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1.
Electromagn Biol Med ; 39(1): 38-43, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31668093

RESUMO

People are increasingly exposed to electromagnetic radiation with the rapid development of technologies such as broadcasting and mobile communication system. There is a concern that long-term exposure at low levels may be associated with various non-specific physical symptoms and ecological effects on animals and plants. It is extremely important to measure and analyze the electromagnetic radiation levels in order to protect people from the possible effects of electromagnetic radiation. A large-scale assessment of the effects of electromagnetic radiation on health or on ecology requires the ambient electromagnetic radiation levels over areas too vast to cover with conventional measurement methods. In this article, detailed information about the measurement tools and measurement method are given. The electromagnetic radiation exposure levels were measured on the main streets in the dense urban areas of Beijing, the capital of China. We apply ordinary kriging as an interpolation technique to assess the electromagnetic radiation exposure in large outdoor areas based on car-mounted measurements along the surrounding roads. The electromagnetic radiation exposure levels for larger areas can be investigated visually on the electromagnetic pollution map, which can assist decision makers by identifying the hotspots.

2.
Hum Psychopharmacol ; 35(1): e2717, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31837240

RESUMO

This study examined randomized controlled trial data for blonanserin and risperidone in Chinese schizophrenia patients (N = 264). Data related to historical changes in the Positive and Negative Syndrome Scale (PANSS) were used to successfully construct a longitudinal Emax model. Results: (a) The efficacy of the two drugs was similar after week 8, showing a small difference in PANSS reduction. (b) Using the model, we predicted that each 5-point increase in the baseline FPOS (positive score in PANSS five-factor subscales) leads to a decrease in the PANSS total scores at week 8 for 2 points in patients administered blonanserin. (c) The effect of blonanserin on prolactin (PRL) elevation was less. The model was used to predict that prolactin elevations in patients administered risperidone were 2.41-fold of those in patients administered blonanserin. (d) Model quantitation showed that gender is a risk factor for prolactin elevation. Prolactin elevations in female patients were 2.95-fold of the value in male patients administered the same drug. The model demonstrated Blonanserin has similar antischizophrenic efficacy and less serum prolactin rising compared to risperidone in Chinese patients.

3.
Int J Neuropsychopharmacol ; 23(2): 76-87, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31774497

RESUMO

OBJECTIVE: Model-based meta-analysis was used to describe the time-course and dose-effect relationships of antidepressants and also simultaneously investigate the impact of various factors on drug efficacy. METHODS: This study is a reanalysis of a published network meta-analysis. Only placebo-controlled trials were included in this study. The change rate in depression rating scale scores from baseline was used as an efficacy indicator because a continuous variable is more likely to reflect subtle differences in efficacy between drugs. RESULTS: A total 230 studies containing 64 346 patients were included in the analysis. The results showed that the number of study sites (single or multi-center) and the type of setting (inpatient or noninpatient) are important factors affecting the efficacy of antidepressants. After deducting the placebo effect, the maximum pure drug efficacy value of inpatients was 18.4% higher than that of noninpatients, and maximum pure drug efficacy value of single-center trials was 10.2% higher than that of multi-central trials. Amitriptyline showed the highest drug efficacy. The remaining 18 antidepressants were comparable or had little difference. Within the approved dose range, no significant dose-response relationship was observed. However, the time-course relationship is obvious for all antidepressants. In terms of safety, with the exception of amitriptyline, the dropout rate due to adverse events of other drugs was not more than 10% higher than that of the placebo group. CONCLUSION: The number of study sites and the type of setting are significant impact factors for the efficacy of antidepressants. Except for amitriptyline, the other 18 antidepressants have little difference in efficacy and safety.

