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1.
Biomed Pharmacother ; 114: 108766, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30901719

RESUMO

Brucea javanica is an important Chinese folk medicine traditionally used for the treatment of dysentery (also known as inflammatory bowel diseases). Brucea javanica oil emulsion (BJOE), the most common preparation of Brucea javanica, has a variety of pharmacological activities. In this follow-up investigation, we endeavored to illuminate the potential benefit of BJOE on 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn's disease (CD) in rats and decipher the mechanism of action. The result illustrated that BJOE treatment significantly reduced the body weight loss, disease activity index and macroscopic scores, ameliorated shortening of colon length, arrested colonic histopathological deteriorations, lowered the histological scores in parallel to the model group. Furthermore, BJOE also decreased the levels of MPO and pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-17, IL-23 and IFN-γ), and increased the levels of anti-inflammatory cytokines (IL-4, IL-10 and TGF-ß) as compared with the model group. In addition, the elevated mRNA expression of MMP-1, MMP-3 and RAGE induced by TNBS was remarkably inhibited by BJOE, SASP or AZA treatments, while the mRNA expression of PPAR-γ was significantly enhanced. Furthermore, the activation of TLR4/NF-κB signaling pathway was significantly inhibited by AZA and BJOE treatment when compared with that of TNBS-treated rats. Our study suggested that BJOE exerted superior therapeutic effect to SASP and AZA in treating TNBS-induced colitis in rats. The protective effect of BJOE may involve the inhibition of the TLR4/NF-κB-mediated inflammatory responses. These results indicated that BJOE held promising potential to be further developed into a novel candidate for the treatment of CD.


Assuntos
Brucea/química , Doença de Crohn/tratamento farmacológico , Emulsões/farmacologia , NF-kappa B/metabolismo , Óleos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Animais , Colo/efeitos dos fármacos , Colo/metabolismo , Doença de Crohn/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley
2.
Exp Biol Med (Maywood) ; 241(2): 193-204, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26290140

RESUMO

Pogostemonis Herba, known as "Guang-Huo-Xiang" in Chinese, has been widely used in the treatment of gastrointestinal dysfunction. Pogostone is one of the major constituents of Pogostemonis Herba. The aim was to scientifically evaluate the possible gastroprotective effect and the underlying mechanisms of pogostone against indomethacin-induced gastric ulcer in rats. Rats were orally treated with vehicle, lansoprazole (30 mg/kg) or pogostone (10, 20 and 40 mg/kg) and subsequently exposed to acute gastric lesions induced by indomethacin. Gross evaluation, histological observation, gastric mucosal superoxide dismutase activity, glutathione content, catalase activity, malonaldehyde level and prostaglandin E2 production were performed. Immunohistochemistry and reverse transcription polymerase chain reaction for cyclooxygenase-1 and cyclooxygenase-2, as well as terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay, immunohistochemistry for heat-shock protein 70, B-cell lymphoma-2 and Bax were conducted. Results indicated that rats pretreated with pogostone showed remarkable protection from the gastric mucosa damage compared to vehicle-treated rats based on the ulcer index and inhibition percentage. Histologically, oral administration of pogostone resulted in observable improvement of gastric injury, characterized by reduction of necrotic lesion, flattening of gastric mucosa and alleviation of submucosal edema with hemorrhage. Pogostone pretreatment significantly raised the depressed activities of superoxide dismutase, glutathione and catalase, while reduced the elevated malonaldehyde level compared with indomethacin-induced group. Pogostone-pretreated group induced a significant increase in gastric mucosal prostaglandin E2 level and obvious up-regulation of protein levels and mRNA expressions of cyclooxygenase-1 and cyclooxygenase-2. Furthermore, antiapoptotic effect of pogostone was verified by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay, and the apoptotic process triggered by pogostone involved the up-expression of heat-shock protein70 and B-cell lymphoma-2 protein, and suppression of Bax protein expressions in the ulcerated tissues. It is speculated that the gastroprotective effect of pogostone against indomethacin-induced gastric ulceration might be associated with its stimulation of cyclooxygenase-mediated prostaglandin E2, antioxidant and antiapoptotic effect.


