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BACKGROUND To investigate the effect that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has on surgical decision making relative to video-electroencephalography (VEEG) and positron emission tomography-computed tomography (PET-CT), and if the differences in these variables translates to differences in surgical outcomes. MATERIAL AND METHODS A total of 166 children with epilepsy undergoing preoperative DCE-MRI, VEEG, and PET-CT examinations, surgical resection of epileptic foci, and intraoperative electrocorticography (ECoG) monitoring were enrolled. All children were followed up for 12 months and grouped by Engles prognostic classification for epilepsy. Based on intraoperative ECoG as gold standard, the diagnostic values of DCE-MRI, VEEG, PET-CT, DCE-MRI combined with VEEG, DCE-MRI combined with PET-CT, and combined application of DCE-MRI, VEEG, and PET-CT in preoperative localization for epileptic foci were evaluated. RESULTS The sensitivity of DCE-MRI, VEEG, and PET-CT was 59.64%, 76.51%, and 93.98%, respectively; the accuracy of DCE-MRI, VEEG, PET-CT, DCE-MRI combined with VEEG, and DCE-MRI combined with PET-CT was 57.58%, 67.72%, 91.03%, 91.23%, and 96.49%, respectively. Localization accuracy rate of the combination of DCE-MRI, VEEG, and PET-CT was 98.25% (56/57), which was higher than that of DCE-MRI combined with VEEG and of DCE-MRI combined with PET-CT. No statistical difference was found in the accuracy rate of localization between these three combined techniques. During the 12-month follow-up, children were grouped into Engles grade I (n=106), II (n=31), III (n=21), and IV (n=8) according to postoperative conditions. CONCLUSIONS All DCE-MRI combined with VEEG, DCE-MRI combined with PET-CT, and DCE-MRI combined with VEEG and PET-CT examinations have excellent accuracy in preoperative localization of epileptic foci and present excellent postoperative efficiency, suggesting that these combined imaging methods are suitable for serving as the reference basis in preoperative localization of epileptic foci in children with epilepsy.
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Epilepsias Parciais/diagnóstico , Criança , Eletroencefalografia/métodos , Epilepsias Parciais/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
Neurocognitive impairment is one of the factors that put heroin abusers at greater risk for relapse, and deficits in related functional brain connections have been found. However, the alterations in structural brain connections that may underlie these functional and neurocognitive impairments remain largely unknown. In the present study, we investigated topological organization alterations in the structural network of white matter in heroin abusers and examined the relationships between the network changes and clinical measures. We acquired diffusion tensor imaging datasets from 76 heroin abusers and 78 healthy controls. Network-based statistic was applied to identify alterations in interregional white matter connectivity, and graph theory methods were used to analyze the properties of global networks. The participants also completed a battery of neurocognitive measures. One increased subnetwork characterizing widespread abnormalities in structural connectivity was present in heroin users, which mainly composed of default-mode, attentional and visual systems. The connection strength was positively correlated with increases in fractional anisotropy in heroin abusers. Intriguingly, the changes in within-frontal and within-temporal connections in heroin abusers were significantly correlated with daily heroin dosage and impulsivity scores, respectively. These findings suggest that heroin abusers have extensive abnormal white matter connectivity, which may mediate the relationship between heroin dependence and clinical measures. The increase in white matter connectivity may be attributable to the inefficient microstructure integrity of white matter. The present findings extend our understanding of cerebral structural disruptions that underlie neurocognitive and functional deficits in heroin addiction and provide circuit-level markers for this chronic disorder.
