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1.
Am Heart J ; 273: 35-43, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38641031

RESUMO

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.


Assuntos
Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Intervenção Coronária Percutânea/métodos , Estudos Prospectivos , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Masculino , Feminino , Angiografia Coronária , Fatores de Tempo , Revascularização Miocárdica/métodos , Tempo para o Tratamento , Pessoa de Meia-Idade
2.
J Cardiovasc Pharmacol ; 82(1): 52-60, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37019077

RESUMO

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.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Infarto do Miocárdio , Humanos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Resultado do Tratamento , Função Ventricular Esquerda , Antagonistas de Receptores de Angiotensina/efeitos adversos
3.
J Org Chem ; 87(11): 7574-7580, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35549260

RESUMO

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.


Assuntos
Aminas , Paládio , Aminação , Aminas/química , Catálise , Paládio/química
4.
J Org Chem ; 87(17): 11919-11924, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36001369

RESUMO

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.


Assuntos
Alcenos , Aminas , Alcenos/química , Aminas/química , Catálise , Isomerismo , Estrutura Molecular
5.
J Cardiovasc Pharmacol ; 79(5): 650-654, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35058412

RESUMO

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.


Assuntos
Antagonistas Adrenérgicos beta , Infarto do Miocárdio , Antagonistas Adrenérgicos beta/uso terapêutico , Estudos de Coortes , Insuficiência Cardíaca/epidemiologia , Humanos , Infarto do Miocárdio/tratamento farmacológico , Reperfusão , Resultado do Tratamento
6.
Cerebrovasc Dis ; 48(3-6): 226-235, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31825937

RESUMO

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.


Assuntos
Isquemia Encefálica/diagnóstico por imagem , Angiografia Cerebral , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Aneurisma Intracraniano/diagnóstico por imagem , Arteriosclerose Intracraniana/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso , Angiografia Digital , Isquemia Encefálica/epidemiologia , Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana/epidemiologia , Estenose Coronária/epidemiologia , Feminino , Humanos , Aneurisma Intracraniano/epidemiologia , Arteriosclerose Intracraniana/epidemiologia , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Acidente Vascular Cerebral/epidemiologia
7.
Echocardiography ; 36(8): 1467-1474, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31403732

RESUMO

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.


Assuntos
Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Circulação Coronária/fisiologia , Vasos Coronários/diagnóstico por imagem , Ecocardiografia Doppler de Pulso/métodos , Fluxo Sanguíneo Regional/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
8.
Biochem Biophys Res Commun ; 476(1): 7-14, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27233602

RESUMO

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.


Assuntos
Regulação da Expressão Gênica , Células Secretoras de Insulina/imunologia , Interferon gama/imunologia , Interleucina-1beta/imunologia , Lipocalina-2/genética , Óxido Nítrico/imunologia , Animais , Apoptose , Linhagem Celular , Sobrevivência Celular , Inflamação/genética , Inflamação/imunologia , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Lipocalina-2/imunologia , RNA Mensageiro/genética , Ratos
9.
J Korean Med Sci ; 31(4): 561-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27051240

RESUMO

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.


Assuntos
Doenças do Sistema Nervoso Central/patologia , Enterovirus Humano A/isolamento & purificação , Infecções por Enterovirus/patologia , Doença Aguda , Encéfalo/diagnóstico por imagem , Doenças do Sistema Nervoso Central/etiologia , Criança , Pré-Escolar , Encefalite/patologia , Enterovirus Humano A/genética , Infecções por Enterovirus/tratamento farmacológico , Infecções por Enterovirus/virologia , Fezes/virologia , Feminino , Humanos , Imunoglobulinas/administração & dosagem , Lactente , Injeções Intravenosas , Leucócitos/citologia , Leucocitose/líquido cefalorraquidiano , Leucocitose/patologia , Imageamento por Ressonância Magnética , Masculino , RNA Viral/genética , RNA Viral/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , República da Coreia , Estudos Retrospectivos , Estações do Ano
10.
Am J Nephrol ; 40(4): 345-52, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25358406

RESUMO

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.


