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BACKGROUND: The sexual dimorphism represents one of the triggers of the metabolic disparities while the identification of sex-specific metabolites in the elderly has not been achieved. METHODS: A group of aged healthy population from Southwest China were recruited and clinical characteristics were collected. Fasting plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomic analyses were performed. Differentially expressed metabolites between males and females were identified from the metabolomic analysis and metabolite sets enrichment analysis was employed. RESULTS: Sixteen males and fifteen females were finally enrolled. According to clinical characteristics, no significant differences can be found except for smoking history. There were thirty-six differentially expressed metabolites between different sexes, most of which were lipids and lipid-like molecules. Twenty-three metabolites of males were increased while thirteen were decreased compared with females. The top four classes of metabolites were fatty acids and conjugates (30.6%), glycerophosphocholines (22.2%), sphingomyelins (11.1%), and flavonoids (8.3%). Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins were significantly enriched in metabolite sets enrichment analysis. CONCLUSIONS: Significant lipid metabolic differences were found between males and females among the elderly. Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins may partly account for sex differences and can be potential treatment targets for sex-specific diseases.
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Metabolismo de los Lípidos , Caracteres Sexuales , Anciano , Humanos , Masculino , Femenino , Esfingomielinas , Ácidos Grasos , Cromatografía Liquida , Espectrometría de MasasRESUMEN
Nitrous oxide (N2O), commonly known as laughing gas, is widely used in clinical practice and food industry. However, an increasing number of young people have been abusing N2O for recreational purpose, resulting in many functional disorders and sometimes irreversible nerve damage. We present the case of a 20-year-old N2O abuser who gradually developed peripheral neuropathy after continuously inhaling N2O for 2 months. The neurological symptoms of the patient had kept exacerbation for the next 2 months until she came for medical care sitting in a wheelchair. We suggested the patient halting N2O intake and supplementing methylcobalamine according to the standardized protocol. Her symptoms had partly recovered during the following 2 weeks but remained unchanged in another 2 weeks. Antibodies against ganglioside complexes were detected and anti-GM1 IgM antibodies were positive in both cerebrospinal fluid and serum. Intravenous immunoglobulin was given as an additional treatment and the patient's symptoms had significantly recovered further. The patient discharged walking by herself. Then she has been continuously followed up in outpatient department for the next 4 months and taking steroid hormone as well as methylcobalamine. Her symptoms gradually disappeared and all the electrophysiological parameters significantly improved. With this case we were able to show that N2O-related peripheral neuropathy is not only a metabolic disorder but also an immune-mediated disease. N2O intake can trigger a mimic Guillain-Barré syndrome.
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OBJECTIVE: We aimed to identify the detailed relationships between serum lipid levels and neuropsychiatric symptoms in patients with Parkinson's disease (PD). METHODS: Consecutive PD patients and healthy controls were recruited and demographic data were collected. The disease stages of PD patients were assessed using Hoehn-Yahr scale while neuropsychiatric symptoms were determined using Hamilton depression rating scale (HAMD), Hamilton anxiety rating scale (HAMA), and mini-mental state examination scale. Fast serum samples were obtained and the serum levels of lipids were identified. Linear regression analyses and correlation analyses were performed to explore the relationships between serum lipid levels and neuropsychiatric symptoms. RESULTS: The serum levels of triglyceride had significantly decreased while the levels of HDL-c and lipoprotein a had increased in PD patients. Linear regression analyses confirmed that the levels of triglyceride were mainly correlated with age and HAMA score, the levels of HDL-c were correlated with disease duration and gender, and the levels of lipoprotein a were correlated with HAMD score. Correlation analyses further confirmed that the levels of triglyceride were negatively correlated with HAMA score when the levels of lipoprotein a were negatively correlated with HAMD score. CONCLUSIONS: Lipid metabolism is significantly correlated with neuropsychiatric disorders in PD patients.