4.
Sleep ; 43(5)2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-31781753

RESUMO

STUDY OBJECTIVES: This study aimed to develop a robust placebo response model for the pharmacotherapy for insomnia to guide drug development and clinical practice. METHODS: PubMed, EMBASE, and Cochrane Library databases were systematically searched for randomized placebo-controlled trials of medications for insomnia dating from the inception dates of the databases to April 18, 2018. Three placebo response models were established to describe the time-course of sleep parameters measured by objective (polysomnography or actigraphy) or subjective methods (sleep diary or questionnaires). The established models were applied to simulate placebo response distribution under different conditions using Monte Carlo simulations. RESULTS: Fifty-four studies involving 6,416 subjects were included. Placebo response increased over time and reached a plateau at approximately 8 weeks from start of therapy. Established models described the observed data reasonably well based on various diagnostic plots. Baseline sleep parameters affected the placebo response. There were significant positive correlations with placebo response and the severity of sleep latency, wake after sleep onset, and total sleep time at baseline. In addition, placebo response, assessed by subjective and objective methods, was consistent after correcting the baseline levels. CONCLUSIONS: The established placebo response models can serve as a tool to predict placebo response at different baseline levels, which can provide valuable reference for clinical trial design, decision-making in drug development, and clinical practice.

5.
BMC Med Inform Decis Mak ; 19(Suppl 6): 271, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856805

RESUMO

BACKGROUND: Nucleus Accumbens (NAc) is a vital brain region for the process of reward and stress, whereas microRNA plays a crucial role in depression pathology. However, the abnormality of NAc miRNA expression during the stress-induced depression and antidepressant treatment, as well as its biological significance, are still unknown. METHODS: We performed the small RNA-sequencing in NAc of rats from three groups: control, chronic unpredictable mild stress (CUMS), and CUMS with an antidepressant, Escitalopram. We applied an integrative pipeline for analyzing the miRNA expression alternation in different model groups, including differential expression analysis, co-expression analysis, as well as a subsequent pathway/network analysis to discover both miRNA alteration pattern and its biological significance. RESULT: A total of 423 miRNAs were included in analysis.18/8 differential expressing (DE) miRNA (adjusted p < 0.05, |log2FC| > 1) were observed in controls Vs. depression/depression Vs. treatment, 2 of which are overlapping. 78% (14/18) of these miRNAs showed opposite trends of alteration in stress and treatment. Two micro RNA, miR-10b-5p and miR-214-3p, appeared to be hubs in the regulation networks and also among the top findings in both differential analyses. Using co-expression analysis, we found a functional module that strongly correlated with stress (R = 0.96, P = 0.003), and another functional module with a moderate correlation with anhedonia (R = 0.89, P = 0.02). We also found that predicted targets of these miRNAs were significantly enriched in the Ras signaling pathway, which is associated with both depression, anhedonia, and antidepressant treatment. CONCLUSION: Escitalopram treatment can significantly reverse NAc miRNA abnormality induced by chronic stress. However, the novel miRNA alteration that is absent in stress pathology also emerges, which means that antidepressant treatment is unlikely to bring miRNA expression back to the same level as the controls. Also, the Ras-signaling pathway may be involved in explaining the depression disease etiology, the clinical symptom, and treatment response of stress-induced depression.


Assuntos
Citalopram/farmacologia , Depressão/genética , Expressão Gênica , MicroRNAs/genética , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Estresse Psicológico/genética , Animais , Antidepressivos/farmacologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Masculino , Ratos , Análise de Sequência de RNA , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Proteínas ras/genética
6.
Front Genet ; 10: 703, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428135

RESUMO

Major depressive disorder (MDD) is a leading cause of disability worldwide, although its etiology and mechanism remain unknown. The aim of our study was to identify hub genes associated with MDD and to illustrate the underlying mechanisms. A weighted gene co-expression network analysis (WGCNA) was performed to identify significant gene modules and hub genes associated with MDD in peripheral blood mononuclear cells (PBMCs) (n = 45). In the blue module (R 2 = 0.95), five common hub genes in both co-expression network and protein-protein interaction (PPI) network were regarded as "real" hub genes. In another independent dataset, GSE52790, four genes were still significantly down-regulated in PBMCs from MDD patients compared with the controls. Furthermore, these four genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in PBMCs from 33 MDD patients and 41 healthy controls. The qRT-PCR analysis showed that ATP synthase membrane subunit c locus 1 (ATP5G1) was significantly down-regulated in samples from MDD patients than in control samples (t = -2.89, p-value = 0.005). Moreover, this gene was significantly differentially expressed between patients and controls in the prefrontal cortex (z = -2.83, p-value = 0.005). Highly significant differentially methylated positions were identified in the Brodmann area 25 (BA25), with probes in the ATP5G1 gene being significantly associated with MDD: cg25495775 (t = 2.82, p-value = 0.008), cg25856120 (t = -2.23, p-value = 0.033), and cg23708347 (t = -2.24, p-value = 0.032). These findings indicate that the ATP5G1 gene is associated with the pathogenesis of MDD and that it could serve as a peripheral biomarker for MDD.

