RESUMEN
That the highly trabeculated ventricular walls of the developing embryos transform to the arrangement during the fetal stages, when the mural architecture is dominated by the thickness of the compact myocardium, has been explained by the coalescence of trabeculations, often erroneously described as 'compaction'. Recent data, however, support differential rates of growth of the trabecular and compact layers as the major driver of change. Here, these processes were assessed quantitatively and visualized in standardized views. We used a larger dataset than has previously been available of mouse hearts, covering the period from embryonic day 10.5 to postnatal day 3, supported by images from human hearts. The volume of the trabecular layer increased throughout development, in contrast to what would be expected had there been 'compaction'. During the transition from embryonic to fetal life, the rapid growth of the compact layer diminished the proportion of trabeculations. Similarly, great expansion of the central cavity reduced the proportion of the total cavity made up of intertrabecular recesses. Illustrations of the hearts with the median value of left ventricular trabeculation confirm a pronounced growth of the compact wall, with prominence of the central cavity. This corresponds, in morphological terms, to a reduction in the extent of the trabecular layer. Similar observations were made in the human hearts. We conclude that it is a period of comparatively slow growth of the trabecular layer, rather than so-called compaction, that is the major determinant of the changing morphology of the ventricular walls of both mouse and human hearts.
Asunto(s)
Ventrículos Cardíacos , Animales , Humanos , Ratones , Ventrículos Cardíacos/anatomía & histología , Ventrículos Cardíacos/embriología , Edad GestacionalRESUMEN
Shrews occupy the lower extreme of the seven orders of magnitude mammals range in size. Their hearts are large relative to body weight and heart rate can exceed a thousand beats a minute. It is not known whether traits typical of mammal hearts scale to these extremes. We assessed the heart of three species of shrew (genus Sorex) following the sequential segmental analysis developed for human hearts. Using micro-computed tomography, we describe the overall structure and find, in agreement with previous studies, a large and elongate ventricle. The atrial and ventricular septums and the atrioventricular (AV) and arterial valves are typically mammalian. The ventricular walls comprise mostly compact myocardium and especially the right ventricle has few trabeculations on the luminal side. A developmental process of compaction is thought to reduce trabeculations in mammals, but in embryonic shrews the volume of trabeculations increase for every gestational stage, only slower than the compact volume. By expression of Hcn4, we identify a sinus node and an AV conduction axis which is continuous with the ventricular septal crest. Outstanding traits include pulmonary venous sleeve myocardium that reaches farther into the lungs than in any other mammals. Typical proportions of coronary arteries-to-aorta do not scale and the shrew coronary arteries are proportionally enormous, presumably to avoid the high resistance to blood flow of narrow vessels. In conclusion, most cardiac traits do scale to the miniscule shrews. The shrew heart, nevertheless, stands out by its relative size, elongation, proportionally large coronary vessels, and extent of pulmonary venous myocardium.
Asunto(s)
Ventrículos Cardíacos , Corazón , Animales , Vasos Coronarios/anatomía & histología , Corazón/anatomía & histología , Atrios Cardíacos , Frecuencia Cardíaca , Humanos , Musarañas , Microtomografía por Rayos XRESUMEN
Photocatalysts use sustainable solar light energy to trigger various catalytic reactions. Metal-free nanomaterials have been suggested as cost-effective and environmentally friendly photocatalysts. In this work, we propose thickness-controlled graphite oxide (GO) as a metal-free photocatalyst, which is produced by exfoliating thick GO particles via stirring and sonication. All GO samples exhibit photocatalytic activity for degrading an organic pollutant, rhodamine B under visible light, and the thickest sample shows the best catalytic performance. UV-vis-NIR diffuse reflectance absorption spectra indicate that thicker GO samples absorb more vis-NIR light than thinner ones. Density-functional theory calculations show that GO has a much smaller band gap than that of single-layer graphene oxide, and thus suggest that the largely-reduced band gap is responsible for this trend of light absorption.
