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1.
Onco Targets Ther ; 11: 4711-4721, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30127619

RESUMO

Purpose: This article aimed to investigate the effect of miR-497 on thyroid papillary carcinoma. Materials and methods: miR-497 expression was analyzed using The Cancer Genome Atlas. A total of 56 papillary thyroid carcinoma patients' tumor tissues and normal tissues were collected. Nthy-ori 3-1 and K1 cells were cultured. K1 cells were also transfected. Quantitative real-time polymerase chain reaction and Western blot were used to detect miR-497 and yes-associated protein 1 (YAP1) expression. Luciferase reporter assay was performed. MTT and Transwell assay were conducted to measure cells' proliferation, migration and invasion. Immunofluorescence detection was used to detect YAP1-positive cells. Results: miR-497 was downregulated, while YAP1 was upregulated in thyroid papillary carcinoma tissues and K1 cells (P<0.05). Compared with the negative control group, the OD495 value and the migrating and invasive cell number were significantly lower in miR-497 mimics group and significantly higher in miR-497 inhibitor group (P<0.05). YAP1 was the target gene of miR-497. Compared with blank group, the OD495 value and the migrating and invasive cell number were significantly lower in si-YAP1 group and significantly higher in miR-497 inhibitor group (P<0.05), while no significant difference was found between si-YAP1+inhibitors group and blank group in these indicators. Conclusion: miR-497 regulated the proliferation, migration and invasion of K1 cells by negatively regulating YAP1 expression.

2.
Proc Natl Acad Sci U S A ; 115(5): 909-914, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29339509

RESUMO

Measuring vital physiological pressures is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft biological systems. Therefore, the devices should be flexible and at the same time biodegradable to avoid invasive removal surgery that can damage directly interfaced tissues. Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensor which only relies on safe medical materials and requires no complex fabrication process to provide accurate information on important biophysiological forces. Here, we present a strategy for material processing, electromechanical analysis, device fabrication, and assessment of a piezoelectric Poly-l-lactide (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force sensor, which only employs medical materials used commonly in Food and Drug Administration-approved implants, for the monitoring of biological forces. We show the sensor can precisely measure pressures in a wide range of 0-18 kPa and sustain a reliable performance for a period of 4 d in an aqueous environment. We also demonstrate this PLLA piezoelectric sensor can be implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction. This piezoelectric sensor offers an appealing alternative to present biodegradable electronic devices for the monitoring of intraorgan pressures. The sensor can be integrated with tissues and organs, forming self-sensing bionic systems to enable many exciting applications in regenerative medicine, drug delivery, and medical devices.


Assuntos
Implantes Absorvíveis , Monitorização Fisiológica/instrumentação , Pressão , Animais , Fenômenos Biomecânicos , Eletricidade , Humanos , Camundongos , Poliésteres
3.
Anal Bioanal Chem ; 409(21): 5091-5099, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28687877

RESUMO

Organophosphorous nerve agents (NAs) pose a great threat to nations and people because of their acute and extreme toxicities. The rapid detection of NAs has attracted growing interest in the first emergency response field. In this work, we demonstrate a simple and sensitive surface-enhanced Raman spectroscopic (SERS) method for NAs detection, and G- and V-agents discrimination. The results show that VX (V-agents) can be directly detected at a 20 ng mL-1 level with pinhole shell-isolated gold nanoparticles (pinSHINs) as the substrate. Moreover, combined with a specific and prompt alkaline keto-oxime transformation approach in a full aqueous solution, G-agents can be measured as low as 10 ng mL-1 with excellent discrimination from V-agents and other common organophosphorous pesticides within several minutes. The achieved discriminative detection of G-agents and VX could be significant not only for reducing the false positive and negative signals but also for providing an appropriate recommendation on the effective medical rescue. A decontamination outcome occurred alongside, any highly toxic G-agents were converted to a less toxic phosphate, and the generated cyanide was fully and firmly adsorbed onto the surface of pinSHINs substrate, which may be further used for on-site detection of extremely toxic NA prototypes. Graphical abstract ᅟ.


