RESUMEN
AIMS: Few studies have investigated the relationship between sleep disorders (SD) and erectile dysfunction (ED). Therefore, this study explored whether patients with SD in an Asian population are at an increased risk of developing ED. METHODS: This longitudinal nationwide population-based cohort study investigated the incidence and risk of developing ED in 34,548 men newly diagnosed with SD between 2002 and 2008 from the National Health Insurance Research Database. A total of 138,192 controls without SD were randomly recruited from the general population and frequency matched according to age and sex. The follow-up period began from the date of entering the study cohort until the date of an ED event, censoring, or 31 December 2010. We conducted Cox proportional hazard regression analyses to estimate the effects of SD on the risk of ED. RESULTS: The SD cohort had a 2.11-fold adjusted hazard ratio (HR) of subsequent ED development compared with the non-SD cohort [95% confidence interval (CI) = 1.89-2.37]. The incidence of ED increased with age for both cohorts and was higher for the patients in the SD cohort. Compared with the participants without SD or comorbidities, the patients without SD with any comorbidity exhibited a 1.79-fold risk of developing ED (95% CI = 1.54-2.09); the highest risk was for those with both SD and any comorbidity (HR = 3.34, 95% CI = 2.82-3.95). Furthermore, SD patients who had a particular number of comorbidities showed the dose-response effect of developing ED. CONCLUSION: This nationwide cohort study determined that ED risk evidently increased in SD patients compared with the general population.
Asunto(s)
Disfunción Eréctil/etiología , Trastornos del Sueño-Vigilia/complicaciones , Adulto , Anciano , Disfunción Eréctil/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiologíaRESUMEN
Cyclooxygenase 2 (COX-2) has been reported to be commonly expressed in advanced stages of human lung adenocarcinoma. In this study, the COX-2 constitutive expression vector was transfected into a human lung adenocarcinoma cell line CL1.0 and several clones were obtained which stably expressed COX-2. These COX-2-overexpressed clones demonstrated remarkable resistance to apoptosis induced by Ultraviolet B (UVB) irradiation, vinblastine B (VBL) cell lymphoma-2 (Bcl-2), or other anti-cancer drugs. To understand how COX-2 prevents apoptosis, the investigators examined the expression level of Bcl-2 family members. Mcl-1, but not other Bcl-2 members, was significantly up-regulated by COX-2 transfection or prostaglandin E(2) (PGE(2)) treatment. Treatment of COX-2-overexpressed cells (cox-2/cl.4) with two specific COX-2 inhibitors, NS-398 and celecoxib, caused an effective reduction of the increased level of Mcl-1. These data suggest that the expression level of Mcl-1 is tightly regulated by COX-2. Moreover, transfection of cox-2/cl.4 cells with antisense Mcl-1 enhanced apoptosis induced by UVB irradiation, revealing that Mcl-1 plays a crucial role in cell survival activity mediated by COX-2. Furthermore, COX-2 transfection or PGE(2) treatment evidently activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Inhibition of the PI3K pathway by LY294002 or wortmannin effectively attenuated the increased level of Mcl-1 induced by COX-2 or PGE(2). Blocking the PI3K activity with a dominant-negative vector, DN-p85, also greatly diminished the level of Mcl-1 and enhanced UVB-elicited cell death in cells transfected by COX-2. In a similar way, LY294002 inhibited cell survival and Mcl-1 level in PGE(2)-treated CL1.0 cells. These findings suggest that COX-2 promotes cell survival by up-regulating the level of Mcl-1 by activating the PI3K/Akt-dependent pathway.
Asunto(s)
Adenocarcinoma/fisiopatología , Apoptosis/fisiología , Isoenzimas/metabolismo , Neoplasias Pulmonares/fisiopatología , Proteínas de Neoplasias/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Proteínas Serina-Treonina Quinasas , Androstadienos/farmacología , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Supervivencia Celular , Medio de Cultivo Libre de Suero , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Fragmentación del ADN , Inhibidores Enzimáticos/farmacología , Humanos , Etiquetado Corte-Fin in Situ , Isoenzimas/genética , Proteínas de la Membrana , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Prostaglandina-Endoperóxido Sintasas/genética , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transducción de Señal/fisiología , Transfección , Células Tumorales Cultivadas , Regulación hacia Arriba , Vinblastina/farmacología , WortmaninaRESUMEN
The fabrication of enzyme electrodes using self-assembled monolayers (SAMs) has attracted considerable interest because of the spatial control over the enzyme immobilization. A model system of glucose oxidase covalently bound to a gold electrode modified with a SAM of 3-mercaptopropionic acid was investigated with regard to the effect of fabrication variables such as the surface topography of the underlying gold electrode, the conditions during covalent attachment of the enzyme and the buffer used. The resultant monolayer enzyme electrodes have excellent sensitivity and dynamic range which can easily be adjusted by controlling the amount of enzyme immobilized. The major drawback of such electrodes is the response which is limited by the kinetics of the enzyme rather than mass transport of substrates. Approaches to bringing such enzyme electrodes into the mass transport limiting regime by exploiting direct electron transfer between the enzyme and the electrode are outlined.