Asunto(s)
Contaminantes Ambientales/química , Grafito/química , Luz , Compuestos Orgánicos/química , Óxidos/química , Catálisis , Microscopía Electrónica de Transmisión , Espectroscopía de FotoelectronesRESUMEN
A two-stage genomewide association (GWA) analysis was conducted to investigate the genetic factors influencing ultraviolet (UV)-induced skin pigmentation in Korean females after UV exposure. Previously, a GWA study evaluating ~500 000 single nucleotide polymorphisms (SNPs) in 99 Korean females identified eight SNPs that were highly associated with tanning ability. To confirm these associations, we genotyped the SNPs in an independent replication study (112 Korean females). We found that a novel SNP in the intron of the WW domain-containing oxidoreductase (WWOX) gene yielded significant replicated associations with skin tanning ability (P-value = 1.16 × 10(-4) ). To understand the functional consequences of this locus located in the non-coding region, we investigated the role of WWOX in human melanocytes using a recombinant adenovirus expressing a microRNA specific for WWOX. Inhibition of WWOX expression significantly increased the expression and activity of tyrosinase in human melanocytes. Taken together, our results suggest that genetic variants in the intronic region of WWOX could be determinants in the UV-induced tanning ability of Korean females. WWOX represents a new candidate gene to evaluate the molecular basis of the UV-induced tanning ability in individuals.
Asunto(s)
Predisposición Genética a la Enfermedad , Oxidorreductasas/genética , Pigmentación de la Piel/genética , Pigmentación de la Piel/efectos de la radiación , Piel/enzimología , Piel/efectos de la radiación , Proteínas Supresoras de Tumor/genética , Rayos Ultravioleta/efectos adversos , Adulto , Pueblo Asiatico , Células Cultivadas , Femenino , Técnicas de Silenciamiento del Gen , Estudio de Asociación del Genoma Completo , Humanos , Intrones , Melanocitos/enzimología , Melanocitos/efectos de la radiación , MicroARNs/genética , Persona de Mediana Edad , Oxidorreductasas/antagonistas & inhibidores , Oxidorreductasas/metabolismo , Fenotipo , Polimorfismo de Nucleótido Simple , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , República de Corea , Pigmentación de la Piel/fisiología , Proteínas Supresoras de Tumor/antagonistas & inhibidores , Proteínas Supresoras de Tumor/metabolismo , Oxidorreductasa que Contiene Dominios WWRESUMEN
OBJECTIVE: To determine whether listening to music during transrectal ultrasound (TRUS)-guided 12-core needle prostate biopsy decreases anxiety, pain and dissatisfaction among patients and results in a more comfortable and better tolerated procedure. PATIENTS AND METHODS: 76 male patients who underwent TRUS-guided prostate biopsy between March 2013 and June 2014 were randomized into the following groups: no music (group I, n = 38) or classical music (group II, n = 38) during the procedure. Before TRUS-guided prostate biopsy, lidocaine gel was instilled into the rectum. Patient anxiety levels were quantified using the State-Trait Anxiety Inventory. A visual analog scale (0-10) was used for self-assessment of satisfaction, discomfort and willingness among patients to have a repeat TRUS-guided prostate biopsy. RESULTS: Demographic characteristics, mean age, procedure duration and procedure indications did not differ statistically between the two groups. The mean anxiety level and mean pain score of group II were significantly lower than those of group I (p = 0.001 and p = 0.003, respectively). Group II also had a significantly higher mean satisfaction score than group I (p = 0.007). Before the procedure, heart rate and systolic blood pressure were similar in groups I and II; however, after the procedure, levels were lower in group II than in group I (heart rate, p = 0.014; systolic blood pressure, p = 0.011). CONCLUSION: Listening to music during TRUS-guided prostate biopsy significantly reduced patients' feelings of pain, discomfort and dissatisfaction. Music can serve as a simple, inexpensive and effective adjunct to sedation during TRUS-guided prostate biopsy. We recommend playing music during TRUS-guided prostate biopsy.
