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1.
Sci Total Environ ; 914: 169595, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38154649

RESUMEN

Municipal solid waste incineration fly ash (MSWI FA) is a kind of hazardous waste that contains a substantial amount of heavy metals. To facilitate the appropriate treatment of MSWI FA, the leaching behavior of heavy metals was evaluated in MSWI FA from various sources using different leaching methods. Nine kinds of MSWI FA were investigated using three kinds of batch leaching tests (TCLP, HJ/T 300, and EN12457-2). The chemical form distributions of heavy metals in MSWI FA were obtained by sequential extraction procedures (SEPs) and the environmental risk posed by MSWI FA was comprehensively evaluated. The results showed that the grate and fluidized bed MSWI FA performed differently in various leaching methods, which was mainly dependent on the leachate pH and the chemical form distributions of the heavy metals. In addition, the BCR SEP was more suitable for the fractionation of heavy metals and the environmental risk assessment of MSWI FA when compared with Tessier's SEP. The overall pollution toxicity index allowed a comprehensive risk assessment specific to the leaching environment, thereby offering valuable guidelines for the stabilization or resource-based treatment of MSWI FA.

2.
Aging (Albany NY) ; 15(21): 12209-12224, 2023 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-37921870

RESUMEN

PURPOSE: The study aimed to investigate whether astrocyte pyroptosis, and the subsequent neuroinflammatory response that exerts amyloid ß (Aß) neurotoxic effects, has an effect on endothelial cells, along with the underlying mechanisms. METHODS: In vivo, 5 µL of disease venom was injected into the lateral ventricle of APP/PS1 mice for treatment. Pyroptosis was induced by treating astrocytes with Aß42 in vitro. Small interfering RNA (siRNA) was used to silence caspase-1 and Gasdermin D (GSDMD) mRNA expression. Cell viability was determined using a CCK-8 detection kit. Scanning electron microscopy (SEM), Annexin V/propidium iodide (PI) double staining, RT-qPCR, immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA) were used to detect cell pyroptosis. The degree of pathological damage to the brain and aortic tissue was assessed by hematoxylin-eosin staining and immunohistochemistry. RESULTS: Aß42 induced astrocyte pyroptosis dependent on the GSDMD/Gasdermin E (GSDME)/Caspase 11/NLRP3 pathway, releasing large amounts of inflammatory factors, such as TNF-α, IL-1α, IL-1ß, and IL-18. Astrocyte pyroptosis caused endothelial cell dysfunction and release of large amounts of vasoconstrictors (ET and vWF). Knockdown of GSDMD reduced astrocyte pyroptosis in the cerebral cortex and hippocampal tissue, decreased the release of inflammatory factors IL-1 ß and IL-18, reduced Aß deposition and tau protein, increased the release of peripheral vasodilator substances (eNOS), and decreased the release of vasoconstrictor substances (ET, vWF), thereby reducing brain tissue damage and vascular injury in APP/PS1 mice. CONCLUSION: Aß42 induced astrocyte pyroptosis, while GSDMD knockout inhibited astrocyte pyroptosis, reduced the release of inflammatory factors, and alleviated brain tissue damage and vascular damage in APP/PS1 mice. Therefore, GSDMD is a novel therapeutic target for Alzheimer's disease. PURPOSE: The study aimed to investigate whether astrocyte pyroptosis, and the subsequent neuroinflammatory response that exerts amyloid ß (Aß) neurotoxic effects, has an effect on endothelial cells, along with the underlying mechanisms. METHODS: In vivo, 5 µL of disease venom was injected into the lateral ventricle of APP/PS1 mice for treatment. Pyroptosis was induced by treating astrocytes with Aß42 in vitro. Small interfering RNA (siRNA) was used to silence caspase-1 and Gasdermin D (GSDMD) mRNA expression. Cell viability was determined using a CCK-8 detection kit. Scanning electron microscopy (SEM), Annexin V/propidium iodide (PI) double staining, RT-qPCR, immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA) were used to detect cell pyroptosis. The degree of pathological damage to the brain and aortic tissue was assessed by hematoxylin-eosin staining and immunohistochemistry. RESULTS: Aß42 induced astrocyte pyroptosis dependent on the GSDMD/Gasdermin E (GSDME)/Caspase 11/NLRP3 pathway, releasing large amounts of inflammatory factors, such as TNF-α, IL-1α, IL-1ß, and IL-18. Astrocyte pyroptosis caused endothelial cell dysfunction and release of large amounts of vasoconstrictors (ET and vWF). Knockdown of GSDMD reduced astrocyte pyroptosis in the cerebral cortex and hippocampal tissue, decreased the release of inflammatory factors IL-1 ß and IL-18, reduced Aß deposition and tau protein, increased the release of peripheral vasodilator substances (eNOS), and decreased the release of vasoconstrictor substances (ET, vWF), thereby reducing brain tissue damage and vascular injury in APP/PS1 mice. CONCLUSION: Aß42 induced astrocyte pyroptosis, while GSDMD knockout inhibited astrocyte pyroptosis, reduced the release of inflammatory factors, and alleviated brain tissue damage and vascular damage in APP/PS1 mice. Therefore, GSDMD is a novel therapeutic target for Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer , Lesiones del Sistema Vascular , Ratones , Animales , Péptidos beta-Amiloides/metabolismo , Enfermedad de Alzheimer/metabolismo , Piroptosis , Proteínas tau/metabolismo , Interleucina-1beta/metabolismo , Astrocitos/metabolismo , Interleucina-18/metabolismo , Gasderminas , Células Endoteliales/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Anexina A5/metabolismo , Anexina A5/farmacología , Eosina Amarillenta-(YS)/metabolismo , Eosina Amarillenta-(YS)/farmacología , Hematoxilina/metabolismo , Hematoxilina/farmacología , Propidio/metabolismo , Propidio/farmacología , Sincalida/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de von Willebrand , Caspasa 1/metabolismo , ARN Interferente Pequeño/metabolismo , ARN Mensajero/metabolismo , Vasoconstrictores/farmacología , Vasodilatadores/farmacología
3.
Front Psychiatry ; 14: 1247063, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37701095

