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1.
BMC Psychiatry ; 24(1): 178, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38439042

RESUMEN

BACKGROUND: Observational studies have suggested a link between panic disorder (PD) and Alzheimer disease (AD). This study aimed to identify the underlying association of PD with the risk of AD using Mendelian randomization. METHODS: Genetic instrumental variables (IVs) were retrieved in the genome-wide association study between PD and AD. Then, five different models, namely inverse variance weighting (IVW), weighted median, weighted mode, MR-Egger and MR-robust adjusted profile scores (MR-RAPS), were used for MR Analysis. Finally, the heterogeneity and pleiotropy of identified IVs were verified by multiple sensitivity tests. RESULTS: The Cochran's Q test based on MR Egger and IVW showed that no evidence of heterogeneity was found in the effects of instrumental variables, so a fixed-effect model was used. IVW analysis (OR 1.000479, 95% CI [1.000147056, 1.000811539], p = 0.005) indicated that PD was associated with an increased risk of AD, and a causal association existed between them. Meanwhile, weighted median (OR 1.000513373, 95% CI [1.000052145, 1.000974814], p = 0.029) and MR-RAPS (OR 1.000510118, 95% CI [1.000148046, 1.00087232], p = 0.006) also showed the similar findings. In addition, extensive sensitivity analyses confirmed the robustness and accuracy of these results. CONCLUSION: This investigation provides evidence of a potential causal relationship between PD and the increased risk of AD. Based on our MR results, when diagnosing and treating patients with PD, clinicians should pay more attention to their AD-related symptoms to choose therapeutic measures or minimize comorbidities. Furthermore, the development of drugs that improve both PD and AD may better treat patients with these comorbidities.


Asunto(s)
Enfermedad de Alzheimer , Trastorno de Pánico , Humanos , Análisis de la Aleatorización Mendeliana , Trastorno de Pánico/genética , Enfermedad de Alzheimer/genética , Estudio de Asociación del Genoma Completo , Análisis de Varianza
2.
Cell Mol Biol (Noisy-le-grand) ; 69(4): 141-146, 2023 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-37329535

RESUMEN

The Parkinson's disease is the second most common neurodegenerative disease with different pathological mechanisms at each stage. To investigate Parkinson's disease further, this study was proposed to develop a continuous staging mouse model of Parkinson's disease to reproduce the pathological features of different stages of Parkinson's disease. We successively treated the mice with MPTP, and assessed the behavioral performance of the mice with the open field test and the rotarod test, and detected the aggregation of α-syn and the expression of TH protein in the substantia nigra of the mice with western blot test and immunofluorescence test. The results showed that the mice injected with MPTP for 3 days had no significant behavioral changes, no significant α-syn aggregation, but reduced TH protein expression and 39.5% loss of dopaminergic neurons in the substantia nigra, similar to the performance in the prodromal phase of Parkinson's disease. However, the behavior of the mice continuously treated with MPTP for 14 days was significantly altered, with significant α-syn aggregation, significant reduction in TH protein expression, and 58.1% loss of dopaminergic neurons in the substantia nigra, corresponding to the early clinical stage of Parkinson's disease. In the mice that were exposed to MPTP for 21 days, the motor impairment was more obvious, the α-syn aggregation was more significant, the reduction of TH protein expression was more evident, and the loss of dopaminergic neurons reached 80.5% in the substantia nigra, showing a clinical progression similar to that of Parkinson's disease. Consequently, this study found that continuous treatment of C57/BL6 mice with MPTP for 3, 14 and 21 days could construct mouse models of prodromal, early clinical and clinical progressive stages of Parkinson's disease, respectively, providing a promising experimental model foundation for the study of the different stages of Parkinson's disease.


Asunto(s)
Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Animales , Ratones , Enfermedad de Parkinson/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Sustancia Negra/metabolismo , Sustancia Negra/patología , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/patología , Ratones Endogámicos C57BL
3.
J Nucl Cardiol ; 28(6): 2812-2822, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-32383080