Asunto(s)
Ansiedad/prevención & control , Biopsia con Aguja/métodos , Música , Dolor/prevención & control , Próstata/patología , Anciano , Biopsia , Humanos , Lidocaína/uso terapéutico , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Satisfacción del Paciente , Proyectos Piloto , Próstata/diagnóstico por imagen , Recto , Ultrasonografía , Escala Visual AnalógicaRESUMEN
Cardiac myxoma is rare in children and often associated with cerebrovascular events. Reported herein is the case of a 9-year-old boy who presented with acute obstruction of the aortic bifurcation associated with a huge left atrial (LA) myxoma, thereby leading to acute ischemia of the lower extremities. Immediate surgical removal of the LA myxoma with concomitant percutaneous embolectomy using a Forgathy catheter was done, with relief of ischemic symptoms. Cardiac myxoma should always be considered in the case of acute embolic events in children, given that it needs immediate intervention to prevent further complications.
Asunto(s)
Aorta Abdominal , Enfermedades de la Aorta/cirugía , Procedimientos Quirúrgicos Cardíacos/métodos , Embolectomía/métodos , Neoplasias Cardíacas/complicaciones , Mixoma/complicaciones , Células Neoplásicas Circulantes , Enfermedades de la Aorta/diagnóstico , Enfermedades de la Aorta/etiología , Niño , Ecocardiografía , Atrios Cardíacos , Neoplasias Cardíacas/cirugía , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Mixoma/diagnóstico , Mixoma/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Nanoscale alloys attract enormous research attentions in catalysis, magnetics, plasmonics and so on. Along with multicomponent synergy, quantum confinement and extreme large surface area of nanoalloys offer novel material properties, precisely and broadly tunable with chemical composition and nanoscale dimension. Despite substantial progress of nanoalloy synthesis, the randomized positional arrangement and dimensional/compositional inhomogeneity of nanoalloys remain significant technological challenges for advanced applications. Here we present a generalized route to synthesize single-crystalline intermetallic nanoalloy arrays with dimensional and compositional uniformity via self-assembly. Specific electrostatic association of multiple ionic metal complexes within self-assembled nanodomains of block copolymers generated patterned monodisperse bimetallic/trimetallic nanoalloy arrays consisting of various elements, including Au, Co, Fe, Pd, and Pt. The precise controllability of size, composition, and intermetallic crystalline structure of nanoalloys facilitated tailored synergistic properties, such as accelerated catalytic growth of vertical carbon nanotubes from Fe-Co nanoalloy arrays.
RESUMEN
The top-gate structure is currently adopted in various flat-panel displays because of its diverse advantages such as passivation from the external environment and process compatibility with industries. However, the mobility of the currently commercialized top-gate oxide thin-film transistors (TFTs) is insufficient to drive ultrahigh-resolution displays. Accordingly, this work suggests metal-capped Zn-Ba-Sn-O transistors with top-gate structures for inducing mobility-enhancing effects. The fabricated top-gate device contains para-xylylene (PPx), which is deposited by a low-temperature chemical vapor deposition (CVD) process, as a dielectric layer and exhibits excellent interfacial and dielectric properties. A technology computer-aided design (TCAD) device simulation reveals that the mobility enhancement in the Al-capped (Zn,Ba)SnO3 (ZBTO) TFT is attributed not only to the increase in the electron concentration, which is induced by band engineering due to the Al work function but also to the increased electron velocity due to the redistribution of the lateral electric field. As a result, the mobility of the Al-capped top-gate ZBTO device is 5 times higher (â¼110 cm2/Vs) than that of the reference device. These results demonstrate the applicability of top-gate oxide TFTs with ultrahigh mobility in a wide range of applications, such as for high-resolution, large-area, and flexible displays.
RESUMEN
BACKGROUND: Dietary polyunsaturated fats increase liver injury in response to ethanol feeding. We evaluated the effect of dietary corn oil (CO), olive oil (OO), and beef tallow (BT) on fatty acid composition of liver microsomal membrane and acute acetaminophen hepatotoxicity. METHODS: Male Sprague-Dawley rats were fed 15% (wt/wt) CO, OO or BT for 6 weeks. After treatment with acetaminophen (600 mg/kg), samples of plasma and liver were taken for analyses of the fatty acid composition and toxicity. RESULTS: Treatment with acetaminophen significantly elevated levels of plasma GOT and GPT as well as hepatic TBARS but reduced hepatic GSH levels in CO compared to OO and BT groups. Acetaminophen significantly induced protein expression of cytochrome P450 2E1 in the CO group. In comparison with the CO diet, lower levels of linoleic acid, higher levels of oleic acids and therefore much lower ratios of linoleic to oleic acid were detected in rats fed OO and BT diets. CONCLUSIONS: Dietary OO and BT produces similar liver microsomal fatty acid composition and may account for less severe liver injury after acetaminophen treatment compared to animals fed diets with CO rich in linoleic acid. These findings imply that types of dietary fat may be important in the nutritional management of drug-induced hepatotoxicity.