RESUMEN

The relationship between adverse childhood experiences (ACEs) and the development of psychotic symptoms is not well understood. Therefore, this study aimed to investigate the frequency and distribution of ACEs among patients with schizophrenia and their potential correlation with symptomatology and personality pathology. We conducted a cross-sectional study involving 571 patients with schizophrenia in Shanghai, China. Symptomatology was assessed using the Positive and Negative Symptoms Scale (PANSS) and personality pathology was assessed using the Personality Diagnostic Questionnaire Fourth Edition Plus (PDQ-4+). ACEs were assessed using the Child Trauma Questionnaire-Short Form (CTQ-SF). ACEs were highly prevalent, with 80.8% of the patients with schizophrenia reporting at least one ACE. The three most common types of ACE were physical neglect (69.8%), emotional neglect (28.2%), and emotional abuse (22.9%). For specific ACE, emotional abuse was significantly associated with PD traits, whereas emotional and physical neglect types of ACE was significantly associated with negative symptoms. A higher level of physical abuse was more commonly reported by men, younger individuals, and those with a higher level of antisocial PD traits. Higher levels of physical neglect were associated with more severe negative symptoms. ACEs are commonly observed in patients with schizophrenia. Therefore, it is strongly recommended that this clinical population be provided with a comprehensive assessment and individualized intervention for those exposed to specific ACEs.