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Metabolismo de los Lípidos/fisiología , Enfermedad de Parkinson/patología , Factores de Edad , Anciano , Ansiedad/patología , Estudios de Casos y Controles , HDL-Colesterol/sangre , Depresión/patología , Femenino , Humanos , Modelos Lineales , Lípidos/sangre , Lipoproteínas/sangre , Masculino , Enfermedad de Parkinson/metabolismo , Factores de Riesgo , Triglicéridos/sangreRESUMEN
Dementia is very common in the late stage of patient with Parkinson's disease (PD). We aim to explore its underlying pathogenesis and identify candidate biomarkers using untargeted metabolomics analysis. Consecutive PD patients and healthy controls were recruited. Clinical data were assessed and patients were categorized into Parkinson's disease without dementia (PDND) and Parkinson's disease dementia (PDD). Fast plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomics analysis was performed. Based on the identified differentially-expressed metabolites from the metabolomics analysis, multivariate linear regression analyses and receiver operating characteristic (ROC) curves were further employed. According to the clinical data, the mean ages of PDND and PDD patients were significantly higher than those of healthy controls. The incidence of hypercholesterolemia was decreased in PDD patients. PDD patients also had lower levels of triglyceride, low-density lipoprotein cholesterol, and apolipoprotein B. There were 24 and 57 differentially expressed metabolites in PDD patients when compared with the healthy controls and PDND patients from the metabolomics analysis. Eleven lipid metabolites were simultaneously decreased between these two groups, and can be further subcategorized into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and prenol lipids. The plasma levels of the eleven metabolites were positively correlated with MMSE score and can be candidate biomarkers for PDD patients with areas under the curve ranging from 0.724 to 0.806 based on the ROC curves. Plasma lipoproteins are significantly lower in PDD patients. A panel of eleven lipid metabolites were also decreased and can be candidate biomarkers for the diagnosis of PDD patients. Lipid metabolic dysregulation is involved in the pathogenesis of Parkinson's disease dementia.
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Demencia/metabolismo , Hipercolesterolemia/metabolismo , Metabolismo de los Lípidos/fisiología , Enfermedad de Parkinson/metabolismo , Anciano , Anciano de 80 o más Años , Apolipoproteínas B/sangre , Biomarcadores/sangre , LDL-Colesterol/sangre , Comorbilidad , Demencia/epidemiología , Femenino , Humanos , Hipercolesterolemia/epidemiología , Incidencia , Masculino , Metaboloma , Metabolómica , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Triglicéridos/sangreRESUMEN
OBJECTIVES: Anxiety disorder is a common non-motor symptom in patient with Parkinson's disease (PD). We aimed to explore its pathogenesis and identify plasma biomarkers using untargeted metabolomics analysis. METHODS: Consecutive PD patients and healthy controls were recruited. Clinical data were assessed and patients with Parkinson's disease related anxiety disorder (PDA) were recognized. Fast plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomics analysis was performed. Based on the differentially expressed metabolites from the above metabolomics analysis, correlation analyses and receiver operating characteristic curves (ROC) were further employed. RESULTS: According to the clinical data, PDA patients had lower plasma levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and apolipoprotein B. There were thirty-nine differentially expressed metabolites in PDA patients when compared with the other two groups from the metabolomics analysis, respectively. Fourteen lipid metabolites were simultaneously altered between these two groups, and all of them were significantly decreased. They can be further subcategorized into fatty acyls, glycerolipids, sterol lipids, sphingolipids, and prenol lipids. The plasma levels of thirteen metabolites were negatively correlated with HAMA scores except 10-oxo-nonadecanoic acid. Based on the ROC curves, the fourteen lipid metabolites can be diagnostic biomarkers for PDA patients separately and the areas under the curve of the fourteen lipid metabolites ranged from 0.681 to 0.798. CONCLUSIONS: Significantly lower plasma lipoproteins can be found in PDA patients. A panel of fourteen lipid metabolites were also significantly decreased and can be clinical biomarkers for the diagnosis of PDA patients.