Asunto(s)
Acetaminofén/toxicidad , Analgésicos no Narcóticos/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Grasas de la Dieta/uso terapéutico , Ácidos Grasos Monoinsaturados/uso terapéutico , Ácidos Grasos/metabolismo , Microsomas Hepáticos/metabolismo , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Grasas/química , Grasas/uso terapéutico , Ácidos Grasos/sangre , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Masculino , Microsomas Hepáticos/efectos de los fármacos , Aceite de Oliva , Oxidación-Reducción , Aceites de Plantas/química , Aceites de Plantas/uso terapéutico , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Glucocorticoids (GCs) are anti-inflammatory drugs widely used to treat acute and chronic inflammatory diseases. However, despite their excellent efficacy, the long-term use of GCs is relatively limited owing to their adverse effects. Recent studies have sought to reduce these adverse effects by developing dissociated GCs that bind to GC receptors (GRs) to induce potent anti-inflammatory effects without the transcription of GC response element (GRE)-promoted genes. Some species of the genus Salsola are used in traditional Chinese medicine to treat cancer, hypertension, and inflammation. In this study, we investigated the potential dissociated GC activities and underlying mechanisms of Salsola komarovii (SK), which is native to Korea. METHODS: To determine whether SK ethanol extract (SEE) directly interacts with the GR, an in vitro fluorescence polarization based-GR competitor assay was performed. The effect of SEE on the transcriptional activity of nuclear factor (NF)-κB and GRE was confirmed in HepG2 cells using the Cignal reporter assay. The anti-inflammatory effect of SK was determined by assessing lipopolysaccharide (LPS)-induced interleukin (IL)-6 production. To confirm whether SEE induces GRE-driven gene expression, preadipocyte differentiation followed by lipid deposition was performed in the presence of SEE. RESULTS: SEE exhibited GR binding activity in the fluorescence polarization competitive binding assay and induced GR nuclear translocation. It also interfered with the nuclear translocation of NF-κB and the NF-κB-dependent transcriptional activity based on the immunofluorescence analysis and reporter assay, respectively. SEE exerted anti-inflammatory effects by reducing LPS-induced IL-6 production as effectively as hydrocortisone (positive control). SK did not induce GRE-driven gene expression and preadipocyte differentiation, which is one of the major adverse effects of GCs. CONCLUSIONS: Collectively, these results suggest that SK could be a novel and safe anti-inflammatory agent with dissociated GC properties and, therefore, it has great potential for use in treating inflammatory disorders.
Asunto(s)
Antiinflamatorios/farmacología , Glucocorticoides/farmacología , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Receptores de Glucocorticoides/metabolismo , Salsola/química , Línea Celular , Células Hep G2 , Humanos , República de CoreaRESUMEN
BACKGROUND: Although echocardiography is the first-line imaging modality in the diagnosis of total anomalous pulmonary venous connection (TAPVC), multidetector CT (MDCT) could have advantages in the diagnosis of TAPVC in certain cases. OBJECTIVE: To compare MDCT with echocardiography in the evaluation of TAPVC. MATERIALS AND METHODS: Enrolled in the study were 23 patients with surgically proven TAPVC. The echocardiography and MDCT findings were independently interpreted by a paediatric cardiologist and cardiac radiologist in terms of: (1) the drainage site of the common pulmonary vein, (2) stenosis of the vertical vein, and (3) the course of the atypical vessel into the systemic vein in the case of vertical vein stenosis. The findings from both modalities were correlated with the results obtained at surgery (n=22) or autopsy (n=1). RESULTS: In all patients, MDCT correctly depicted the drainage site of the common pulmonary vein, stenosis of the vertical vein and the course of the atypical vessel into the systemic vein (sensitivity 100%, specificity 100%). The specificity of echocardiography was 100% for the three defined findings. The sensitivity of echocardiography, however, was 87%, 71% and 0%, respectively. CONCLUSION: MDCT can facilitate the diagnosis of TAPVC in certain cases.