7.
J Child Adolesc Psychopharmacol ; 29(9): 712-720, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31368787

RESUMO

Objective: The high placebo response rate may hamper the discovery of antidepressants in children and adolescents with major depressive disorder (MDD). The aim of the study was to clarify the relationship between the placebo response rate and clinical trial outcomes of the use of antidepressants in children and adolescents, and distinguish main factors responsible to placebo response rate. Methods: The PubMed and Cochrane Library databases were searched for double-blind randomized placebo-controlled trials of the new-generation antidepressants for the acute treatment of MDD in children and adolescents. The response rate differences (RDs) between placebo group and treatment group under different level of placebo response rate were pooled by random-effects meta-analysis. The classification thresholds for low, medium, and high placebo response rate were set at <40%, 40%-50%, and ≥50%, respectively. Predictors of placebo response rate were explored using meta-regression. Results: The analysis included 18 trials with 4365 participants. This study found that the lower the placebo response rate, the greater the efficacy differences between antidepressants and placebo. In the high, moderate, and low placebo response rate subgroups, the response RDs (95% CI) between antidepressants and placebo were 8 (1-14)%, 10 (2-17)%, and 21 (9-32)%, respectively. The meta-regression showed that the number of study sites was the factor most associated with placebo response rate, and that response rate increased 3% with every additional 10 study sites. Conclusions: The clinical outcome was related to the placebo response rates in the clinical trials of antidepressants in children and adolescents with MDD. The efficacy differences between antidepressants and placebo will be maximized when placebo response rates are reduced. The number of study sites was the factor most associated with the placebo response rates.

8.
Acta Pharmacol Sin ; 40(12): 1611-1620, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31388088

RESUMO

Atypical antipsychotics exert remarkable long-term efficacy on the personal and social functions of schizophrenic patients. However, quantitative information on the social function of schizophrenic patients treated with atypical antipsychotics is scarce in the current clinical guidelines. In this study, we established pharmacodynamic models to quantify the time-efficacy relationship of three antipsychotic drugs based on the data from a real-world study conducted in China. A total of 373 schizophrenic patients who received antipsychotic monotherapy with olanzapine (n = 144), risperidone (n = 160), or aripiprazole (n = 69) were selected from a three-year prospective, multicenter study. The follow-up times were 13, 26, 52, 78, 104, 130, and 156 weeks after baseline. A time-efficacy model was developed with nonlinear mixed effect method based on changes in Personal and Social Performance (PSP) score compared with the baseline level. Crucial pharmacodynamic parameters, including maximum efficacy and drug onset time, were used to distinguish the efficacy of the three drugs. We quantified the time course of PSP improvement in patients after treatment with these three antipsychotics: olanzapine, risperidone, and aripiprazole reached an Emax value of 80.3%, 68.2%, and 23.9% at weeks 56.7, 29.2, and 36.8, respectively. General psychotic symptoms, onset frequency, and illness course were identified as significant factors affecting the efficacy of these drugs. The newly constructed models provide an evidence of the benefit of long-term maintenance therapy with atypical antipsychotics in individualized schizophrenia treatment in China.