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Trastornos de Ansiedad/sangre , Metabolismo de los Lípidos/fisiología , Lípidos/sangre , Lipoproteínas/sangre , Metabolómica/métodos , Enfermedad de Parkinson/sangre , Anciano , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/epidemiología , Biomarcadores/sangre , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/epidemiologíaRESUMEN
Objective: The dopaminergic system is involved in many psychiatric disorders as a GABAergic, serotonergic, and glutamatergic system. A systematic review and meta-analysis was performed to elucidate the alteration of the dopaminergic system in anxiety and compulsive disorders. Methods: The databases of Pubmed, Embase, and ScienceDirect were searched and articles reporting the involvement of the dopaminergic system in patients with anxiety disorder and obsessive compulsive disorder (OCD) were recognized. The key research data were extracted from the included articles and standardized mean differences were calculated using meta-analyses if there were more than two studies with obtainable data. Sensitivity analyses were further performed to detect the stability of results, and the qualities of all the included studies were assessed using the Newcastle Ottawa scale. Results: Finally, we identified 8 and 11 studies associated with anxiety disorder and OCD for further analysis, respectively. Most consistently, the striatal dopamine D2 receptor (D2R) of OCD patients had decreased while no significant correlation was found between striatal D2R and disease severity. The striatal dopamine transporter (DAT) had not been significantly altered in both the anxiety disorder and OCD patients. The heterogeneity values from the meta-analyses were extremely high while those results remained stable after sensitivity analyses. Inconsistent data were found in the striatal D2R of patients with anxiety disorder. Limited data had suggested that dopamine synthesis increased in most regions of the cerebral cortex and cerebellum in OCD patients. Conclusions: The most convincing finding was that the D2 receptor decreased in patients with obsessive compulsive disorder. The dopamine transporter may have no relationship with anxiety and compulsive disorder.
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Parkinson's disease (PD) is a common neurodegenerative disease in the elderly with a pathogenesis that remains unclear. We aimed to explore its pathogenesis through plasma integrated metabolomics and proteomics analysis. The clinical data of consecutively recruited PD patients and healthy controls were assessed. Fasting plasma samples were obtained and analyzed using metabolomics and proteomics methods. After that, differentially expressed metabolites and proteins were identified for further bioinformatics analysis. No significant difference was found in the clinical data between these two groups. Eighty-three metabolites were differentially expressed in PD patients identified by metabolomics analysis. These metabolites were predominately lipid and lipid-like molecules (63%), among which 25% were sphingolipids. The sphingolipid metabolism pathway was enriched and tended to be activated in the following KEGG pathway analysis. According to the proteomics analysis, forty proteins were identified to be differentially expressed, seven of which were apolipoproteins. Furthermore, five of the six top ranking Gene Ontology terms from cellular components and eleven of the other fourteen Gene Ontology terms from biological processes were directly associated with lipid metabolism. In KEGG pathway analysis, the five enriched pathways were also significantly related with lipid metabolism (p < 0.05). Overall, Parkinson's disease is associated with plasma lipid metabolic disturbance, including an activated sphingolipid metabolism and decreased apolipoproteins.
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The gut microbiome is composed of an enormous number of microorganisms, generally regarded as commensal bacteria. Resident gut bacteria are an important contributor to health and significant evidence suggests that the presence of healthy and diverse gut microbiota is important for normal cognitive and emotional processing. Here we measured the expression of monoamine neurotransmitter-related genes in the hippocampus of germ-free (GF) mice and specific-pathogen-free (SPF) mice to explore the effect of gut microbiota on hippocampal monoamine functioning. In total, 19 differential expressed genes (Htr7, Htr1f, Htr3b, Drd3, Ddc, Maob, Tdo2, Fos, Creb1, Akt1, Gsk3a, Pik3ca, Pla2g5, Cyp2d22, Grk6, Ephb1, Slc18a1, Nr4a1, Gdnf) that could discriminate between the two groups were identified. Interestingly, GF mice displayed anxiolytic-like behavior compared to SPF mice, which were not reversed by colonization with gut microbiota from SPF mice. Besides, colonization of adolescent GF mice by gut microbiota was not sufficient to reverse the altered gene expression associated with their GF status. Taking these findings together, the absence of commensal microbiota during early life markedly affects hippocampal monoamine gene-regulation, which was associated with anxiolytic behaviors and monoamine neurological signs.