Assuntos
Agentes Neurotóxicos/análise , Compostos Organofosforados/análise , Análise Espectral Raman/métodos , Limite de Detecção , Microscopia Eletrônica de Transmissão , Propriedades de Superfície
4.
Biophys J ; 112(9): 1997-2010, 2017 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-28494969

RESUMO

The atrial-specific ultrarapid delayed rectifier K+ current (IKur) inactivates slowly but completely at depolarized voltages. The consequences for IKur rate-dependence have not been analyzed in detail and currently available mathematical action-potential (AP) models do not take into account experimentally observed IKur inactivation dynamics. Here, we developed an updated formulation of IKur inactivation that accurately reproduces time-, voltage-, and frequency-dependent inactivation. We then modified the human atrial cardiomyocyte Courtemanche AP model to incorporate realistic IKur inactivation properties. Despite markedly different inactivation dynamics, there was no difference in AP parameters across a wide range of stimulation frequencies between the original and updated models. Using the updated model, we showed that, under physiological stimulation conditions, IKur does not inactivate significantly even at high atrial rates because the transmembrane potential spends little time at voltages associated with inactivation. Thus, channel dynamics are determined principally by activation kinetics. IKur magnitude decreases at higher rates because of AP changes that reduce IKur activation. Nevertheless, the relative contribution of IKur to AP repolarization increases at higher frequencies because of reduced activation of the rapid delayed-rectifier current IKr. Consequently, IKur block produces dose-dependent termination of simulated atrial fibrillation (AF) in the absence of AF-induced electrical remodeling. The inclusion of AF-related ionic remodeling stabilizes simulated AF and greatly reduces the predicted antiarrhythmic efficacy of IKur block. Our results explain a range of experimental observations, including recently reported positive rate-dependent IKur-blocking effects on human atrial APs, and provide insights relevant to the potential value of IKur as an antiarrhythmic target for the treatment of AF.


Assuntos
Fibrilação Atrial/metabolismo , Átrios do Coração/metabolismo , Canais de Potássio/metabolismo , Antiarrítmicos/farmacologia , Fibrilação Atrial/tratamento farmacológico , Relação Dose-Resposta a Droga , Átrios do Coração/efeitos dos fármacos , Humanos , Cinética , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Modelos Cardiovasculares , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia
5.
J Med Chem ; 59(24): 11138-11147, 2016 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-28002964

RESUMO

We describe a highly efficient route for the synthesis of 4a (BMS-986104). A key step in the synthesis is the asymmetric hydroboration of trisubstituted alkene 6. Particularly given the known difficulties involved in this type of transformation (6 → 7), the current methodology provides an efficient approach to prepare this class of compounds. In addition, we disclose the efficacy of 4a in a mouse EAE model, which is comparable to 4c (FTY720). Mechanistically, 4a exhibited excellent remyelinating effects on lysophosphatidylcholine (LPC) induced demyelination in a three-dimensional brain cell culture assay.


Assuntos
Encefalomielite Autoimune Experimental/tratamento farmacológico , Naftalenos/farmacologia , Receptores de Lisoesfingolipídeo/agonistas , Animais , Células Cultivadas , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Células HEK293 , Humanos , Linfócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Estrutura Molecular , Naftalenos/síntese química , Naftalenos/química , Relação Estrutura-Atividade
6.
J Pharmacol Exp Ther ; 358(3): 371-86, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27411717

RESUMO

To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the adapter protein-2 associated kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase I formalin), but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL). Based on these findings, potent, small-molecule inhibitors of AAK1 were identified. Studies in mice showed that one such inhibitor, LP-935509, caused a reduced pain response in phase II formalin and reversed fully established pain behavior following the SNL procedure. Further studies showed that the inhibitor also reduced evoked pain responses in the rat chronic constriction injury (CCI) model and the rat streptozotocin model of diabetic peripheral neuropathy. Using a nonbrain-penetrant AAK1 inhibitor and local administration of an AAK1 inhibitor, the relevant pool of AAK1 for antineuropathic action was found to be in the spinal cord. Consistent with these results, AAK1 inhibitors dose-dependently reduced the increased spontaneous neural activity in the spinal cord caused by CCI and blocked the development of windup induced by repeated electrical stimulation of the paw. The mechanism of AAK1 antinociception was further investigated with inhibitors of α2 adrenergic and opioid receptors. These studies showed that α2 adrenergic receptor inhibitors, but not opioid receptor inhibitors, not only prevented AAK1 inhibitor antineuropathic action in behavioral assays, but also blocked the AAK1 inhibitor-induced reduction in spinal neural activity in the rat CCI model. Hence, AAK1 inhibitors are a novel therapeutic approach to neuropathic pain with activity in animal models that is mechanistically linked (behaviorally and electrophysiologically) to α2 adrenergic signaling, a pathway known to be antinociceptive in humans.