4.
Front Public Health ; 11: 1073141, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37304081

RESUMEN

Background: Childhood trauma confers risks to mental health. However, little is known about whether home quarantine (HQ) during the coronavirus disease 2019 (COVID-19) pandemic exaggerated or mitigated the effect of childhood trauma on mental health. Objective: To examine the modulating effects of prior childhood traumas on the longitudinal changes of psychiatric symptoms in college students before and after HQ during the pandemic. Methods: This was a two-wave longitudinal study on the mental health of 2,887 college students before and after HQ during the COVID-19 pandemic. The relationships between the changes in the Patient Health Questionnaire-9 (PHQ-9), Symptom Checklist-90 (SCL-90), 16-item Prodromal Questionnaire (PQ-16), Childhood Trauma Questionnaire (CTQ), and Social Support Rating Scale (SSRS) scores were analyzed. Results: The students with childhood trauma showed a significantly greater decrement in psychiatric symptoms after HQ (F = 17.21, 14.11, 18.87, and 17.42 for PHQ-9, PQ-16 objective and distress, and SCL-90, respectively). The correlation coefficients between the CTQ and these symptoms scales were significant at baseline (r = 0.42, 0.34, 0.37, and 0.39), and decreased after HQ (r = 0.17, 0.20, 0.18, and 0.19). The decrement of depressive, psychotic, and overall symptoms was positively correlated with the scores of the CTQ (r = 0.08-0.27) but negatively correlated with SSRS (r = -0.08--0.14). Multilinear regression analysis confirmed the results of the CTQ and SSRS regarding the modulation of the dynamic changes in psychiatric symptoms. A constructed structural equation model indicated that the total effects of childhood trauma on decreased psychiatric symptoms were partly mediated by lower baseline social support. Conclusion: Home quarantine during the COVID-19 pandemic could blunt the adverse effects of childhood trauma on mental health, especially for prodromal psychotic symptoms in college students. Changes in relative deprivation and social support may be mediating factors.


Asunto(s)
Experiencias Adversas de la Infancia , COVID-19 , Humanos , Estudios Longitudinales , Pandemias , Cuarentena , COVID-19/epidemiología , Estudiantes
5.
Front Psychiatry ; 13: 925007, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35722555

RESUMEN

Studies have found that repetitive transcranial magnetic stimulation rTMS can produce antidepressant effects by affecting inflammatory cytokines in patients with depression, which plays a key role in the therapeutic mechanism of antidepressants. This study aimed to explore the changes in inflammatory cytokine levels in patients with depression after 4 weeks of rTMS treatment to determine the possible antidepressant mechanism of rTMS. This prospective, double-blind, pseudo-stimulus-controlled study was conducted, and a total of 57 patients with depression and 30 healthy controls were recruited. Patients were randomly divided into the active rTMS (n = 29) and sham rTMS groups (n = 28). The Hamilton Depression Scale was used to evaluate depressive symptoms and their severity. The serum levels of seven inflammatory cytokines were measured using enzyme-linked immunosorbent assay. Inflammatory cytokines include high-sensitivity C-reactive protein (CRP-hc); tumor necrosis factor (TNF-α); interferon (IFN-γ); interleukin-2 (IL-2); interleukin-4 (IL-4); interleukin-6 (IL-6); and interleukin-8 (IL-8). At baseline, TNF-α (F = 36.699, p < 0.001), IFN-γ (F = 8.907, p < 0.001), IL-4 (F = 66.256, p < 0.001), and IL-2 (F = 9.162, p < 0.001) levels in the depression group were significantly different from those of healthy controls. In the self-control analysis of the active rTMS group, the levels of IL-2 and CRP-hc increased significantly after 2 and 12 weeks of treatment. In the sham-rTMS group, IFN-γ increased after 2 and 12 weeks of treatment. Our results revealed that the changes in inflammatory cytokines after rTMS treatment showed different patterns compared to the sham group, suggesting that the antidepressant effect of rTMS may be related to changes in inflammatory cytokines.

6.
Comput Intell Neurosci ; 2022: 4493347, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35300397

RESUMEN

Cutaneous melanoma (CM) is attracting increasing attention due to high mortality. In response to this, we synthetically analyze the CM dataset from the TCGA database and explore microenvironment-related genes that effectively predict patient prognosis. Immune/stromal scores of cases are calculated using the ESTIMATE algorithm and are significantly associated with overall patient survival. Then, differentially expressed genes are identified by comparing the immune score and stromal score, also prognostic genes are subsequently screened. Functional analysis shows that these genes are enriched in different activities of immune system. Moreover, 19 prognosis-related hub genes are extracted from the protein-protein interaction network, of which four unreported genes (IL7R, FLT3, C1QC, and HLA-DRB5) are chosen for validation. A significant negative relationship is found between the expression levels of the 4 genes and pathological stages, notably T grade. Furthermore, the K-M plots and TIMER results show that these genes have favorable value for CM prognosis. In conclusion, these results give a novel insight into CM and identify IL7R, FLT3, C1QC, and HLA-DRB5 as crucial roles for the diagnosis and treatment of CM.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Biología Computacional/métodos , Computadores , Perfilación de la Expresión Génica/métodos , Humanos , Melanoma/genética , Pronóstico , Neoplasias Cutáneas/genética , Microambiente Tumoral/genética
8.
Front Aging Neurosci ; 13: 722836, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34658837