Assuntos
Fármacos Gastrointestinais/administração & dosagem , Indometacina/toxicidade , Óleos Voláteis/administração & dosagem , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/prevenção & controle , Administração Oral , Animais , Modelos Animais de Doenças , Mucosa Gástrica/patologia , Fármacos Gastrointestinais/isolamento & purificação , Histocitoquímica , Humanos , Imuno-Histoquímica , Indometacina/administração & dosagem , Masculino , Microscopia , Óleos Voláteis/isolamento & purificação , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Úlcera Gástrica/induzido quimicamente , Resultado do Tratamento
3.
J Psychiatry Neurosci ; 40(6): 401-11, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25853283

RESUMO

BACKGROUND: Published meta-analyses of resting-state regional cerebral blood flow (rCBF) studies of major depressive disorder (MDD) have included patients receiving antidepressants, which might affect brain activity and thus bias the results. To our knowledge, no meta-analysis has investigated regional homogeneity changes in medication-free patients with MDD. Moreover, an association between regional homogeneity and rCBF has been demonstrated in some brain regions in healthy controls. We sought to explore to what extent resting-state rCBF and regional homogeneity changes co-occur in the depressed brain without the potential confound of medication. METHODS: Using the effect-size signed differential mapping method, we conducted 2 meta-analyses of rCBF and regional homogeneity studies of medication-free patients with MDD. RESULTS: Our systematic search identified 14 rCBF studies and 9 regional homogeneity studies. We identified conjoint decreases in resting-state rCBF and regional homogeneity in the insula and superior temporal gyrus in medication-free patients with MDD compared with controls. Other changes included altered resting-state rCBF in the precuneus and in the frontal-limbic-thalamic-striatal neural circuit as well as altered regional homogeneity in the uncus and parahippocampal gyrus. Meta-regression revealed that the percentage of female patients with MDD was negatively associated with resting-state rCBF in the right anterior cingulate cortex and that the age of patients with MDD was negatively associated with rCBF in the left insula and with regional homogeneity in the left uncus. LIMITATIONS: The analysis techniques, patient characteristics and clinical variables of the included studies were heterogeneous. CONCLUSION: The conjoint alterations of rCBF and regional homogeneity in the insula and superior temporal gyrus may be core neuropathological changes in medication-free patients with MDD and serve as a specific region of interest for further studies on MDD.


Assuntos
Encéfalo/fisiopatologia , Circulação Cerebrovascular/fisiologia , Sincronização Cortical/fisiologia , Transtorno Depressivo Maior/fisiopatologia , Encéfalo/irrigação sanguínea , Mapeamento Encefálico , Humanos , Descanso
4.
Soc Cogn Affect Neurosci ; 10(11): 1497-505, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25862672

RESUMO

Although acute impact of traumatic experiences on brain function in disaster survivors is similar to that observed in post-traumatic stress disorders (PTSD), little is known about the long-term impact of this experience. We have used structural and functional magnetic resonance imaging to investigate resting-state functional connectivity and gray and white matter (WM) changes occurring in the brains of healthy Wenchuan earthquake survivors both 3 weeks and 2 years after the disaster. Results show that while functional connectivity changes 3 weeks after the disaster involved both frontal-limbic-striatal and default-mode networks (DMN), at the 2-year follow-up only changes in the latter persisted, despite complete recovery from high initial levels of anxiety. No gray or WM volume changes were found at either time point. Taken together, our findings provide important new evidence that while altered functional connectivity in the frontal-limbic-striatal network may underlie the post-trauma anxiety experienced by survivors, parallel changes in the DMN persist despite the apparent absence of anxiety symptoms. This suggests that long-term changes occur in neural networks involved in core aspects of self-processing, cognitive and emotional functioning in disaster survivors which are independent of anxiety symptoms and which may also confer increased risk of subsequent development of PTSD.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiopatologia , Desastres , Terremotos , Rede Nervosa/fisiopatologia , Trauma Psicológico/fisiopatologia , Sobreviventes/psicologia , Adulto , Ansiedade/fisiopatologia , Feminino , Seguimentos , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
5.
J Ethnopharmacol ; 162: 69-78, 2015 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-25557028