RESUMEN

OBJECTIVE: To assess the benefits of coronary collateral circulation on myocardial perfusion, viability and function in patients with total occlusion of a single coronary artery using the 99mTc-sestamibi SPECT and 18F-fluorodeoxyglucose PET. METHODS: 164 Consecutive patients were included who underwent coronary angiography results exhibited total occlusion of a single coronary artery and received 99mTc-MIBI SPECT and 18F-FDG PET within 90 days of angiography. Myocardial perfusion and viability in patients with collateral circulation and those without it were compared. Long-term follow-up was performed through a review of patient clinical records. RESULTS: Collateral circulation was present in 56 patients (34%) and absent in 108 patients (66%). The total perfusion defect size in patients with collateral circulation decreased when compared to those without (30% ± 13% to 35% ± 14%, P < .05). The myocardial viability was 22% ± 12% in patients with collateral circulation, and 12% ± 9% in those without (P < .001). The left ventricular ejection fraction was higher, and the end-diastolic and end-systolic left ventricular volumes were lower in patients with collateral circulation (39% ± 11%, 138 ± 66, 89 ± 57) compared to patients without collateral circulation (31% ± 9%, 177 ± 55, 125 ± 48, all P < .001, respectively). Multi-factor logistic regression identified that concerning the variables of sex, age, viable myocardium, collateral circulation, treatment type and others, only treatment type was significantly associated with therapeutic effects (OR 3.872, 95% CI 1.915-7.830, P < .001). CONCLUSION: Collateral circulation can preserve resting myocardial blood perfusion and myocardial viability, and help maintain the function of the left ventricular myocardium. The appropriate treatment strategy will have a substantial impact on the therapeutic outcome.


Asunto(s)
Circulación Colateral , Circulación Coronaria , Oclusión Coronaria/fisiopatología , Fluorodesoxiglucosa F18 , Radiofármacos , Tecnecio Tc 99m Sestamibi , Tomografía Computarizada de Emisión de Fotón Único/métodos , Anciano , Femenino , Corazón/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Supervivencia Tisular
4.
J Nucl Cardiol ; 28(2): 560-574, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-30993654

RESUMEN

BACKGROUND: This study aimed to compare the accuracy of gated-SPECT (GSPECT) and gated-PET (GPET) in the assessment of left ventricular (LV) end-diastolic volumes (EDVs), end-systolic volumes (ESVs) and LV ejection fractions (LVEFs) among patients with prior myocardial infarction (MI). METHODS: One hundred and sixty-eight consecutive patients with MI who underwent GSPECT and GPET were included. Of them, 76 patients underwent CMR in addition to the two imaging modalities. The measurements of LV volumes and LVEF were performed using Quantitative Gated SPECT (QGS), Emory Cardiac Toolbox (ECTB), and 4D-MSPECT (4DM). RESULTS: The correlation between GPET, GSPECT, and CMR were excellent for LV EDV (r = 0.855 to 0.914), ESV (r = 0.852 to 0.949), and LVEF (r = 0.618 to 0.820), as calculated from QGS, ECTB, and 4DM. In addition, subgroup analysis revealed that EDV, ESV, and LVEF measured by GPET were accurate in patients with different extents of total perfusion defect (TPD), viable myocardium, and perfusion/metabolic mismatch. Furthermore, multivariate regression analysis identified that mismatch score was associated with the difference in EDV (P < 0.05) measurements between GPET and CMR. CONCLUSIONS: In patients with MI, LV volumes and LVEF scores measured by both GSPECT and GPET imaging were comparable to those determined by CMR, but should not be interchangeable in individual patients.


Asunto(s)
Fluorodesoxiglucosa F18 , Imagen de Acumulación Sanguínea de Compuerta/métodos , Infarto del Miocardio/fisiopatología , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Tecnecio Tc 99m Sestamibi , Tomografía Computarizada de Emisión de Fotón Único/métodos , Función Ventricular Izquierda , Anciano , Volumen Cardíaco/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Volumen Sistólico/fisiología
5.
J Nucl Cardiol ; 26(3): 944-953, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-29214612

RESUMEN

OBJECTIVES: To compare the outcomes among patients treated by complete coronary revascularization (CCR) or incomplete coronary revascularization (ICR) and no coronary revascularization (NCR) by myocardial perfusion imaging (MPI), as well as to evaluate the impact of severity of ischemia on patients with coronary artery disease (CAD) by different therapy strategies. BACKGROUND: Using myocardial ischemia severity determined by MPI guiding treatment strategies for CAD patients still lacks strong clinical evidences. METHODS: Consecutive patients (N = 286) underwent clinical stress-rest SPECT MPI and were retrospectively followed-up. For assessment of outcome of treatment, all patients were classified into three groups (CCR, ICR, and NCR), and further divided into two subgroups as mild ischemia (< 10% ischemic myocardium) and moderate-severe ischemia (≥ 10% ischemic myocardium). All-cause death was defined as the primary endpoint, and the composite of deaths, nonfatal myocardial infarction, and repeat revascularization (MACE) as the secondary endpoint. RESULTS: Two-hundred eighty-six patients were followed-up for 46 ± 21 months. Thirty deaths and 65 MACEs were recorded. Patients treated by revascularization had significantly lower MACE (P < .001) but not mortality (P = .158) than patients treated by NCR. Outcomes of CCR related to mortality rate were greater than ICR and NCR (death: P = .019, MACE: P < .001). In patients with moderate-severe ischemia, CCR showed improved outcomes than ICR and NCR (death: P = .034; and MACE: P < .001). In patients with mild ischemia, the outcomes of CCR, ICR, and NCR had no significant difference (P > .05). Multivariate regression Cox analysis revealed that summed difference score [death: HR 1.09 (1.03, 1.15), P = .004] was an independent risk factor and CCR was an independent negative predictor [death: HR 0.31 (0.12, 0.81), P = .017; MACE: HR 0.30 (0.16, 0.57), P < .001]. CONCLUSIONS: Outcomes of patients treated by CCR were most likely more promising in comparison with treatment of ICR and NCR, especially when patients had over 10% ischemic myocardium.


Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Infarto del Miocardio/epidemiología , Imagen de Perfusión Miocárdica , Revascularización Miocárdica , Tomografía Computarizada de Emisión de Fotón Único , Anciano , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
6.
J Nucl Cardiol ; 23(3): 546-55, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26037599

RESUMEN

BACKGROUND: Coronary revascularization in patients with coronary artery disease may be guided by coronary angiography (CA) or alternatively by ischemia on stress myocardial perfusion imaging (MPI). Which strategy leads to optimal cardiac outcomes is uncertain. METHODS: We performed a retrospective analysis of 170 patients with MPI ischemia and percutaneous coronary intervention. The primary endpoint was all-cause mortality at a mean follow-up of 47 ± 21 months; the secondary end point was the composite of deaths, nonfatal myocardial infarction, and repeat coronary revascularization (MACE). The coronary revascularization was defined as complete (CCR) or incomplete (ICR) as judged by CA criteria and by MPI ischemia matched with CA criteria. RESULTS: Nighty-two patients (54%) had ICR by CA criteria (ICR-CA) and 84 (49%) had ICR by MPI criteria (ICR-MPI). Mortality and MACE were lower in patients with CCR-MPI than with ICR-MPI (P = .048, and P = .025). Survival of patients with CCR-CA and ICR-CA was not different (P = .081). Patients with both ICR-MPI and ICR-CA had the worst survival, whereas patients with CCR-MPI and CCR-CA had the best survival (P = .047). By multivariate analysis, ICR-MPI + ICR-CA was an independent predictor of death (P = .025). CONCLUSION: Patients with ICR by MPI were at higher risk than those with CCR. Patients with both ICR by MPI and CA were at the highest risk, while patients with CCR by both MPI and CA had the best long-term event-free survival.


Asunto(s)
Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/cirugía , Imagen de Perfusión Miocárdica/métodos , Revascularización Miocárdica/mortalidad , Revascularización Miocárdica/estadística & datos numéricos , China/epidemiología , Angiografía Coronaria/estadística & datos numéricos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Imagen de Perfusión Miocárdica/estadística & datos numéricos , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Insuficiencia del Tratamiento
7.
J Nucl Cardiol ; 21(6): 1230-44, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25189143

RESUMEN

BACKGROUND: To compare the accuracy of end-diastolic and end-systolic volumes (EDV, ESV) and LV ejection fraction (LVEF) measured by both GSPECT and GPET, using cardiac magnetic resonance imaging (CMR) as a reference. Furthermore, the impacts of severe perfusion defects, akinetic/dyskinetic segments, and residual viable myocardium on the accuracy of LV functional parameters were investigated. METHODS: Ninety-six consecutive patients with LV aneurysm and LV dysfunction (LVEF 32 ± 9%) diagnosed by CMR were studied with GSPECT and GPET. EDV, ESV, and LVEF were calculated using QGS software. RESULTS: Correlations of volumes were excellent (r 0.81-0.86) and correlation of LVEF was moderate (r 0.65-0.76) between GSPECT vs CMR and between GPET vs CMR. Compared with CMR, ESV was overestimated by GSPECT (P < .01) and underestimated by GPET (P < .0001); EDV was underestimated by GPET (P < .001); LVEF was underestimated by GSPECT but overestimated by GPET (both P < .001). Multivariate regression analysis revealed that the number of segments with severe perfusion defects (P < .001) was the only independent factor which was correlated to the EDV difference between GSPECT and CMR, the number of akinetic/dyskinetic segments with absent wall thickening (WT) was the only independent factor which was significantly correlated to the differences of ESV and LVEF measurements between GSPECT vs CMR and between GPET vs CMR (P < .0001), respectively. Neither the mismatch score nor the segments with viable myocardium were correlated to the differences of LV volumes and LVEF measurements between different imaging modalities. CONCLUSIONS: In LV aneurysm patients, LV volumes and LVEF measured by both GSPECT and GPET imaging correlated well with those determined by CMR, but should not be interchangeable in individual patients. The accuracy of LVEF measured by GSPECT and GPET was affected by the akinetic/dyskinetic segments with absent WT.