RESUMEN

Background: This study investigated the impact of metabolic syndrome on the progression from mild parkinsonian signs (MPS) to Parkinson's disease (PD). Methods: A total of 1,563 participants with MPS completed 6 years of follow-up. The diagnosis of metabolic syndrome was made according to Adult Treatment Panel III of the National Cholesterol Education Program. The evaluations of MPS and PD were based on the motor portion of the Unified Parkinson's Disease Rating Scale. Cox proportional hazard models were used to identify the association between metabolic syndrome and PD conversion. Results: Of the 1,563 participants, 482 (30.8%) with MPS developed PD at the end of the follow-up. Metabolic syndrome (HR: 1.69, 95% CI: 1.29-2.03) was associated with the risk of PD conversion. Metabolic syndrome was associated with the progression of bradykinesia (HR: 1.85, 95% CI: 1.43-2.34), rigidity (HR: 1.36, 95% CI: 1.19-1.57), tremor (HR: 1.98, 95% CI: 1.73-2.32), and gait/balance impairment (HR: 1.66, 95% CI: 1.25-2.11). The effect of metabolic syndrome on the progression of bradykinesia and tremor was nearly two fold. Participants treated for two or three to four components of metabolic syndrome, including high blood pressure, high fasting plasma glucose, hypertriglyceridemia, and low HDL-C, had a lower risk of PD conversion. Conclusion: Metabolic syndrome increased the risk of progression from MPS to PD. Participants treated for two or more components of metabolic syndrome had a lower risk of PD conversion.

9.
Curr Alzheimer Res ; 18(5): 428-442, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34488598

RESUMEN

BACKGROUND: High cholesterol aggravates the risk development of Alzheimer's disease (AD). AD is closely related to the transport impairment of Amyloid-ß (Aß) in the blood-brain barrier. It is unclear whether high cholesterol affects the risk of cognitive impairment in AD by affecting Aß transport. The purpose of the study is to investigate whether high cholesterol regulates Aß transport through low-density Lipoprotein Receptor-Related Protein 1 (LRP1) and Receptor for Advanced Glycation End products (RAGE) in the risk development of AD. METHODS: We established high cholesterol AD mice model. The learning and memory functions were evaluated by Morris Water Maze (MWM). Cerebral microvascular endothelial cells were isolated, cultured, and observed. The expression levels of LRP1 and RAGE of endothelial cells and their effect on Aß transport in vivo were observed. The expression level of LRP1 and RAGE was detected in cultured microvessels after using Wnt inhibitor DKK-1 and ß-catenin inhibitor XAV-939. RESULTS: Hypercholesterolemia exacerbated spatial learning and memory impairment. Hypercholesterolemia increased serum Aß40 level, while serum Aß42 level did not change significantly. Hypercholesterolemia decreased LRP1 expression and increased RAGE expression in cerebral microvascular endothelial cells. Hypercholesterolemia increased brain apoptosis in AD mice. In in vitro experiment, high cholesterol decreased LRP1 expression and increased RAGE expression, increased Aß40 expression in cerebral microvascular endothelial cells. High cholesterol regulated the expressions of LRP1 and RAGE and transcriptional activity of LRP1 and RAGE promoters by the Wnt/ß-catenin signaling pathway. CONCLUSION: High cholesterol decreased LRP1 expression and increased RAGE expression in cerebral microvascular endothelial cells, which led to Aß transport disorder in the blood-brain barrier. Increased Aß deposition in the brain aggravated apoptosis in the brain, resulting to cognitive impairment of AD mice.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Barrera Hematoencefálica/metabolismo , Colesterol , Modelos Animales de Enfermedad , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Encéfalo/metabolismo , Colesterol/farmacología , Células Endoteliales/metabolismo , Humanos , Hipercolesterolemia , Ratones , Fragmentos de Péptidos
10.
Neurobiol Aging ; 96: 267-276, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33130544