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Dependência de Heroína/fisiopatologia , Imageamento por Ressonância Magnética , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologia , Adulto , Estudos Transversais , Humanos , Masculino , Testes NeuropsicológicosRESUMO
Drug addiction shares common neurobiological pathways and risk genes with other psychiatric diseases, including psychosis. One of the commonly identified risk genes associated with broad psychosis has been ZNF804A. We sought to test whether psychosis risk variants in ZNF804A increase the risk of heroin addiction by modulating neurocognitive performance and gray matter volume (GMV) in heroin addiction. Using case-control genetic analysis, we compared the distribution of ZNF804A variants (genotype and haplotype) in 1035 heroin abusers and 2887 healthy subjects. We also compared neurocognitive performance (impulsivity, global cognitive ability and decision-making ability) in 224 subjects and GMV in 154 subjects based on the ZNF804A variants. We found significant differences in the distribution of ZNF804A intronic variants (rs1344706 and rs7597593) allele and haplotype frequencies between the heroin and control groups. Decision-making impairment was worse in heroin abusers who carried the ZNF804A risk allele and haplotype. Subjects who carried more risk alleles and haplotypes of ZNF804A had greater GMV in the bilateral insular cortex, right temporal cortex and superior parietal cortex. The interaction between heroin addiction and ZNF804A variants affected GMV in the left sensorimotor cortex. Our findings revealed several ZNF804A variants that were significantly associated with the risk of heroin addiction, and these variants affected decision making and GMV in heroin abusers compared with controls. The precise neural mechanisms that underlie these associations are unknown, which requires future investigations of the effects of ZNF804A on both dopamine neurotransmission and the relative increases in the volume of various brain areas.
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Cognição , Tomada de Decisões , Substância Cinzenta/patologia , Dependência de Heroína/genética , Fatores de Transcrição Kruppel-Like/genética , Adulto , Alelos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Estudos de Casos e Controles , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Feminino , Predisposição Genética para Doença , Substância Cinzenta/diagnóstico por imagem , Haplótipos , Dependência de Heroína/psicologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/patologia , Polimorfismo de Nucleotídeo Único , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/patologiaRESUMO
Iron is the most abundant metal element to support the body's physiological activities and play crucial roles in the central nervous system. Iron homeostasis is under strict control in normal circumstances, and some diseases will occur once the homeostasis was disrupted. Numerous researches suggest that iron homeostasis disruptes in Alzheimer's disease (AD) and the homeostasis disruption interacts with AD's hallmarks. Dispute still exists on how iron plays a role in AD despite of the great number of researches. This article will focus on iron metabolism, normal function in the brain and recent therapies of AD based on iron chelation.
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Doença de Alzheimer/tratamento farmacológico , Encéfalo/metabolismo , Homeostase , Ferro/metabolismo , Quelantes , HumanosRESUMO
BACKGROUND To compare risk of carpal tunnel syndrome (CTS) in distal radius fracture (DRF) patients after 7 treatments using bridging external fixation (BrEF), non-bridging external fixation (non-BrEF), plaster fixation, K-wire fixation, dorsal plating fixation, volar plating fixation, and dorsal and volar plating by performing a network meta-analysis. MATERIAL AND METHODS An exhaustive search of electronic databases identified randomized controlled trails (RCTs) closely related to our study topic. The published articles were screened, based on predefined inclusion and exclusion criteria, to select high-quality studies for the present network meta-analysis. Data extracted from the selected studies were analyzed using STATA version 12.0 software. RESULTS The literature search and selection process identified 12 eligible RCTs that contained a total of 1370 DRF patients (394 patients with BrEF, 377 patients with non-BrEF, 89 patients with K-wire fixation, 192 patients with plaster fixation, 42 patients with dorsal plating fixation, 152 patients with volar plating fixation, and 124 patients with dorsal and volar plating fixation). Our network meta-analysis results demonstrated no significant differences in CTS risk among the 7 treatments (P>0.05). The value of surface under the cumulative ranking curve (SUCRA), however, suggested that dorsal plating fixation is the optimal treatment, with the lowest risk of CTS in DRF patients (dorsal plating fixation: 89.2%; dorsal and volar plating: 57.8%; plaster fixation: 50.9%; non-BrEF: 50.6%; volar plating fixation: 39.6%; BrEF: 38.4%; K-wire fixation: 23.6%). CONCLUSIONS Our network meta-analysis provides evidence that dorsal plating fixation significantly decreases the risk of CTS and could be the method of choice in DRF patients.