Asunto(s)
Tomografía Computarizada por Emisión de Fotón Único Sincronizada Cardíaca/métodos , Fluorodesoxiglucosa F18 , Aneurisma Cardíaco/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Volumen Sistólico , Tecnecio Tc 99m Sestamibi , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Aneurisma Cardíaco/etiología , Humanos , Imagen por Resonancia Cinemagnética/métodos , Imagen por Resonancia Cinemagnética/normas , Masculino , Persona de Mediana Edad , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología
8.
Front Psychol ; 15: 1305570, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756498

RESUMEN

Background: With increased life expectancy, cognitive decline has emerged as a prevalent neurodegenerative disorder. Objective: This study aimed to examine the correlation between concentrations of Plasma long-chain n-3 polyunsaturated fatty acids (LCPUFAs) and cognitive performance in elderly Americans. Methods: Data were analyzed from older adults enrolled in two NHANES cycles. Participants completed four cognitive assessments, including the Immediate Recall Test (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Linear regression and restricted cubic spline modeling examined associations between plasma LCPUFAs levels and cognitive test outcomes. Results: The cohort included 610 adults aged 69 years on average, 300 (49.2%) males and 310 (50.8%) females. The median LCPUFAs concentration was 309.4 µmol/L, with an interquartile range of 244.7-418.9 µmol/L. In unadjusted and adjusted generalized linear regression model analyses, circulating LCPUFAs exhibited significant positive correlations with DRT performance. No relationships were detected among those with chronic conditions (chronic heart failure, stroke, diabetes). A significant association between LCPUFAs levels and DRT scores was evident in males but not females. Conclusion: Plasma LCPUFAs concentrations were significantly associated with DRT performance in males free of chronic illnesses, including heart failure, stroke, and diabetes.

9.
Exp Neurol ; 379: 114878, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38944330

RESUMEN

Pharyngeal electrical stimulation (PES), a novel noninvasive peripheral nerve stimulation technique, can effectively improve neurogenic dysphagia and increase the safety and effectiveness of swallowing in the clinic. However, the lack of animal models for dysphagia has limited the mechanistic research on PES, which affects its wide application. Therefore, determining optimal parameters for PES in rats is needed to enable mechanistic studies. Modified PES (mPES), which has different waves and pulse widths from PES, was used; in previous studies mPES was found to have a neurological mechanism like that of PES. A poststroke dysphagia (PSD) model was established, and rats with dysphagia were grouped into three different intensities (0.1 mA, 0.5 mA, and 1 mA) for the selection of optimal intensity and three different frequencies (1 Hz, 2 Hz, and 5 Hz) for the selection of optimal frequency based on a stimulation duration of 10 min in the clinic. A Videofluroscopic Swallow Screen (VFSS) was used to assess swallowing function in rats before and after mPES treatment. The results showed that the 1 mA group had better swallowing function (p < 0.05) than the model group. Compared with the model group, the 1 Hz and 5 Hz groups had the same improvement in swallowing function (p < 0.05). However, the increase in excitatory signals in the sensorimotor cortex was more pronounced in the 5 Hz group than in the other frequency stimulation groups (p < 0.05). Combining the clinical findings with the above results, we concluded that the optimal stimulation parameter for mPES in rats is "frequency: 5 Hz, current intensity: 1 mA for 10 min/day", which provides a basis for future basic experimental studies of mPES in animals.

10.
Mol Neurobiol ; 61(3): 1833-1844, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37787950

RESUMEN

Norepinephrine (NE) is involved in auditory fear conditioning (AFC) in posttraumatic stress disorder (PTSD). However, it is still unclear how it acts on neurons. We aimed to investigate whether the activation of the ß-adrenergic receptor (ß-AR) improves AFC by sensitization of the prelimbic (PL) cortex at the animal, cellular, and molecular levels. In vivo single-cell electrophysiological recording was used to characterize the changes in neurons in the PL cortex after AFC. Then, PL neurons were locally administrated by the ß-AR agonist isoproterenol (ISO), the GABAaR agonist muscimol, or intervened by optogenetic method, respectively. Western blotting and immunohistochemistry were finally used to assess molecular changes. Noise and low-frequency tones induced similar AFC. The expression of ß-ARs in PL cortex neurons was upregulated after fear conditioning. Microinjection of muscimol into the PL cortex blocked the conformation of AFC, whereas ISO injection facilitated AFC. Moreover, PL neurons can be distinguished into two types, with type I but not type II neurons responding to conditioned sound and being regulated by ß-ARs. Our results showed that ß-ARs in the PL cortex regulate conditional fear learning by activating type I PL neurons.