Assuntos
Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Olanzapina/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Estudos Prospectivos , Adulto Jovem
9.
Front Behav Neurosci ; 13: 163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396062

RESUMO

MK-801, also known as dizocilpine, is a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist that induces schizophrenia-like symptoms. Our previous study showed that brain-derived neurotrophic factor (BDNF) signaling was upregulated in cultured hippocampal astrocytes in response to MK-801. However, dysfunctional NMDA receptors are mainly expressed in neurons. The effects of MK-801 on neuron-derived BDNF expression and of risperidone on MK-801-induced cognitive impairment and changes in BDNF expression are unclear. To address this issue, we examined BDNF expression in the hippocampus of rats that received repeated injections of MK-801 (0.5 mg/kg body weight for 6 days) and in primary cultured hippocampal neurons incubated with 20 µM MK-801 for 24 h. BDNF expression and cognitive function were also evaluated in rats receiving intraperitoneal injections of risperidone (1 mg/kg body weight) once daily for 7 days and in hippocampal neurons incubated with 10 µM risperidone following MK801 treatment. MK-801 treatment decreased BDNF expression in the rat hippocampus as well as the expression and secretion of BDNF in hippocampal neurons in vitro. However, risperidone reversed the effects of MK801 on BDNF level and improved cognitive function in rats treated with MK801. These findings suggest that risperidone may alleviate cognitive impairment caused by MK801 via upregulation of BNDF signaling in the hippocampus.

10.
Acta Biomater ; 97: 657-670, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31401346

RESUMO

In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24 months. Micro-CT analysis showed that the implanted stent was able to maintain structural integrity after 6 months, while its disintegration occurred after 9 months of implantation. After 24 months of implantation, approximately 28 ±â€¯13 vol% of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24 months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24 months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications. STATEMENT OF SIGNIFICANCE: Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research.

11.
J Affect Disord ; 257: 143-149, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301615

RESUMO

BACKGROUND: This study evaluated the non-inferiority of bupropion extended-release (XL) compared to escitalopram for acute-phase treatment of Chinese patients with major depressive disorder (MDD). METHODS: This randomized (1:1), double-blind, active-control study conducted between February 2015 and October 2016 included patients with MDD (DSM-IV) (N = 538). The treatment phase had three dose levels (level 1 [Week 1], level 2 [Week 2-4], and level 3 [Week 5-8]), which included either bupropion XL 150 mg, 300 mg, 300 mg or escitalopram 10 mg, 10 mg, 10-20 mg (once-daily), respectively. Primary outcome was mean change from baseline in Hamilton Depression Rating Scale-17 (HAMD-17) total score at Week 8. RESULTS: Overall, 534 patients (bupropion XL, n = 266; escitalopram, n = 268) received at least one dose of study medication. The least square mean (standard error) change from baseline in HAMD-17 total score at Week 8 was -14.5 (0.41) in bupropion XL group and -15.4 (0.39) in escitalopram group (mean difference: 0.8 [-0.27, 1.94]). The response rate was 69.6% versus 72.9%, remission rate was 39.7% versus 47.2%, sustained response rate was 51.6% versus 56.3%, and sustained remission rate was 25.5% versus 28.6%, respectively, for bupropion XL versus escitalopram group. Adverse events were reported by 313 patients (bupropion XL, n = 157; escitalopram, n = 156); the most common on-treatment adverse event in both groups was nausea (10.5% versus 18.7%, respectively). LIMITATIONS: A non-inferiority short-term (8 weeks) study without a placebo arm. CONCLUSION: Results from this study demonstrated that the efficacy of bupropion XL was non-inferior to that of escitalopram in Chinese patients with MDD.