Asunto(s)
Angiografía/métodos , Flebografía/métodos , Venas Pulmonares/anomalías , Venas Pulmonares/diagnóstico por imagen , Ecocardiografía , Femenino , Humanos , Recién Nacido , Masculino , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The growth potential of the neoaorta after the stage I Norwood procedure could be limited when the patient has a small ascending aorta. Patients with hypoplastic left heart syndrome usually have a large main pulmonary artery (MPA) and from its posterior wall both pulmonary arteries arise. We describe a modified technique that spares a large anterior wall of the MPA in the neoaortic reconstruction of Norwood procedure to enhance the growth potential of the neoaorta.
Asunto(s)
Procedimientos Quirúrgicos Cardiovasculares/métodos , Síndrome del Corazón Izquierdo Hipoplásico/cirugía , Arteria Pulmonar , Aorta/cirugía , HumanosRESUMEN
The coordination structure between small molecules and metalloporphyrins plays a crucial role in functional reactions such as bio-oxidation and catalytic activation. Their vertical, tilting, and dynamic structures have been actively studied with diffraction and resonance spectroscopy for the past four decades. Contrastingly, real-space visualization beyond simple protrusion and depression is relatively rare. In this paper, high-resolution scanning tunnelling microscopy (STM) images are presented of di-, tri-, and tetra-atomic small molecules (O2, NO2, and NH3, respectively) coordinated to Co-porphyrin on Au(111). A square ring structure was observed for O2, a rectangular ring structure for NO2, and a bright-center structure for NH3 at 80 K. The symmetries of experimental STM images were reproduced in density functional theory (DFT) calculations, considering the precession motion of the small molecules. Thus, this study shows that the structure of small molecules coordinated to metalloporphyrins can be visualized using high-resolution STM and DFT calculations.
RESUMEN
BACKGROUND: Skin hydration is a common problem both in elderly and young people as dry skin may cause irritation, dermatological disorders, and wrinkles. While both genetic and environmental factors seem to influence skin hydration, thorough genetic studies on skin hydration have not yet been conducted. OBJECTIVE: We used a genome-wide association study (GWAS) to explore the genetic elements underlying skin hydration by regulating epidermal differentiation and skin barrier function. METHODS: A GWAS was conducted to investigate the genetic factors influencing skin hydration in 100 Korean females along with molecular studies of genes in human epidermal keratinocytes for functional study in vitro. RESULTS: Among several single nucleotide polymorphisms identified in GWAS, we focused on Single Stranded DNA Binding Protein 3 (SSBP3) which is associated with DNA replication and DNA damage repair. To better understand the role of SSBP3 in skin cells, we introduced a calcium-induced differentiation keratinocyte culture system model and found that SSBP3 was upregulated in keratinocytes in a differentiation dependent manner. When SSBP3 was overexpressed using a recombinant adenovirus, the expression of differentiation-related genes such as loricrin and involucrin was markedly increased. CONCLUSION: Taken together, our results suggest that genetic variants in the intronic region of SSBP3 could be determinants in skin hydration of Korean females. SSBP3 represents a new candidate gene to evaluate the molecular basis of the hydration ability in individuals.
RESUMEN
[This corrects the article on p. 432 in vol. 30, PMID: 30065583.].
RESUMEN
We developed a technique of translocation of the pulmonary artery anterior to the ascending aorta without transection of the aorta in the repair of tetralogy of Fallot with absent pulmonary valve. Our technique includes detachment of the main pulmonary artery (MPA) from the pulmonary annulus, vertical division of the MPA, anterior translocation of the pulmonary artery with patch augmentation between the vertically divided MPA.
