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Objective: To explore the gene mutation characteristics and the relationship between gene mutations and long-term prognosis in clinical stage â A lung adenocarcinoma patients. Methods: A retrospective analysis was conducted on 63 clinical stage â A lung adenocarcinoma patients who underwent surgical resection at the Cancer Hospital of the Chinese Academy of Medical Sciences from January 2007 to October 2012, with documented postoperative recurrence or metastasis, as well as those who had a follow-up duration of 10 years or more without recurrence or metastasis. Whole exome sequencing (WES) technology was used to analyze the gene mutation profiles in tumor tissues and univariate and multivariate Cox regression analysis were used to clarify the influencing factors for patient prognosis. Results: After long term follow-up, 13 out of the 63 patients (21%) experienced recurrence or metastasis. WES technology analysis revealed that the most common tumor related gene mutations occurred in epidermal growth factor receptor (EGFR), with a mutation rate of 65.1% (41/63), followed by tumor protein p53 (TP53), fatatypical cadherin 1 (FAT1), low density lipoprotein receptor-related protein 1B (LRP1B), mechanistic target of rapamycin (MTOR), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), and SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), with mutation rates of 30.2% (19/63), 20.6% (13/63), 15.9% (10/63), 15.9% (10/63), 15.9% (10/63), and 15.9% (10/63), respectively. Multivariate Cox regression analysis showed that PIK3CG mutations (HR=21.52, 95% CI: 3.19-145.01),smoothened (SMO) mutations (HR=35.28, 95% CI: 3.12-398.39), catenin beta 1 (CTNNB1) mutations (HR=332.86, 95% CI: 15.76-7 029.05), colony stimulating factor 1 receptor (CSF1R) mutations (HR=8 109.60, 95% CI: 114.19-575 955.17), and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations (HR=23.65, 95% CI: 1.86-300.43) were independent risk factors affecting the prognosis of clinical stage â A lung adenocarcinoma patients. Conclusions: PIK3CG, SMO, CTNNB1, CSF1R, BRAF gene mutations are closely related to long-term recurrence or metastasis in clinical stage â A lung adenocarcinoma. Patients with these gene mutations should be given closer clinical attention.
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Adenocarcinoma del Pulmón , Receptores ErbB , Neoplasias Pulmonares , Mutación , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Proteína p53 Supresora de Tumor , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Estudios Retrospectivos , Pronóstico , Receptores ErbB/genética , Proteína p53 Supresora de Tumor/genética , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Cadherinas/genética , Cadherinas/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Secuenciación del Exoma , Estudios de Seguimiento , Masculino , Femenino , Persona de Mediana Edad , Proteínas de Unión al ADN , Receptores de LDL , Factores de TranscripciónRESUMEN
The development of dynamic navigation system (DNS) has facilitated the development of modern digital medicine. In the field of dentistry, the cutting-edge technology is garnering widespread recognition. Based on the principles of 3-dimensional visualization, virtual design, and precise motion tracking, DNS is mainly composed of a computer, a tracking system, specialized tracer instruments, and navigation software. DNS employs a workflow that begins with preoperative data acquisition and imaging data reconstruction, followed by surgical instrument calibration and spatial registration, culminating in real-time guided operations. Currently, the system has been applied in a broad spectrum of dental procedures, encompassing dental implants, oral and maxillofacial surgery (such as tooth extraction, the treatment of maxillofacial fractures, tumors, and foreign bodies, orthognathic surgery, and temporomandibular joint ankylosis surgery), intraosseous anesthesia, and endodontic treatment (including root canal therapy and endodontic surgery). These applications benefit from its enhancements in direct visualization, treatment precision, efficiency, safety, and procedural adaptability. However, the adoption of DNS is not without substantial upfront costs, required comprehensive training, additional preparatory time, and increased radiation exposure. Despite challenges, the ongoing advancements in DNS are poised to broaden its utility and substantially strengthen digital dentistry.