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Técnicas Biosensibles , Enzimas Inmovilizadas/química , Compuestos de Sulfhidrilo/química , Tampones (Química) , Calibración , Electroquímica , Electrodos , Glucosa/química , Glucosa Oxidasa/química , Oro , Peróxido de Hidrógeno/química , Indicadores y Reactivos , Membranas Artificiales , Oxidación-Reducción , Peroxidasas/químicaRESUMEN
BACKGROUND: Diabetes mellitus causes multiple cardiovascular complications. High glucose can induce reactive oxygen species and apoptosis in endothelial cells. Little is known about the molecular mechanisms in high glucose-induced endothelial cell apoptosis. METHODS AND RESULTS: We elucidated the signaling pathway of high glucose-induced apoptosis in human umbilical vein endothelial cells (HUVECs). HUVECs were treated with media containing 5.5, 19, or 33 mmol/L of glucose in the presence or absence of an antioxidant, ascorbic acid. The level of intracellular H(2)O(2) was measured by flow cytometry. For detection of apoptosis, the cell death detection ELISA assay and the morphological Hoechst staining were used. High glucose was capable of inducing the activity of c-Jun NH(2)-terminal kinase (JNK) but not extracellular signal-regulated kinase 1/2 or p38 mitogen-activated protein kinase during the treatment periods, as evidenced by immunocomplex kinase assay. Moreover, we found that the interleukin 1beta-converting enzyme (ICE)/CED-3 family protease (caspase-3) became activated in high glucose-induced apoptosis. Caspase-3/CPP32-specific inhibitor, Ac-DEVD-CHO, could inhibit high glucose-induced apoptosis. Furthermore, we found that JNK1 specific antisense oligonucleotide could suppress caspase-3 activity but not affect H(2)O(2) generation and could block apoptosis induced by high glucose. Also, H(2)O(2) generation, JNK activity, caspase-3 activity, and the subsequent apoptosis induced by high glucose could be suppressed by ascorbic acid. CONCLUSIONS: The present study indicates that reactive oxygen species induced by high glucose may be involved in JNK activation, which in turn triggers the caspase-3 that facilitates the apoptosis in HUVECs.
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Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Endotelio Vascular/citología , Endotelio Vascular/enzimología , Glucosa/farmacología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Elementos sin Sentido (Genética)/farmacología , Western Blotting , Caspasa 3 , Caspasas/análisis , Caspasas/genética , Células Cultivadas , Relación Dosis-Respuesta a Droga , Regulación Enzimológica de la Expresión Génica , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/análisis , Proteínas Quinasas Activadas por Mitógenos/genética , Especies Reactivas de Oxígeno/metabolismo , Venas Umbilicales/citologíaRESUMEN
Hyperglycemia is a major cause of diabetic vascular disease. High glucose can induce reactive oxygen species (ROS) and nitric oxide (NO) generation, which can subsequently induce endothelial dysfunction. High glucose is also capable of triggering endothelial cell apoptosis. Little is known about the molecular mechanisms and the role of ROS and NO in high glucose-induced endothelial cell apoptosis. This study was designed to determine the involvement of ROS and NO in high glucose-induced endothelial cell apoptosis. Expression of endothelial nitric oxide synthase (eNOS) protein and apoptosis were studied in cultured human umbilical vein endothelial cells (HUVECs) exposed to control-level (5.5 mM) and high-level (33 mM) glucose at various periods (e.g., 2, 12, 24, 48 h). We also examined the effect of high glucose on H(2)O(2) production using flow cytometry. The results showed that eNOS protein expression was up-regulated by high glucose exposure for 2-6 h and gradually reduced after longer exposure in HUVECs. H(2)O(2) production and apoptosis, which can be reversed by vitamin C and NO donor (sodium nitroprusside), but enhanced by NOS inhibitor (N(G)-nitro-L-arginine methyl ether), were collated to a different time course (24-48 h) to HUVECs. These results provide the molecular basis for understanding that NO plays a protective role from apoptosis of HUVECs during the early stage (<24 h) of high glucose exposure, but in the late stage (>24 h), high glucose exposure leads to the imbalance of NO and ROS, resulting to the observed apoptosis. This may explain, at least in part, the impaired endothelial function and vascular complication of diabetic mellitus that would occur at late stages.
