RESUMEN
BACKGROUND: Current guidelines recommend complete revascularization (CR) in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD). With regard to the timing of percutaneous coronary intervention (PCI) for non-infarct-related artery (non-IRA), recent randomized clinical trials have revealed that immediate CR was non-inferior to staged CR. However, the optimal timing of CR remains uncertain. The OPTION-STEMI trial compared immediate CR and in-hospital staged CR guided by fractional flow reserve (FFR) for intermediate stenosis of the non-IRA. METHODS: The OPTION-STEMI is a multicenter, investigator-initiated, prospective, open-label, non-inferiority randomized clinical trial. The study included patients with at least 1 non-IRA lesion with ≥50% stenosis by visual estimation. Patients fulfilling the inclusion criteria were randomized into 2 groups at a 1:1 ratio: immediate CR (i.e., PCI for the non-IRA performed during primary angioplasty) or in-hospital staged CR. In the in-hospital staged CR group, PCI for non-IRA lesions was performed on another day during the index hospitalization. Non-IRA lesions with 50%-69% stenosis by visual estimation were evaluated by FFR, whereas those with ≥70% stenosis was revascularized without FFR. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, and all unplanned revascularization at 1 year after randomization. Enrolment began in December 2019 and was completed in January 2024. The follow-up for the primary endpoint will be completed in January 2025, and primary results will be available in the middle of 2025. CONCLUSIONS: The OPTION-STEMI is a multicenter, non-inferiority, randomized trial that evaluated the timing of in-hospital CR with the aid of FFR in patients with STEMI and MVD. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04626882; and URL: https://cris.nih.go.kr. Unique identifier: KCT0004457.
Asunto(s)
Enfermedad de la Arteria Coronaria , Reserva del Flujo Fraccional Miocárdico , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Reserva del Flujo Fraccional Miocárdico/fisiología , Infarto del Miocardio con Elevación del ST/fisiopatología , Infarto del Miocardio con Elevación del ST/cirugía , Infarto del Miocardio con Elevación del ST/terapia , Intervención Coronaria Percutánea/métodos , Estudios Prospectivos , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico , Masculino , Femenino , Angiografía Coronaria , Factores de Tiempo , Revascularización Miocárdica/métodos , Tiempo de Tratamiento , Persona de Mediana EdadRESUMEN
ABSTRACT: There have been few studies of angiotensin receptor blocker (ARB) dose in myocardial infarction (MI) with preserved left ventricular (LV) systolic function. We evaluated the association of ARB dose with clinical outcomes after MI with preserved LV systolic function. We used MI multicenter registry. Six months after discharge, the ARB dose was indexed to the target ARB doses used in randomized clinical trials and grouped as >0%-25% (n = 2333), >25% of the target dose (n = 1204), and no ARB (n = 1263). The primary outcome was the composite of cardiac death or MI. Univariate analysis showed that mortality of those with any ARB dose was lower than those without ARB therapy. After multivariable adjustment, patients receiving >25% of target dose had a similar risk of cardiac death or MI compared with those receiving ≤25% or no ARB [hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.83-1.33; HR 0.94, 95% CI 0.82-1.08, respectively]. Propensity score analysis also demonstrated that patients with >25% dose had no difference in primary endpoint compared with those ≤25% dose or the no ARB group (HR 1.03, 95% CI 0.79-1.33; HR 0.86, 95% CI 0.64-1.14, respectively). The present study demonstrates that patients treated with >25% of target ARB dose do not have better clinical outcomes than those treated with ≤25% of target ARB dose or those with no ARB dose in MI patients with preserved LV systolic function.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , Infarto del Miocardio , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Resultado del Tratamiento , Función Ventricular Izquierda , Antagonistas de Receptores de Angiotensina/efectos adversosRESUMEN
A simple and efficient AgOTf-promoted tandem olefin isomerization/intramolecular hydroamination of 1,1-disubstituted alkenyl amines has been developed. This one-pot process represents a facile and attractive route for the synthesis of diverse 2-alkyl-substituted 1,3-X,N-heterocycles through chemo- and regioselective C(sp3)-N bond formation with atom economy. Advantages such as the operationally simple and practical procedure that uses a readily available catalyst under aerobic conditions, good to excellent chemical yields, the high functional group tolerance, the broad substrate scope, and high efficiency and selectivity are noteworthy.