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Ansiedad/genética , Microbioma Gastrointestinal/fisiología , Vida Libre de Gérmenes/fisiología , Hipocampo/metabolismo , Neurotransmisores/genética , Neurotransmisores/metabolismo , Animales , Ansiedad/etiología , Ansiedad/psicología , Monoaminas Biogénicas/metabolismo , Redes Reguladoras de Genes/fisiología , Masculino , Ratones , Ratones Endogámicos BALB C , Distribución AleatoriaRESUMEN
Depression is a common comorbidity in Parkinson's disease (PD) but is underdiagnosed. We aim to investigate the altered metabolic pathways of Parkinson's disease-related depression (PDD) in plasma and to identify potential biomarkers for clinical diagnosis. Consecutive patients with PD were recruited, clinically assessed, and patients with PDD identified. Fasting plasma samples were collected from 99 patients and differentially expressed metabolites and proteins between patients with PDD and PD were identified using non-targeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics and tandem mass tag (TMT)-based proteomics analysis, followed by an integrated analysis. Based on the above results, enzyme-linked immune sorbent assay (ELISA) tests were then performed to identify potential biomarkers for PDD. In clinics, patients with PDD suffered less hypertension and had lower serum low-density lipoprotein cholesterol and apolipoprotein B levels when compared to the other patients with PD. A total of 85 differentially expressed metabolites were identified in metabolomics analysis. These metabolites were mainly lipids and lipid-like molecules, involved in lipid and glucose metabolic pathways. According to proteomics analysis, 17 differentially expressed proteins were identified, and 12 metabolic pathways were enriched, which were predominantly related to glucose metabolism. Integrated analysis indicated that altered lipid and glucose metabolism in PDD may induce cellular injury through oxidative stress. Additionally, plasma levels of several proteins were confirmed to be significantly altered and correlated with depressive severity. NOTCH2 may be a potential blood biomarker for PDD, with an optimal cut-off point of 0.91 ng/ml, a sensitivity value of 95.65%, and a specificity value of 81.58%. Depressive symptoms are associated with lipid and glucose metabolism in patients with PD and NOTCH2 may be a potential blood biomarker for the clinical diagnosis of PDD.
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Major depressive disorder (MDD) is a debilitating psychiatric illness. However, there is currently no objective laboratory-based diagnostic tests for this disorder. Although, perturbations in multiple neurotransmitter systems have been implicated in MDD, the biochemical changes underlying the disorder remain unclear, and a comprehensive global evaluation of neurotransmitters in MDD has not yet been performed. Here, using a GC-MS coupled with LC-MS/MS-based targeted metabolomics approach, we simultaneously quantified the levels of 19 plasma metabolites involved in GABAergic, catecholaminergic, and serotonergic neurotransmitter systems in 50 first-episode, antidepressant drug-naïve MDD subjects and 50 healthy controls to identify potential metabolite biomarkers for MDD (training set). Moreover, an independent sample cohort comprising 49 MDD patients, 30 bipolar disorder (BD) patients and 40 healthy controls (testing set) was further used to validate diagnostic generalizability and specificity of these candidate biomarkers. Among the 19 plasma neurotransmitter metabolites examined, nine were significantly changed in MDD subjects. These metabolites were mainly involved in GABAergic, catecholaminergic and serotonergic systems. The GABAergic and catecholaminergic had better diagnostic value than serotonergic pathway. A panel of four candidate plasma metabolite biomarkers (GABA, dopamine, tyramine, kynurenine) could distinguish MDD subjects from health controls with an AUC of 0.968 and 0.953 in the training and testing set, respectively. Furthermore, this panel distinguished MDD subjects from BD subjects with high accuracy. This study is the first to globally evaluate multiple neurotransmitters in MDD plasma. The altered plasma neurotransmitter metabolite profile has potential differential diagnostic value for MDD.