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Síndrome do Túnel Carpal/etiologia , Fixação de Fratura/métodos , Fraturas do Rádio/cirurgia , Bases de Dados Factuais , Fixação de Fratura/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Time-dependent increases in cue-induced nicotine and methamphetamine craving during abstinence were recently reported in human drug-dependent individuals. In the present study, we sought to determine whether this 'incubation of craving' phenomenon also occurs in alcoholics. Four groups of 80 inpatient adult male alcoholics were assessed in a single session (between-group design) for cue-induced alcohol craving at 7, 14, 30 and 60 days of abstinence. Another group that included 19 patients was repeatedly tested for cue-induced alcohol craving at the same abstinence days as above. Other psychological and physiological measures were assessed at the four abstinence timepoints. Cue-induced alcohol craving measured with visual analogue scales was the highest at 60 days of abstinence both between and within groups. However, heart rate, blood pressure and skin conductance responses did not differ between abstinent groups. These results provide evidence of the incubation of alcohol craving in humans, extending previous reports with smokers and methamphetamine addicts.
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Abstinência de Álcool/psicologia , Alcoolismo/psicologia , Fissura , Adolescente , Adulto , Análise de Variância , Pressão Sanguínea/fisiologia , Sinais (Psicologia) , Resposta Galvânica da Pele/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Abstinência a Substâncias/psicologia , Adulto JovemRESUMO
Tobacco smoking is a global healthcare problem that poses a substantial and costly health burden. Nicotine is the major constituent responsible for the addiction to tobacco. Current strategies helping tobacco smokers have limited utility in increasing rates of smoking cessation, consequently indicating the need for alternative therapies. A novel therapeutic method is vaccination against nicotine. Nicotine vaccine can generate specific antibodies that can sequester nicotine from cigarette smoke in the blood, and prevent its access to the brain and minimize positive reinforcing effects, which may help smokers to stop smoking. The vaccine will have great potential for the treatment of nicotine addiction and for relapse prevention. Here we will review the current status of vaccines against nicotine addiction and discuss the problems associated with the development of nicotine vaccines.
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Nicotina/antagonistas & inibidores , Tabagismo/terapia , Vacinas/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Nicotina/imunologia , Fumar/imunologia , Fumar/terapia , Abandono do Hábito de Fumar/métodos , Tabagismo/imunologia , Vacinação/métodosRESUMO
There are two independent mol-ecules in the asymmetric unit of the title compound, C(15)H(10)ClNO(2), which differ in the dihedral angles between the mean planes of the phenyl ring and the 4-chloro-indoline-2,3-dione ring system [59.48â (9) and 79.0â (1)°]. In the crystal, mol-ecules are linked through C-Hâ¯O hydrogen bonds, forming polymeric chains in [100].
RESUMO
The present study examined the association between microRNA (miR)296 and angiogenesis following cerebral ischemic injury, and the underlying mechanisms. A cerebral ischemic model was established in rats via right middle cerebral artery occlusion. The animals were randomly divided into four groups (baseline, 1 day, 3 day and 7 day). Quantitative polymerase chain reaction and western blot analyses were performed to examine the expression levels of miR296 and hepatocyte growth factorregulated tyrosine kinase substrate (HGS), respectively. Angiogenesis was assessed by examining microvessel density. The results demonstrated that miR296 and angiogenesis were significantly upregulated, while HGS was significantly downregulated following ischemic injury. Adenovirusmediated overexpression of miR296 markedly enhanced the formation of capillarylike structures in human umbilical vein endothelial cells, parallel with significantly increased expression levels of vascular endothelial growth factor (VEGF) and VEGF receptor 2, and reduced expression levels of DLL4 and Notch1. The results of the present study provided in vivo and in vitro evidence suggesting that miR296 promotes angiogenesis in the ischemic brain through upregulating VEGF and downregulating Notch1 following cerebral ischemic injury.