Asunto(s)
Alquenos , Aminas , Alquenos/química , Aminas/química , Catálisis , Isomerismo , Estructura MolecularRESUMEN
Pd-Catalyzed intramolecular allylic C-H amination of 1,1-disubstituted alkenyl amines with various allylic tethers (X = O, NMs, CH2) was developed. This process allows for the divergent synthesis of 1,3-X,N-heterocycles through a regioselective allylic C-H cleavage and π-allylpalladium formation. Particularly noteworthy is the use of substrates containing a labile allylic moiety and new simple catalytic systems capable of promoting highly chemo- and regioselective allylic C-H amination by overcoming significant challenges.
Asunto(s)
Aminas , Paladio , Aminación , Aminas/química , Catálisis , Paladio/químicaRESUMEN
ABSTRACT: Beta-blockers are recommended as a standard treatment for patients who experience a myocardial infarction (MI). However, the evidence supporting this recommendation is based on the prereperfusion era data. This review aims to evaluate the effectiveness of long-term (≥1 year) beta-blocker therapy in post-MI patients without clinical heart failure (HF) in the reperfusion era. We included observational cohort studies, which compared at least 1 year use of beta-blockers to no beta-blockers in patients with an acute MI, but without HF. The clinical endpoint considered was all-cause mortality, except for cardiovascular death in one study. Five cohort studies and 217,532 patients were included. One study demonstrated a reduction in all-cause mortality with beta-blockers, whereas, in 4 studies, there was no difference in the death rate. The pooled estimate by random effect showed that beta-blocker treatment does not reduce mortality (odds ratio 0.800, 95% confidence interval 0.559-1.145) with high heterogeneity (I2 = 94%). This meta-analysis shows that the use of oral beta-blockers for 1 year or more does not reduce the mortality of MI patients without HF. Large randomized trials need to evaluate beta-blocker discontinuation after an acute MI.
Asunto(s)
Antagonistas Adrenérgicos beta , Infarto del Miocardio , Antagonistas Adrenérgicos beta/uso terapéutico , Estudios de Cohortes , Insuficiencia Cardíaca/epidemiología , Humanos , Infarto del Miocardio/tratamiento farmacológico , Reperfusión , Resultado del TratamientoRESUMEN
OBJECTIVE: There are few existing data on the status of coronary artery disease (CAD) in patients with atherosclerosis of the cerebral artery detected by brain imaging studies. We aimed to analyze the predictors of asymptomatic angiographically significant CAD detected by simultaneous cerebral and coronary angiography. METHODS: This retrospective cohort study screened data obtained between August 2009 and April 2019; 11,047 patients underwent cerebral angiography for atherosclerotic change (>50% stenosis or aneurysm) seen in brain magnetic resonance angiography (MRA) or computed tomography angiography (CTA) at a single center by endovascular neurosurgeon's decision. Of these, 700 patients including 622 patients who underwent simultaneous coronary and cerebral angiography and 78 patients who underwent coronary angiography within a month were enrolled. We investigated the characteristics and predictors of angiographically significant CAD (>50% stenosis). Furthermore, we also analyzed the major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, myocardial infarction, and stroke for 5 years. RESULTS: The frequency of significant CAD was 59% (413/700), the mean age was 68.9 ± 10.3 years, and 60.6% were male. During mean follow-up of 50 months, the MACCE rate of our whole cohort was significantly higher in the CAD group (21.5%) than in the non-CAD group (14.6%; hazard ratio 1.65, 95% CI 1.17-2.33, p value = 0.005). Considering that the embolic stroke is less associated with atherosclerotic change, our predictive model of significant CAD was made without embolic stroke (n = 599). In our multivariate model 2 including univariate <0.1, the independent predictors of significant CAD were male (OR 1.62, 95% CI 1.11-2.35, p = 0.012), diabetes mellitus (OR 1.81, 95% CI 1.22-2.68, p = 0.003), previous stroke (OR 1.63, 95% CI 1.02-2.60, p = 0.039), low ankle-brachial index (ABI; <0.9; OR 3.25, 95% CI 1.21-8.73, p = 0.019), left ventricular ejection fraction (EF) <50% on echocardiography (OR 2.82, 95% CI 1.25-6.35, p = 0.012), troponin I or T positive (OR 2.76, 95% CI 1.69-4.53, p < 0.001), and complex features on cerebral angiography (OR 2.73, 95% CI 1.78-4.19, p < 0.001). CONCLUSIONS: Accurate coronary evaluation by coronary angiography might be considered when patients with atherosclerotic cerebral artery detected on brain MRA or CTA planned cerebral angiography were male or have diabetes mellitus, previous stroke, low ABI (<0.9), left ventricular EF <50% on echocardiography, troponin I or T positivity, and complex features on cerebral angiography.