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Trastorno Depresivo Mayor/diagnóstico , Metabolómica/métodos , Neurotransmisores/sangre , Adulto , Área Bajo la Curva , Biomarcadores/sangre , Trastorno Bipolar/sangre , Trastorno Bipolar/diagnóstico , Estudios de Casos y Controles , Estudios de Cohortes , Trastorno Depresivo Mayor/sangre , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Modelos Logísticos , Masculino , Redes y Vías Metabólicas , Persona de Mediana Edad , Neurotransmisores/metabolismo , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
Restless legs syndrome (RLS) is defined as an irresistible urge to move the legs, which is usually accompanied by paresthesias or dysesthesias at least twice weekly, and affects 2%-4% of adults in Europe and North America. This systematic review assesses the current complementary and alternative options for RLS and the potential benefits of those treatments on sleep quality, mood disorder, and quality of life. A systematic search of the PubMed, Embase, Cochrane, and Web of Science databases was conducted. Eighteen studies met the inclusion criterion, which included the use of the international RLS study group criteria. Complementary and alternative therapies have been found to be effective in both primary and secondary RLS. The severity of primary RLS symptoms can be significantly ameliorated by exercise training, transcutaneous spinal direct current stimulation, pneumatic compression devices, light therapy, repetitive transcranial magnetic stimulation, and acupuncture. Pneumatic compression devices and yoga also improve RLS-related disorders. Exercise training is highly efficacious in the reduction of symptom severity in uremic RLS and related effects such as poor quality of life. Endovenous laser ablation may be a good choice for patients with concurrent RLS and superficial venous insufficiency.
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Terapias Complementarias/métodos , Ejercicio Físico , Síndrome de las Piernas Inquietas/terapia , Depresión/psicología , Humanos , Calidad de Vida , Sueño/fisiologíaRESUMEN
OBJECTIVES: Recombinant tissue plasminogen activator (rtPA) is widely used for patients with thromboembolic disease, and increasing evidence indicates that it can directly induce neurotoxicity independent of its thrombolysis property. Here, we aimed to confirm the long-term effect of rtPA on animal's behavior, and investigate the underlying pathogenesis. METHODS AND RESULTS: Male Sprague-Dawley rats randomly received a dose of rtPA (10 mg/kg) or sterile saline. Three months later, the animals receiving rtPA displayed anxiety-like behaviors in the open field and novelty-suppressed feeding tests. To investigate the possible pathogenesis, gas chromatography-mass spectrometry-based metabolomics analysis was performed, with 18 differential metabolites identified in the hippocampus 24 h after the treatments. Based upon these differential metabolites, a metabolite-protein integrated network was generated, which indicated that ERK1/2-glutamic acid decarboxylase (GAD) 1-γ aminobutyric acid (GABA) cascade may be related to long-term anxiety-like behaviors. The GABA levels in hippocampus were decreased 24 h post-treatment and three months later, confirmed by a high performance liquid chromatography method. We also examined the expression of GAD1 and GAD2 using western blotting or immunohistochemical staining. Levels of GAD1 were persistently decreased after treatment, while GAD2 levels, GAD1-immunoreactive, and GAD2-immunoreactive neurons showed no significant differences. The underlying pathogenesis also involved activation of ERK1/2, confirmed by increased phospho-ERK1/2 24 h post-treatment. CONCLUSIONS: RtPA can induce long-term anxiety-like behaviors after a clinical injected dose. The underlying pathogenesis involves the ERK1/2-GAD1-GABA cascade in the hippocampus. This pharmacological side effect of rtPA may further exacerbate post-stroke anxiety disorder for stroke patients.
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Ansiedad/inducido químicamente , Ansiedad/patología , Hipocampo/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Activador de Tejido Plasminógeno/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Modelos Animales de Enfermedad , Conducta Exploratoria/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Glutamato Descarboxilasa/metabolismo , Suspensión Trasera , Hipocampo/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Redes y Vías Metabólicas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Parkinson's disease (PD), a progressive and age-related neurodegenerative condition, is a common neurodegenerative disorder. However, no validated biomarkers for PD have been identified to date. Accumulating evidence supports the role of proNGF-p75NTR-sortilin signaling in the neurodegeneration and pathogenesis of PD. The aim of our study was to investigate alterations in serum proNGF concentrations in PD patients and related anxiety. Seventy-seven consecutive PD patients and 39 healthy controls were enrolled, and clinical data were collected. Modified Hoehn-Yahr Staging Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and Hamilton Anxiety (HAMA) Scale scores were assessed upon admission. Serum proNGF concentration was compared between that of PD patients and healthy controls. Pearson correlation coefficients were determined to explore the relationship between proNGF concentration and UPDRS, Hoehn-Yahr, and HAMA scores. Received operating characteristic (ROC) curves and proNGF optimal cutoff point were used to distinguish PD and related anxiety. The median concentration of proNGF was significantly lower (p = 0.000) in PD patients (94.91 ng/L, range 85.92-118.06 ng/L) compared with that of healthy controls (106.67 ng/L, range 102.39-122.06 ng/L). The optimal proNGF cutoff point for distinguishing PD patients was 102.29 ng/L, and the sensitivity and specificity values were 87.0 and 100%, respectively. proNGF concentration positively correlated with UPDRS (r = 0.281, p = 0.013), Hoehn-Yahr (r = 0.260, p = 0.023), and HAMA (r = 0.276, p = 0.015) scores. Our results indicate that serum proNGF concentration may represent a biomarker for PD and its role in the pathogenesis of PD thus warrants further investigation.