Asunto(s)
Arteria Pulmonar/cirugía , Válvula Pulmonar/anomalías , Tetralogía de Fallot/cirugía , Aorta , Procedimientos Quirúrgicos Cardíacos/métodos , Resultado Fatal , Humanos , Lactante , Masculino , Tetralogía de Fallot/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: Patch closure of the subarterial ventricular septal defect requires suture placement at the pulmonary annulus. We aimed to identify whether patch closure of subarterial ventricular septal defect would affect the growth of pulmonary annulus in comparison with that of perimembranous ventricular septal defect. METHODS: Of 361 patients who underwent patch closure of ventricular septal defect from January 1992 to December 1999, 98 (51 subarterial, 47 perimembranous) had echocardiographic data available for measurement of both preoperative and postoperative (more than 5 years after operation) pulmonary and aortic annular diameters. The pulmonary/aortic annular diameter ratio and their growth rates in the subarterial group were compared with those in the perimembranous group. The perioperative variables correlated with the pulmonary annular growth in subarterial group were also identified. RESULTS: The mean follow-up duration was 7.2 years. Preoperative pulmonary/aortic annular diameter ratio was 1.45 (range, 0.94-2.31) in the subarterial group and 1.57 (range, 1.15-2.51) in the perimembranous group (p=0.059). The latest postoperative ratio was significantly lower in the subarterial group [subarterial: 1.02 (range, 0.77-1.41) vs perimembranous: 1.36 (range, 1.11-1.75), p<0.01]. Twenty-three patients (45%) in the subarterial group had the ratio less than 1. The pulmonary annular growth rate in the subarterial group was lower than that in the perimembranous group (subarterial: 0.34 mm/year, perimembranous: 1.03 mm/year, p<0.01). Preoperative pulmonary/aortic annular diameter ratio (r=0.885, p<0.01), age at operation (r=-0417, p<0.01), weight at operation (r=-0.357, p<0.05), and ventricular septal defect size (r=0.298, p<0.05) were found to have correlation with pulmonary annular growth in the subarterial group. CONCLUSIONS: Our data show that pulmonary annular growth after patch repair of subarterial ventricular septal defect is suboptimal compared with perimembranous ventricular septal defect. Careful attention must be paid to the possible late clinical implication caused by impaired pulmonary annular growth after patch repair of subarterial ventricular septal defect.
Asunto(s)
Defectos del Tabique Interventricular/cirugía , Prótesis e Implantes , Válvula Pulmonar/crecimiento & desarrollo , Factores de Edad , Válvula Aórtica/patología , Presión Sanguínea , Peso Corporal , Niño , Preescolar , Estudios de Seguimiento , Defectos del Tabique Interventricular/patología , Humanos , Lactante , Recién Nacido , Prótesis e Implantes/efectos adversos , Válvula Pulmonar/patología , Válvula Pulmonar/fisiopatología , Válvula Pulmonar/cirugía , Insuficiencia de la Válvula Pulmonar/etiología , Suturas/efectos adversosRESUMEN
Oxygen-containing functional groups such as epoxy, hydroxyl, carboxylic, and carboxyl groups have a great influence on the luminescence properties of graphene oxide quantum dots (GOQDs). Understanding their roles is essential for the design and optimization of GOQD performance. Herein, we investigate the effect of epoxide functional groups in GOQDs on the luminescence mechanism through passivation of the epoxide functional groups using the alkyl ligand oleylamine. Luminescence in the as-synthesized GOQDs has two separate origins: intrinsic states derived from localized sp2 carbon subdomains and extrinsic states formed by oxygen-functional groups. When the oleylamine ligand is conjugated on the GOQDs, intrinsic PL emission from the localized sp2 carbon subdomains decreases. This is discussed in detail, based on optical characterization and first-principles density functional theory calculations, which reveal that the role of the epoxide functional groups is to form localized sp2 carbon subdomains emitting intrinsic PL. To the best of our knowledge, this is the first investigation of the role of epoxide functional groups on the luminescence mechanism in GOQDs.