12.
Front Psychiatry ; 10: 378, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244689

RESUMO

Currently, the choice of medical treatment for major depressive disorder (MDD) is primarily based on a trial-and-error process. Thus, identification of individual factors capable of predicting treatment response is of great clinical relevance. Recent work points towards beclin-1 and inflammatory factors as potential biomarkers of antidepressant treatment response. The primary aim of the study was to investigate whether pre-treatment serum levels of beclin-1 and inflammatory factors could predict antidepressant treatment response in Chinese Han patients with MDD. Forty patients with MDD were treated with either a selective serotonin reuptake inhibitor (SSRI) (paroxetine in 20 cases) or a serotonin-norepinephrine reuptake inhibitor (SNRI) (duloxetine in 13 cases and venlafaxine in 7 cases). Depression scores and serum levels of beclin-1 were measured at the baseline and after 8 weeks of antidepressant treatment. Serum C-reactive protein (CRP), interleukin (IL)-1B, and IL-6 levels were determined using enzyme-linked immunosorbent assay kits at the baseline. Twenty-seven patients were identified as treatment responders, whereas 13 were identified as non-responders after 8 weeks of antidepressant treatment. Baseline serum beclin-1 levels were significantly higher in non-responders than in responders (p = 0.001), whereas no differences were found in baseline serum CRP, IL-1B, or IL-6 levels between responders and non-responders. There were no significant correlations between baseline levels of beclin-1 and baseline IL-1ß, IL-6, and CRP levels-neither in the total sample nor in responder and non-responder groups. Moreover, logistic regression models and a random forest model showed that baseline serum beclin-1, but not inflammatory factors, was an independent and the most important predictor for antidepressant treatment response. Furthermore, serum beclin-1 levels were significantly increased in responders (p = 0.027) but not in non-responders after 8 weeks of treatment (p = 0.221). Baseline serum beclin-1 levels may be a predictive biomarker of antidepressant response in patients with MDD. Moreover, beclin-1 may be involved in the therapeutic effect of antidepressant drugs.

13.
Gen Psychiatr ; 32(1): e100026, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31179423

RESUMO

Background: Extrapyramidal symptoms (EPS) are one of the most common and neglected side effects during the treatment of schizophrenia. The risk factors of EPS in Chinese patients with schizophrenia and its relationship with psychiatric symptoms and mood symptoms of schizophrenia remain unknown. Aims: The main objective of this study is to explore the risk factors of EPS caused by antipsychotics and the relationship between EPS and psychotic symptoms and mood symptoms of schizophrenia. Method: This study included 679 patients with schizophrenia who have met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. Patients were divided into the EPS group and the non-EPS group according to the scale rating criteria and whether the anticholinergics have been used. The differences between demographic data and characters of drug intake were compared between the two groups, and the risk factors of EPS were selected between those factors. Correlation analysis was performed on the severity of schizophrenia (Positive and Negative Symptoms Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS) score) and EPS scale (Simpson-Angus Scale (SAS), Barnes Akathisia Rating Scale (BARS), Abnormal Involuntary Movement Scale (AIMS) score) in 679 patients. The differences between the PANSS subscale score and the CDSS score between the EPS group and the non-EPS group were compared. Result: Compared with the non-EPS group, the EPS group patients are older, and they have a longer duration since first prescribed antipsychotics. The EPS group patients have higher frequency of atypical antipsychotics polytherapy and typical and atypical antipsychotics polytherapy or combined treatments with mood stabilisers. Logistic regression analysis shows that antipsychotics with high D2 receptor antagonistic effect and illness duration are the risk factors of EPS. The SAS score was significantly correlated with PANSS negative score, PANSS general psychopathological score and PANSS total score. The BARS scale score was significantly correlated with PANSS positive score, PANSS general psychopathological score, PANSS total score and CDSS total score. The AIMS scale score was significantly correlated with PANSS negative score. Compared with the non-EPS group, the EPS group patients have significantly higher PANSS negative score, PANSS general psychopathological score, PANSS total score and CDSS total score. Conclusion: Antipsychotic drugs with high D2 receptor antagonism and disease duration are risk factors of EPS in Chinese patients with schizophrenia. The severity of various types of EPS is significantly correlated with the psychiatric and mood symptoms of schizophrenia, and psychiatric symptoms and mood symptoms were significantly more severe in the EPS group. The occurrence of EPS is associated with poor treatment outcome of schizophrenia.