Asunto(s)
Corteza Prefrontal , Receptores Adrenérgicos beta , Animales , Corteza Prefrontal/fisiología , Muscimol , Relación Señal-Ruido , Isoproterenol/farmacología , Miedo/fisiología
11.
Cardiology ; 125(2): 104-9, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23711817

RESUMEN

OBJECTIVES: Gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging is useful in assessing left ventricular (LV) myocardial perfusion and function. This study evaluated the LV functional changes after adenosine vasodilator stress, using gated SPECT. METHODS: The study population consisted of 70 patients who underwent adenosine-mediated stress and rest SPECT. All patients underwent coronary angiography. Semi-quantitative assessment of perfusion was analyzed and produced the summed rest score (SRS), the summed stress score (SSS) and the summed difference score (SDS). The global LV function parameters [ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV)] and regional LV function [the summed motion score (SMS) and the summed thickening score (STS)] were quantified by gated SPECT. RESULTS: Patients were divided into 2 groups: group 1 comprised 16 patients with worsening of LVEF (LVEFrest-LVEFado ≥5%), and group 2 comprised the other 54 patients. Compared with group 2, patients in group 1 had a significantly higher SSS and SDS (9.1 ± 6.8 vs. 5.6 ± 4.5 and 6.6 ± 3.8 vs. 3.6 ± 4.0, respectively; p < 0.05) and the severity of coronary artery stenosis was more serious (p < 0.05). CONCLUSION: Worsening of LVEF after adenosine-induced vasodilator stress, as shown by (99m)Tc-MIBI gated SPECT, is a valuable nonperfusion marker of significant CAD.


Asunto(s)
Adenosina , Tomografía Computarizada por Emisión de Fotón Único Sincronizada Cardíaca , Enfermedad de la Arteria Coronaria/fisiopatología , Vasodilatadores , Función Ventricular Izquierda , Adenosina/farmacología , Anciano , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/etiología , Volumen Sistólico , Vasodilatadores/farmacología
12.
Curr Pharm Des ; 29(19): 1535-1545, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37345246

RESUMEN

BACKGROUND: Shudihuang has been clinically proven to be an effective Chinese medicine compatible with the treatment of amyotrophic lateral sclerosis. However, the underlying mechanism of Shudihuang against amyotrophic lateral sclerosis remains unclear. OBJECTIVES: The present study aims to elucidate the possible mechanism of Shudihuang in treating ALS using network pharmacology and molecular docking. METHODS: The primary active components of Shudihuang and their relevant targets were identified by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Swiss Target Prediction database, respectively. The ALS-related targets were obtained from the Disgenet and OMIM databases. The shared targets were derived by the intersection of disease-associated and component-associated targets and then introduced into the Cytoscape software to construct a network of drug-component-target. In addition, protein interaction relationships among the shared targets were analyzed by the STRING and Cytoscape software. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) functional enrichment analysis were conducted by the Metascape platform. The binding activities between the hub targets and the active components were assessed with molecular docking. RESULTS: Stigmasterol and sitosterol were identified as the core components of Shudihuang, and the hub targets of ALS are PTGS2, PPARG, ESR1, IGF-1R, and MAPK3, with the highest degrees in the PPI network. The finding that stigmasterol and sitosterol had a good affinity with PTGS2, PPARG, ESR1, IGF-1R, and MAPK3 also supported this. Finally, it was revealed that Shudihuang treatment of ALS predominantly involves estrogen- related pathways such as nuclear receptor activity and steroid binding. CONCLUSION: In summary, this study suggested that the main active components of Shudihuang (stigmasterol and sitosterol) may exert a critical effect in ALS treatment by binding to hub targets (PTGS2, PPARG, ESR1, IGF-1R, and MAPK3) and then modulating estrogen receptor-related pathways to attenuate glutamate excitotoxicity, inhibit oxidative stress and antagonize inflammation.


Asunto(s)
Esclerosis Amiotrófica Lateral , Medicamentos Herbarios Chinos , Humanos , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Farmacología en Red , Sitoesteroles , Ciclooxigenasa 2 , PPAR gamma , Estigmasterol , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China
13.
Behav Brain Res ; 452: 114569, 2023 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-37419331