RESUMEN
CONTEXT: Polymorphisms in the serotonin transporter gene (5-HTT) may influence antidepressant response to selective serotonin reuptake inhibitors (SSRIs). The norepinephrine transporter (NET) is the analogous target for norepinephrine reuptake inhibitors (NRIs). OBJECTIVE: To determine whether antidepressant responses to SSRIs or NRIs are associated with genetic polymorphisms of the corresponding monoamine transporters. DESIGN, SETTING, AND PATIENTS: A 6-week naturalistic treatment study with blinded outcome evaluation of 241 Korean inpatients and outpatients with major depression at an academic psychiatry service. Patients were recruited to the study from March 1998 through February 2003. INTERVENTIONS: Treatment with an SSRI (fluoxetine or sertraline; n = 136) or an NRI (nortriptyline; n = 105) antidepressant. Adherence was assessed by measuring plasma concentration at 4 weeks. Patients were genotyped for s/l polymorphisms in 5-HTT promoter region (5-HTTLPR), 5-HTT intron 2 s/l variation, and NET G1287A variation of exon 9. MAIN OUTCOME MEASURES: An SSRI and NRI response (defined as > or =50% decrease in Hamilton Rating Scale for Depression score at 6 weeks). RESULTS: NRI response was associated with the NET G1287A polymorphism (odds ratio [OR], 7.54; 95% confidence interval [CI], 2.53-22.49; P<.001). An SSRI response was associated with the 5-HTT intron 2 s/l variation (OR, 20.11; 95% CI, 4.27-94.74; P<.001). The 5-HTTLPR was also associated with an SSRI response (OR, 3.34; 95% CI, 1.41-7.91; P = .006). In contrast to studies in white patients, the favorable allele for SSRI response was S 5-HTTLPR. The S 5-HTTLPR was associated also with NRI response (OR, 3.73; 95% CI, 1.32-10.53; P = .01). The NET polymorphism was not associated with an SSRI response. The NET G1287A GG genotype (56% of the population) was associated with better response to the NRI (83.3% [35/42]) than to SSRI (58.7% [44/75]) (OR, 3.52; 95% CI, 1.39-8.95; P = .006). Some genotype combinations were associated with high rates of antidepressant response and others with low rates of response. CONCLUSIONS: Monoamine transporter gene polymorphisms were associated with response to antidepressants with homologous monoamine transporter targets. Combinations of polymorphisms were informative for response and nonresponse. Confirmation of these preliminary findings would permit refined pharmacogenetic selection of antidepressant treatment.
Asunto(s)
Antidepresivos/uso terapéutico , Pueblo Asiatico/genética , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/genética , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/genética , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adulto , Anciano , Femenino , Fluoxetina/uso terapéutico , Humanos , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Norepinefrina/antagonistas & inhibidores , Nortriptilina/uso terapéutico , Polimorfismo Genético , Regiones Promotoras Genéticas , Sertralina/uso terapéuticoRESUMEN
Based on density functional theory calculations, we investigated the axial bindings of diatomic molecules (NO, CO, and O2) to metalloporphyrins and their spin switching behaviors. These binding reactions provide the ways to control molecular states and spins in metalloporphyrin systems that can be used in bio-sensing and spintronic applications. To microscopically understand the non-trivial axial binding structures and spin-switching behaviors of diatomic molecules (NO, CO, and O2) adsorbed onto Co-tetraphenylporphyrin (CoTPP), we performed spin-polarized density functional theory (DFT) calculations for various CoTPP systems on Au(111), Ag(111), and Cu(111) substrates. We also systematically evaluated the effects of van der Waals and Hubbard U corrections by directly comparing the electronic structure with the results of scanning tunnelling microscopy. From the calculation results, we have found that a NO molecule, almost 60° tilted away from the axial direction, is coordinated with CoTPP with a binding energy of 1.2-1.7 eV depending on substrates, and the spin state of CoTPP is completely switched off due to the charge transfer from NO to CoTPP. On the other hand, CO and O2 molecules rather weakly interact with a binding energy of 0.4-0.8 eV, and a spin polarization of â¼1µB is still present at CoTPP. A CO molecule is expected to be almost straightly coordinated along the axial direction of CoTPP, but O2 is tilted similarly to the NO case. Regarding the substrate effects, we have found that there is noticeable charge transfer from Ag(111) and Cu(111) to CoTPP, but no significant charge transfer from Au(111) to CoTPP. These findings of the axial coordination and spin states for NO, CO, and O2 adsorbed CoTPP systems will be useful for understanding bio-sensing mechanisms and designing molecular spintronic systems.