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Apoptosis/fisiología , Endotelio Vascular/metabolismo , Glucosa/metabolismo , Óxido Nítrico/fisiología , Ácido Ascórbico/farmacología , Western Blotting , Células Cultivadas , Inhibidores Enzimáticos/farmacología , Citometría de Flujo , Depuradores de Radicales Libres/farmacología , Glucosa/farmacología , Humanos , Peróxido de Hidrógeno/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/fisiología , Nitroprusiato/farmacología , Factores de TiempoRESUMEN
Effect of acupuncture at Nei-Kuan (EH-6) on left ventricular ejection fraction (LVEF) was examined in 22 patients with angiographically proved coronary artery disease (CAD) and 22 normal subjects. Serial equilibrium radionuclide angiography was done to measure LVEF at 4 different times (at baseline, at 1 to 15 minutes, and 16 to 30 minutes during acupuncture, and immediately after acupuncture). One week later, each patient had an identical imaging protocol with acupuncture performed at a dummy point. Our results showed that in normal subjects, the mean values of LVEF did not change significantly during or after acupuncture. In contrast, in patients with CAD, the mean values of LVEF in the initial 15 minutes of acupuncture significantly increased from baseline (42.5 +/- 15.6% vs. 40.6 +/- 15.4%, p < 0.05). The increase persisted through the next 15 minutes of acupuncture and 15 minutes after acupuncture, but became insignificant at one week. Thus, acupuncture at Nei-Kuan can temporarily improve LV function in patients with CAD.
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Puntos de Acupuntura , Terapia por Acupuntura , Enfermedad Coronaria/fisiopatología , Enfermedad Coronaria/terapia , Función Ventricular Izquierda/fisiología , Adulto , Anciano , Cateterismo Cardíaco , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , CintigrafíaRESUMEN
Congenital aneurysm of the sinus of Valsalva is a rare cardiovascular anomaly. It is usually silent until rupture occurs. The natural history of unruptured aneurysm of the sinus of Valsalva is still not clear, and the therapeutic strategy is uncertain. Here we reported a case of unruptured aneurysm of the sinus of Valsalva which was correctly diagnosed before invasive diagnostic procedures. A 30-year-old female noted mild palpitation and dyspnea for 1 month. Physically, a grade 3/6 systolic ejection murmur at upper left sternal border was detected. Echocardiography revealed dilatation and irregular protrusion of the right sinus of Valsalva encroaching on right ventricular outflow tract to cause obstruction. With these findings, unruptured aneurysm of the sinus of Valsalva with pulmonary stenosis was diagnosed. Cardiac catheterization and angiography confirmed the diagnosis. The aneurysm was repaired with a Dacron patch with good results. It is concluded that sinus of Valsalva aneurysm can be diagnosed by echocardiography before its rupture so as to render a proper management for this potentially life-threatening anomaly.
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Aneurisma de la Aorta/diagnóstico , Estenosis de la Válvula Pulmonar/etiología , Seno Aórtico , Obstrucción del Flujo Ventricular Externo/etiología , Adulto , Aneurisma de la Aorta/complicaciones , Aneurisma de la Aorta/congénito , Aneurisma de la Aorta/diagnóstico por imagen , Ecocardiografía Transesofágica , Femenino , HumanosRESUMEN
PURPOSE: Local compression has been advocated for the treatment of femoral artery pseudoaneurysms. Although it is effective and has a high success rate, this method bears some limitations; among them are prolonged procedure time, discomfort for patients, and recurrence. As a potent thrombosis-inducing agent, thrombin has been used topically, and occasionally intravascularly, for hemostasis. Pseudoaneurysms with a narrow connecting tract to the native artery may be suitable for treatment with thrombin injection to induce intracavitary coagulation. METHODS: Patients with pseudoaneurysms of the femoral artery were evaluated by ultrasonography. Under ultrasound guidance, an intravenous catheter was introduced percutaneously into the pseudoaneurysm, with the catheter position confirmed by contrast ultrasonography. One thousand units of thrombin dissolved in normal saline solution was then injected slowly into the pseudoaneurysm through the catheter to induce thrombosis. The patients were monitored closely for any adverse effects after thrombin injection. RESULTS: A total of five patients with femoral artery pseudoaneurysms were treated with direct percutaneous thrombin injection under ultrasound guidance. Within seconds of thrombin injection thrombus formation was evident, and blood flow in the pseudoaneurysm soon ceased when the thrombosis extended to the connecting tract. All procedures were uneventful and successful. No recurrence was noted during follow-up periods of 1 to 28 months. CONCLUSION: Our initial experience with the small number of patients demonstrates the simplicity, lack of morbidity, and high success rate for ultrasound-guided percutaneous thrombin injection for the treatment of femoral artery pseudoaneurysms.