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Isquemia Encefálica/genética , Regulação da Expressão Gênica , MicroRNAs/fisiologia , Receptor Notch1/genética , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Isquemia Encefálica/metabolismo , Artérias Cerebrais/metabolismo , Regulação para Baixo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Patológica , Fosfoproteínas/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Notch1/metabolismo , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
In this study, we performed a network meta-analysis to compare the outcomes of seven most common surgical procedures to fix DRF, including bridging external fixation, non-bridging external fixation, K-wire fixation, plaster fixation, dorsal plating, volar plating, and dorsal and volar plating. Published studies were retrieved through PubMed, Embase and Cochrane Library databases. The database search terms used were the following keywords and MeSH terms: DRF, bridging external fixation, non-bridging external fixation, K-wire fixation, plaster fixation, dorsal plating, volar plating, and dorsal and volar plating. The network meta-analysis was performed to rank the probabilities of postoperative complication risks for the seven surgical modalities in DRF patients. This network meta-analysis included data obtained from a total of 19 RCTs. Our results revealed that compared to DRF patients treated with bridging external fixation, marked differences in pin-track infection (PTI) rate were found in patients treated with plaster fixation, volar plating, and dorsal and volar plating. Cluster analysis showed that plaster fixation is associated with the lowest probability of postoperative complication in DRF patients. Plaster fixation is associated with the lowest risk for postoperative complications in DRF patients, when compared to six other common DRF surgical methods examined.
Assuntos
Fixação Interna de Fraturas/efeitos adversos , Complicações Pós-Operatórias/patologia , Fraturas do Rádio/cirurgia , Pinos Ortopédicos/efeitos adversos , Moldes Cirúrgicos/efeitos adversos , Fixação Interna de Fraturas/métodos , Humanos , Complicações Pós-Operatórias/epidemiologia , Fraturas do Rádio/epidemiologia , Fraturas do Rádio/patologia , Fatores de RiscoRESUMO
Previous studies have shown that peripheral electrical stimulation (PES) can suppress morphine-induced conditioned place preference (CPP) and the reinstatement of extinguished CPP in the rat. The present study was performed to elucidate if preproenkephalin (PPE) and preprodynorphin (PPD) mRNAs in the nucleus accumbens (NAc) play a role in this event. Rats were trained with morphine for 4 days to establish CPP paradigm. They were then given 15-min test once a day for eight consecutive days for extinction trial. Twenty-four hours after the 8th session of extinction trials, rats were given peripheral electrical stimulation (PES) at 2 or 100 Hz once a day for 3 days, then a morphine-priming injection at a dose of 1, 2, or 4 mg/kg to reinstate the extinguished CPP. At the end of the experiment, PPE and PPD mRNA levels in the nucleus acccumbens (NAc) were determined by the semiquantitative RT-PCR technique. The results showed that PES at 2- and 100-Hz administered 30 min a day for 3 days suppressed both the expression of morphine-induced CPP and the reinstatement of extinguished CPP. PES at 2 Hz increased preproenkephalin (PPE) mRNA levels, whereas PES of 100 Hz that of preprodynorphin (PPD) mRNA levels in the NAc. These findings suggest that enkephalin and dynorphin in NAc may play important roles in the mechanisms underlying the inhibitory effect of PES on the expression and reinstatement of morphine-induced CPP in rats.