14.
Gen Psychiatr ; 32(1): e100042, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31179425

RESUMO

Background: Risperidone (RSP) has a rapid onset in vivo, low dosage and high plasma protein binding rate, therefore therapeutic drug monitoring (TDM) is needed to ensure safety in clinical treatment. However, compared with blood, hair is non-invasive, safe, non-infectious and easy to transport and store. Aims: This study aims to investigate the correlations among the drug concentrations of RSP in hair and serum, which provides an experimental basis to explore hair as a novel biomaterial to meet the needs of clinical detection. Methods: 34 patients with schizophrenia treated with RSP for more than 3 months were enrolled in this study. About 1 cm section of hair near the scalp was taken from the subjects, pretreated and detected by liquid chromatography-mass spectrometry. A correlation analysis was conducted among the drug concentrations in hair, the serum concentrations and the daily dosage. The data were analysed using SPSS 20.0 software. Results : There was significant correlation between the hair concentration of RSP (two-tailed test, r=0.440, p=0.009) with the serum concentration of RSP, and the hair concentration of 9-hydroxyrisperidone (9-HR) with the serum concentration of 9-HR had no significant correlation (two-tailed test, r=-0.217, p=0.217); the total concentration of the RSP and 9-HR had no significant correlation between hair and serum (r=0.227, p=0.196). The dosage had no statistically significant correlation with the concentration of RSP in hair (r=0.207, p=0.241), 9-HR in hair (r=-0.194, p=0.271) and the total concentration of RSP and 9-HR in hair (r=0.188, p=0.288). There was no statistical correlation between the dosage and the concentration of RSP in serum (r=-0.059, p=0.741), but significant correlation between the dosage and 9-HR in serum (r=0.581 p<0.001) was found, and the correlation between the dosage and the total concentration of the two drugs RSP and 9-HR in serum was also significant (r=0.437, p=0.01). Conclusion: The correlation analysis showed that the concentration of RSP in hair was statistically significant with the serum RSP concentration. In this study, we provided some experimental basis for hair as a new biomaterial to monitor the therapeutic drug concentration.

15.
Eur J Clin Pharmacol ; 75(4): 497-509, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30612155

RESUMO

PURPOSE: This study aimed to establish a non-linear mixed effects model to quantitatively analyze the placebo responses of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD). METHODS: A comprehensive literature search was conducted in public databases. Placebo-controlled randomized AD clinical trials using the neuropsychiatric inventory (NPI) score as the primary or secondary outcome were included. Non-linear mixed effects model was used to describe the time course of the placebo responses of NPS in AD clinical trials. Potential affecting factors were tested as covariates. RESULTS: A total of 32 clinical studies (involving 3942 subjects) were included in model-based analysis. We found that the maximal placebo responses of NPS were reached at week 4 approximately, after which rebound effects appeared. The baseline NPI score had a significant impact on the placebo responses. Higher baseline NPI score tended to cause greater reductions in NPI score at week 8 and a smaller degree of rebound. For AD patients whose normalized baseline NPI score was 10 points and 30 points, the reduction in normalized NPI score at week 8 was estimated to be 0.83 and 7.43 points, respectively; and the rebound rate after week 8 was estimated to be 0.1 points/week and 0.08 points/week, respectively. CONCLUSIONS: The duration of 4 weeks is sufficient to determine the drug efficacy for assessing NPS in AD clinical trials. The baseline NPI score was a key factor associated with placebo responses of NPS, which should be considered when designing future clinical trials and conducting comparisons across trials.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Dinâmica não Linear , Efeito Placebo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Inibidores da Colinesterase/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Nootrópicos/uso terapêutico , Escalas de Graduação Psiquiátrica , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Eur J Drug Metab Pharmacokinet ; 44(3): 339-352, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30520001

RESUMO

BACKGROUND AND OBJECTIVE: Bupropion is used for the treatment of major depressive disorder. We determined the pharmacokinetics, safety, and tolerability of extended-release bupropion XL in healthy Chinese volunteers. METHODS: This open-label, single-center pharmacokinetic study was conducted between May 2016 and June 2016. Eligible volunteers received bupropion XL 150 mg once daily for 5 days, then 300 mg once daily from days 6 to 14. Pharmacokinetic parameters were evaluated after first and repeated doses by non-compartmental and population pharmacokinetic analyses. RESULTS: Fifteen out of 16 enrolled volunteers completed the study. The geometric mean of the bupropion area under the concentration-time curve from 0 to 24 h (AUC0-24) was 498.2 and 1,165.7 h·ng/mL on days 1 and 14, respectively; maximum plasma concentration (Cmax) was 49.9 ng/mL on day 1 and steady-state maximum observed plasma concentration (Css_max) was 111.9 ng/mL on day 14. Among the three metabolites, hydroxybupropion showed the highest AUC0-24 and Cmax. The population pharmacokinetic model findings indicated an apparent oral clearance of 221 L/h for bupropion in a typical healthy 60.9-kg Chinese volunteer. CONCLUSIONS: This was the first pharmacokinetic study for bupropion XL and its active metabolites in the Chinese population. The AUC and Cmax of bupropion XL and its three metabolites increased approximately in a dose-proportional manner with an increase from 150 mg to 300 mg. Adverse events were similar to those reported in studies outside China. A population pharmacokinetic model was developed for bupropion XL, with pharmacokinetics of bupropion adequately described by a two-compartment model with first-order absorption and linear elimination plus lag time. TRIAL REGISTRATION NUMBER: NCT02698553.