Assuntos
Fibrilação Atrial/complicações , Transtornos Cerebrovasculares/etiologia , Infarto do Miocárdio/complicações , Sistema de Registros , Insuficiência Renal Crônica/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Estudos Prospectivos , República da Coreia/epidemiologia
11.
Poult Sci ; 93(9): 2253-61, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25002553

RESUMO

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.


Assuntos
Proteínas Aviárias/genética , Galinhas/genética , Conexinas/genética , Regulação da Expressão Gênica no Desenvolvimento , Animais , Proteínas Aviárias/metabolismo , Embrião de Galinha , Galinhas/classificação , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Clonagem Molecular , Conexinas/metabolismo , Dados de Sequência Molecular , Especificidade de Órgãos , Filogenia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Reação em Cadeia da Polimerase Via Transcriptase Reversa/veterinária , Homologia de Sequência de Aminoácidos
12.
Insects ; 15(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38249030

RESUMO

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.

13.
J Cell Biochem ; 114(4): 844-53, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23097217

RESUMO

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.


Assuntos
AMP Cíclico/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Peptídeos/farmacologia , Peçonhas/farmacologia , Regiões 3' não Traduzidas , Animais , Linhagem Celular , Dactinomicina/farmacologia , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Estabilidade Enzimática , Exenatida , Regulação Enzimológica da Expressão Gênica , Receptor do Peptídeo Semelhante ao Glucagon 1 , Iminas/farmacologia , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Nitritos/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Proteólise , Estabilidade de RNA , Receptores de Glucagon/agonistas
14.
Pharmacogenet Genomics ; 23(10): 558-62, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23922007

RESUMO

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.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Aspirina/uso terapêutico , Isquemia Miocárdica/cirurgia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/análogos & derivados , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Clopidogrel , Citocromo P-450 CYP2C19 , Esquema de Medicação , Ligação Genética , Variação Genética , Genótipo , Hemorragia/etiologia , Humanos , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Polimorfismo Genético , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Ticlopidina/uso terapêutico
15.
Biochem Biophys Res Commun ; 434(3): 577-83, 2013 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-23583381

RESUMO

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.


Assuntos
Interferon gama/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Lipocalinas/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Linhagem Celular , Primers do DNA , Ensaio de Desvio de Mobilidade Eletroforética , Interleucina-1beta/farmacologia , Ilhotas Pancreáticas/metabolismo , Lipocalina-2 , Lipocalinas/genética , Dados de Sequência Molecular , NF-kappa B/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Reação em Cadeia da Polimerase em Tempo Real
16.
J Interv Cardiol ; 26(4): 343-50, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23941652

RESUMO

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.


Assuntos
Angioplastia Coronária com Balão/instrumentação , Cateteres Cardíacos , Oclusão Coronária/terapia , Idoso , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents
17.
Heart Vessels ; 28(3): 301-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22526378

RESUMO

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.


Assuntos
Angina Pectoris Variante/diagnóstico por imagem , Angiografia Coronária , Vasoespasmo Coronário/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Acetilcolina , Idoso , Angina Pectoris Variante/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/administração & dosagem , Distribuição de Qui-Quadrado , Vasoespasmo Coronário/tratamento farmacológico , Vasos Coronários/efeitos dos fármacos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sistema de Registros , Indução de Remissão , República da Coreia , Fatores de Tempo , Resultado do Tratamento , Vasoconstritores , Vasodilatadores/administração & dosagem
18.
Artif Organs ; 37(4): 368-79, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23461583

RESUMO

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.


Assuntos
Stents , Análise de Elementos Finitos , Humanos , Maleabilidade , Desenho de Prótese , Reprodutibilidade dos Testes , Estresse Mecânico
19.
Insects ; 14(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36661994

RESUMO

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.

20.
Insects ; 14(4)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37103156

RESUMO

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.

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