RESUMEN

This study aimed to explore the role of SYNJ1 in Parkinson's disease (PD) and its potential as a neuroprotective factor. We found that SYNJ1 was decreased in the SN and striatum of hSNCA*A53T-Tg and MPTP-induced mice compared to normal mice, associated with motor dysfunction, increased α-synuclein and decreased tyrosine hydroxylase. To investigate its neuroprotective effects, SYNJ1 expression was upregulated in the striatum of mice through injection of the rAdV-Synj1 virus into the striatum, which resulted in the rescue of behavioral deficiencies and amelioration of pathological changes. Subsequently, transcriptomic sequencing, bioinformatics analysis and qPCR were conducted in SH-SY5Y cells following SYNJ1 gene knockdown to identify its downstream pathways, which revealed decreased expression of TSP-1 involving extracellular matrix pathways. The virtual protein-protein docking further suggested a potential interaction between the SYNJ1 and TSP-1 proteins. This was followed by the identification of a SYNJ1-dependent TSP-1 expression model in two PD models. The coimmunoprecipitation experiment verified that the interaction between SYNJ1 and TSP-1 was attenuated in 11-month-old hSNCA*A53T-Tg mice compared to normal controls. Our findings suggest that overexpression of SYNJ1 may protect hSNCA*A53T-Tg and MPTP-induced mice by upregulating TSP-1 expression, which is involved in the extracellular matrix pathways. This suggests that SYNJ1 could be a potential therapeutic target for PD, though more research is needed to understand its mechanism.


Asunto(s)
Neuroblastoma , Fármacos Neuroprotectores , Enfermedad de Parkinson , Ratones , Humanos , Animales , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/tratamiento farmacológico , Trombospondina 1 , Neuroblastoma/tratamiento farmacológico , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Fármacos Neuroprotectores/farmacología , Neuroprotección , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
14.
Zhonghua Xin Xue Guan Bing Za Zhi ; 39(6): 497-502, 2011 Jun.
Artículo en Zh | MEDLINE | ID: mdl-21924073

RESUMEN

OBJECTIVE: To evaluate the myocardial perfusion and function in patients with hypertrophic obstructive cardiomyopathy (HOCM) before and after percutaneous transluminal septal myocardial ablation (PTSMA). METHODS: Sixty-eight patients with hypertrophic obstructive cardiomyopathy were included and (99)Tc(m)-MIBI SPECT MPI was applied before and at 1 week after PTSMA, six-month follow-up was finished in 11 patients. Semi quantity and QGS quantity perfusion and function assessment was performed in 17 LV segments. RESULTS: Myocardial perfusion post-PTSMA was significantly reduced in 98% patients, especially in basal anterosepta, basal interseptal, mid-anteroseptal, mid-interseptal and apical septal segments compared with pre-PTSMA (all P < 0.05). Perfusion was significantly increased at 6 months follow-up than at 1 week post-PTSMA but still lower than pre-PTSMA (all P < 0.05). LVEF (evaluated by gated SPECT) was similar before and after the procedure (P > 0.05). Regional wall motion after PTSMA was lower than pre-PTSMA in basal anterior, basal anteroseptal, basal interseptal and basal inferior (P < 0.05). Regional wall thinkening was lower than pre-PTSMA in basal interseptal, mid-anteroseptal, mid-interseptal (P < 0.05). CONCLUSIONS: (99)Tc(m) MIBI SPECT can be used to monitor myocardial perfusion post PTSMA in patients with HOCM.


Asunto(s)
Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/cirugía , Ablación por Catéter/métodos , Adolescente , Adulto , Anciano , Angioplastia de Balón , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada de Emisión de Fotón Único , Adulto Joven
16.
Zhonghua Xin Xue Guan Bing Za Zhi ; 36(11): 999-1003, 2008 Nov.
Artículo en Zh | MEDLINE | ID: mdl-19102913

RESUMEN

OBJECTIVE: To evaluate the impact of viable myocardium assessed by (99)Tc()m-MIBI SPECT and (18)F-fluorodeoxyglucose (FDG) PET imaging in patients with left ventricular aneurysm (LVA) underwent revascularization (RVS). METHODS: Forty-six consecutive patients with LVA (mean LVEF 36% +/- 7%), underwent (99)Tc(m)-sestamibi SPECT and (18)F-FDG PET examinations and received RVS therapy, were followed-up for a mean period of 80 +/- 27 months. Viable myocardium in aneurysm was defined as perfusion-metabolism mismatch score (MMS) >/= 2.0. Patients were divided into four groups by aneurysm viability and aneurysmectomy. Group A1 (n = 8): viability-; Group A2 (n = 15): viability-, aneurysmectomy; Group B1 (n = 10): viability +; and Group B2 (n = 13): viability +, aneurysmectomy. RESULTS: The cardiac event rates during follow up were similar among groups [A1 (25%, 2/8), B1 (40%, 6/15), A2 (20%, 2/10) and B2 (31%, 4/13; P > 0.05)]. After revascularization, LVEF was improved (> 10%) in groups A2, B1 and B2 (P < 0.05). Multivariate logistic regression analysis showed that LV-MMS (OR = 2.34, 95% CI 1.08 - 5.06, P < 0.05), distal vessel disease (OR = 0.008, 95% CI 0.001 - 0.560, P < 0.05) and nonaneurysm perfusion score (OR = 0.24, 95% CI 0.07 - 0.85, P < 0.05) were significantly associated with the improvement of LVEF after revascularization. CONCLUSIONS: Long term cardiac events rate post revascularization was not affected by viable myocardium or aneurysmectomy in LVA patients. Viable myocardium in LVA patients was associated with better LVEF improvement after revascularization.


