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Petunia hybrida, widely grown as a bedding plant, has reduced growth and flower quality at temperatures above 30 °C (heat stress), primarily due to heat stress-induced ethylene (ET) production. The gene acdS encodes the 1-aminocyclopropane-1-carboxylate (ACC) deaminase (ACCD) enzyme, which is known for its role in reducing ET production by breaking down the ET precursor, ACC, in plant tissues. This study investigated the impact of heat stress on both 'Mirage Rose' WT petunia and its acdS-overexpressing transgenic lines. Heat stress-induced growth inhibition was observed in WT plants but not in transgenic plants. The increased stress tolerance of transgenic plants over WT plants was associated with lower ET production, ROS accumulation, higher SPAD values, water content, and relative water content. Furthermore, higher sensitivity of the WT to heat stress than the transgenic plants was confirmed by analysing ET signalling genes, heat shock transcription factor genes, and antioxidant- and proline-related genes, more strongly induced in WT than in transgenic plants. Overall, this study suggests the potential application of acdS overexpression in other floriculture plants as a viable strategy for developing heat stress-tolerant varieties. This approach holds promise for advancing the floricultural industry by overcoming challenges related to heat-induced growth inhibition and loss of flower quality.
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Etilenos , Respuesta al Choque Térmico , Petunia , Plantas Modificadas Genéticamente , Petunia/genética , Petunia/fisiología , Petunia/metabolismo , Etilenos/metabolismo , Respuesta al Choque Térmico/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Liasas de Carbono-Carbono/metabolismo , Liasas de Carbono-Carbono/genética , Especies Reactivas de Oxígeno/metabolismo , Termotolerancia/genética , Termotolerancia/fisiología , CalorRESUMEN
microRNAs (miRs) are fundamental regulators of protein coding genes. In the CNS, miR-9 is highly enriched and critical for neuronal development and function. Mature miRs are derived from a duplex precursor, and the -5p strand ("guide") is preferentially incorporated into an RNA-induced silencing complex (RISC) to exert its regulatory functions, while the complementary -3p strand ("passenger") is thought to be rapidly degraded. By contrast, both strands of the miR-9 duplex have unique functions critical for neuronal physiology, yet their respective degradation rates and mechanisms governing degradation are not well understood. Therefore, we determined the degradation kinetics of miR-9-5p and miR-9-3p and investigated the cis and trans elements that affected their stability in the brain. Using a combination of homogeneous neuronal/astrocyte cell models and heterogeneous brain tissue lysate, we demonstrate the novel finding that miR-9-3p was more stable than the miR-9-5p guide strand in all models tested. Moreover, the degradation kinetics of both miR-9-5p and miR-9-3p were brain-region specific, suggesting that each brain region was differentially enriched for specific degradation factors. We also determined that the 3' nucleotides harbor important cis elements required to not only maintain stability, but also to recruit potential protein degradation factors. We used mass spectrometry to assess the miR-9 interacting proteins and found that the -5p and -3p strands were associated with functionally distinct proteins. Overall, these studies revealed unique miR-9-5p and miR-9-3p degradation kinetics in the brain and proposed critical nucleotide sequences and protein partners that could contribute to this differential stability.
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MicroARNs , Secuencia de Bases , Encéfalo , MicroARNs/genéticaRESUMEN
BACKGROUND AND PURPOSE: We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation. METHODS: The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K-ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence. RESULTS: Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2 DS2 -VASc score were not significantly different between patients with and without recurrent stroke. CONCLUSIONS: A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.
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Fibrilación Atrial , Isquemia Encefálica , Accidente Cerebrovascular , Administración Oral , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/epidemiología , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Sistema de Registros , República de Corea/epidemiología , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/epidemiologíaRESUMEN
In cuprate superconductors, the doping of carriers into the parent Mott insulator induces superconductivity and various other phases whose characteristic temperatures are typically plotted versus the doping level p. In most materials, p cannot be determined from the chemical composition, but it is derived from the superconducting transition temperature, Tc, using the assumption that the Tc dependence on doping is universal. Here, we present angle-resolved photoemission studies of Bi2Sr2CaCu2O8+δ, cleaved and annealed in vacuum or in ozone to reduce or increase the doping from the initial value corresponding to Tc = 91 K. We show that p can be determined from the underlying Fermi surfaces and that in-situ annealing allows mapping of a wide doping regime, covering the superconducting dome and the non-superconducting phase on the overdoped side. Our results show a surprisingly smooth dependence of the inferred Fermi surface with doping. In the highly overdoped regime, the superconducting gap approaches the value of 2Δ0 = (4 ± 1)kBTc.