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Cirugía Asistida por Computador , Cirugía Bucal , Cirugía Asistida por Computador/métodos , Programas Informáticos , Huesos Faciales , Procesamiento de Imagen Asistido por ComputadorAsunto(s)
Enfermedad de la Arteria Coronaria , Reserva del Flujo Fraccional Miocárdico , Humanos , Angiografía Coronaria , Microcirculación , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Resultado del Tratamiento , Resistencia Vascular , Vasos Coronarios , Circulación Coronaria , Valor Predictivo de las PruebasRESUMEN
The aim of this study was to explore the dynamic changes in characteristic serum metabolic markers and pathways during early sepsis in rats. By using cecal ligation and puncture (CLP), we made rat models of sepsis, which were randomly divided into 5 groups with 10 rats in each group: group A, group B, group C, group D, and group E. We collected 2 mL of arterial blood at 0, 6, 12, 24, and 48 hours from rats in group A-E respectively and isolated serum via centrifugation. Next, adopting metabolomics analysis methods, we screened for metabolites from the animal serum with statistically and biologically significant abundance changes, and used the KEGG database to analyze the respective metabolic pathways. In all, our findings reveal that D-glucosamine 6-phosphate, D-glucosamine phosphate, α-D-glucosamine 1-phosphate, D-glucosamine 1-phosphate, and 5-hydroxy isocyanate decline continuously from 12 hours, while L-phenylalanine, (S) -α-amino-ß-phenylpropionic acid, 5-methoxy indole acetic acid salt, 5-methoxy indole acetic acid, goose deoxyglycolic acid salt, goose deoxyglycolic acid, and Chen's deoxygenated sugar alcohol started to decrease from 6 hours. Additionally, 3.2,3-Bis-O-(geranyl geranyl)-sn-glycerol- 1-phosphoric acid-L-serine levels rose continuously from 12 hours. We found 13 differentially regulated ions, primarily ones involved in pathways responsible for the metabolism of sugar, amino acids, and lipids, which are related to the disorder of energy metabolism. Our findings mark serum-derived D-glucosamine and its phosphorous derivatives as characteristic metabolic markers of sepsis in rats.
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Punciones/efectos adversos , Sepsis , Animales , Modelos Animales de Enfermedad , Redes y Vías Metabólicas , Metabolómica , Ratas , Ratas Sprague-Dawley , Sepsis/etiologíaRESUMEN
miR-382-3p can regulate apoptosis through multiple pathways, but the mechanism remains unknown. In this experiment, we explored whether miR-382-3p can modulate the N-methyL-D-aspartate (NMDA)- induced HT22 cell apoptosis by regulating the RhoC/ROCK1 signaling pathway. An excitatory neurotoxicity model of HT22 cells was induced in vitro with 2 mmol/L NMDA. The cells were divided into normal control, NMDA-induced, NMDA + miR-382-3p mimic, and NMDA + miR-382-3p inhibitor groups. The 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method, Real-time PCR, Western blot, and flow cytometry were performed to investigate the mechanisms. The results found that NMDA can increase the oxidative stress of HT22 cells in a dose-dependent manner, downregulate the expression of miR-382-3p, upregulate the expression of mRNA and protein abundance of ROCK1 and RhoC, increase the expression levels of proapoptotic proteins Bax, Caspase-3, and Caspase-9, increase the apoptosis of HT22 cells, and reduce the activity and survival rate of HT22 cells. Compared with the NMDA-induced group, the miR-382-3p mimic-transfected HT22 cells increased the expression of miR- 382-3p, reduced the expression of the mRNA and protein abundance of ROCK1 and RhoC, inhibited the expression of proapoptotic proteins Bax, Caspase-3, and Caspase-9, reduced the apoptosis of HT22 cells, and increased the activity and survival rate of HT22 cells. The results suggest that increasing the expression of miR-382-3p can inhibit the activity of the RhoC/ROCK1 signaling pathway, reduce the expression of proapoptotic proteins, reduce the oxidative stress and apoptosis of HT22 cells, and increase the activity and survival rate of HT22 cells.