Assuntos
Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/farmacocinética , Bupropiona/efeitos adversos , Bupropiona/farmacocinética , Modelos Biológicos , Administração Oral , Adulto , Antidepressivos de Segunda Geração/administração & dosagem , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Bupropiona/administração & dosagem , China , Preparações de Ação Retardada , Transtorno Depressivo Maior/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Meia-Vida , Voluntários Saudáveis , Humanos , Masculino
17.
Microb Pathog ; 126: 63-73, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30366126

RESUMO

The capacity of Mycobacterium tuberculosis to survive and cause disease is strongly correlated with its ability to escape multiple defense strategies in hosts. In particular, M. tuberculosis has the remarkable capacity to survive within the hostile environment of macrophages. Here, we found that the PE17 (Rv1646) protein promoted intracellular survival of M. smegmatis in peritoneal macrophages from mice. Further experiments confirmed that the recombinant PE17 protein was localized in the cell wall of M. smegmatis. Results from the macrophage infection model showed that PE17 significantly downregulated pro-inflammatory cytokines (interleukin-6, interleukin-12, and tumer necrosis factor-α) secretion from macrophages induced by M. smegmatis and promoted macrophage necrosis. Furthermore, a C57BL/6 mouse infection model confirmed that PE17 significantly prolonged the survival of M. smegmatis in vivo and aggravated lesions in organs of infected mice. Moreover, persistent high levels of interferon-γ and interleukin-1ß in infected mice indicated that the bacteria were not easily removed in vivo. Overall, our present results suggested that the PE17 may act as an important pathogenic factor in M. tuberculosis.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Macrófagos/imunologia , Macrófagos/microbiologia , Mycobacterium smegmatis/metabolismo , Mycobacterium tuberculosis/metabolismo , Fatores de Virulência/metabolismo , Animais , Antígenos de Bactérias/genética , Apoptose , Proteínas de Bactérias/genética , Morte Celular , Parede Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Regulação Bacteriana da Expressão Gênica , Interações Hospedeiro-Patógeno , Interferon gama/metabolismo , Interleucina-12/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Rim/microbiologia , Rim/patologia , Fígado/microbiologia , Fígado/patologia , Pulmão/microbiologia , Pulmão/patologia , Macrófagos/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Viabilidade Microbiana , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium smegmatis/genética , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade , Proteínas Recombinantes , Baço/microbiologia , Baço/patologia , Fator de Necrose Tumoral alfa/metabolismo , Virulência , Fatores de Virulência/genética
18.
Clin Pharmacol Drug Dev ; 8(6): 721-733, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30427594