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Baicalin and scutellarin are the principal bioactive components of Scutellaria baicalensis Georgi which has extensively been incorporated into heat-clearing and detoxification formulas for the treatment of Helicobacter pylori-related gastrointestinal disorders in traditional Chinese medicine. However, the mechanism of action remained to be defined. AIM OF THE STUDY: To explore the inhibitory effect, kinetics and mechanism of Helicobacter pylori urease (the vital pathogenetic factor for Helicobacter pylori infection) inhibition by baicalin and scutellarin, for their therapeutic potential. MATERIALS AND METHODS: The ammonia formations, indicator of urease activity, were examined using modified spectrophotometric Berthelot (phenol-hypochlorite) method. The inhibitory effect of baicalin and scutellarin was characterized with IC50 values, compared to acetohydroxamic acid (AHA), a well known Helicobacter pylori urease inhibitor. Lineweaver-Burk and Dixon plots for the Helicobacter pylori urease inhibition of baicalin and scutellarin was constructed from the kinetic data. SH-blocking reagents and competitive active site Ni(2+) binding inhibitors were employed for mechanism study. Molecular docking technique was used to provide some information on binding conformations as well as confirm the inhibition mode. Moreover, cytotoxicity experiment using Gastric Epithelial Cells (GES-1) was evaluated. RESULTS: Baicalin and scutellarin effectively suppressed Helicobacter pylori urease in dose-dependent and time-independent manner with IC50 of 0.82±0.07 mM and 0.47±0.04 mM, respectively, compared to AHA (IC50=0.14±0.05 mM). Structure-activity relationship disclosed 4'-hydroxyl gave flavones an advantage to binding with Helicobacter pylori urease. Kinetic analysis revealed that the types of inhibition were non-competitive and reversible with inhibition constant Ki of 0.14±0.01 mM and 0.18±0.02 mM for baicalin and scutellarin, respectively. The mechanism of urease inhibition was considered to be blockage of the SH groups of Helicobacter pylori urease, since thiol reagents (L,D-dithiothreitol, L-cysteine and glutathione) abolished the inhibitory action and competitive active site Ni(2+) binding inhibitors (boric acid and sodium fluoride) carried invalid effect. Molecular docking study further supported the structure-activity analysis and indicated that baicalin and scutellarin interacted with the key residues Cys321 located on the mobile flap through S-H·π interaction, but did not interact with active site Ni(2+). Moreover, Baicalin (at 0.59-1.05 mM concentrations) and scutellarin (at 0.23-0.71 mM concentrations) did not exhibit significant cytotoxicity to GES-1. CONCLUSIONS: Baicalin and scutellarin were non-competitive inhibitors targeting sulfhydryl groups especially Cys321 around the active site of Helicobacter pylori urease, representing potential to be good candidate for future research as urease inhibitor for treatment of Helicobacter pylori infection. Furthermore, our work gave additional scientific support to the use of Scutellaria baicalensis in traditional Chinese medicine (TCM) to treat gastrointestinal disorders.


Assuntos
Apigenina/farmacologia , Flavonoides/farmacologia , Glucuronatos/farmacologia , Helicobacter pylori/enzimologia , Urease/antagonistas & inibidores , Apigenina/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Flavonoides/química , Glucuronatos/química , Humanos , Simulação de Acoplamento Molecular , Urease/química , Urease/metabolismo
6.
Artigo em Inglês | MEDLINE | ID: mdl-25174680

RESUMO

BACKGROUND: Functional magnetic resonance imaging (fMRI) studies in major depressive disorder (MDD) have revealed cortical-limbic-subcortical dysfunctions during working memory (WM) processing, but the results are inconsistent and it is unclear to what extent these findings are influenced by demographic, clinical characteristics and task performance of patients. The present study conducted a quantitative coordinate-based meta-analysis of fMRI data to investigate the hypothesized dysfunction in the neural correlates during WM processing in MDD. METHODS: A systematic research was conducted for fMRI studies during WM processing comparing MDD patients with healthy controls (HC). Meta-analysis was performed using effect size signed differential mapping (ES-SDM). Meta-regression analyses with age, sex and medication as factors were performed in MDD group. RESULTS: Functional MRI data of 160 MDD patients and 203 HC from 13 WM experiments across 11 studies were included in this meta-analysis. In the pooled meta-analysis of all included studies, significant increased activation during WM in the left lateral prefrontal cortex, left precentral gyrus, left insula, right superior temporal and right supramarginal areas, and significant decreased activity in the right precentral gyrus, right precuneus and right insula were observed in MDD compared with controls. In the subgroup analysis of the studies with matched task performance, MDD subgroup showed hyperactivation only in the left prefrontal cortex and hypoactivation in the regions similar to the pooled analysis. The meta-regression with age, sex and medication showed no significance in MDD group. CONCLUSIONS: Regardless of differences in task performance between groups, patients with MDD showed consistent functional abnormalities in the cortical-limbic-subcortical circuitry during WM processing. Distinct patterns of neural engagement may reflect compensatory neural strategies to potential dysfunction in MDD.


Assuntos
Mapeamento Encefálico , Encéfalo/patologia , Transtorno Depressivo Maior/complicações , Transtornos da Memória/etiologia , Transtornos da Memória/patologia , Memória de Curto Prazo/fisiologia , Adulto , Encéfalo/irrigação sanguínea , Bases de Dados Bibliográficas/estatística & dados numéricos , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Metanálise como Assunto , Testes Neuropsicológicos , Oxigênio/sangue
7.
Epilepsy Behav ; 41: 33-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25277976