Assuntos
Neuralgia/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Animais , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Técnicas de Inativação de Genes , Células HEK293 , Humanos , Masculino , Camundongos , Neuralgia/metabolismo , Neuralgia/fisiopatologia , Nociceptividade/efeitos dos fármacos , Fenótipo , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/deficiência , Proteínas Serina-Treonina Quinases/genética , Ratos , Medula Espinal/efeitos dos fármacos , Medula Espinal/enzimologia , Medula Espinal/fisiopatologia
7.
Anal Bioanal Chem ; 406(21): 5203-12, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24924210

RESUMO

A highly sensitive method for the determination of sulfur mustard (SM) metabolites thiodiglycol (TDG) and thiodiglycol sulfoxide (TDGO) in urine was established and validated using isotope-dilution negative-ion chemical ionization (NICI) gas chromatography-mass spectrometry (GC-MS). TDGO in the samples was reduced with TiCl3, and then determined together with TDG as a single analyte. The sample preparation procedures, including two solid-phase-extraction (SPE) clean-up steps, were optimized to improve the sensitivity of the method. The limits of detection (LOD) for both TDG and TDG plus TDGO (TDG + TDGO) were 0.1 ng mL(-1), and the limits of quantitation (LOQ) for both were 0.3 ng mL(-1). The method was used in a rabbit cutaneous SM exposure model. Domestic rabbits were exposed to neat liquid SM at three dosage levels (0.02, 0.05, and 0.15 LD50), and the urinary excretion of four species of hydrolysis metabolites, namely free TDG, free plus conjugated TDG (total TDG), free TDG + TDGO, and free plus conjugated TDG + TDGO (total TDG + TDGO), was evaluated to investigate the metabolic processes. The total urinary excretion profiles of the metabolites, including the peak time, time window, and dose-response and time-response relationships, were clarified. The results revealed that the concentrations of TDG and TDG + TDGO in the urine increased quickly and then decreased rapidly in the first two days after SM exposure. The cumulative amount of total TDG + TDGO excreted in urine during the first five days accounted for 0.5-1% of the applied dose of SM. It is also concluded that TDG and TDGO in urine existed mainly in free form, the levels of glucuronide and of sulfate conjugates of TDG or TDGO were very low, and most hydrolysis metabolites were present in the oxidized form (TDGO). The study indicates that the abnormal increase of TDG and TDGO excretion levels can be used as a diagnostic indicator and establishes a reference time-window for retrospective analysis and sampling after SM exposure.


Assuntos
Substâncias para a Guerra Química/toxicidade , Fármacos Dermatológicos/toxicidade , Gás de Mostarda/toxicidade , Compostos de Sulfidrila/urina , Sulfóxidos/urina , Administração Cutânea , Animais , Biotransformação , Substâncias para a Guerra Química/metabolismo , Fármacos Dermatológicos/metabolismo , Relação Dose-Resposta a Droga , Cromatografia Gasosa-Espectrometria de Massas/métodos , Técnicas de Diluição do Indicador , Masculino , Gás de Mostarda/metabolismo , Oxirredução , Coelhos , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Pele/metabolismo , Extração em Fase Sólida , Titânio/química
8.
Artigo em Inglês | MEDLINE | ID: mdl-24858262

RESUMO

Sulfur mustard (SM) is a classic vesicant agent, which has been greatly employed in several wars or military conflicts. The most lesion mechanism is its strong alkylation of DNAs in vivo. Until now there are four specific DNA adducts of SM identified for further retrospective detection, i.e., N(7)-(2-hydroxyethylthioethyl)-2'-guanine (N(7)-HETEG), bis(2-ethyl-N(7)-guanine)thioether (Bis-G), N(3)-(2-hydroxyethylthioethyl)-2'-adenine (N(3)-HETEA) and O(6)-(2-hydroxyethylthioethyl)-2'-guanine (O(6)-HETEG), respectively. Here, a novel and sensitive method of isotope-dilution ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) combining with solid phase extraction was reported for the simultaneous determination of four SM-DNA adducts. A lower limit of detection of 2-5ngL(-1), and a lower limit of quantitation of 5-10ngL(-1) were achieved, respectively, and the recoveries ranged from 87% to 116%. We applied this method in the determination of four SM-DNA adducts in rabbit urine after dermal exposure by SM in three dose levels (2, 5, 15mgkg(-1)), so as to investigate the related metabolic behavior in vivo. For the first time, in SM exposed rabbit urine, our results revealed the relative accumulation abundance of four SM-DNA adducts, i.e., 67.4% for N(7)-HETEG, 22.7% for Bis-G, 9.8% for N(3)-HETEA, 0.1% for O(6)-HETEG, and significant dose and time dependent responses of these SM-DNA adducts. The four adducts were detectable after 8h, afterwards, their contents continuously increased, achieved maximum in the first two or three days and then gradually decreased till the end of one month. Meanwhile, the amounts of SM-DNA adducts were positively correlated with the exposure doses.