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Apoptosis , Línea Celular Tumoral , Humanos , MicroARNs/genética , N-Metilaspartato/toxicidad , Transducción de Señal , Quinasas Asociadas a rho , Proteína rhoC de Unión a GTPAsunto(s)
Infecciones por Coronavirus , Brotes de Enfermedades , Pandemias , Neumonía Viral , Betacoronavirus , COVID-19 , China , Humanos , SARS-CoV-2RESUMEN
Naringenin is a flavonoid compound with antioxidant effects. It is used to treat oxidative stress-related diseases, but its mechanism is unclear. In this experiment, we explored whether naringenin can increase the expression of superoxide dismutase 1(SOD1), reduce the oxidative stress of PC12 cells induced by homocysteine (Hcy), and decrease the apoptosis of PC12 cells induced by Hcy by inhibiting the expression of mir-224-3p. Different concentrations of Hcy (1, 3, 5, 8, and 10 mmol/L) was used to analyze effect of homocysteine on PC12 cells. A total of 5 mmol/L Hcy was used to induce the excitatory and neurotoxicity model of PC12 cells in vitro. The cells were divided into normal control, Hcy induction, Hcy + Naringenin (25 µM), Hcy + Naringenin (50 µM), Hcy + Naringenin (75 µM), Hcy + Naringenin (100 µM), and Hcy + Naringenin (150 µM) groups. The relative survival rate and activities of the PC12 cells were determined by the MTT method, and the apoptosis rate of the PC12 cells was determined by using flow cytometry. The Western blot method was used to determine the expressions of SOD1, Bax, Caspase-3, Caspase-8, and Bcl-2 in the PC12 cells induced by Hcy. The expressions of SOD1 mRNA and miR-224-3p in the Hcy-induced PC12 cells were determined by RT-PCR. Results found that Hcy increased the expression of miR-224-3p in a dose-dependent manner but decreased that of SOD1 mRNA and protein. Hcy also increased oxidative stress in the PC12 cells and the proapoptotic proteins Bax, Caspase-3, and Caspase-9. Furthermore, it decreased the expression of anti-apoptotic protein Bcl-2 and the activity and survival rate of the HT22 cells, but it increased the apoptosis of the PC12 cells. The treatment of Hcy-induced PC12 cells with different concentrations of naringenin for 24 h decreased the expression of miR-224-3p in a dose-dependent manner and increased the expressions of SOD1 mRNA and protein. The treatment also decreased the oxidative stress in the PC12 cells and the expressions of pro-apoptotic proteins Bax, Caspase-3, and Caspase-9; increased the expression of anti-apoptotic protein Bcl- 2; decreased the apoptosis of the PC12 cells; and increased the PC12 cells.The results suggest that Naringenin can decrease the apoptosis and oxidative stress of PC12 cells induced by Hcy and increase the activities and survival rates of PC12 cells. The mechanism may be related to naringenin decreasing the expression of miR-224-3p in PC12 cells induced by Hcy and increasing the expressions of SOD1 mRNA and protein.
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Flavanonas/farmacología , MicroARNs/genética , Neuroprotección , Superóxido Dismutasa-1/genética , Animales , Apoptosis , Caspasa 3 , Caspasa 9 , Homocisteína , Estrés Oxidativo , Células PC12 , Ratas , Regulación hacia Arriba , Proteína X Asociada a bcl-2RESUMEN
Baicalin has been used in China to treat inflammation-related diseases, such as inflammation-induced acute kidney injury (AKI). However, the specific mechanism of baicalin remains unclear. To observe the protective effects of baicalin on lipopolysaccharide (LPS)-induced inflammatory injury of renal tubular epithelial cells (HK-2 cells) and to explore its protective mechanism. LPS (1 mg/L) was used to induce an HK-2 cell inflammatory injury model in vitro. The cells were divided into seven groups: the normal control group, LPS-induced group, LPS plus 5 µmol/L baicalin treatment group, LPS plus 15 µmol/L baicalin treatment group, LPS plus 25 µmol/L baicalin treatment group, LPS plus 50 µmol/L baicalin treatment group, and LPS plus 75 µmol/L baicalin treatment group. 3-(4,5-dimethyl-2-thiazolyl)-2,5- diphenyl-2-H-tetrazolium bromide (MTT) assay was employed for detecting the relative survival rate of HK-2 cells. Enzyme-linked immunosorbent assay was used for detecting the levels of inflammatory factors, including interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α). Moreover, the expression of inducible nitric oxide synthase (iNOS); cyclooxygenase-2 (COX-2); nuclear factor kB65 (NF-κB65); phosphorylated NF-κB inhibitory protein-α (p-IκB-α); NF-κB inhibitory protein (IκB); human thioredoxin interacting protein (TXNIP); and human NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) were determined by Western blot analysis. The expression levels of NLRP3 and TXNIP mRNA and miR-223-3p were determined by RT-PCR. Results found that the relative survival rate of HK-2 cells treated with different baicalin concentrations was significantly increased (P<0.05) and the levels of the inflammatory factors IL-6, IL-1ß, and TNF-α were significantly decreased (P<0.05) compared with those of the LPS-induced group. The expression levels of the inflammatory proteins inducible nitric oxide synthase and cyclooxygenase-2 and the genes expressions of TXNIP and NLRP3 were significantly decreased in the cells (P<0.05), while the expression level of miR-223- 3p was significantly increased (P<0.05). These changes were induced in a dose-dependent manner. The results suggest that baicalin significantly inhibited the expression of inflammation-related proteins and alleviated LPS-induced inflammatory injury in HK-2 cells. The mechanism may be associated with the inhibition of activation of the TXNIP/NLRP3 inflammatory pathway, which might be mediated by increased expression of miR-223-3p. Thus, NLRP3 is a regulatory target of miR-223-3p.