RESUMO

OBJECTIVE: Seizure-related respiratory and cardiac dysfunctions were once thought to be the direct cause of sudden unexpected death in epilepsy (SUDEP), but both may be secondary to postictal cerebral inhibition. An important issue that has not been explored to date is the neural network basis of cerebral inhibition. Our aim was to investigate the features of neural networks in patients at high risk for SUDEP using a blood oxygen level-dependent (BOLD) resting-state functional connectivity (FC) approach. SUBJECTS AND METHODS: Resting-state functional magnetic resonance imaging (Rs-fMRI) data were recorded from 13 patients at high risk for SUDEP and 12 patients at low risk for SUDEP. Thirteen cerebral regions that are closely related to cardiorespiratory activity were selected as regions of interest (ROIs). The ROI-wise resting-state FC analysis was compared between the two groups. RESULTS: Compared with patients at low risk for SUDEP, patients at high risk exhibited significant reductions in the resting-state FC between the pons and the right thalamus, the midbrain and the right thalamus, the bilateral anterior cingulate cortex (ACC) and the right thalamus, and the left thalamus and the right thalamus. CONCLUSIONS: This investigation is the first to use neuroimaging methods in research on the mechanism of SUDEP and demonstrates the abnormally decreased resting-state FC in the ACC-thalamus-brainstem circuit in patients at high risk for SUDEP. These findings highlight the need to understand the fundamental neural network dysfunction in SUDEP, which may fill the missing link between seizure-related cardiorespiratory dysfunction and SUDEP, and provide a promising neuroimaging biomarker for risk prediction of SUDEP.


Assuntos
Tronco Encefálico/fisiopatologia , Morte Súbita , Epilepsia/fisiopatologia , Giro do Cíngulo/fisiopatologia , Rede Nervosa/fisiopatologia , Tálamo/fisiopatologia , Adulto , Mapeamento Encefálico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Risco , Adulto Jovem
8.
J Clin Neurosci ; 21(8): 1413-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24908373

RESUMO

We investigated the short-term postoperative cognitive function of patients with unilateral mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE/HS). Fourteen unilateral MTLE/HS patients who had undergone selective amygdalohippocampectomy (SAH) or anterior temporal lobectomy (ATL) were enrolled. Cognitive functions related to the frontal and temporal lobes were evaluated using a battery of neuropsychological tests administered before surgery and 3months after surgery. The battery included the Verbal Fluency Test (VFT), Boston Naming Test (BNT), Stroop Color-Word Test (TST), Trail Making Test (TMT) and Wechsler Memory Scale (WMS). MTLE/HS patients demonstrated significantly improved postoperative performance on the TST regardless of the surgical method or side of resection. There was no significant difference in any of the other neuropsychological tests before and after surgery. After left-side resection, performance on the VFT and the TMT-B was worse than at baseline. After right-side resection, performance on the VFT and WMS short-term memory improved; however, these differences were not statistically significant. SAH patients exhibited improved TST performance but worse TMT-A performance; however, performance on all tests was not significantly different after surgery in ATL patients. In summary, MTLE/HS patients demonstrated improved frontal lobe-related cognitive function after surgery, but no such improvement in temporal lobe-related function was observed. Based on cognitive evaluation, right-sided MTLE/HS patients may be more appropriate surgical candidates than left-sided MTLE/HS patients. SAH may not be better than ATL in improving cognitive function. We hypothesise that postoperative cognitive changes depend on whether the excised cerebral regions are related to the neuropsychological functions examined by specific assessment instruments.


Assuntos
Epilepsia do Lobo Temporal/psicologia , Epilepsia do Lobo Temporal/cirurgia , Adolescente , Adulto , Tonsila do Cerebelo/cirurgia , Lobectomia Temporal Anterior , Epilepsia do Lobo Temporal/patologia , Feminino , Lateralidade Funcional , Hipocampo/patologia , Hipocampo/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Procedimentos Neurocirúrgicos , Esclerose/patologia , Esclerose/cirurgia , Lobo Temporal/patologia , Lobo Temporal/cirurgia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
9.
J Neurol ; 261(7): 1413-24, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24792726

RESUMO

Patterns of white matter (WM) abnormalities and correlation with clinical features in patients with blepharospasm (BSP) and patients with blepharospasm-oromandibular dystonia (BOM) remain unknown. Using voxel-based analysis, diffusion behaviors of WM including fractional anisotropy (FA), mean diffusivity (MD) and eigenvalues were compared between 20 BSP patients vs. 11 healthy controls (HCs) and 11 patients with BOM vs. 11 HCs. Correlation analyses were performed to assess possible association between diffusion behaviors of significantly different areas and clinical measures. Compared with HCs, BSP patients showed significant FA reductions in the left anterior lobe of cerebellum. Significant increases of MD and radial diffusivity (RD) were detected in right lentiform nucleus and thalamus. Significantly decreased FA in the right precuneus of parietal lobe, increased MD in the right lentiform nucleus and insula, and increased axial diffusivity in the right insula were observed in BOM patients. The FA values in the WM of left cerebellum negatively correlated with disease severity in BSP patients measured by JRS (r = -0.655, p = 0.002). The FA values in the right parietal WM negatively correlated with disease duration in BOM patients (r = -0.745, p = 0.008). Both BSP and BOM are related to microstructural abnormalities of WM in the basal ganglia. WM changes outside the basal ganglia may present trait features that are specific for individual dystonia phenotype. The correlation between FA abnormalities and symptom severity suggests that DTI parameters might be of clinical value in assessing and following disability in BSP patients.