Asunto(s)
Isquemia Encefálica/diagnóstico por imagen , Angiografía Cerebral , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estenosis Coronaria/diagnóstico por imagen , Aneurisma Intracraneal/diagnóstico por imagen , Arteriosclerosis Intracraneal/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Anciano , Angiografía de Substracción Digital , Isquemia Encefálica/epidemiología , Angiografía por Tomografía Computarizada , Enfermedad de la Arteria Coronaria/epidemiología , Estenosis Coronaria/epidemiología , Femenino , Humanos , Aneurisma Intracraneal/epidemiología , Arteriosclerosis Intracraneal/epidemiología , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , República de Corea/epidemiología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/epidemiologíaRESUMEN
BACKGROUND: The turbulence of blood flow caused by stenosis has an impact on the surrounding coronary artery tissue and creates an audio-frequency vibration to the adjacent myocardial wall. We investigated the diagnostic feasibility of a novel diagnostic method using wide range gate (WRG) ultrasound data acquisition for diagnosing coronary artery disease (CAD). WRG data acquisition detects high-frequency vibrations from coronary artery stenosis, using pulse-wave Doppler ultrasound. METHODS: We used a Verasonics ultrasound data acquisition system to implement the WRG data acquisition. Investigators performed clinical trials for 80 subjects, with suspected CAD. All enrolled patients participated in WRG data acquisition before coronary angiography (CAG). RESULTS: As compared with the results of CAG, the sensitivity and specificity of the WRG data analysis were 80% and 84%, respectively. The WRG data analysis showed that the sensitivity and specificity were 81% and 79% in the left anterior descending artery, respectively, 75% and 89% in the left circumflex artery, respectively, and 85% and 82% in the right coronary artery, respectively. In a multivariate analysis, a positive vibrometry result was an independent predictive factor for CAD. CONCLUSIONS: We proposed a new diagnostic method for detecting CAD using ultrasound. The new data acquisition method showed good potential as an initial diagnostic tool for CAD.
Asunto(s)
Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico , Circulación Coronaria/fisiología , Vasos Coronarios/diagnóstico por imagen , Ecocardiografía Doppler de Pulso/métodos , Flujo Sanguíneo Regional/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/fisiopatología , Vasos Coronarios/fisiopatología , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
We previously reported that proinflammatory cytokines (interleukin-1ß and interferon-γ) induced the expression of lipocalin-2 (LCN-2) together with inducible nitric oxide synthase (iNOS) in RINm5F beta-cells. Therefore, we examined the effect of nitric oxide (NO) on LCN-2 expression in cytokines-treated RINm5F beta-cells. Additionally, we observed the effect of LCN-2 on cell viability. First, we found the existence of LCN-2 receptor and the internalization of exogenous recombinant LCN-2 peptide in RINm5F and INS-1 beta-cells. Next, the effects of NO on LCN-2 expression were evaluated. Aminoguanidine, an iNOS inhibitor and iNOS gene silencing significantly inhibited cytokines-induced LCN-2 expression while sodium nitroprusside (SNP), an NO donor potentiated it. Luciferase reporter assay showed that transcription factor NF-κB was not involved in LCN-2 expression. Both LCN-2 mRNA and protein stability assays were conducted. SNP did not affect LCN-2 mRNA stability, however, it significantly reduced LCN-2 protein degradation. The LCN-2 protein degradation was significantly attenuated by MG132, a proteasome inhibitor. Finally, the effect of LCN-2 on cell viability was evaluated. LCN-2 peptide treatment and LCN-2 overexpression significantly reduced cell viability. FACS analysis showed that LCN-2 induced the apoptosis of the cells. Collectively, NO level affects LCN-2 expression via regulation of LCN-2 protein stability under inflammatory condition and LCN-2 may reduce beta-cell viability by promoting apoptosis.