Assuntos
Condicionamento Operante/efeitos da radiação , Dinorfinas/metabolismo , Estimulação Elétrica , Encefalinas/metabolismo , Extinção Psicológica/efeitos da radiação , Regulação da Expressão Gênica/efeitos da radiação , Núcleo Accumbens/efeitos da radiação , Precursores de Proteínas/metabolismo , Análise de Variância , Animais , Comportamento Animal , Condicionamento Operante/efeitos dos fármacos , Condicionamento Operante/fisiologia , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Dinorfinas/genética , Encefalinas/genética , Membro Posterior/inervação , Membro Posterior/efeitos da radiação , Masculino , Morfina/farmacologia , Atividade Motora/efeitos dos fármacos , Atividade Motora/efeitos da radiação , Entorpecentes/farmacologia , Precursores de Proteínas/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Fatores de TempoRESUMO
Conditioned place preference (CPP) paradigm has been suggested as one of the animal models for drug craving. The present study was performed to examine the effect of 100 Hz peripheral electric stimulation (PES) on the expression of morphine-induced CPP. Rats were trained with morphine for 4 days to establish the CPP paradigm in a three-chamber "unbiased" apparatus. Morphine-induced CPP was maintained up to 4 weeks when tests were given once a week. PES of 100 Hz administered 30 min a day for 3 days significantly attenuated morphine-induced CPP (P<0.01). I.c.v. injection of the delta-opioid receptor antagonist naltrindole (NTI) or the kappa-antagonist norbinaltorphimine (nor-BNI) but not the mu-antagonist cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP), completely blocked the inhibitory effect of 100 Hz PES on the expression of morphine-induced CPP (P<0.05-0.01). These results indicate that the anti-craving effects induced by repeated PES of 100 Hz is mediated by the activation of supra-segmental delta- and kappa-opioid receptors in the central nervous system.
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Condicionamento Psicológico/efeitos dos fármacos , Inibição Psicológica , Morfina/farmacologia , Entorpecentes/farmacologia , Sistema Nervoso Periférico , Animais , Comportamento Animal , Condicionamento Operante/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estimulação Elétrica , Masculino , Antagonistas de Entorpecentes/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Opioides/fisiologia , Restrição Física , Fatores de TempoRESUMO
The profile of microRNAs (miRNAs) altered following middle cerebral artery occlusion (MCAO) and miRNAs are involved in angiogenesis following cerebral ischemia. miR376b5p was decreased following MCAO, however, whether miR376b5p is important in angiogenesis remains to be elucidated. The present study was designed to identify whether miR376b5p is involved in angiogenesis following cerebral ischemia and to elucidate the underlying mechanisms. A rat MCAO model was established and quantitative polymerase chain reaction was performed to analyze the mRNA expression level of miR376b5p for 1 to 7 days. In addition, the density of microvessels and the relative mRNA and protein levels of hypoxiainducible factor1 α (HIF1α), vascular endothelial growth factor A (VEGFA) and Notch1 were measured. The miR376b5p mimic or the miR376b5p inhibitor were transfected into hypoxic human umbilical vein endothelial cells (HUVECs), and the proliferation, migration and tube formation were measured. To further examine the underlying mechanisms, shRNA was transfected into cells to knock down HIF1α, and angiogenesis and the expression of associated molecules, including HIF1α, VEGFA and Notch1 were compared between each group. Our results demonstrated that miR376b5p repressed angiogenesis in vivo and in vitro, and miR376b5p inhibited angiogenesis in HUVECs by targeting the HIF1αmediated VEGFA/Notch1 signaling pathway. These findings provide new insights into angiogenesis therapy for cerebral ischemia.
