxiety, and spatial working memory were evaluated in adulthood (postnatal day 71–84), using an open field test, elevated plus maze, and Y-maze, respectively. In addition, we assessed D2R levels in the dorsolateral and medial prefrontal cortex (PFC), dorsal and ventral striatum, and hippocampus using western blot analysis. RESULTS: Spontaneous alternation performance (SAP) in the Y-maze, a measure of spatial working memory, differed significantly among the 3 groups (F = 3.89, p = 0.033). A post-hoc test confirmed that SAP in the aripiprazole group was significantly higher than that in the risperidone group (post-hoc test p = 0.013). D2R levels in the medial PFC (F = 8.72, p = 0.001) and hippocampus (F = 13.54, p < 0.001) were different among the 3 groups. D2R levels in the medial PFC and hippocampus were significantly lower in the aripiprazole-treated rats than that in the risperidone-treated rats (post-hoc test p = 0.025 and p < 0.001, respectively) and controls (post-hoc test p < 0.001, all). CONCLUSION: This study showed that aripiprazole treatment in adolescence could influence cognitive function and dopaminergic neurotransmission into early adulthood.


Assuntos
Adolescente , Adulto , Animais , Ansiedade , Aripiprazol , Western Blotting , Cognição , Dopamina , Hipocampo , Humanos , Locomoção , Masculino , Memória de Curto Prazo , Modelos Animais , Córtex Pré-Frontal , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D2 , Risperidona , Transmissão Sináptica , Estriado Ventral
13.
Artigo | WPRIM (Pacífico Ocidental) | ID: wprim-763546

RESUMO

Methylphenidate (MPH) is the most preferred drug for treatment of the attention deficit hyperactivity disorder (ADHD). Here, we aimed to discuss the possible effects and mechanisms of MPH on precocious puberty (PP) via a case series with seven children who had normal body mass index. In this case series we evaluated seven children with ADHD, who had received MPH for at least 6 months (0.5 mg/kg/dose three times a day, maximum 60 mg) and admitted to Department of Pediatric Endocrinology with PP symptoms. The mean age was 8.16 years. Basal hormonal levels (luteinizing hormone [LH], follicle stimulating hormone, and estrogen/testosterone) were within normal range. Results of LH-releasing hormone stimulation tests demonstrated central pubertal responses. Glutamine, dopamine and noradrenaline are most important excitatory neurotransmitters that have a role at the beginning of puberty. The effect of MPH, cumulating dopamine and noradrenaline in the synaptic gap could be associated with the acceleration of puberty with the excitatory effect of dopamine’s gonadotropin-releasing hormone (GnRH) release, excitatory effect of noradrenaline’s GnRH release and the disappearance of GnRH receptor expression suppressor effect on prolactin disinhibitory effect.


Assuntos
Aceleração , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade , Índice de Massa Corporal , Criança , Dopamina , Endocrinologia , Hormônio Foliculoestimulante , Glutamina , Hormônio Liberador de Gonadotropina , Humanos , Metilfenidato , Neurotransmissores , Norepinefrina , Prolactina , Puberdade , Puberdade Precoce , Receptores LHRH , Valores de Referência
14.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763532

RESUMO

OBJECTIVE: Dopamine plays a significant role in working memory by acting as a key neuromodulator between brain networks. Additionally, treatment of patients with schizophrenia using amisulpride, a pure dopamine class 2/3 receptor antagonist, improves their clinical symptoms with fewer side effects. We hypothesized that patients with schizophrenia treated with amisulpride and aripiprazole show increased working memory and glucose metabolism compared with those treated with cognitive behavioral therapy (CBT) and aripiprazole instead. METHODS: Sixteen patients with schizophrenia (eight in the amisulpride group [aripiprazole+amisulpride] and eight in the CBT group [aripiprazole+CBT]) and 15 age- and sex-matched healthy control subjects were recruited for a 12-week-long prospective trial. An [18F]-fluorodeoxyglucose-positron emission tomography/computerized tomography scanner was used to acquire the images. RESULTS: After 12 weeks of treatment, the amisulpride group showed greater improvement in the Letter-Number Span scores than the CBT group. Additionally, although brain metabolism in the left middle frontal gyrus, left occipital lingual gyrus, and right inferior parietal lobe was increased in all patients with schizophrenia, the amisulpride group exhibited a greater increase in metabolism in both the right superior frontal gyrus and right frontal precentral gyrus than the CBT group. CONCLUSION: This study suggests that a small dose of amisulpride improves the general psychopathology, working memory performance, and brain glucose metabolism of patients with schizophrenia treated with aripiprazole.