Asunto(s)
Regulación de la Expresión Génica , Células Secretoras de Insulina/inmunología , Interferón gamma/inmunología , Interleucina-1beta/inmunología , Lipocalina 2/genética , Óxido Nítrico/inmunología , Animales , Apoptosis , Línea Celular , Supervivencia Celular , Inflamación/genética , Inflamación/inmunología , Células Secretoras de Insulina/citología , Células Secretoras de Insulina/metabolismo , Lipocalina 2/inmunología , ARN Mensajero/genética , RatasRESUMEN
Enterovirus 71 frequently involves the central nervous system and may present with a variety of neurologic manifestations. Here, we aimed to describe the clinical features, magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) profiles of patients presenting with neurologic complications of enterovirus 71 infection. We retrospectively reviewed the records of 31 pediatric patients hospitalized with acute neurologic manifestations accompanied by confirmed enterovirus 71 infection at Ulsan University Hospital between 2010 and 2014. The patients' mean age was 2.9 ± 5.5 years (range, 18 days to 12 years), and 80.6% of patients were less than 4 years old. Based on their clinical features, the patients were classified into 4 clinical groups: brainstem encephalitis (n = 21), meningitis (n = 7), encephalitis (n = 2), and acute flaccid paralysis (n = 1). The common neurologic symptoms included myoclonus (58.1%), lethargy (54.8%), irritability (54.8%), vomiting (48.4%), ataxia (38.7%), and tremor (35.5%). Twenty-five patients underwent an MRI scan; of these, 14 (56.0%) revealed the characteristic increased T2 signal intensity in the posterior region of the brainstem and bilateral cerebellar dentate nuclei. Twenty-six of 30 patients (86.7%) showed CSF pleocytosis. Thirty patients (96.8%) recovered completely without any neurologic deficits; one patient (3.2%) died due to pulmonary hemorrhage and shock. In the present study, brainstem encephalitis was the most common neurologic manifestation of enterovirus 71 infection. The characteristic clinical symptoms such as myoclonus, ataxia, and tremor in conjunction with CSF pleocytosis and brainstem lesions on MR images are pathognomonic for diagnosis of neurologic involvement by enterovirus 71 infection.
Asunto(s)
Enfermedades del Sistema Nervioso Central/patología , Enterovirus Humano A/aislamiento & purificación , Infecciones por Enterovirus/patología , Enfermedad Aguda , Encéfalo/diagnóstico por imagen , Enfermedades del Sistema Nervioso Central/etiología , Niño , Preescolar , Encefalitis/patología , Enterovirus Humano A/genética , Infecciones por Enterovirus/tratamiento farmacológico , Infecciones por Enterovirus/virología , Heces/virología , Femenino , Humanos , Inmunoglobulinas/administración & dosificación , Lactante , Inyecciones Intravenosas , Leucocitos/citología , Leucocitosis/líquido cefalorraquídeo , Leucocitosis/patología , Imagen por Resonancia Magnética , Masculino , ARN Viral/genética , ARN Viral/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , República de Corea , Estudios Retrospectivos , Estaciones del AñoRESUMEN
BACKGROUND/AIMS: Atrial fibrillation (AF) often coexists with acute myocardial infarction (AMI), and chronic kidney disease (CKD) is a major risk for AMI. However, the combined impact of CKD and AF on the mortality and morbidity in AMI population has not been determined. METHODS: Between January 2004 and December 2009, a total of 4,738 AMI patients were enrolled prospectively. Patients were divided into four groups according to the combined status of CKD and AF. The primary endpoint was a combination of 5-year major adverse cardiac and cerebrovascular events (MACCE). RESULTS: The prevalence of AF was significantly higher in CKD patients than in non-CKD patients (6.76 vs. 3.31%, p < 0.001). The highest cumulative event rate of MACCE and death was observed in patients with both CKD and AF (68.5 and 64.0%), respectively. In multivariable analyses, compared with patients with neither AF nor CKD, hazard ratios (HR) for composite of MACCE were 1.66 (95% CI, 1.14-2.41), 1.24 (95% CI, 1.06-1.46), and 2.10 (95% CI, 1.42-3.13) for patients with AF only, those with CKD only, and those with both CKD and AF, respectively (p for interaction = 0.935). Patients with both CKD and AF had a greatest risk for all-cause mortality (HR 2.54; 95% CI, 1.60-4.53), and the significant synergistic interaction was observed between CKD and AF (p for interaction = 0.015). CONCLUSION: The combined effect of AF and CKD on the risk of MACCE after an AMI is stronger than any separate condition, and it confers a synergistic effect on the all-cause mortality risk.