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Isquemia Encefálica/genética , Infarto da Artéria Cerebral Média/genética , MicroRNAs/metabolismo , Neovascularização Fisiológica , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Hipóxia Celular , Modelos Animais de Doenças , Regulação para Baixo , Células Endoteliais da Veia Umbilical Humana , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Masculino , MicroRNAs/antagonistas & inibidores , Oligonucleotídeos Antissenso/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Notch1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de von Willebrand/metabolismoRESUMO
Taking the 2-year old Ginkgo biloba seedlings as test materials, a pot experiment was conducted in an artificial climate chamber to study the effects of air temperature and soil moisture on the flavonoids accumulation in leaves. Three levels of air temperature (15/5 degrees C, 25/15 degrees C, and 35/25 degrees C day/night) and three levels of soil moisture (55%-60%, 40%-45%, and 30%-35% of field capacity) were installed, yielding nine temperature-soil moisture combinations. Under the three levels of soil moisture, the quercetin, kaempferol, isorhamnetin, and total flavonoids contents in the leaves were higher at 15/5 degrees C than at 25/15 degrees C and 35/25 degrees C. Soil moisture had minor effects on the flavonoids accumulation. The leaf kaempferol content was the highest, followed by quercetin and isorhamnetin. The total flavonoids yield per plant at 35/25 degrees C was higher than that at 15/5 degrees C and 25/15 degrees C. It was suggested that to adopt appropriate soil covering and watering before harvesting to decrease the ambient temperature could benefit the enhancement of leaf flavonoids content and the improvement of per unit area flavonoids production in G. biloba leaf-harvesting plantation.
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Flavonoides/química , Ginkgo biloba/química , Solo/química , Temperatura , Água/análise , China , Ecossistema , Folhas de Planta/químicaRESUMO
BACKGROUND: Impulsivity refers to a wide spectrum of actions characterized by quick and nonplanned reactions to external and internal stimuli, without taking into account the possible negative consequences for the individual or others, and decision-making is one of the biologically dissociated impulsive behaviors. Changes in impulsivity may be associated with norepinephrine. Various populations of drug addicts all performed impulsive decision making, which is a key risk factor in drug dependence and relapse. The present study investigated the effects of clonidine, which decreased norepinephrine release through presynaptic alpha-2 receptor activation, on the impaired decision-making performance in abstinent heroin addicts. METHODOLOGY/PRINCIPAL FINDINGS: Decision-making performance was assessed using the original version of Iowa Gambling Task (IGT). Both heroin addicts and normal controls were randomly assigned to three groups receiving clonidine, 0, 75 µg or 150 µg orally under double blind conditions. Psychiatric symptoms, including anxiety, depression and impulsivity, were rated on standardized scales. Heroin addicts reported higher scores on the Barratt Impulsiveness Scale and exhibited impaired decision-making on the IGT. A single high-dose of clonidine improved the decision-making performance in heroin addicts. CONCLUSIONS/SIGNIFICANCE: Our results suggest clonidine may have a potential therapeutic role in heroin addicts by improving the impaired impulsive decision-making. The current findings have important implications for behavioral and pharmacological interventions targeting decision-making in heroin addiction.
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Clonidina/farmacologia , Tomada de Decisões/efeitos dos fármacos , Dependência de Heroína/psicologia , Síndrome de Abstinência a Substâncias/psicologia , Adulto , Técnicas de Laboratório Clínico , Clonidina/administração & dosagem , Clonidina/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Jogo de Azar/psicologia , Dependência de Heroína/tratamento farmacológico , Dependência de Heroína/reabilitação , Humanos , Comportamento Impulsivo/tratamento farmacológico , Comportamento Impulsivo/psicologia , Masculino , Testes Neuropsicológicos , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/prevenção & controle , Simpatolíticos/administração & dosagem , Simpatolíticos/farmacologia , Simpatolíticos/uso terapêutico , Análise e Desempenho de Tarefas , Adulto JovemRESUMO
RATIONALE: Relapse is a persistent problem in the management of addiction. Drug-related cues are powerful instigators of relapse. Impulsive decision making may contribute to relapse through a poorly considered assessment of the consequences of drug use. Drug cues robustly increase subjective craving, which is frequently associated with relapse. OBJECTIVE: The present study explored the effects of drug-related cues on decision making and craving in heroin addicts at different abstinence times: 1, 3, 12, and 24 months. METHODS: The 75 male participants were given 5 min exposure to neutral and drug-associated cues while decision making performance, craving, blood pressure, heart rate, and emotional state pre- and post-exposure were assessed. The Iowa Gambling Task was used to evaluate decision making ability in heroin addicts. RESULTS: Drug-related cues exacerbated impulsive decision making and increased craving, heart rate, and systolic pressure in heroin addicts at all abstinence times. CONCLUSIONS: Drug-related cues aggravated decision making and increased craving in former heroin addicts who had been drug-free for 1-24 months, which might have significant clinical implications for the prevention of relapse.