Assuntos
Blefarospasmo/patologia , Encéfalo/patologia , Imagem de Tensor de Difusão , Síndrome de Meige/patologia , Idoso , Anisotropia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estatísticas não Paramétricas , Substância Branca/patologia
10.
Neurobiol Aging ; 35(2): 431-41, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24074808

RESUMO

Although cardinal motor symptoms in Parkinson's disease (PD) are attributed to dysfunction of corticostriatal loops, early clinical nonmotor features are more likely to be associated with other pathologic mechanisms. We enrolled 52 early-stage drug-naive PD patients and 52 age- and sex-matched healthy controls and used resting-state functional connectivity magnetic resonance imaging to evaluate alteration of the functional brain network in PD, focusing in particular on the functional connectivity of the striatum subregions. Relative to healthy controls, the PD patient group showed reduced functional connectivity in mesolimbic-striatal and corticostriatal loops. Although the deceased functional connectivity within cortical sensorimotor areas was only evident in the most affected putamen subregion, reduced functional connectivity with mesolimbic regions was prevalent throughout the striatum. No increased functional connectivity was found in this cohort. By studying a cohort of early-stage drug-naive PD patients, we ruled out the potential confounding effect of prolonged antiparkinson medication use on the functional integration of neural networks. We demonstrate decreased functional integration across neural networks involving striatum, mesolimbic cortex, and sensorimotor regions in these patients and postulate that the prevalent disconnection in mesolimbic-striatal loops is associated with some early clinical nonmotor features in PD. This study offers additional insight into the early functional integration of neural networks in PD.


Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , Neuroimagem Funcional/métodos , Imagem por Ressonância Magnética/métodos , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Descanso/fisiologia , Adulto , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico
11.
J Neurol ; 260(11): 2754-60, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23900755

RESUMO

The resting state amplitude of low-frequency fluctuations (ALFF) in functional magnetic resonance imaging (fMRI) is believed to reflect spontaneous cerebral neural activity. The pathophysiology of blepharospasm (BSP), which is characterized by motor symptoms and also sensory symptoms, remains unclear. The present study aims to localize possible cerebral functional abnormalities in BSP patients using resting state fMRI, and explore their possible associations with clinical variables. Voxel-based analysis was used to characterize the difference of ALFF between eighteen BSP patients and eighteen matched healthy controls. Separate correlation analyses were conducted to explore the possible association between ALFF values of significantly different areas and clinical measures including onset age, disease duration, symptom severity evaluated by Jankovic rating scale (JRS), and presence of geste antagoniste. The whole-brain analysis indicated that the BSP group had significantly decreased ALFF in the left thalamus while increased ALFF in the left orbitofrontal areas extending from middle frontal gyrus to inferior frontal gyrus. The mean ALFF in the left thalamus was negatively correlated with the subscore of JRS-frequency (r = -0.484, p = 0.042) and JRS total score (r = -0.477, p = 0.045). A borderline positive correlation was detected between the mean ALFF in the left orbitofrontal area and disease duration(r = 0.485, p = 0.049). Our findings suggest sensorimotor integration is abnormal in BSP, and dysfunctional activity of thalamus may be used to measuring symptom severity in BSP patients.


Assuntos
Blefarospasmo/patologia , Mapeamento Encefálico , Encéfalo/irrigação sanguínea , Adulto , Idoso , Blefarospasmo/fisiopatologia , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Descanso , Índice de Gravidade de Doença
12.
Fitoterapia ; 91: 60-67, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23978581

RESUMO

In the present study, the inactivation effect of scutellarin (SL) on jack bean urease was investigated to elucidate the inhibitory potency, kinetics and mechanism of inhibition. It was revealed that SL acted as a concentration- and time-dependent inactivator of urease characteristic of slow-binding inhibition with an IC50 of 1.35±0.15 mM. The rapid formation of the initial SL-urease complex with an inhibition constant of Ki=5.37×10(-2) mM was followed by a slow isomerization into the final complex with the overall inhibition constant of Ki*=3.49×10(-3) mM. High effectiveness of thiol protectors, such as L-cysteine (L-cys), 2-mercaptoethanol (2-ME) and dithiothreitol (DTT) significantly slowed down the rate of inactivation, indicating the strategic role of the active site sulfhydryl group in the blocking process. While the insignificant protection by boric acid and fluoride from the inactivation further confirmed that the active site cysteine should be obligatory for urease inhibition, which was also rationalized by the molecular docking study. The inhibition of SL on urease proved to be reversible since SL-blocked urease could be reactivated by DTT application and multidilution. The results obtained indicated that urease inactivation resulted from the reaction between SL and the sulfhydryl group.