Asunto(s)
Fibrilación Atrial/complicaciones , Trastornos Cerebrovasculares/etiología , Infarto del Miocardio/complicaciones , Sistema de Registros , Insuficiencia Renal Crónica/complicaciones , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Estudios Prospectivos , República de Corea/epidemiologíaRESUMEN
Pannexins (Panx) are a family of proteins that share sequences with the invertebrate gap junction proteins, innexins, and have a similar structure to that of the vertebrate gap junction proteins, connexins. To date, the Panx family consists of 3 members, but their genetic sequences have only been completely determined in a few vertebrate species. Moreover, expression of the Panx family has been reported in several rodent tissues: Panx1 is ubiquitously expressed in mammals, whereas Panx2 and Panx3 expressions are more restricted. Although members of the Panx family have been detected in mammals, their genetic sequences in avian species have not yet been fully elucidated. Here, we obtained the full-length mRNA sequences of chicken PANX genes and evaluated the homology of the amino acids from these sequences with those of other species. Furthermore, PANX gene expression in several chicken tissues was investigated based on mRNA levels. PANX1 was detected in the brain, cochlea, chondrocytes, eye, lung, skin, and intestine, and PANX2 was expressed in the brain, eye, and intestine. PANX3 was observed in the cochlea, chondrocytes, and bone. In addition, expression of PANX3 was higher than PANX1 in the cochlea. Immunofluorescent staining revealed PANX1 in hair cells, as well as the supporting cells, ganglion neurons, and the tegmentum vasculosum in chickens, whereas PANX3 was only detected in the bone surrounding the cochlea. Overall, the results of this study provide the first identification and characterization of the sequence and expression of the PANX family in an avian species, and fundamental data for confirmation of Panx function.
Asunto(s)
Proteínas Aviares/genética , Pollos/genética , Conexinas/genética , Regulación del Desarrollo de la Expresión Génica , Animales , Proteínas Aviares/metabolismo , Embrión de Pollo , Pollos/clasificación , Pollos/crecimiento & desarrollo , Pollos/metabolismo , Clonación Molecular , Conexinas/metabolismo , Datos de Secuencia Molecular , Especificidad de Órganos , Filogenia , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Homología de Secuencia de AminoácidoRESUMEN
Pineapple mealybug, Dysmicoccus brevipes (Hemiptera: Pseudococcidae), is a significant pest in pineapple production and a key trade barrier. We explored the potential use of ethyl formate (EF) as a methyl bromide alternative for the postharvest fumigation of D. brevipes in imported pineapples. When treated at 8 °C for 4 h, EF fumigation was effective against D. brevipes with LCt99, the lethal concentration × time product of EF necessary to achieve 99% mortality of D. brevipes nymphs and adults at 64.2 and 134.8 g h/m3, respectively. Sorption trials conducted with 70 g/m3 EF for 4 h at 8 °C using 7.5, 15 and 30% pineapple loading ratios (w/v) indicated that loading ratio lower than 30% is necessary to achieve the LCt99 values required to control D. brevipes. In a scaled up trial using 1 m3 chamber, EF fumigation with 70 g/m3 for 4 h at 8 °C with 20% pineapple loading ratio (w/v) resulted in a complete control of D. brevipes treated. There were no significant differences in hue values, sugar contents, firmness, and weight loss between EF-treated and untreated pineapples. Our results suggest that EF is a promising alternative to methyl bromide fumigation for the postharvest phytosanitary disinfection of D. brevipes in pineapples.