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Aneurisma Falso/terapia , Cateterismo/efectos adversos , Arteria Femoral/lesiones , Trombina/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/etiología , Femenino , Arteria Femoral/diagnóstico por imagen , Humanos , Inyecciones Intraarteriales , Masculino , Persona de Mediana Edad , Ultrasonografía IntervencionalRESUMEN
To compare the diagnostic value of dobutamine stress echocardiography with dipyridamole thallium-201 single-photon emission computed tomography (SPECT) in detecting coronary artery disease (CAD), we performed both tests on 54 patients who also underwent coronary arteriography. Dobutamine was infused at an incremental regimen of 5, 10, 20, 30 and 40 micrograms.kg-1.min-1. Dipyridamole was infused at a rate of 0.14 mg.kg-1.min-1 over 4 min. Dobutamine stress echocardiography detected 40 (93%) and SPECT 42 (98%, P = ns) of the 43 patients with significant CAD, defined as > or = 50% diameter stenosis. The specificity was 73% (8 of 11) for both tests. The sensitivity for detecting individual coronary artery stenosis with dobutamine stress echocardiography was 81% (30 of 37) for the left anterior descending artery, 75% (24 of 32) for the right coronary artery, and 61% (17 of 28) for the left circumflex artery. For SPECT it was 89%, 97% (P < 0.05 vs dobutamine stress echocardiography) and 75%, respectively. Among the 97 stenotic coronary arteries, 17 had mild to moderate stenosis (50%-69% diameter stenosis) and 80 had severe stenosis (> or = 70% diameter stenosis). With dobutamine stress echocardiography, 53% of the arteries with mild to moderate stenosis were identified vs 78% of those with severe stenosis (P < 0.05). With SPECT, the sensitivity was 82% (14 of 17) in mild to moderate stenosis and 89% (71 of 80) in severe stenosis (P = ns). No major side effects occurred during either test. Thus, both dobutamine stress and SPECT are highly sensitive for detection and localization of CAD.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Enfermedad Coronaria/diagnóstico , Dipiridamol , Dobutamina , Ecocardiografía/métodos , Radioisótopos de Talio , Tomografía Computarizada de Emisión de Fotón Único/métodos , Adulto , Anciano , Angiografía Coronaria , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Estrés FisiológicoRESUMEN
Dipyridamole thallium-201 imaging, using single-photon emission computed tomography, was evaluated for its safety and diagnostic efficacy in 109 patients with angiographically documented coronary artery disease and 35 normal subjects. The most common side effects after the intravenous administration of dipyridamole thallium-201 (0.56 mg/kg) included chest pain in 41 patients, dizziness in 20 patients, headache in 16 patients, and ST segment depression > or = 1 mm in 15 patients. Aminophylline was required to reverse the side-effects in 46 patients, and 45 of the 46 patients experienced complete relief of symptoms. Of the 109 patients with coronary artery disease, 104 had abnormal dipyridamole thallium images. The per patient sensitivity was 95%. Of the 35 normal subjects, 27 had normal thallium images. The per patient specificity was 77%. The sensitivity and specificity for the individual vessels were 84% and 87% for the left anterior descending artery, 67% and 97% for the left circumflex artery, and 89% and 85% for the right coronary artery, respectively. Dipyridamole thallium-201 imaging is a relatively safe noninvasive method and is an effective alternative to exercise thallium-201 scintigraphy for the diagnosis of coronary artery disease.
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Enfermedad Coronaria/diagnóstico por imagen , Dipiridamol , Corazón/diagnóstico por imagen , Radioisótopos de Talio , Anciano , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
The ability of single-photon emission computed tomography (SPECT) with thallium-201 to detect transmural myocardial infarction was compared with that of planar imaging. Planar imaging was performed at rest after SPECT in 80 patients with the first myocardial infarction and in 20 patients without myocardial infarction. The planar and SPECT images were interpreted qualitatively. Tomography was significantly more sensitive than planar imaging in detecting inferior infarctions (43/46 or 93% vs 22/46 or 48%; p less than 0.05). In detecting anterior infarctions, the sensitivity rate was 92% (35/38) for SPECT and 79% (30/38) for planar imaging (p = NS). The overall sensitivity was 93% for tomography and 63% for planar imaging (p less than 0.05). The specificity was similar (100%) with the 2 techniques. It is concluded that SPECT significantly improves the detection of thallium-201 myocardial perfusion defects in patients with myocardial infarctions, especially those occurring on the inferior wall.