RESUMEN

This study investigated the impact of white matter hyperintensities (WMHs) on the progression from mild parkinsonian signs (MPS) to parkinsonism and Parkinson's disease (PD). Participants with MPS completed 5 years of follow-up. WMHs were divided into periventricular WMHs and deep WMHs according to magnetic resonance imaging scans. The diagnosis of MPS, parkinsonism, and PD was based on the motor portion of the Unified Parkinson's Disease Rating Scale. Cox proportional hazard models were used to identify the association between WMHs and MPS progression. Of the 636 participants, 166 (26.1%) with MPS developed parkinsonism and PD after follow-up. After adjusting for potential factors, severe WMHs were associated with an increased risk of MPS progression, moderate and severe periventricular WMHs and severe deep WMHs were associated with the risk of MPS progression, and severe WMHs were associated with the progression of gait/balance impairment, bradykinesia, and rigidity. Additionally, participants treated for vascular risk factors such as hypertension, diabetes mellitus, and hypercholesterolemia had a lower risk of MPS progression.


Asunto(s)
Imagen por Resonancia Magnética , Enfermedad de Parkinson/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Anciano , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Marcha , Humanos , Hipocinesia , Masculino , Persona de Mediana Edad , Rigidez Muscular , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/fisiopatología , Equilibrio Postural , Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Sustancia Blanca/patología
11.
Int J Neurosci ; 130(11): 1136-1141, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32053409

RESUMEN

Purpose: Depression, which affects about 52% of Alzheimer's disease (AD) patients, can worsen cognitive impairment and increase mortality and suicide rates. We hope to provide clinical evidence for the prevention and treatment of depression in AD patients by investigating related risk factors of depression in AD patients.Methods: 158 AD inpatients of the Department of Neurology, Daping Hospital from September 2017 to March 2019 were enrolled. General information, laboratory tests, cognitive and emotional function assessments of the inpatients were collected. Logistic regression was used to analyze the risk factors of depression in AD patients, and the relationship between 17 Hamilton depression scale scores and HbA1c levels in AD patients was further analyzed.Results: The prevalence of age, gender, hypertension, hyperlipidemia, Type 2 diabetes mellitus (T2DM), and white matter lesions (WML) in the AD with depression group was significantly different from without depression group. Hypertension, T2DM, and WML are independent risk factors for depression in AD patients. The depression scores of AD patients with HbA1c>6.5% were significantly higher than AD patients with HbA1c ≤ 6.5%, and there were significant difference in depression scale scores between using anti-diabetes drugs group and not using anti-diabetes drugs group whose HbA1c level is >6.5%, while no difference in depression scores between using anti-diabetes drugs group and not using anti-diabetes drugs group whose HbA1c level is ≤6.5%.Conclusion: T2DM is an independent risk factor for AD patients with depression. Increased HbA1c levels aggravate depression in AD patients, and controlling HbA1c levels and anti-diabetes drugs can reduce the severity of depression in AD patients.


Asunto(s)
Enfermedad de Alzheimer/epidemiología , Trastorno Depresivo/epidemiología , Trastorno Depresivo/etiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/sangre , China/epidemiología , Comorbilidad , Trastorno Depresivo/sangre , Trastorno Depresivo/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Hemoglobina Glucada , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la Enfermedad
12.
Eur Neurol ; 82(4-6): 99-105, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31865320