Assuntos
Apigenina/farmacologia , Canavalia/enzimologia , Erigeron/química , Glucuronatos/farmacologia , Extratos Vegetais/farmacologia , Urease/antagonistas & inibidores , Cinética , Extratos Vegetais/metabolismo , Compostos de Sulfidrila/química
13.
J Psychiatry Neurosci ; 38(6): 381-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23710694

RESUMO

BACKGROUND: Stress responses have been studied extensively in animal models, but effects of major life stress on the human brain remain poorly understood. The aim of this study was to determine whether survivors of a major earthquake, who were presumed to have experienced extreme emotional stress during the disaster, demonstrate differences in brain anatomy relative to individuals who have not experienced such stressors. METHODS: Healthy survivors living in an area devastated by a major earthquake and matched healthy controls underwent 3-dimentional high-resolution magnetic resonance imaging (MRI). Survivors were scanned 13-25 days after the earthquake; controls had undergone MRI for other studies not long before the earthquake. We used optimized voxel-based morphometry analysis to identify regional differences of grey matter volume between the survivors and controls. RESULTS: We included 44 survivors (17 female, mean age 37 [standard deviation (SD) 10.6] yr) and 38 controls (14 female, mean age 35.3 [SD 11.2] yr) in our analysis. Compared with controls, the survivors showed significantly lower grey matter volume in the bilateral insula, hippocampus, left caudate and putamen, and greater grey matter volume in the bilateral orbitofrontal cortex and the parietal lobe (all p < 0.05, corrected for multiple comparison). LIMITATIONS: Differences in the variance of survivor and control data could impact study findings. CONCLUSION: Acute anatomic alterations could be observed in earthquake survivors in brain regions where functional alterations after stress have been described. Anatomic changes in the present study were observed earlier than previously reported and were seen in prefrontal-limbic, parietal and striatal brain systems. Together with the results of previous functional imaging studies, our observations suggest a complex pattern of human brain response to major life stress affecting brain systems that modulate and respond to heightened affective arousal.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/patologia , Terremotos , Sobreviventes/psicologia , Adulto , Atrofia/patologia , Estudos de Casos e Controles , Feminino , Humanos , Hipertrofia/patologia , Masculino , Fibras Nervosas Amielínicas/patologia , Neuroimagem
14.
Phytomedicine ; 20(3-4): 249-57, 2013 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-23141427

RESUMO

Kangtai capsule (KT) is one type of traditional Chinese medicine preparation derived from the proved recipe, which was frequently applied as an effective clinical treatment of IBS. However, there still lack the reasonable and all-round analytical approach and the scientific studies on its underlying mechanisms. Therefore, our study aimed to develop the novel method for evaluating its quality as well as to interpret the potential mechanisms. In our study, high performance liquid chromatography (HPLC) fingerprint was applied to provide a chemical profile of KT. The neonatal maternal separation (NMS) on Sprague-Dawley pups was employed to evaluate the therapeutic effect of KT by virtue of various parameters including visceral hyperalgesia, serum nitric oxide (NO) level, and tissue 5-hydroxytryptamine (5-HT) level. Consequently, a chromatographic condition, which was carried at 30°C with a flow rate of 0.5 ml/min on AQUA 3µ C18 column with mobile phase of acetonitrile and water-phosphoric acid (100:0.1, v/v), was established to give a common fingerprint chromatography under 254 nm with a similarity index of 0.963 within ten batches of KT samples. On the NMS model, KT markedly elevated the pain threshold of NMS rats. Furthermore, KT at three doses significantly decreased 5-HT content from distal colon of visceral hyperalgesia rats induced by NMS, while the significant decrease of 5-HT content in serum was only observed in the group with KT at high dose. However, compared with that in NMS rats without KT, there was no apparent difference of 5-HT level from brain issue in the rats with various doses. Besides, KT could substantially elevate the concentration of NO in the serum. The results showed our study developed the simple, rapid, accurate, reproducible qualitative and quantitative analysis by HPLC fingerprint for the quality control for KT. Data from the pharmacological investigation suggested that the curative effect of KT to the visceral hypersensitivity may be concerned with the level of 5-HT and NO in vivo, promising its potential in irritable bowel syndrome treatment.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Síndrome do Intestino Irritável/tratamento farmacológico , Óxido Nítrico/sangue , Serotonina/sangue , Animais , Animais Recém-Nascidos , Encéfalo/metabolismo , Cromatografia Líquida de Alta Pressão , Colo/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Síndrome do Intestino Irritável/sangue , Síndrome do Intestino Irritável/complicações , Privação Materna , Fitoterapia , Ratos , Ratos Sprague-Dawley
15.
Hum Brain Mapp ; 34(2): 367-73, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22042533