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Sinais (Psicologia) , Tomada de Decisões , Dependência de Heroína/psicologia , Comportamento Impulsivo/psicologia , Adulto , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Dependência de Heroína/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Secundária , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: Drug abuse is associated with substantial impairments in decision making. However, little is known about the time course of changes in decision-making ability after abstinence or about the effects of stress on decision making in individuals recovering from heroin dependence after different durations of abstinence. METHOD: First, the authors assessed decision-making performance with the original card version of the Iowa Gambling Task in formerly heroin-dependent patients who had been abstinent for 3, 7, 15, or 30 days or 3, 6, 12, or 24 months. Second, patients who had been abstinent from heroin for 15 or 30 days or 3, 12, or 24 months were challenged with acute stress induced by the Trier Social Stress Test. Third, the ß-adrenoceptor antagonist propranolol (40 mg) was administered 1 hour before stress to those who had been abstinent for 30 days or 12 or 24 months. RESULTS: The short-term abstinence groups (3-30 days) performed worse on the Iowa Gambling Task compared with the long-term abstinence groups (3-24 months). Psychosocial stress unmasked a latent impairment in decision making in the 24-month abstinence group, which seemed to perform identically to healthy comparison subjects in the absence of stress. Propranolol blocked the stress-induced impairment of decision making, which was seen only in the formerly heroin-dependent patients. CONCLUSIONS: Stress can exacerbate an already existing impairment of decision making or unmask a latent one in individuals recovering from heroin dependence. The ß-adrenergic blockade reduces this effect and might hold promise for treatment of substance use disorders.
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Tomada de Decisões/efeitos dos fármacos , Dependência de Heroína/psicologia , Estresse Psicológico/psicologia , Síndrome de Abstinência a Substâncias/psicologia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hidrocortisona/análise , Masculino , Testes Neuropsicológicos , Propranolol/uso terapêutico , Estresse Psicológico/metabolismo , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Fatores de TempoRESUMO
Alleviating opiate withdrawal syndrome in addicts is a critical precondition to break away from drug and further to prevent reuse. Electroacupuncture (EA) was claimed to be effective for alleviating withdrawal syndrome, but the optimal protocol remained unclear. In the present study we found that (1) 100 Hz EA administered 12-24h after the last morphine injection suppressed the withdrawal syndrome in rats, multiple sessions of EA were more effective than single session, with the after-effect lasting for at least 7 days. (2) A down-regulation of preprodynorphin (PPD) mRNA level was observed in spinal cord, PAG and hypothalamus 60 h after the last morphine injection, which could be reversed by multiple sessions, but not a single session of EA. (3) Accompanied with the decrease of PPD mRNA level, there was an up-regulation of p-CREB in the three CNS regions, which was abolished by 100 Hz EA treatment. The findings suggest that down-regulation of p-CREB and acceleration of dynorphin synthesis in spinal cord, PAG and hypothalamus may be implicated in the cumulative effect of multiple 100Hz EA treatment for opioid detoxification.
Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Dinorfinas/genética , Eletroacupuntura , Morfina/efeitos adversos , Precursores de Proteínas/genética , RNA Mensageiro/genética , Síndrome de Abstinência a Substâncias/terapia , Animais , Sequência de Bases , Primers do DNA , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
AIM: To generate recombinant adenoviral vector containing calreticulin (CRT)-hepatitis B surface antigen (HBsAg) fusion gene for developing a safe, effective and HBsAg-specific therapeutic vaccine. METHODS: CRT and HBsAg gene were fused using polymerase chain reaction (PCR), endonuclease digestion and ligation methods. The fusion gene was cloned into pENTR/D-TOPO transfer vector after the base pairs of DNA (CACC) sequence was added to the 5' end. Adenoviral expression vector containing CRT-HBsAg fusion gene was constructed by homologous recombinantion. The human embryo kidney (HEK) 293A cells were transfected with linearized DNA plasmid of the recombinant adenoviral vector to package and amplify recombinant adenovirus. The recombinant adenovirus titer was characterized using the end-dilution assay. The expression of the CRT/HBsAg fusion protein in Ad-CRT/HBsAg infected 293A cells was detected by Western blotting. RESULTS: The CRT-HBsAg fusion gene was characterized by PCR and sequencing and its length and sequence were confirmed to be accurate. The CRT-HBsAg fusion gene recombinant pENTR/D-TOPO transfer vector was constructed. The recombinant adenoviral vector, Ad-CRT/HBsAg, was generated successfully. The titer of Ad-CRT/HBsAg was characterized as 3.9 x 10(11) pfu/mL. The CRT-HBsAg fusion protein was expressed by HEK 293A cells correctly. CONCLUSION: CRT/HBsAg fusion gene recombinant replication-defective adenovirus expression vector is constructed successfully and this study has provided an experimental basis for further studies of Hepatitis B virus gene therapy.
Assuntos
Adenoviridae/genética , Calreticulina/genética , Vetores Genéticos , Antígenos de Superfície da Hepatite B/genética , Proteínas Recombinantes de Fusão/genética , Adenoviridae/metabolismo , Animais , Calreticulina/metabolismo , Linhagem Celular , Expressão Gênica , Terapia Genética/métodos , Vetores Genéticos/genética , Vetores Genéticos/metabolismo , Hepatite B/genética , Hepatite B/terapia , Antígenos de Superfície da Hepatite B/metabolismo , Humanos , Proteínas Recombinantes de Fusão/metabolismoRESUMO
Aimed to understand the waterlogging tolerance and adaptation mechanisms of different tree species, a simulated field experiment was conducted to study the growth and energy-metabolic enzyme activities of one-year-old seedlings of Taxodium distichum, Carya illinoensis, and Sapium sebiferum. Three treatments were installed, i. e., CK, waterlogging, and flooding, with the treatment duration being 60 days. Under waterlogging and flooding, the relative growth of test tree species was in the order of T. distichum > C. illinoensis > S. sebiferum, indicating that T. distichum had the strongest tolerance against waterlogging and flooding, while S. sebiferum had the weakest one. Also under waterlogging and flooding, the root/crown ratio of the three tree species increased significantly, suggesting that more photosynthates were allocated in roots, and the lactate dehydrogenase (LDH) and alcohol dehydrogenase (ADH) activities of the tree species also had a significant increase. Among the test tree species, T. distichum had the lowest increment of LDH and ADH activities under waterlogging and flooding, but the increment could maintain at a higher level in the treatment duration, while for C. illinoensis and S. sebiferum, the increment was larger during the initial and medium period, but declined rapidly during the later period of treatment. The malate dehydrogenase (MDH), phosphohexose (HPI), and glucose-6-phosphate dehydrogenase (G6PDH) -6-phosphogluconate dehydrogenase (6PGDH) activities of the tree species under waterlogging and flooding had a significant decrease, and the decrement was the largest for T. distichum, being 35.6% for MDH, 21.0% for HPI, and 22.7% for G6PDH - 6PGDH under flooding. It was suggested that under waterlogging and flooding, the tree species with strong waterlogging tolerance had a higher ability to maintain energy-metabolic balance, and thus, its growth could be maintained at a certain level.