RESUMO

The pharmacokinetics (PK) and safety of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) after single and repeat dosing in healthy Chinese adults were assessed. In this open-label study (NCT02837380), subjects received once-daily FF/UMEC/VI 100/62.5/25 µg on day 1 and repeat doses on days 2-7. PK parameters (days 1 and 7) included maximum observed concentration (Cmax ) and area under the plasma concentration-time curve (AUC) from time zero (predose) to last time of quantifiable concentration (AUC0-t ). Terminal phase half-life (t½ ) on day 1 was estimated. The primary objective was to assess systemic exposure of FF 100 µg, UMEC 62.5 µg, and VI 25 µg following single-inhaler triple therapy on days 1 and 7. On day 1, geometric mean t½ of UMEC and VI was 0.36 and 0.52 hours, respectively; t½ of FF was not representative because of nonquantifiable concentration data. On days 1 and 7, geometric mean Cmax of FF was 10.46 and 27.32 pg/mL, respectively; Cmax of UMEC was 144.14 and 241.35 pg/mL, respectively; and Cmax of VI was 120.42 and 196.78 pg/mL, respectively. AUC0-t of FF was 1.77 and 276.96 pg·h/mL, respectively; AUC0-t of UMEC was 28.44 and 117.19 pg·h/mL, respectively; and AUC0-t of VI, 42.46 and 101.12 pg·h/mL, respectively. The PK of FF/UMEC/VI was as expected for the individual-component PK previously reported in healthy Chinese adults. No new safety signals were observed.

19.
Int J Psychiatry Med ; 54(1): 11-21, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30122100

RESUMO

OBJECTIVE: Few studies have addressed informed consent in Chinese psychiatric practice. We wished to explore psychiatrists' attitudes toward informed consent in Shanghai after promulgation of the first national law for mental health care in China: the National Mental Health Law. METHOD: A total of 398 psychiatrists were recruited from seven psychiatric hospitals in Shanghai. Their anthropometric data were collected. A confidential, self-report questionnaire addressing attitudes toward the informed consent process was completed by all participants. RESULTS: Most respondents would like to inform patients/guardians of the diagnosis (95.2%), treatment plan (93.5%), treatment goals and potential adverse effects of prescribed medications (94.7%), and alternative treatment plans (71.9%). In addition, 58.4% of psychiatrists thought that the informed consent process for physical restraint was difficult to follow. According to logistic regression, psychiatrists not trained to use the National Mental Health Law were more likely to have a negative attitude toward the informed consent process compared with those trained (adjusted odds ratio = 0.21; 95% confidence interval: 0.07-0.59; p = 0.003). CONCLUSIONS: Psychiatrists trained to use the National Mental Health Law had more positive attitudes toward the informed consent process. Lack of such training could affect the attitudes of psychiatrists toward the informed consent process in China.


Assuntos
Atitude do Pessoal de Saúde , Consentimento Livre e Esclarecido , Psiquiatria , Adulto , China , Feminino , Hospitais Psiquiátricos , Humanos , Masculino , Saúde Mental/legislação & jurisprudência , Saúde Mental/tendências , Serviços de Saúde Mental/organização & administração , Serviços de Saúde Mental/tendências , Pessoa de Meia-Idade , Inquéritos e Questionários
20.
Psychiatry Res ; 268: 413-418, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30125872

RESUMO

Post-traumatic stress disorder (PTSD) is characterized by cognitive deficits including impaired explicit memory. Nitric oxide (NO), which is generated by nitric oxide synthase (NOS), has been considered to modulate learning and memory. In current study, we evaluated the role of NOS in the mouse model of PTSD. We established the immobilization (IMO) mouse model of PTSD and analyzed mice behavior, NOS expression and hippocampal excitatory synaptic transmission after immobilization. We inhibited iNOS by applying of iNOS inhibitor 1400 W and monitored the effect of iNOS inhibition by 1400 W in IMO mice. IMO induced iNOS expression and resulted in abnormal behavior and deficits in synaptic plasticity and memory in mice. Inhibition of iNOS rescued abnormal hippocampal long-term potentiation and abnormal behavior in IMO mice. Inhibition of iNOS ameliorates traumatic stress-induced deficits in synaptic plasticity and memory.


Assuntos
Aprendizagem/fisiologia , Memória/fisiologia , Plasticidade Neuronal/fisiologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Transtornos de Estresse Pós-Traumáticos/metabolismo , Animais , Comportamento Animal/fisiologia , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/psicologia , Modelos Animais de Doenças , Hipocampo/metabolismo , Hipocampo/fisiologia , Masculino , Transtornos da Memória/metabolismo , Transtornos da Memória/psicologia , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Transtornos de Estresse Pós-Traumáticos/psicologia , Transmissão Sináptica
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