RESUMO

A characterization of the impact of natural disasters on the brain of survivors is critical for a better understanding of posttraumatic responses and may inform the development of more effective early interventions. Here we report alterations in white matter microstructure in survivors soon after Wenchuan earthquake in China in 2008. Within 25 days after the Wenchuan earthquake, 44 healthy survivors were recruited and scanned on a 3T MR imaging system. The survivors were divided into two groups according to their self-rating anxiety scale (SAS) score, including the SAS(+) (SAS > 55 after correction) group and "SAS(-)" (SAS < 55 after correction) group. Thrity-two healthy volunteers were also recruited as control group before earthquake. Individual maps of fractional anisotropy (FA) were calculated and voxel-based analysis (VBA) was performed to allow the comparison between survivors and controls using ANCOVAs in SPM2. In addition, a correlation between SAS score and regional FA value was examined using Pearson's correlation analysis in SPSS 11.5. Compared with the healthy cohort, the whole group of 44 survivors showed significantly decreased FA values in the right prefrontal lobe, the parietal lobe, the basal ganglia, and the right parahippocampus. These effects did not appear to depend on self-rating anxiety. For the first time we provide evidence that acute trauma altered cerebral microstructure within the limbic system; furthermore, these alterations are evident shortly after the traumatic event, highlighting the need for early evaluation and intervention for trauma survivors.


Assuntos
Encéfalo/patologia , Terremotos , Estresse Psicológico/patologia , Sobreviventes , Adulto , Ansiedade/patologia , Ansiedade/psicologia , Gânglios da Base/patologia , Interpretação Estatística de Dados , Imagem de Difusão por Ressonância Magnética , Feminino , Lobo Frontal/patologia , Hipocampo/patologia , Humanos , Sistema Límbico/patologia , Masculino , Córtex Pré-Frontal/patologia
16.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 43(2): 210-3, 225, 2012 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-22650033

RESUMO

OBJECTIVE: To investigate the prevalence of four common neuropsychiatric disorders in Tibet, with an aim to providing information support to health planning. METHODS: The survey was carried out in four regions of Tibet. The sampling strategy was adapted from that of a national psychiatric epidemiological survey in China in 1982 and 1993. The Neurosis Screening Inventory, Screening Inventory for Alcohol Dependence and Related Problems, Child Intelligence Screening Inventory, and a questionnaire for the Detection of Epileptic Seizures were administered to the respondents through face to face interview. Those with a positive response and 10% of those with a negative response were further interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders (research version) (SCID-I ). Anxiety disorders and alcohol used disorders were diagnosed according to the American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV). Hysteria and mental retardation were diagnosed according to the International Classification of Diseases, 10th edition (ICD-10), and the Chinese Classification of Mental Disorders, 3rd edition (CCMD-3). RESULTS: The point prevalence of neuroses, alcohol-related disorders, mental retardation and epilepsy was 2. 56%, 4. 06%, 0. 28% and 0. 68%, respectively. The lifetime prevalence of neuroses, alcohol-related disorders, mental retardation and epilepsy was 2. 62%, 4. 24%, 0. 28% and 0.72%, respectively. CONCLUSION: Alcohol-related disorders and neuroses are the two common mental health problems in Tibet. Mental retardation and epilepsy are the two serious neuropsychiatric disorders affecting Tibetan children and adolescence. These disorders should be identified as priorities in the reginonal health planning in Tibet.


Assuntos
Transtornos Relacionados ao Uso de Álcool/epidemiologia , Epilepsia/epidemiologia , Deficiência Intelectual/epidemiologia , Transtornos Neuróticos/epidemiologia , Adolescente , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Amostragem , Inquéritos e Questionários , Tibet/epidemiologia , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-22001316

RESUMO

BACKGROUND: Voxel-based morphometry (VBM) has been widely used in studies of major depressive disorder (MDD) and has provided cumulative evidence of gray matter abnormalities in patients relative to controls. Thus we performed a meta-analysis to integrate the reported studies to determine the consistent gray matter alterations in MDD. METHODS: A systematic search was conducted to identify VBM studies which contrasted MDD patients against a comparison group. The coordinates of gray matter change across studies were meta-analyzed using the activation likelihood estimation (ALE) method hybridized with the rank-based Genome Scan Meta-Analysis (GSMA) to quantitatively estimate regional gray matter reductions in MDD. RESULTS: A total of 20 VBM studies comparing 543 major depressive patients with 750 healthy control subjects were included. Consistent gray matter reductions in all MDD patients relative to healthy controls were identified in the bilateral anterior cingulate cortex (ACC), right middle and inferior frontal gyrus, right hippocampus and left thalamus. CONCLUSIONS: Meta-analysis of all primary VBM studies indicates that significant gray matter reductions in MDD are localized in a distributed neural network which includes frontal, limbic and thalamic regions. Future studies will benefit from the use of a longitudinal approach to examine anatomical and functional abnormalities within this network and their relationship to clinical profile, particularly in first-episode and drug-naive MDD patients.