Assuntos
Aripiprazol , Encéfalo , Cognição , Terapia Cognitivo-Comportamental , Dopamina , Elétrons , Lobo Frontal , Glucose , Humanos , Memória de Curto Prazo , Metabolismo , Neurotransmissores , Lobo Occipital , Lobo Parietal , Tomografia por Emissão de Pósitrons , Córtex Pré-Frontal , Estudos Prospectivos , Psicopatologia , Esquizofrenia , Sulpirida
15.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763050

RESUMO

G protein-coupled receptors (GPCRs) are membrane receptors whose agonist-induced dynamic conformational changes trigger heterotrimeric G protein activation, followed by GRK-mediated phosphorylation and arrestin-mediated desensitization. Cytosolic regions of GPCRs have been studied extensively because they are direct contact sites with G proteins, GRKs, and arrestins. Among various cytosolic regions, the role of helix 8 is least understood, although a few studies have suggested that it is involved in G protein activation, receptor localization, and/or internalization. In the present study, we investigated the role of helix 8 in dopamine receptor signaling focusing on dopamine D1 receptor (D1R) and dopamine D2 receptor (D2R). D1R couples exclusively to Gs, whereas D2R couples exclusively to Gi. Bioinformatic analysis implied that the sequences of helix 8 may affect GPCR-G protein coupling selectivity; therefore, we evaluated if swapping helix 8 between D1R and D2R changed G protein selectivity. Our results suggest that helix 8 is not involved in D1R-Gs or D2R-Gi coupling selectivity. Instead, we observed that D1R with D2R helix 8 or D1R with an increased number of hydrophobic residues in helix 8 relative to wild-type showed diminished β-arrestin-mediated desensitization, resulting in increased Gs signaling.


Assuntos
Arrestina , Arrestinas , Biologia Computacional , Citosol , Dopamina , Características da Família , Proteínas de Ligação ao GTP , Membranas , Fosforilação , Receptores de Dopamina D1 , Receptores de Dopamina D2 , Receptores Dopaminérgicos
16.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-763028

RESUMO

Limonene is a cyclic terpene found in citrus essential oils and inhibits methamphetamine-induced locomotor activity. Drug dependence is a severe neuropsychiatric condition that depends in part on changes in neurotransmission and neuroadaptation, induced by exposure to recreational drugs such as morphine and methamphetamine. In this study, we investigated the effects of limonene on the psychological dependence induced by drug abuse. The development of sensitization, dopamine receptor supersensitivity, and conditioned place preferences in rats was measured following administration of limonene (10 or 20 mg/kg) and methamphetamine (1 mg/kg) for 4 days. Limonene inhibits methamphetamine-induced sensitization to locomotor activity. Expression of dopamine receptor supersensitivity induced by apomorphine, a dopamine receptor agonist, was significantly reduced in limonene-pretreated rats. However, there was no significant difference in methamphetamine-induced conditioned place preferences between the limonene and control groups. These results suggest that limonene may ameliorate drug addiction-related behaviors by regulating postsynaptic dopamine receptor supersensitivity.


Assuntos
Animais , Apomorfina , Citrus , Agonistas de Dopamina , Dopamina , Metanfetamina , Morfina , Atividade Motora , Óleos Voláteis , Ratos , Receptores Dopaminérgicos , Drogas Ilícitas , Transtornos Relacionados ao Uso de Substâncias , Transmissão Sináptica
17.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-786457

RESUMO

A 36-year-old male patient initially presented with hypertension, tinnitus, bilateral carotid masses, a right jugular foramen, and a periaortic arch mass with an elevated plasma dopamine level but an otherwise normal biochemical profile. On surveillance MRI 4 years after initial presentation, he was found to have a 2.2-cm T2 hyperintense lesion with arterial enhancement adjacent to the gallbladder, which demonstrated avidity on ⁶⁸Ga-DOTATATE PET/CTand retrospectively on ¹⁸F-FDOPA PET/CT but was nonavid on ¹⁸F-FDG PET/CT. Biochemical work-up including plasma catecholamines, metanephrines, and chromogranin A levels were found to be within normal limits. This lesion was surgically resected and was confirmed to be a paraganglioma (PGL) originating from the gallbladder wall on histopathology. Pheochromocytoma (PHEO) and PGL are rare tumors of the autonomic nervous system. Succinate dehydrogenase subunit D (SDHD) pathogenic variants of the succinate dehydrogenase complex are usually involved in parasympathetic, extra-adrenal, multifocal head, and neck PGLs. We report an unusual location of PGL in the gallbladder associated with SDHD mutation which could present as a potential pitfall on ¹⁸F-FDOPA PET/CT as its normal excretion occurs through biliary system and gallbladder. This case highlights the superiority of ⁶⁸Ga-DOTATATE in comparison to ¹⁸F-FDOPA and ¹⁸F-FDG in the detection of SDHD-related parasympathetic PGL.ClinicalTrials.gov Identifier: NCT00004847.