Assuntos
Adutos de DNA/urina , Animais , Cromatografia Líquida de Alta Pressão/métodos , Guanina/análogos & derivados , Guanina/análise , Gás de Mostarda/administração & dosagem , Gás de Mostarda/análise , Gás de Mostarda/química , Coelhos , Compostos de Sulfidrila/análise , Compostos de Sulfidrila/química , Espectrometria de Massas em Tandem/métodos
9.
Anal Bioanal Chem ; 406(21): 5213-20, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24633564

RESUMO

A simple and sensitive method has been developed and validated for determining ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), isobutyl methylphosphonic acid (iBuMPA), and pinacolyl methylphosphonic acid (PMPA) in human urine using gas chromatography-tandem mass spectrometry (GC-MS/MS) coupled with solid phase derivatization (SPD). These four alkyl methylphosphonic acids (AMPAs) are specific hydrolysis products and biomarkers of exposure to classic organophosphorus (OP) nerve agents VX, sarin, RVX, and soman. The AMPAs in urine samples were directly derivatized with pentafluorobenzyl bromide on a solid support and then extracted by liquid-liquid extraction. The analytes were quantified with isotope-dilution by negative chemical ionization (NCI) GC-MS/MS in a selected reaction monitoring (SRM) mode. This method is highly sensitive, with the limits of detection of 0.02 ng/mL for each compound in a 0.2 mL sample of human urine, and an excellent linearity from 0.1 to 50 ng/mL. It is proven to be very suitable for the qualitative and quantitative analyses of degradation markers of OP nerve agents in biomedical samples.


Assuntos
Substâncias para a Guerra Química/análise , Organofosfonatos/urina , Compostos Organofosforados/urina , Compostos Organotiofosforados/urina , Sarina/urina , Soman/análogos & derivados , Soman/urina , Biotransformação , Substâncias para a Guerra Química/metabolismo , Fluorbenzenos/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Técnicas In Vitro , Técnicas de Diluição do Indicador , Limite de Detecção , Extração Líquido-Líquido
10.
Toxicol Rep ; 1: 533-543, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-28962267

RESUMO

In one event, Chinese male individuals accidentally exposed to unknown chemicals and emerged erythema or blisters on contacted organism derma, then hospitalized. To identify the causative agents, blood, urine and exudate samples were collected from the patients during the therapeutic course. Five established liquid chromatography-mass spectrometry (LC-MS) and gas chromatography (GC)-MS methods were employed to analyze the samples. Here, an overall analysis of four types of sulfur mustard biomarkers, including the hydrolysis/oxidation products, ß-lyase metabolites, DNA adducts and hemoglobin adducts, was conducted toward the samples from exposed individuals. The results of all the four types of biomarkers in different biomedical matrices showed high relevance, and verified that this exposure is indeed originated from sulfur mustard. The concentrations of the biomarkers in specimens revealed a good correlation with the severity of the patient's symptom. The concentration-time profile demonstrated that most of the biomarkers quickly achieved maximum at the beginning of the course, and then decreased and kept a detectable level until the 7th day after exposure. The DNA adducts in urine samples still appeared on the 30th day, and the N-terminal valine adducts in hemoglobin could be monitored for over 90 days, which was meaningful for the concurrent study of clinical samples. To the best of our knowledge, this work provides the total analysis and profile of four categories of biomarkers in human specimens for the first time, and the good accordance between concentration and level of burns, between time course and biomarkers will be of great importance for early diagnosis and medical treatment monitoring of sulfur mustard exposure.