RESUMEN
Glucagon-like peptide-1 (GLP-1) and its potent agonists have been widely studied in pancreatic islet ß-cells. However, GLP-1 receptors are present in many extrapancreatic tissues including macrophages, and thus GLP-1 may have diverse actions in these tissues and cells. Therefore, we examined the mechanism by which exendin-4 (EX-4), a potent GLP-1 receptor agonist, inhibits lipopolysaccharide (LPS)-induced iNOS expression in Raw264.7 macrophage cells. EX-4 significantly inhibited LPS-induced iNOS protein expression and nitrite production. However, Northern blot and promoter analyses demonstrated that EX-4 did not inhibit LPS-induced iNOS mRNA expression and iNOS promoter activity. Electrophoretic mobility shift assay (EMSA) showed that EX-4 did not alter the binding activity of NF-κB to the iNOS promoter. Consistent with the result of EMSA, LPS-induced IκBα phosphorylation and nuclear translocation of p65 were not inhibited by EX-4. Also, actinomycin D chase study and the promoter assay using the construct containing 3'-untranslated region of iNOS showed that EX-4 did not affect iNOS mRNA stability. Meanwhile, cycloheximide chase study demonstrated that EX-4 significantly accelerated iNOS protein degradation. The EX-4 inhibition of LPS-induced iNOS protein was significantly reversed by adenylate cyclase inhibitors (MDL-12330A and SQ 22536), a PKA inhibitor (H-89) and PKAα gene silencing. These findings suggest that EX-4 inhibited LPS-induced iNOS expression at protein level, but not at transcriptional mechanism of iNOS gene and this inhibitory effect of EX-4 was mainly dependent on cAMP/PKA system.
Asunto(s)
AMP Cíclico/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Péptidos/farmacología , Ponzoñas/farmacología , Regiones no Traducidas 3' , Animales , Línea Celular , Dactinomicina/farmacología , Activación Enzimática , Inhibidores Enzimáticos/farmacología , Estabilidad de Enzimas , Exenatida , Regulación Enzimológica de la Expresión Génica , Receptor del Péptido 1 Similar al Glucagón , Iminas/farmacología , Macrófagos/metabolismo , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Nitritos/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Proteolisis , Estabilidad del ARN , Receptores de Glucagón/agonistasRESUMEN
The impact of the CYP2C19*17 polymorphism on the clinical outcome in Asians undergoing percutaneous coronary intervention (PCI) is unknown. We sought to assess the long-term impact of CYP2C19*17 on the risk for adverse clinical events in 2188 Korean patients taking clopidogrel after PCI. The prevalence of the CYP2C19*17 allele [*wt/*17: 2.4% (n = 53), *17/*17: 0%] was very low. The 2-year cumulative event rates for bleeding [*wt/*17 vs. *wt/*wt: 2 vs. 2.3%; adjusted hazard ratio (HR), 1.23; 95% confidence interval (CI), 0.16-9.45], stent thrombosis (2 vs. 1.1%; HR, 3.98; 95% CI, 0.49-31.6) or composite of any death, and myocardial infarction or stroke (5.4 vs. 7.1%; HR, 1.37; 95% CI, 0.32-5.73) did not differ on the basis of the presence of CYP2C19*17. In conclusion, in our study population of Asian patients, the CYP2C19*17 polymorphism was not associated with adverse clinical outcomes after PCI because of its low prevalence, the rarity of homozygotes, and the relatively low rate of adverse clinical events.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas/genética , Aspirina/uso terapéutico , Isquemia Miocárdica/cirugía , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticlopidina/análogos & derivados , Aspirina/administración & dosificación , Aspirina/efectos adversos , Clopidogrel , Citocromo P-450 CYP2C19 , Esquema de Medicación , Ligamiento Genético , Variación Genética , Genotipo , Hemorragia/etiología , Humanos , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/efectos adversos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/efectos adversos , Polimorfismo Genético , Ticlopidina/administración & dosificación , Ticlopidina/efectos adversos , Ticlopidina/uso terapéuticoRESUMEN
Lipocalin-2 (LCN-2) was known to play a role in obesity and insulin resistance, however, little is known about the expression of LCN-2 in pancreatic islet ß-cells. We examined the molecular mechanisms by which proinflammatory cytokines interleukin-1ß (IL-1ß) and interferon-γ (IFN-γ) induce LCN-2 expression in RINm5F ß-cells. IL-1ß significantly induced LCN-2 expression while IFN-γ alone did not induce it. IFN-γ significantly potentiated IL-1ß-induced LCN-2 protein and mRNA expression. However, promoter study and EMSA showed that IFN-γ failed to potentiate IL-1ß-induced LCN-2 promoter activity and binding activity of transcription factors on LCN-2 promoter. Furthermore, LCN-2 mRNA stability and transcription factors NF-κB and STAT-1 were not involved in the stimulatory effect of IFN-γ on IL-1ß-induced LCN-2 expression. Meanwhile, Western Blot and promoter analyses showed that NF-κB was a key factor in IL-1ß-induced LCN-2 expression. Collectively, IL-1ß induces LCN-2 expression via NF-κB activation in RINm5F ß-cells. IFN-γ potentiates IL-1ß-induced LCN-2 expression at mRNA and protein levels, but not at promoter level and the stimulatory effect of IFN-γ is independent of NF-κB and STAT-1 activation. These data suggest that LCN-2 may play a role in ß-cell function under an inflammatory condition.