Asunto(s)
Aneurisma Cardíaco/diagnóstico por imagen , Tomografía de Emisión de Positrones , Tomografía Computarizada de Emisión de Fotón Único , Anciano , Fluorodesoxiglucosa F18 , Aneurisma Cardíaco/metabolismo , Humanos , Persona de Mediana Edad , Miocardio/metabolismo , Tecnecio Tc 99m Sestamibi
17.
Chin Med Sci J ; 22(4): 228-31, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18246669

RESUMEN

OBJECTIVE: To explore the infarct sites in patients with inferior wall acute myocardial infarction (AMI) concomitant with ST segment elevation in leads V1-V3 and leads V3R-V5R. METHODS: Five patients diagnosed as inferior, right ventricular, and anteroseptal walls AMI at admission were enrolled. Electrocardiographic data and results of isotope 99mTc-methoxyisobutylisonitrile (MIBI) myocardial perfusion imaging and coronary angiography (CAG) were analyzed. RESULTS: Electrocardiogram showed that ST segment significantly elevated in standard leads II, III, aVF, and leads V1-V3, V3R-V5R in all five patients. The magnitude of ST segment elevation was maximal in lead V1 and decreased gradually from lead V1 to V3 and from lead V1 to V3R-V5R. There was isotope 99mTc-MIBI myocardial perfusion imaging defect in inferior and basal inferior-septal walls. CAG showed that right coronary artery was infarct-related artery. CONCLUSIONS: The diagnostic criteria for basal inferior-septal wall AMI can be formulated as follows: (1) ST segment elevates > or = 2 mm in lead V1 in the clinical setting of inferior wall AMI; (2) the magnitude of ST segment elevation is the tallest in lead V1 and decreases gradually from lead V1 to V3 and from lead V1 to V3R-V5R. With two conditions above, the basal inferior-septal wall AMI should be diagnosed.


Asunto(s)
Infarto del Miocardio/diagnóstico , Anciano , Angiografía Coronaria , Errores Diagnósticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Cintigrafía
18.
Zhonghua Yi Xue Za Zhi ; 87(37): 2623-6, 2007 Oct 09.
Artículo en Zh | MEDLINE | ID: mdl-18162150

RESUMEN

OBJECTIVE: To assess the diagnostic efficacy of stress myocardial perfusion imaging (MPI) in female coronary artery disease (CAD) patients. METHODS: Two hundred and fifty-nine consecutive female patients, aged 60 +/- 8, underwent stress myocardial perfusion single photon emission computed tomography (SPECT) imaging and coronary angiography with an interval of < 60 days. Among them, 227 patients underwent exercise MPI, injected intravenously with (99m)Tc-methoxyisobutyl isonitrile (MIBI) 740 - 925 MBq when the exercise end point was reached, and 32 patients underwent pharmacologic stress MPI, injected intravenously with persantine or adenosine and then (99m)Tc-MIBI. RESULTS: Among the 227 patients undergoing exercise MPI 79 had significant coronary artery stenosis with the overall sensitivity and specificity for detecting coronary artery disease of 63% and 97% respectively. According to the exercise heart rate, the 227 patients were divided into two groups: group 1 (n = 137) the patients of which achieved adequate exercise end points, and group 2 (n = 90) the patients of which only reached submaximal exercise. The sensitivity of exercise MPI for detecting CAD was 86% in the group 1 and 38% in the group 2. Among the 32 patients who underwent pharmacologic stress MPI 13 had significant CAD with the sensitivity and specificity of 85% and 84% respectively. CONCLUSION: Stress MPI is an efficient protocol for the detection of CAD in women, and pharmacologic stress MPI is more suitable for the women with decreased exercise capacity and advanced age.


Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adulto , Anciano , Anciano de 80 o más Años , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/fisiopatología , Prueba de Esfuerzo , Femenino , Humanos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad
19.
Zhonghua Xin Xue Guan Bing Za Zhi ; 35(3): 248-50, 2007 Mar.
Artículo en Zh | MEDLINE | ID: mdl-17582291

RESUMEN

OBJECTIVE: To assess the value of (99m)Tc-N-NOET ((99m)Tc-N-ethoxy-N-ethyl dithiocarbamato-nitrito) myocardial perfusion SPECT for the diagnosis of coronary artery disease. METHODS: A total of 42 patients [mean age (54 +/- 9) years, 35 men] with suspected chest pain were included in this study. 740 MBq of (99m)Tc-N-NOET was injected intravenously during bicycle exercise when the heart rate attained reached more than 85% of the expected maximum, or in cases of angina pectoris, severe arrhythmias and ischemic ST segment changes. (99m)Tc-N-NOET 740 MBq, SPECT myocardial imaging acquisitions were obtained at 15 minutes and 2 hours after (99m)Tc-N-NOET injection. Coronary angiography was performed in all patients. RESULTS: Coronary artery stenosis was detected in 26 patients and normal coronary angiography was shown in 16 patients. (99m)Tc-N-NOET myocardial perfusion imaging was abnormal in twenty-one patients out of the 26 patients with significant coronary artery stenosis (sensitivity, 81%); 14 out of 16 patients with normal angiography had a normal myocardial perfusion imaging (specificity, 88%). The positive predictive value, negative predictive value and predictive accuracy of (99m)Tc-N-NOET myocardial perfusion imaging for detection of CAD was 91%, 74% and 83%, respectively. The sensitivity of the imaging for detecting single vessel, double vessels and triple vessels disease were 60% (6/10), 86% (6/7) and 100% (9/9), respectively. There was mild (99m)Tc-N-NOET lung uptake in patients with coronary artery stenosis 15 minutes post (99m)Tc-N-NOET injection. CONCLUSION: SPECT myocardial perfusion imaging with (99m)Tc-N-NOET supplied an important diagnostic tool for detecting coronary artery disease. Lung uptake with stress (99m)Tc-N-NOET might be related to coronary artery disease.


Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Prueba de Esfuerzo , Compuestos de Organotecnecio , Tiocarbamatos , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
20.
Circulation ; 108(10): 1208-13, 2003 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-12939208

RESUMEN

BACKGROUND: Scintigraphic myocardial perfusion imaging is the most widely used noninvasive modality for the detection of coronary artery disease (CAD). A technique for direct imaging of exercise-induced myocardial ischemia is highly desirable and preferable over perfusion imaging but is presently unavailable. We evaluated the feasibility and diagnostic accuracy of direct imaging of exercise-induced myocardial ischemia with fluorine-18-2-deoxyglucose (18FDG). METHODS AND RESULTS: Twenty-six patients with known or suspected CAD and no prior myocardial infarction underwent simultaneous myocardial perfusion and ischemia imaging after the intravenous injection of Tc-99m-sestamibi (99mTc-sestamibi) and 18FDG at peak exercise. Rest perfusion imaging was carried out separately. All patients underwent coronary angiography. Exercise 18FDG myocardial images were compared with exercise-rest 99mTc-sestamibi images and coronary angiography. Of 22 patients with > or =50% narrowing of > or =1 coronary arteries, 18 had perfusion abnormalities (sensitivity 82%) whereas 20 had abnormal myocardial 18FDG uptake (sensitivity 91%, P=NS). Perfusion abnormalities were seen in myocardial segments corresponding to 25 vascular territories of a total of 51 vessels with > or =50% luminal narrowing in 22 patients (sensitivity 49%), whereas increased 18FDG uptake was seen in 34 vascular territories (sensitivity 67%, P=0.008). 18FDG images were of high quality and easy to interpret but required simultaneous perfusion images for localizing abnormal myocardial 18FDG uptake. CONCLUSIONS: Exercise-induced myocardial ischemia can be imaged directly with 18FDG. Combined exercise 18FDG-99mTc-sestamibi imaging provides a better assessment of exercise-induced myocardial ischemia compared with exercise-rest perfusion imaging. Direct ischemia imaging eliminates some of the limitations of presently used myocardial perfusion imaging. Large-scale clinical studies are warranted.


Asunto(s)
Enfermedad de la Arteria Coronaria/diagnóstico , Prueba de Esfuerzo , Fluorodesoxiglucosa F18 , Isquemia Miocárdica/diagnóstico por imagen , Tecnecio Tc 99m Sestamibi , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/complicaciones , Vasos Coronarios/diagnóstico por imagen , Complicaciones de la Diabetes , Diabetes Mellitus/fisiopatología , Prueba de Esfuerzo/efectos adversos , Estudios de Factibilidad , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/etiología , Isquemia Miocárdica/fisiopatología , Cintigrafía , Sensibilidad y Especificidad , Tecnecio Tc 99m Sestamibi/farmacocinética
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