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Factor de Crecimiento Nervioso/sangre , Enfermedad de Parkinson/sangre , Precursores de Proteínas/sangre , Ansiedad/sangre , Ansiedad/complicaciones , Biomarcadores/sangre , Femenino , Humanos , Masculino , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Escalas de Valoración Psiquiátrica , Curva ROC , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: This study aim to determine changes of serum butyrylcholinesterase (BChE) activity in PD patients and related dementia. PATIENTS AND METHODS: Consecutive PD patients and healthy controls were included and clinical data were collected. Fast serum BChE activity was determined and compared between healthy controls and PD patients. Independent risk factors were performed for BChE activity, PD, and related dementia. The relationship between BChE activity and disease severity was also evaluated. Receiver operating characteristic (ROC) curves were obtained to explore serum BChE activity in distinguishing PD patients and related dementia. RESULTS: Serum BChE activity mainly independently correlated with gender, albumin, triglyceride, body mass index, and PD. Serum BChE activity decreased in PD patients compared with healthy controls. Based on the ROC curve, the optimal cut-off point was 6864.08 IU/L for distinguishing PD patients, and the sensitivity and specificity values were 61.8% and 72.1%. It inversely correlated with Unified Parkinson's Disease Rating Scale score. BChE activity decreased in PD-related dementia compared with those without dementia. The sensitivity and specificity values were 70.6% and 76.3%, respectively, with an optimal cut-off point of 6550.00 IU/L. CONCLUSIONS: Serum BChE activity can be regarded as a biomarker for PD and related dementia.
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Biomarcadores/sangre , Butirilcolinesterasa/sangre , Demencia/sangre , Enfermedad de Parkinson/sangre , Anciano , Estudios de Cohortes , Demencia/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , Curva ROCRESUMEN
To determine cerebrovascular risk factors for patients with cerebral watershed infarction (CWI) from Southwest China.Patients suffering from acute ischemic stroke were categorized into internal CWI (I-CWI), external CWI (E-CWI), or non-CWI (patients without CWI) groups. Clinical data were collected and degrees of steno-occlusion of all cerebral arteries were scored. Arteries associated with the circle of Willis were also assessed. Data were compared using Pearson chi-squared tests for categorical data and 1-way analysis of variance with Bonferroni post hoc tests for continuous data, as appropriate. Multivariate binary logistic regression analysis was performed to determine independent cerebrovascular risk factors for CWI.Compared with non-CWI, I-CWI had higher degrees of steno-occlusion of the ipsilateral middle cerebral artery, ipsilateral carotid artery, and contralateral middle cerebral artery. E-CWI showed no significant differences. All the 3 arteries were independent cerebrovascular risk factors for I-CWI confirmed by multivariate binary logistic regression analysis. I-CWI had higher degrees of steno-occlusion of the ipsilateral middle cerebral artery compared with E-CWI. No significant differences were found among arteries associated with the circle of Willis.The ipsilateral middle cerebral artery, carotid artery, and contralateral middle cerebral artery were independent cerebrovascular risk factors for I-CWI. No cerebrovascular risk factor was identified for E-CWI.