Assuntos
Córtex Cerebral/patologia , Transtorno Depressivo Maior/patologia , Atrofia , Mapeamento Encefálico/métodos , Transtorno Depressivo Maior/epidemiologia , Humanos , Rede Nervosa/patologia
18.
Pharmacology ; 88(5-6): 322-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22116025

RESUMO

Anesthesia, a state of profound central nervous system suppression, involves a sequence of events that is still not well understood. In the present study, we examined the action of propofol (a sedative-hypnotic drug commonly used as anesthetic) on thalamocortical functional connectivity in rats by using functional connectivity magnetic resonance imaging (fcMRI) with a 3.0-tesla MR scanner. Intraperitoneal injections of propofol (80 or 160 mg/kg) were administered to Sprague-Dawley rats. Synchronized low-frequency fluctuations (LFF) of blood oxygen level-dependent (BOLD) signals were found between the thalamic and somatosensory cortices (S1/S2) after administration of 80 mg/kg propofol. However, after application of 160 mg/kg propofol, synchronized LFF of BOLD signals disappeared. These observations indicate that thalamocortical connectivity may play an important role in propofol anesthesia. We also observed that regionally specific long-range correlations of spontaneous low-frequency physiological fluctuations in BOLD signals may be present across somatosensory networks of the brain in the absence of external stimulation. However, our experiment suggests that fcMRI can be used to investigate brain networks that exhibit correlated fluctuations.


Assuntos
Anestésicos Intravenosos/farmacologia , Propofol/farmacologia , Tálamo/efeitos dos fármacos , Animais , Imagem por Ressonância Magnética , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/efeitos dos fármacos , Córtex Somatossensorial/fisiopatologia , Tálamo/fisiopatologia
19.
Neurosci Lett ; 502(2): 89-93, 2011 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-21810451

RESUMO

Abnormal baseline brain functional connectivity in attention-deficit/hyperactivity disorder (ADHD) has been revealed in a number of studies by using resting-state functional MRI (rfMRI). The aim of this study was to investigate the spontaneous frontal activities in medication-naïve ADHD boys using the rfMRI derived index, amplitude of low-frequency fluctuation (ALFF). In total 17 ADHD boys and 17 matched controls were recruited to undergo rfMRI scan on a 3.0T MRI system. For each subject, six oblique slices covering the frontal areas were acquired with a rapid sampling rate (TR=400ms). Functional images were processed in AFNI for calculation of ALFF and then group comparison was performed using voxel-based t-test. With a corrected threshold of p<0.05 determined by AlphaSim, we found that in comparison with controls, ADHD patients demonstrated higher ALFF values in the left superior frontal gyrus and sensorimotor cortex (SMC), and lower ALFF values in the bilateral anterior, middle cingulate and the right middle frontal gyrus (MFG). Significant correlations were found between patients' WSCT measures and the peak ALFF located in the right MFG (r=0.69, p=0.02), and the left SMC (r=0.65, p=0.03). Our results revealed abnormal frontal activities at resting state associated with underlying physiopathology of ADHD, and suggested the ALFF analysis to be a potential approach in further exploration of this disorder.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Mapeamento Encefálico/métodos , Lobo Frontal/fisiopatologia , Imagem por Ressonância Magnética/métodos , Descanso/fisiologia , Criança , Giro do Cíngulo/fisiopatologia , Humanos , Masculino , Córtex Motor/fisiopatologia , Córtex Somatossensorial/fisiopatologia
20.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 42(3): 397-400, 2011 May.
Artigo em Chinês | MEDLINE | ID: mdl-21827007

RESUMO

OBJECTIVE: To explore the pathogenesis of posttraumatic stress disorder (PTSD) by studying default mode network during the resting state in patients with PTSD after homologous traumatic experience. METHODS: Seventeen PTSD patients and 20 matched normal controls received the examnation of resting-state fMRI scanning. Left and right posterior cingulate cortex was regarded as seed region respectively, and the functional connectivity about whole brain was assessed by using resting-state functional connectivity analysis. RESULTS: Compared with control group, the patients with PTSD showed that the brain area with decreased functional connectivity included left superior frontal gyrus and right fusiform gyrus, while the brain area with increased functional connectivity included right precuneus, right superior temporal gyrus and right middle temporal gyrus. CONCLUSION: The brain default mode network of PTSD patients is abnormal in resting state. These abnormalities might be the neuropathological mechanisms of PTSD.


Assuntos
Terremotos , Giro do Cíngulo/fisiopatologia , Imagem por Ressonância Magnética , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , China , Desastres , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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