11.
World J Nucl Med ; 12(1): 3-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23961248

RESUMO

Phase analysis has been validated to measure left ventricular (LV) dyssynchrony from resting gated SPECT myocardial perfusion imaging (MPI). In 1-day rest/stress protocols, often only post-stress gated data are acquired. The purpose of this study was to determine whether LV dyssynchrony parameters measured at post-stress significantly differ from those measured at rest. Sixty normal subjects, 40 patients with stress-induced ischemia but normal LV function, and 29 patients with LV dysfunction were included in this study. All patients were scanned using a 2-day Technetium-99m sestamibi (MIBI) MPI protocol, where gated SPECT data were acquired at 60 min post injection of the radiotracer. LV dyssynchrony parameters at post-stress and at rest were calculated and compared using paired t-test. There were no significant differences in the LV dyssynchrony parameters between post-stress and resting in all cohorts. No patient showed differences in the LV dyssynchrony parameters between the post-stress and resting scans significantly greater than the reported variations in these parameters between serial resting scans. There was no significant difference in dyssynchrony parameters measured at rest and 60 min after stress on MPI gated images.

12.
Eur J Nucl Med Mol Imaging ; 39(7): 1191-8, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22532253

RESUMO

PURPOSE: The purpose of this study was to evaluate left ventricular (LV) mechanical dyssynchrony in patients with Wolff-Parkinson-White (WPW) syndrome pre- and post-radiofrequency catheter ablation (RFA) using phase analysis of gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). METHODS: Forty-five WPW patients were enrolled and had gated SPECT MPI pre- and 2-3 days post-RFA. Electrophysiological study (EPS) was used to locate accessory pathways (APs) and categorize the patients according to the AP locations (septal, left and right free wall). Electrocardiography (ECG) was performed pre- and post-RFA to confirm successful elimination of the APs. Phase analysis of gated SPECT MPI was used to assess LV dyssynchrony pre- and post-RFA. RESULTS: Among the 45 patients, 3 had gating errors, and thus 42 had SPECT phase analysis. Twenty-two patients (52.4%) had baseline LV dyssynchrony. Baseline LV dyssynchrony was more prominent in the patients with septal APs than in the patients with left or right APs (p < 0.05). RFA improved LV synchrony in the entire cohort and in the patients with septal APs (p < 0.01). CONCLUSION: Phase analysis of gated SPECT MPI demonstrated that LV mechanical dyssynchrony can be present in patients with WPW syndrome. Septal APs result in the greatest degree of LV mechanical dyssynchrony and afford the most benefit after RFA. This study supports further investigation in the relationship between electrical and mechanical activation using EPS and phase analysis of gated SPECT MPI.


Assuntos
Feixe Acessório Atrioventricular/diagnóstico por imagem , Tecnécio Tc 99m Sestamibi , Disfunção Ventricular Esquerda/diagnóstico por imagem , Síndrome de Wolff-Parkinson-White/diagnóstico por imagem , Feixe Acessório Atrioventricular/complicações , Feixe Acessório Atrioventricular/patologia , Adulto , Tomografia Computadorizada por Emissão de Fóton Único de Sincronização Cardíaca/métodos , Ablação por Cateter/métodos , Ecocardiografia/métodos , Eletrocardiografia/métodos , Técnicas Eletrofisiológicas Cardíacas/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio/métodos , Compostos Radiofarmacêuticos , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/patologia , Síndrome de Wolff-Parkinson-White/complicações , Síndrome de Wolff-Parkinson-White/patologia
13.
Neurobiol Aging ; 33(7): 1481.e13-23, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22227005

RESUMO

Transgenic mice are used to model increased brain amyloid-ß (Aß) and amyloid plaque formation reflecting Alzheimer's disease pathology. In our study hippocampal network oscillations, population spikes, and long-term potentiation (LTP) were recorded in APPswe/PS1dE9 (APP/PS1) and presenilin1 (PS1) transgenic and wild type mice at 2, 4, and 8 months of age under urethane anesthesia. Hippocampal theta oscillations elicited by brainstem stimulation were similar in wild type and PS1 mice at all age groups. In contrast, APP/PS1 mice showed an age-dependent decrease in hippocampal activity, characterized by a significant decline in elicited theta power and frequency at 4 and 8 months. Magnitudes of population spikes and long-term potentiation in the dentate gyrus were similar across groups at both 4 and 8 months. In APP/PS1 mice, soluble and insoluble Aß, and hippocampal and cortical plaque load increased with age, and the disruption in hippocampal theta oscillation showed a significant correlation with plaque load. Our study shows that, using in vivo electrophysiological methods, early Aß-related functional deficits can be robustly detected in the brainstem-hippocampus multisynaptic network.