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Infarto Cerebral/diagnóstico por imagen , Trastornos Cerebrovasculares/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Anciano , Arterias Carótidas/diagnóstico por imagen , Estudios de Casos y Controles , Arterias Cerebrales/diagnóstico por imagen , Infarto Cerebral/epidemiología , Trastornos Cerebrovasculares/epidemiología , China , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Migraine, ranked as the 7th-highest specific cause of disability worldwide, has caused an enormous burden on the economy and society. Tricyclic antidepressant (TCA) is one of the most commonly drugs for migraine prevention. However, evidence about the efficacy and tolerability of TCAs in the prophylaxis of migraine in adults is somewhat confusing. METHODS: A computerized literature search of the PubMed, Embase, Cochrane, and Web of Science databases from inception to July 2016 was conducted. We reviewed all randomized controlled trials that assigned adults with a clinical diagnosis of migraine to TCAs or other treatments (placebo or other antidepressants). Reduction in migraine frequency or index and response rates to treatment were defined as the efficacy outcomes. Rates of dropout due to adverse effects were defined as the tolerability outcomes. RESULTS: In total 12 trials consisting of 1006 participants were identified: 9 trials compared TCAs with placebo, and the other 3 compared amitriptyline with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). A significant advantage of TCAs compared with placebo in the prevention of migraine in adults was observed (standardized mean difference [SMD] = -.75; 95% confidence interval [CI] = -1.05 to -.46; Pâ<â.00001). Participants receiving TCAs were more likely to experience an ≥50% reduction in their headache burden than those receiving placebo (risk ratio [RR] =1.40; 95% CI = 0.89-2.20; Pâ=â.14). In addition, the efficacy between amitriptyline and SSRIs or SNRIs did not differ for migraine prevention in adults (SMD = -.01; 95% CI = -0.31 to 0.28; Pâ=â.94) based on the available limited trials. However, TCAs were less well tolerated than placebo (RR = 1.73; 95% CI = 1.00-2.99; Pâ=â.05) and SSRI or SNRI (RR = 2.85; 95% CI = 0.97-8.41; Pâ=â.06) on account of adverse events. CONCLUSIONS: This research reveals that TCAs were more effective than placebo, but no more than SSRI or SNRI in ameliorating the headache burden in adults with migraine. However, TCAs appeared to be less tolerated than placebo and SSRIs or SNRIs for some side effects.
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Antidepresivos Tricíclicos/uso terapéutico , Trastornos Migrañosos/tratamiento farmacológico , Adulto , Antidepresivos Tricíclicos/efectos adversos , Humanos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Inhibidores de Captación de Serotonina y Norepinefrina/efectos adversos , Inhibidores de Captación de Serotonina y Norepinefrina/uso terapéuticoRESUMEN
BACKGROUND: Depression greatly impacts the quality of life in most stroke survivors. Therefore, effective treatment of post-stroke depression (PSD) is critically important. However, evidence supporting the effectiveness and feasibility of antidepressant treatment in this population is limited and somewhat confusing. METHODS: A comprehensive literature search of the Cochrane, PubMed, Web of Science, and Embase databases from inception up to November 2015 was conducted. We reviewed all randomized controlled trials (RCTs) that assigned patients with a clinical diagnosis of PSD to antidepressant or placebo treatment. Reduction in depression rating scale scores and response rate to antidepressants were defined as the efficacy outcomes. Rates of dropout for any reason and for adverse effects were defined as the acceptability outcomes. We also assessed improvements in activities of daily living (ADL) as functional outcomes. RESULTS: In total, 11 trials consisting of 740 participants were indentified. A significant advantage of antidepressants compared with placebo treatment in PSD was observed in overall pooled effect size analysis (SMDâ=â-0.96; 95% CIâ=â-1.41 to -0.51; Pâ<0.0001). In addition, patients receiving antidepressants presented a much greater improvement in various depressive symptoms than those with placebo (RRâ=â1.36; 95% CIâ=â1.01-1.83; Pâ=â0.04). However, antidepressants were less well tolerated than placebo because of some adverse events (RRâ=â2.72; 95% CIâ=â1.37-5.43; Pâ=â0.04). Intriguingly, no consistent evidence was found for a positive effect of antidepressants on ADL in our analysis. CONCLUSIONS: This meta-analysis suggests that antidepressants treatment confers potentially positive effects in patients with PSD as compared with simple placebo treatment. However, this must be carefully considered in light of its possible adverse events in some individual patients.