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Proteínas Portadoras/metabolismo , Células Epiteliales/efectos de los fármacos , Flavonoides/farmacología , MicroARNs/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Transducción de Señal , Células Cultivadas , Citocinas/metabolismo , Humanos , Inflamación , Túbulos Renales/citología , LipopolisacáridosRESUMEN
AIM: To compare the efficacy of ultrasonically activated irrigation (UAI), photon-induced photoacoustic streaming (PIPS) and shock wave enhanced emission photoacoustic streaming (SWEEPS) activation for the removal of accumulated hard-tissue debris (AHTD) from the root canal system of mandibular molars when assessed using microcomputed tomography (micro-CT). METHODOLOGY: A total of 30 mandibular first and second molars with joining mesial root canals containing an isthmus and a single distal canal were subjected to three micro-CT scans (before and after canal instrumentation and after final irrigation) at a resolution of 15 µm. Mesial canals were prepared up to a ProTaper F3 rotary file, and distal canals were prepared up to a ProTaper F4 rotary file. Teeth were randomly assigned to three groups according to the irrigant activation method (n = 10): the UAI group, the PIPS group and the SWEEPS group. The final irrigation procedures were performed using a total of 15.5 mL of 1% NaOCl for each tooth with an activation time of 3 × 30 s. After three-dimensional model reconstruction and volumetric measurement of root canals, the percentage reduction (%Rd) of AHTD was calculated. The %Rd of AHTD was analysed statistically using one-way analysis of variance and nonparametric tests at a significance level of 5%. RESULTS: There were no significant differences between the three groups in terms of canal volume before or after instrumentation, or the volume of debris after canal preparation (P > 0.05). In the mesial canals, irrigation with SWEEPS reduced the overall debris by 84.31%, which was significantly more than the reduction associated with PIPS and UAI (58.79% and 50.27%, respectively). In the distal canals, the %Rd of AHTD was significantly different between PIPS and SWEEPS and between UAI and SWEEPS (P < 0.05), but was not significantly different between PIPS and UAI groups (P > 0.05). The SWEEPS was associated with a greater %Rd of AHTD than the PIPS and UAI groups. CONCLUSIONS: SWEEPS was associated with significantly less debris compared than PIPS and UAI, especially in isthmus-containing mesial roots. None of the activation techniques completely removed debris from root canal systems.
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Cavidad Pulpar , Irrigantes del Conducto Radicular , Humanos , Diente Molar , Preparación del Conducto Radicular , Irrigación Terapéutica , Microtomografía por Rayos XRESUMEN
BACKGROUND AND PURPOSE: Vessel wall imaging can identify intracranial atherosclerotic plaque and give clues about its components. We aimed to investigate whether the plaque hyperintensity in the middle cerebral artery on T2-weighted vessel wall imaging is associated with ischemic stroke. MATERIALS AND METHODS: We retrospectively reviewed our institutional vessel wall MR imaging data base. Patients with an acute ischemic stroke within 7-day onset in the MCA territory were enrolled. Patients with stroke and stenotic MCA plaque (stenosis degree, ≥50%) were included for analysis. Ipsilateral MCA plaque was defined as symptomatic, and contralateral plaque, as asymptomatic. Plaque was manually delineated on T2-weighted vessel wall imaging. The plaque signal was normalized to the ipsilateral muscle signal. The thresholds and volume of normalized plaque signal were investigated using logistic regression and receiver operating characteristic analysis to determine the association between normalized plaque signal and stroke. RESULTS: One hundred eight stenotic MCAs were analyzed (from 88 patients, 66 men; mean age, 58 ± 15 years), including 72 symptomatic and 36 asymptomatic MCA plaques. Symptomatic MCA plaque showed larger plaque hyperintensity volume compared with asymptomatic MCA plaque. The logistic regression model incorporating stenosis degree, remodeling ratio, and normalized plaque signal 1.3-1.4 (OR, 6.25; 95% CI, 1.90-20.57) had a higher area under curve in differentiating symptomatic/asymptomatic MCA plaque, compared with a model with only stenosis degree and remodeling ratio (area under curve, 0.884 versus 0.806; P =.008). CONCLUSIONS: The MCA plaque hyperintensity on T2-weighted vessel wall imaging is independently associated with ischemic stroke and adds value to symptomatic MCA plaque classification. Measuring the normalized signal intensity may serve as a practical and integrative approach to the analysis of intracranial atherosclerotic plaque.