Assuntos
Adulto , Sistema Nervoso Autônomo , Sistema Biliar , Catecolaminas , Cromogranina A , Dopamina , Vesícula Biliar , Cabeça , Humanos , Hipertensão , Imagem por Ressonância Magnética , Masculino , Pescoço , Paraganglioma , Feocromocitoma , Plasma , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Succinato Desidrogenase , Zumbido
19.
Neonatal Medicine ; : 102-110, 2019.
Artigo em Coreano | WPRIM (Pacífico Ocidental) | ID: wprim-760576

RESUMO

PURPOSE: We investigated the effect of delayed elevation of thyrotropin (TSH) (deTSH) on gastrointestinal motility in very low birth weight infants (VLBWI). METHODS: This study retrospectively investigated 228 premature VLBWI aged ≥4 weeks with normal neonatal TSH screening test results and free serum thyroxine levels. Infants with serum TSH levels ranging from 5 to 10 µIU/mL were categorized as the deTSH group (n=76), when TSH was measured at 4 (n=53), 8 (n=20), or 12 (n=3) weeks of age. Serum TSH levels in the control group (n=152) were <5 µIU/mL. Multivariate logistic regression analysis was used to determine the risk factors for the development of deTSH. Covariance analysis was used to analyze the relationship between deTSH and gastrointestinal motility. RESULTS: The mean gestational age and birth weight were 29.11±2.25 weeks and 1,157.4±218.0 g, respectively. Risk factors affecting deTSH were dopamine administration (odds ratio [OR], 8.71; 95% confidence interval [CI], 1.80 to 42.05; P=0.007) and operation time (OR, 6.95; 95% CI, 1.43 to 33.75; P=0.016) when the cumulative operating time was ≥1 hour. The mean±standard deviation (SD) duration of a nil per os (NPO) status was significantly higher in the deTSH (99.57±134.99 hours) than in the control group (37.25±59.02 hours) (P from analysis of covariance [ANCOVA]=0.001). The mean±SD duration (33.84±22.34 days) of total parenteral nutrition (TPN) was considerably longer in the deTSH group than in the control group (27.68±13.08 days) (P from ANCOVA=0.003). CONCLUSION: Clinicians must consider deTSH in VLBWI showing feeding intolerance with a prolonged NPO and TPN status.


Assuntos
Peso ao Nascer , Dopamina , Motilidade Gastrointestinal , Idade Gestacional , Humanos , Lactente , Recém-Nascido de muito Baixo Peso , Modelos Logísticos , Programas de Rastreamento , Nutrição Parenteral , Nutrição Parenteral Total , Estudos Retrospectivos , Fatores de Risco , Tireotropina , Tiroxina
20.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-719388

RESUMO

BACKGROUND AND PURPOSE: We aimed to determine the association between the annual changes in dopamine transporter (DAT) availability as measured by 123I-ioflupane (123I-FP-CIT) single-photon-emission computed tomography and single-nucleotide polymorphisms (SNPs) known to be risk factors in Parkinson's disease (PD). METHODS: In total, 150 PD patients were included from the Parkinson's Progression Markers Initiative database. Specific SNPs that are associated with PD were selected for genotyping. SNPs that were not in Hardy-Weinberg equilibrium or whose minor allele frequency was less than 0.05 were excluded. Twenty-three SNPs met the inclusion criteria for this study. The Kruskal-Wallis test was used to compare annual percentage changes in DAT availability for three subgroups of SNP. RESULTS: None of the 23 SNPs exerted a statistically significant effect (p < 0.0022) on the decline of DAT availability in PD patients. However, we observed trends of association (p < 0.05) between three SNPs of two genes with the annual percentage change in DAT availability: 1) rs199347 on the putamen (p=0.0138), 2) rs356181 on the caudate nucleus (p=0.0105), and 3) rs3910105 on the caudate nucleus (p=0.0374). A post-hoc analysis revealed that DAT availability was reduced the most for 1) the putamen in the CC genotype of rs199347 (vs. CT, p=0.0199; vs. TT, p=0.0164), 2) the caudate nucleus in the TT genotype of rs356181 (vs. CC, p=0.0081), and 3) the caudate nucleus in the CC genotype of rs3910105 (vs. TT, p=0.0317). CONCLUSIONS: Significant trends in the associations between three SNPs and decline of DAT availability in PD patients have been discovered.


Assuntos
Núcleo Caudado , Proteínas da Membrana Plasmática de Transporte de Dopamina , Dopamina , Frequência do Gene , Genótipo , Humanos , Doença de Parkinson , Polimorfismo de Nucleotídeo Único , Putamen , Fatores de Risco , Tomografia Computadorizada de Emissão de Fóton Único
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