Asunto(s)
Interferón gamma/farmacología , Islotes Pancreáticos/efectos de los fármacos , Lipocalinas/metabolismo , Animales , Secuencia de Bases , Sitios de Unión , Línea Celular , Cartilla de ADN , Ensayo de Cambio de Movilidad Electroforética , Interleucina-1beta/farmacología , Islotes Pancreáticos/metabolismo , Lipocalina 2 , Lipocalinas/genética , Datos de Secuencia Molecular , FN-kappa B/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
OBJECTIVES: To investigate the use of the GuideLiner "mother-and-child" guide catheter extension system as a simple solution to facilitate initial device delivery in balloon uncrossable chronic total occlusions (CTOs) undergoing percutaneous coronary intervention (PCI). BACKGROUND: During PCIs for CTO lesions, an important reason for procedural failure is the inability to deliver a balloon or microcatheter across the lesion. METHODS: We retrospectively accessed our interventional registry for 07/01/2010 to 03/21/2012 and extracted data on all CTO lesions involving GuideLiner catheter use. Cine review was performed to identify cases where a guidewire had crossed the CTO and the use of a GuideLiner catheter facilitated initial device delivery. RESULTS: We identified 28 patients that underwent PCI for CTO with a GuideLiner catheter used to assist initial balloon or microcatheter advancement across the culprit lesion. Mean overall CTO length was 26.3 ± 18.1 mm. The GuideLiner catheter was successful in delivering a small balloon to the CTO lesion in 85.7% of cases (24/28). A single CTO PCI resulted in a distal guidewire perforation, but there was no hemodynamic compromise or pericardial effusion and the patient was discharged the next day. Overall procedural success in these selected cases (where a guidewire had already crossed the CTO) was 89.3% (25/28). CONCLUSIONS: The GuideLiner mother-and-child catheter is a simple, safe and efficacious adjunctive device for difficult CTO PCIs where despite standard measures it is not possible to deliver an initial balloon or microcatheter across the occluded segment.
Asunto(s)
Angioplastia Coronaria con Balón/instrumentación , Catéteres Cardíacos , Oclusión Coronaria/terapia , Anciano , Diseño de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , StentsRESUMEN
For patients with variant angina it is very important to start medical therapy using calcium-channel blockers. However, the decision of physicians regarding whether to decrease the dose of the drug or discontinue it is controversial. We investigated whether the nature of spasm is remissive and whether the termination of medications is safe. The subjects studied were included in the Vasospastic Angina in Catholic Medical Center Registry from March 2001 to December 2009. We analyzed 37 patients (62 lesions) with variant angina, diagnosed using coronary angiography (CAG) and he acetylcholine provocation test, without any organic coronary stenosis, whose symptoms were well controlled after medication. The follow-up CAG with provocation test was performed at a median interval of 44 months. The characteristics of spasm were analyzed on each pair of CAGs. The study group consisted of 23 men (62.2 %) and 14 women (37.8 %) with a mean age of 59 ± 11.1 years. The follow-up CAG with provocation test showed that the characteristics of the spasmodic nature were consistent with the first test in all patients. Although the patients with variant angina had no chest pain after medical treatment, the spasmodic nature of coronary arteries still remained. We may decrease the drug dosage after carefully checking the patient's symptoms but recommend not discontinuing therapy, even if the patient is asymptomatic.