RESUMEN

OBJECTIVE: To explore the relationship between metabolic syndrome (MetS) and cognitive impairment in elderly patients with white matter lesions (WML). METHODS: From -January 2016 to June 2017, a cross-sectional study was conducted on the clinical data of 358 WML patients over 65 years old in the Department of Neurology of the Daping Hospital. Mini-mental state examination scales were used to evaluate the cognitive function of the patients, and the cognitive impairment was diagnosed and grouped according to the scoring and diagnostic criteria. All WML patients were divided into the cognitive impairment group and normal cognition group. Clinical data of age, sex, education level, body mass index, abdominal circumference, smoking and alcohol consumption, blood pressure, fasting blood glucose, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) were collected. Multivariate logistic regression analyses were performed to examine the relationship between MetS and cognitive impairment in WML patients. RESULTS: Compared with the normal cognition group, the proportion of MetS in the cognitive impairment group was significantly higher (χ2 = 11.211, p < 0.01), the proportion of MetS components such as elevated blood pressure, elevated blood glucose, elevated TG, decreased HDL-C and abdominal obesity in the cognitive impairment group was also higher (p < 0.01 or p < 0.05). After adjustment for age, sex, low education level, current smoking, daily drinking, severity of WML, MetS, and its components, multivariate logistic regression analysis showed that MetS was an independent risk factor for cognitive impairment in WML patients (OR 3.32, 95% CI 1.31-5.19). In addition, The greater the number of MetS components, the higher the risk of cognitive impairment in WML patients (ptrend < 0.01). CONCLUSION: MetS is an independent risk factor for cognitive impairment in patients with WML.


Asunto(s)
Disfunción Cognitiva/etiología , Leucoaraiosis/complicaciones , Síndrome Metabólico/complicaciones , Sustancia Blanca/patología , Anciano , Disfunción Cognitiva/patología , Estudios Transversales , Femenino , Humanos , Leucoaraiosis/patología , Masculino , Factores de Riesgo
13.
PeerJ ; 7: e8077, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31772839

RESUMEN

BACKGROUND: To investigate the molecular mechanisms determining the coat color of native breed sheep in Xinjiang. METHODS: Bashibai sheep, Yemule white sheep and Tulufan black sheep were selected. Illumina HiSeq X Ten sequencing technology was used to detect the genes responsible for the white, light brown, black and cyan gray coat colors in sheep. Sequence analysis and functional gene annotation analysis were performed to analyze the results. The signal pathways and differentially expressed genes related to sheep hair color production regulation were screened and finally verified by real-time polymerase chain reaction. RESULTS: Functional annotation by Kyoto Encyclopedia of Genes and Genomes analysis revealed significant differences in enrichment of immunity-related pathways as well as melanogenesis synthetic and tyrosine metabolism pathways. Our results showed that the DCT, TYR, TYRP1, PMEL, SLC45A2 and MLANA six genes may be associated with the regulation of coat color development and provide a theoretical basis for selecting natural coat colors of sheep.

14.
Infant Behav Dev ; 46: 135-143, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28142061

RESUMEN

BACKGROUND: Although an increasing amount of evidence supports a "two-hit" hypothesis for the neurodevelopmental model of schizophrenia, there has been no development in animal models to test this hypothesis. METHODS: An animal model was established by chronic administration of 0.1, 0.3, and 0.5mg/kg MK-801 in P7-P21 rats followed by four weeks of social isolation in childhood and then five days of social housing. Animal behaviors were measured by the open field (OF) test, the novel object recognition (NOR) test, the prepulse inhibition (PPI) test, and the elevated plus maze (EPM) test. RESULTS: We found a significant decrease in the NOR index in adolescent rats compared to saline control rats when administering 0.5mg/kg of MK-801 (P=0.02). We found that social isolation had no significant effect on NOR index, though social isolation significantly increased the total distance traveled and significantly decreased the resting time in adolescent rats in the OF test (P<0.001 and P=0.003, respectively). In contrast, we observed that MK-801 administration showed no significant effects on either total distance traveled or resting time. Both MK-801 administration and social isolation had no significant effect on the percent of PPI and startle amplitudes in adolescent rats. Social isolation significantly reduced the open arm entries in adolescent rats in the EPM test (P=0.023), but it did not reduce the ratio to enter the open arms and the stay time in open arm. Administration of MK-801 showed no significant effect on the indexes of entering the open arms in the EPM test on adolescent rats. CONCLUSION: MK-801 intervention in infancy is associated with the damage of long-term visual memory, whereas social isolation in childhood is associated with the increased spontaneous activity and anxiety levels. Administration of MK-801 in infancy and social isolation in childhood are two independent factors on the neurodevelopmental defects.