Assuntos
Envelhecimento/genética , Envelhecimento/metabolismo , Peptídeos beta-Amiloides/biossíntese , Peptídeos beta-Amiloides/genética , Hipocampo/fisiologia , Ritmo Teta/fisiologia , Precursor de Proteína beta-Amiloide/genética , Animais , Potenciação de Longa Duração/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Presenilina-1/genética
14.
Chin Med J (Engl) ; 123(22): 3282-7, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21163131

RESUMO

BACKGROUND: Stem cell transplantation has been shown to have beneficial effects on dilated cardiomyopathy. However, mechanism for stem cell homing to cardiac tissue in dilated cardiomyopathy has not yet been elucidated. METHODS: Mesenchymal stem cells were obtained from rat bone marrow, expanded in vitro, and labeled with (99m)Tc. Cardiomyopathy model was induced by doxorubicin in rats. (99m)Tc labeled cells were infused into the left ventricles in cardiomyopathy and control rats. Sixteen hours after injection, animals were sacrificed and different tissues were harvested to measure specific radioactivity. By use of real-time polymerase chain reaction and immunohistochemistry, mRNA and protein expressions for stromal-cell-derived factor 1 in cardiac tissue were measured. RESULTS: Labeling efficiency of mesenchymal stem cells was (70.0 ± 11.2)%. Sixteen hours after mesenchymal stem cell transplantation, the heart-to-muscle radioactivity ratio was increased significantly in cardiomyopathy hearts as compared to control hearts. Both mRNA and protein expressions of stromal-cell-derived factor 1 were up-regulated in cardiomyopathy hearts as compared with control hearts. CONCLUSION: In dilated cardiomyopathy induced by doxorubicin up-regulated expression of stromal-cell-derived factor 1 in heart may induce mesenchymal stem cells home to the heart.


Assuntos
Células da Medula Óssea/citologia , Cardiomiopatia Dilatada/terapia , Quimiocina CXCL12/metabolismo , Células-Tronco Mesenquimais/citologia , Animais , Células da Medula Óssea/metabolismo , Células Cultivadas , Quimiocina CXCL12/genética , Imuno-Histoquímica , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
J Nucl Cardiol ; 17(3): 486-93, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20238192

RESUMO

BACKGROUND: The purpose of this study is to assess diagnostic performance of the current quantification packages using Western normal databases in detecting coronary artery disease in Chinese population. METHODS: Seventy-five patients who underwent rest/stress myocardial perfusion SPECT and coronary angiography (CAG) were enrolled. Emory Cardiac Toolbox (ECTb) and Quantitative Perfusion SPECT (QPS) with its standard (QPS-standard) and simplified (QPS-simplified) methods were used to quantify these studies. A preliminary Chinese normal database was created from 80 normal subjects (QPS-simplified-Chinese). Receiver operator characteristic (ROC) was used to assess the accuracy of the four normal databases in detecting >or=50% or >or=70% stenosis given by CAG. RESULTS: The enrolled cohorts had lower body mass index (BMI) and smaller heart size than Western population. The areas under ROC curve of ECTb, QPS-standard, and QPS-simplified were significantly lower than QPS-simplified-Chinese in detecting >or=50% stenosis, but not in detecting >or=70% stenosis. Diagnostic accuracy was much lower in the RCA and LCX territory. CONCLUSION: Chinese normal database is needed for accurately applying these quantification methods to Chinese population, especially for detecting moderate defects in regions with relatively greater attenuation impact. An alternative approach could be modification of the existing Western normal databases for low-BMI and/or small-heart subjects.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Imagem de Perfusão do Miocárdio , Tomografia Computadorizada de Emissão de Fóton Único , China , Circulação Coronária , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Software , Estados Unidos
16.
Nucl Med Commun ; 30(9): 700-5, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19550363