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Arteriosclerosis Intracraneal/complicaciones , Arteriosclerosis Intracraneal/diagnóstico por imagen , Arteria Cerebral Media/diagnóstico por imagen , Neuroimagen/métodos , Accidente Cerebrovascular/etiología , Adulto , Anciano , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/etiología , Isquemia Encefálica/patología , Constricción Patológica/complicaciones , Constricción Patológica/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/patología , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/diagnóstico por imagen , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/patologíaRESUMEN
This paper presents an enhanced model that considers the specifications of personal space to describe uni- and bi-directional pedestrian movement on stairs. The shape of the personal space of each pedestrian is regarded as an oval shape, which is composed of four arcs, to precisely quantify movements. Specific models that facilitate the simulation of movement include adjustments to individual speeds based on the proximity of other members, conflict avoidance, overtaking, and direction finding. By implementing these parameters in the simulation, basic data concerning these movement behaviours were collected from the experiment, which was carried out at one a Shanghai subway station. Twenty-four young college students participated in this experiment. Numerical simulation results for a stochastic case under those parameters were obtained. The fundamental diagrams and moving behaviours according to different proportions of ascending and descending pedestrians are analysed and discussed. The results indicate that the simulation platform for personal space can serve as a useful tool to evaluate pedestrian movement on stairs.
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Peatones/psicología , Espacio Personal , Subida de Escaleras , China , Femenino , Humanos , Masculino , Movimiento/fisiologíaRESUMEN
OBJECTIVES: Findings regarding the benefits of fruit and vegetables (FV) on weight control are inconsistent and little is known among Chinese populations. Therefore, we examined the relationship between change in FV consumption, weight, and change in body mass index (BMI) among Chinese adults, participants of the China Health and Nutrition Survey (CHNS). STUDY DESIGN: A prospective cohort study. METHODS: Two waves of CHNS conducted in 2006 and 2011 were used. Continuous FV consumption increase was considered as the exposure and changes in weight and BMI as outcomes. Change in FV consumption was categorized into quintiles. Analysis of covariance and multiple linear regression models, after controlling for potential confounders such as energy intake, physical activity, and smoking, were used to describe the relationship between change in FV consumption and change in weight and BMI. RESULTS: A total of 4357 participants aged 18-65 years were included in this study. The respective weight and BMI gains in male individuals were 1.81 kg and 0.73 kg/m2 in the fifth quintile of FV change relative to individuals in the first quintile (3.67 kg for weight gain and 1.48 kg/m2 for BMI gain). An increase in FV consumption by 100 g was associated with a 211 g weight loss (B = -2.11; 95% confidence interval [CI], -3.34, -0.89, P < 0.001) and a decrease in BMI by 0.94 kg/m2 (B = -0.94; 95% CI, -1.36, -0.46, P < 0.001) in men; and a 140 g weight loss (B = -0.14; 95% CI, -0.97, 0.69, P = 0.74) and a decrease in BMI by 0.29 kg/m2 BMI (B = -0.29; 95% CI, -0.63, 0.06, P = 0.11) in women. CONCLUSIONS: Increase in FV consumption was associated with statistically significant weight loss and decrease in BMI among Chinese men, and, although suggested, weight loss among women was not significant. Considering the protective effect of FV on human health, increasing FV consumption in the Chinese population is recommended.