Asunto(s)
Modelos Animales de Enfermedad , Maleato de Dizocilpina/administración & dosificación , Esquizofrenia/inducido químicamente , Psicología del Esquizofrénico , Aislamiento Social/psicología , Factores de Edad , Animales , Animales Recién Nacidos , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Maleato de Dizocilpina/toxicidad , Relación Dosis-Respuesta a Droga , Antagonistas de Aminoácidos Excitadores/administración & dosificación , Antagonistas de Aminoácidos Excitadores/toxicidad , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Inhibición Prepulso/efectos de los fármacos , Inhibición Prepulso/fisiología , Ratas , Ratas Sprague-Dawley , Esquizofrenia/fisiopatología , Método Simple Ciego
15.
Behav Brain Res ; 320: 517-525, 2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-27725171

RESUMEN

Although N-methyl-d-aspartate receptor antagonists-induced hypoglutamate rodent models are the most well-established models for preclinical studies of schizophrenia-related deficits, they also evoke a wide spectrum of psychotomimetic side effects. It is significant to increase the specificity of hypoglutamate rodent models. In this study, the recognition memory was evaluated in rats by object recognition test (ORT), sensorimotor gating was evaluated by prepulse inhibition of the startle reflex (PPI), and locomotor activity was measured using open field test. High-performance liquid chromatography was used to measure neurotransmitters content in the medial prefrontal cortex (mPFC) and thalamus (THA). Total Akt and phospho-Akt protein was measured by Western blots. Results showed that 0.3mg/kg of MK-801 was most effective in inducing locomotion. 0.3mg/kg of MK-801 was most effective in decreasing PPI. 0.03mg/kg of MK-801 was most effective in decreasing object memory while not affecting exploration manners in the training session. 0.03mg/kg of MK-801 significantly increased HVA and Glu content in the mPFC. 0.1mg/kg of MK-801 significantly decreased GABA content in the THA. 0.03mg/kg of MK-801 significantly decreased Akt phosphorylation in the mPFC, which was related to the ORT index. In conclusion, a dose of 0.03mg/kg MK-801 can establish a "pure" memory impairment model without contaminations of sensorimotor gating and locomotor activity. MK-801-induced cognitive deficits is associated with increased DA metabolites and glutamate content in the mPFC and decreased GABA content in the THA as well as decrease in Akt phosphorylation in the mPFC.


Asunto(s)
Modelos Animales de Enfermedad , Maleato de Dizocilpina/toxicidad , Antagonistas de Aminoácidos Excitadores/toxicidad , Trastornos de la Memoria/inducido químicamente , Aminoácidos/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Locomoción/efectos de los fármacos , Masculino , Neurotransmisores/metabolismo , Proteína Oncogénica v-akt/metabolismo , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Inhibición Prepulso/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Reconocimiento en Psicología/efectos de los fármacos , Reflejo de Sobresalto/efectos de los fármacos , Filtrado Sensorial/efectos de los fármacos , Tálamo/efectos de los fármacos , Tálamo/metabolismo
16.
Artículo en Chino | MEDLINE | ID: mdl-24330873

RESUMEN

OBJECTIVE: To research the role of lymph tracers to protect parathyroid in surgery for papillary thyroid carcinoma. METHODS: Patients with papillary thyroid carcinoma who met selected criteria were enrolled in this study. Patients were divided into carbon nanoparticle group, methylene blue group, and conventional surgery group. RESULTS: No significant complication occurred in the patients of carbon nanoparticle and methylene blue groups. In carbon nanoparticle group, methylene blue group and conventional surgery group, the mean numbers of parathyroid glands detected during surgery were 3.1 ± 0.3, 2.9 ± 0.4 and 2.3 ± 0.3 (F = 3.78, P < 0.01) , the rates that parathyroid was cut mistakenly were 1.37% (2/146) , 2.62% (2/97) and 7.14% (6/84) respectively (χ(2) = 17.372, P < 0.05) ; and the incidence of postoperative hypocalcemia were 10.4% (5/48) , 9.1% (3/33) and 17.5% (7/40,χ(2) = 0.671, P = 0.037) . CONCLUSION: Thyroid lymphography technique is helpful to protect from the injury to the parathyroid glands in surgery.


Asunto(s)
Linfografía , Tiroidectomía , Humanos , Hipocalcemia , Glándulas Paratiroides
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