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Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Depresión/etiología , Accidente Cerebrovascular/complicaciones , Actividades Cotidianas , Estudios de Factibilidad , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Recombinant tissue plasminogen activator (rtPA) is the only effective drug approved by US FDA to treat ischemic stroke, and it contains pleiotropic effects besides thrombolysis. We performed a meta-analysis to clarify effect of tissue plasminogen activator (tPA) on cerebral infarction besides its thrombolysis property in mechanical animal stroke. METHODS: Relevant studies were identified by two reviewers after searching online databases, including Pubmed, Embase, and ScienceDirect, from 1979 to 2016. We identified 6, 65, 17, 12, 16, 12 and 13 comparisons reporting effect of endogenous tPA on infarction volume and effects of rtPA on infarction volume, blood-brain barrier, brain edema, intracerebral hemorrhage, neurological function and mortality rate in all 47 included studies. Standardized mean differences for continuous measures and risk ratio for dichotomous measures were calculated to assess the effects of endogenous tPA and rtPA on cerebral infarction in animals. The quality of included studies was assessed using the Stroke Therapy Academic Industry Roundtable score. Subgroup analysis, meta-regression and sensitivity analysis were performed to explore sources of heterogeneity. Funnel plot, Trim and Fill method and Egger's test were obtained to detect publication bias. RESULTS: We found that both endogenous tPA and rtPA had not enlarged infarction volume, or deteriorated neurological function. However, rtPA would disrupt blood-brain barrier, aggravate brain edema, induce intracerebral hemorrhage and increase mortality rate. CONCLUSIONS: This meta-analysis reveals rtPA can lead to neurological side effects besides thrombolysis in mechanical animal stroke, which may account for clinical exacerbation for stroke patients that do not achieve vascular recanalization with rtPA.
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Infarto Cerebral/complicaciones , Accidente Cerebrovascular/complicaciones , Terapia Trombolítica/efectos adversos , Activador de Tejido Plasminógeno/efectos adversos , Animales , Animales Modificados Genéticamente , Barrera Hematoencefálica/efectos de los fármacos , Edema Encefálico/inducido químicamente , Edema Encefálico/complicaciones , Infarto Cerebral/tratamiento farmacológico , Interpretación Estadística de Datos , Modelos Animales de Enfermedad , Masculino , Ratas , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Sensibilidad y Especificidad , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéuticoRESUMEN
BACKGROUND AND PURPOSE: Early hematoma growth is not uncommon in patients with intracerebral hemorrhage and is an independent predictor of poor functional outcome. The purpose of our study was to report and validate the use of our newly identified computed tomographic (CT) blend sign in predicting early hematoma growth. METHODS: Patients with intracerebral hemorrhage who underwent baseline CT scan within 6 hours after onset of symptoms were included. The follow-up CT scan was performed within 24 hours after the baseline CT scan. Significant hematoma growth was defined as an increase in hematoma volume of >33% or an absolute increase of hematoma volume of >12.5 mL. The blend sign on admission nonenhanced CT was defined as blending of hypoattenuating area and hyperattenuating region with a well-defined margin. Univariate and multivariable logistic regression analyses were performed to assess the relationship between the presence of the blend sign on nonenhanced admission CT and early hematoma growth. RESULTS: A total of 172 patients were included in our study. Blend sign was observed in 29 of 172 (16.9%) patients with intracerebral hemorrhage on baseline nonenhanced CT scan. Of the 61 patients with hematoma growth, 24 (39.3%) had blend sign on admission CT scan. Interobserver agreement for identifying blend sign was excellent between the 2 readers (κ=0.957). The multivariate logistic regression analysis demonstrated that the time to baseline CT scan, initial hematoma volume, and presence of blend sign on baseline CT scan to be independent predictors of early hematoma growth. The sensitivity, specificity, positive and negative predictive values of blend sign for predicting hematoma growth were 39.3%, 95.5%, 82.7%, and 74.1%, respectively. CONCLUSIONS: The CT blend sign could be easily identified on regular nonenhanced CT and is highly specific for predicting hematoma growth.