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Índice de Masa Corporal , Peso Corporal , Dieta/estadística & datos numéricos , Frutas , Verduras , Adolescente , Adulto , Anciano , China/epidemiología , Dieta/efectos adversos , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Obesidad/epidemiología , Sobrepeso/epidemiología , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Despite availability of an approved drug to treat acute cerebral ischemia, most patients with stroke do not realize a good outcome. A method that would rapidly increase or restore cerebral perfusion before irreversible cell death should improve patient outcomes. MATERIALS AND METHODS: We recently had the opportunity to treat 6 middle-aged-to-elderly patients who presented with signs and symptoms of acute cerebral ischemia, by mechanically removing their (predominantly) middle cerebral artery clots by using a new retrieval device that had been previously approved by the US Food and Drug Administration for intravascular retrieval of foreign bodies. During a 2-month period, the 6 patients were treated in 5 separate institutions. No patient had an unsuccessful attempt at clot removal. The cases were collected by personal communication with each operator. RESULTS: In all instances, use of the device resulted in rapid clot removal. Each patient had a large improvement in National Institutes of Health Stroke Scale score. Two of the 6 patients had experienced failure of another clot retrieval device, and 3 patients required no systemic thrombolytics, reducing the likelihood of one of the most feared complications of stroke therapy, intracranial hemorrhage. SUMMARY: We believe that use of this device may result in improved outcomes for patients with acute ischemic stroke. In our limited experience, it provided a rapid, safe, and effective means for achieving revascularization.
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Isquemia Encefálica/terapia , Revascularización Cerebral/instrumentación , Infarto de la Arteria Cerebral Media/terapia , Trombectomía/instrumentación , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico por imagen , Angiografía Cerebral , Revascularización Cerebral/métodos , Femenino , Humanos , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Persona de Mediana Edad , Trombectomía/métodosRESUMEN
To elucidate the direct effect of rosiglitazone (RSG), a new thiazolidinedione antihyperglycemic agent, on pancreatic insulin secretion, an in situ investigation by rat pancreatic perfusion was performed. At a basal glucose concentration of 6 mmol/l, RSG (0.045-4.5 micromol/l) stimulated insulin release in a dose-dependent manner. In addition, 4.5 micromol/l RSG potentiated the glucose (10 mmol/l)-induced insulin secretion. Both the first and second phases of glucose-induced insulin secretion were significantly enhanced by RSG, by 80.7 and 52.4%, respectively. The effects of RSG on insulin secretion were inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. In contrast, the glucose-stimulated insulin secretion was not affected by LY294002. The potentiation effect of RSG on glucose-stimulated insulin secretion, in both the first and second phases, was significantly blocked by LY294002. These results suggest that RSG has a direct potentiation effect on insulin secretion in the presence of 10 mmol/l glucose, mediated through PI3K activity. The inability of LY294002 to inhibit glucose-induced insulin secretion suggests that different pathways are responsible for glucose and RSG signaling.
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Hipoglucemiantes/farmacología , Insulina/metabolismo , Fosfatidilinositol 3-Quinasas/fisiología , Tiazoles/farmacología , Tiazolidinedionas , Animales , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Glucosa/farmacología , Técnicas In Vitro , Secreción de Insulina , Masculino , Ratas , Ratas Sprague-Dawley , RosiglitazonaRESUMEN
OBJECTIVES: TEE is performed in many patients with ischemic stroke, and it is possible to examine the proximal coronaries by TEE in these patients. Our purpose was to (1) determine the accuracy of transesophageal echocardiography (TEE) in the diagnosis of proximal coronary stenosis in patients with ischemic stroke and (2) show that TEE detection of proximal coronary stenosis changed management in a substantial number of patients. METHODS: Thirty-two patients with ischemic stroke undergoing TEE, in whom the proximal coronaries were examined and who had angiographic results available, were studied. RESULTS: Proximal coronaries were visualized as follows: left main (LM) in 31 (97%), left anterior descending (LAD) in 32 (100%), left circumflex (LCx) in 30 (94%) and right coronary artery (RCA) in 21 (66%). The sensitivity and specificity of TEE in diagnosing significant coronary stenosis in visualized vessels were as follows: LM 100% and 100%, LAD 100% and 95%, LCx 100% and 96%, and RCA 100% and 100%, respectively. When visualized and nonvisualized segments were considered, TEE detected significant stenosis as follows: 4 of 5 in the LM (80%), 13 of 13 in the LAD (100%), 2 of 3 in the LCx (66%), and 2 of 8 in the RCA (25%). Of the 32 patients, TEE results changed management in 17 patients (53%). Angiographic findings resulted in 10 of the 17 patients (59%) undergoing revascularization. CONCLUSIONS: TEE was very accurate in diagnosing significant coexisting coronary artery disease in patients with ischemic stroke. TEE diagnosis of these lesions prompted coronary angiography and subsequent revascularization in a substantial number of patients.