Asunto(s)
Angina Pectoris Variable/diagnóstico por imagen , Angiografía Coronaria , Vasoespasmo Coronario/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Acetilcolina , Anciano , Angina Pectoris Variable/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/administración & dosificación , Distribución de Chi-Cuadrado , Vasoespasmo Coronario/tratamiento farmacológico , Vasos Coronarios/efectos de los fármacos , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sistema de Registros , Inducción de Remisión , República de Corea , Factores de Tiempo , Resultado del Tratamiento , Vasoconstrictores , Vasodilatadores/administración & dosificaciónRESUMEN
This study seeks to improve the mechanical performance of stents by conducting reliability performance testing and finite element method (FEM)-based simulations for coronary stents. Three commercially available stent designs and our own new design were tested to measure the factors affecting performance, specifically foreshortening, recoil, radial force, and flexibility. The stents used in the present experiments were 3 mm in working diameter and 18 mm of working length. The results of the experiments indicate that the foreshortening of stents A, B, C, and our new design, D, was equivalent to 2.25, 0.67, 0.46, and 0.41%, respectively. The recoil of stents A, B, C, and D was 6.00, 4.35, 3.50, and 4.36%, respectively. Parallel plate radial force measurements were A, 3.72 ± 0.28 N; B, 3.81 ± 0.32 N; C, 4.35 ± 0.18 N; and D, 4.02 ± 0.24 N. Radial forces determined by applying uniform pressure in the circumferential direction were A, 28.749 ± 0.81 N; B, 32.231 ± 1.80 N; C, 34.522 ± 3.06 N; and D, 42.183 ± 2.84 N. The maximum force of crimped stent at 2.2-mm deflection was 1.01 ± 0.08 N, 0.82 ± 0.08 N, 0.92 ± 0.12 N, and 0.68 ± 0.07 N for each of stents A, B, C and D. The results of this study enabled us to identify several factors to enhance the performance of stents. In comparing these stents, we found that our design, stent D, which was designed by a collaborative team from seven universities, performed better than the commercial stents across all parameter of foreshortening, recoil, radial force, and flexibility.
Asunto(s)
Stents , Análisis de Elementos Finitos , Humanos , Docilidad , Diseño de Prótesis , Reproducibilidad de los Resultados , Estrés MecánicoRESUMEN
Invasive snails and flies are major pests of imported orchids, controlled by methyl bromide (MB) fumigation in Korea. We compared the efficacy and phytotoxicity of ethyl formate (EF) and MB on four species of imported orchids using juvenile stages of Achatina fulica and third and fourth instars of Lycoriella mali. EF was as effective as MB. The LCt99 values of EF were 68.1 and 73.1 g h/m3 at 15 °C; and those of MB were 95.9 and 78.4 g h/m3 at 15 °C for A. fulica and L. mali, respectively. In the scale-up trials, EF treatment at 35 g/m3 for 4 h at 15 °C resulted in complete control of both pests. MB treatment based on the current treatment guidelines for imported orchids (48 g/m3, 2 h, at >15 °C) resulted in complete control of L. mali but not of A. fulica. Chlorophyll content and hue values of treated orchids were not affected by EF treatment but significantly changed by MB (p-value < 0.05). All four treated species of orchids died within 30 d of MB treatment, while only one species died from EF treatment. Our results suggest that EF is a potential alternative to MB in phytosanitary treatment of imported orchids.
RESUMEN
Sweet persimmons are a valuable export commodity. However, the presence of live insects such as Asiacornococcus kaki limits their access to many export markets. Methyl bromide, traditionally used for pest control, is damaging to human health and the environment. Ethyl formate (EF) is a viable alternative; however, its effectiveness against A. kaki on sweet persimmon fruit is unknown. We evaluated the effectiveness of EF fumigation in controlling A. kaki present under the calyx of persimmon fruit. The hatching rate of eggs and the survival rates of nymphs and adults of A. kaki at low temperatures, its LCt50 and LCt99 after EF exposure, and phytotoxic damage caused by EF were evaluated in laboratory-scale and commercial-scale tests. The dose-response tests showed that the EF LCt99 at 5 °C was 9.69, 42.13, and 126.13 g h m-3 for adults, nymphs, and eggs, respectively. Commercial-scale tests demonstrated EF efficacy against all A. kaki stages without causing phytotoxic effects on persimmons, though the eggs of A. kaki were not completely controlled in linear low-density polyethylene (LLDPE)-packaged fruit. This study demonstrated that EF is a potential fumigant for quarantine pretreatment, especially before persimmon fruit is packed with LLDPE film, to control A. kaki infesting sweet persimmon fruit.