RESUMO

OBJECTIVES: Phase analysis (SyncTool) has been developed to assess left-ventricular (LV) dyssynchrony from gated myocardial perfusion single-photon emission computed tomography (GSPECT) studies. Conventionally, GSPECT data are reconstructed using filtered backprojection (FBP). This study is intended to determine the impact of various iterative reconstruction methods on SyncTool. METHODS: Thirty consecutive patients, acquired using a Philips CardioMD system, were enrolled in this study. The GSPECT data were reconstructed using FBP, maximum likelihood expectation maximization (MLEM), MLEM with three-dimensional resolution recovery (Astonish), MLEM with Vantage attenuation correction (AC), and MLEM with Vantage AC and three-dimensional Monte Carlo-based scatter correction (ACSC), respectively. The reconstructed data were then submitted to SyncTool to measure LV dyssynchrony (phase standard deviation and histogram bandwidth). The paired t-test was used to compare the LV dyssynchrony indices given by MLEM, Astonish, AC, and ACSC, respectively, with those given by the FBP. RESULTS: No statistical significance was observed for any comparison between iterative reconstruction methods and the FBP. CONCLUSION: Reconstruction methods have insignificant impact on the LV dyssynchrony indices, indicating that the standard FBP reconstruction is sufficient for accurate phase analysis, supporting the widespread clinical use of SyncTool in measuring LV dyssynchrony.


Assuntos
Tomografia Computadorizada por Emissão de Fóton Único de Sincronização Cardíaca/métodos , Eletrocardiografia/métodos , Processamento de Imagem Assistida por Computador/métodos , Imagem de Perfusão do Miocárdio/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Humanos , Funções Verossimilhança
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 26(12): 2264-7, 2006 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-17361726

RESUMO

To develop a rapid, simple and sensitive method for determining the concentration of tetrodotoxin(TTX), TTX was hydrolyzed in the strong alkali solution of water mixed with isopropanol. The concentration of TTX can be indirectly analyzed by the fluorescence signal of its alkaline hydrolysis product which can be enhanced by the microwave method. The maximum excitation and emission wavelengths of the alkaline hydrolysis product of tetrodotoxin were 380 and 496 nm, respectively. The linear range of the calibration curve was 0. 1-10 micromol x L(-1) with r=0. 9991. The limit of detection was 0. 05 micromol x L(-1) , which was twenty times lower than before. A rapid, highly sensitive and accurate method was thus established. It can be used as a quantitative method for detecting TTX.


Assuntos
Álcalis/química , Micro-Ondas , Espectrometria de Fluorescência , Tetrodotoxina/química , Hidrólise , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray
18.
Assay Drug Dev Technol ; 1(5): 647-54, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15090237

RESUMO

Although techniques such as (86)Rb(+) flux provide a sensitive measure of K(+) channel activity, the relatively short half-life and high-energy emission, together with the quantities of radioactive material generated, hinder the usefulness of flux-based formats in high throughput screening efforts. This study elaborates on the utilization of flame atomic absorption spectrometry (AAS) techniques for a nonradioactive rubidium efflux assay for large conductance Ca(2+)-activated K(+) channels (BK(Ca)) channels. Utilizing human embryonic kidney (HEK293) cells expressing the BK(Ca) alpha subunit, a 96-well cell-based nonradioactive rubidium efflux screen for channel openers and inhibitors was established. Known BK(Ca) channel openers, including NS1608, NS1619, and NS-8, activated rubidium efflux with EC(50) values ranging from 1 to 4 microM in both radioactive and nonradioactive efflux formats. Compounds such as iberiotoxin, paxilline, and charybdotoxin inhibited rubidium efflux responses evoked by the BK(Ca) channel opener NS1608 in both radioactive and nonradioactive efflux formats. The IC(50) values of the inhibitors in AAS format were comparable to those derived from (86)Rb(+) efflux assays. The present studies show that the pharmacological profiles of BK(Ca) channels assessed by AAS compare well with those obtained using the (86)Rb(+) efflux assay, and support the utility of nonradioactive efflux format for higher throughput screening campaigns for novel K(+) channel modulators.


Assuntos
Ativação do Canal Iônico/fisiologia , Rim/metabolismo , Canais de Potássio Cálcio-Ativados/fisiologia , Rubídio/metabolismo , Espectrofotometria Atômica/métodos , Benzimidazóis/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Transporte de Íons/fisiologia , Rim/efeitos dos fármacos , Rim/embriologia , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio Cálcio-Ativados/efeitos dos fármacos , Técnica de Diluição de Radioisótopos , Reprodutibilidade dos Testes , Radioisótopos de Rubídio/metabolismo , Sensibilidade e Especificidade
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