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Oestrogen receptor (ER)ß is a multifunctional nuclear receptor that mediates the actions of oestrogenic compounds. Despite its well defined role in mediating the actions of oestrogens, a substantial body of evidence demonstrates that ERß has a broad range of physiological functions independent of those normally attributed to oestrogen signalling. These functions can partly be achieved by the activity of several alternatively spliced isoforms that have been identified for ERß. This short review describes structural differences between the ERß splice variants that are known to be translated into proteins. Moreover, we discuss how these alternative structures contribute to functional differences in the context of both healthy and pathological conditions. Our review also describes the principal factors that regulate alternative RNA splicing. The alternatively spliced isoforms of ERß are differentially expressed according to brain region, age and hormonal milieu, emphasising the likelihood that there are precise cell-specific mechanisms regulating ERß alternative splicing. However, despite these correlative data, the molecular factors regulating alternative ERß splicing in the brain remain unknown. We also review the basic mechanisms that regulate alternative RNA splicing and use that framework to make logical predictions about ERß alternative splicing in the brain.
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Envejecimiento/metabolismo , Encéfalo/metabolismo , Receptor beta de Estrógeno/metabolismo , Isoformas de Proteínas/metabolismo , Empalme Alternativo/fisiología , Animales , Receptor beta de Estrógeno/genética , Estrógenos/metabolismo , Humanos , Isoformas de Proteínas/genéticaRESUMEN
Nitrogen-doped nano-onions (NNO) were prepared as electrocatalytic materials for the oxygen reduction reaction (ORR). The nano-onions (NO), spherical graphitic material particles, were prepared by pyrolysis of nanodiamonds (ND). Oxidized NO (ONO) was prepared from NO by a modified Hummers' method, and this was mixed with urea, followed by pyrolysis, resulting in the formation of NNO. The nitrogen content and molar ratio of nitrogen-containing groups in the NNOs were varied by controlling the oxygen content of ONO to explore the effect of nitrogen content on the ORR activity. The formation of NO was confirmed by Raman spectroscopy, X-ray diffraction analysis, and high-resolution transmission electron microscopy. X-ray photoelectron spectroscopy analyses were conducted to confirm the formation of the NNO and the structures of the nitrogen-containing groups in the NNOs. The ORR activities of the NNOs were investigated using a rotating disk electrode. The NNOs showed a higher onset potential than that of NO, and the ORR activity of the NNO could be improved by increasing the number of active sites (nitrogen-containing groups) in the NNO. In addition, the NNO exhibited better long-term stability and resistance toward methanol crossover in the ORR than the platinum-based catalysts.
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BACKGROUND AND PURPOSE: The occurrence of stroke in cancer patients is caused by conventional vascular risk factors and cancer-specific mechanisms. However, cryptogenic stroke in patients with cancer was considered to be more related to cancer-specific hypercoagulability. In this study, we investigated the potential of the D-dimer level to serve as a predictor of early neurologic deterioration (END) in cryptogenic stroke patients with active cancer. METHODS: We recruited 109 cryptogenic stroke patients with active cancer within 72 h of symptom onset. We defined END as an increase of ≥1 point in the motor National Institutes of Health Stroke Scale (NIHSS) score or ≥2 points in the total NIHSS score within 72 h of admission. After adjusting for potential confounding factors in the multivariate analysis, we calculated the odds ratios (ORs) and confidence intervals (CIs) of D-dimer in the prediction of END. RESULTS: Among 109 patients, END events were identified in 34 (31%) patients within 72 h. END was significantly associated with systemic metastasis, multiple vascular territory lesions on the initial magnetic resonance imaging (MRI), initial NIHSS score and D-dimer levels. In the multivariate analysis, the D-dimer level (adjusted OR, 1.11; 95% CI, 1.04-1.17; P < 0.01) and initial NIHSS score (adjusted OR, 1.08; 95% CI, 1.01-1.15; P = 0.03) predicted END after adjusting for potential confounding factors. In the subgroup analysis of 72 follow-up MRIs, D-dimer level was also correlated with new territory lesions on the follow-up MRI in a dose-dependent manner. CONCLUSION: Ischemic stroke patients with active cancer and elevated D-dimer levels appear to be at increased risk for END recurrent thromboembolic stroke.
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Productos de Degradación de Fibrina-Fibrinógeno/análisis , Neoplasias/complicaciones , Accidente Cerebrovascular/complicaciones , Anciano , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/diagnóstico por imagen , Factores de Riesgo , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico por imagen , Factores de TiempoRESUMEN
BACKGROUND AND PURPOSE: Although abnormal sleep duration is positively associated with increased risk for cardiovascular disease and mortality, the specific impact on intracerebral haemorrhage (ICH) risk remains unclear. The relationship between sleep duration and the risk of ICH was investigated in our study. METHODS: A nationwide, multicentre matched case-control study was performed to investigate the risk factors for haemorrhagic stroke, using patients from 33 hospitals in Korea. In all, 490 patients with ICH and 980 age- and sex-matched controls were enrolled. Detailed information regarding sleep, sociodemographic factors, lifestyle and medical history before ICH onset was obtained using qualified structured questionnaires. Sleep duration was categorized and the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a conditional logistic regression with 7 h as the reference duration. RESULTS: The number of subjects with long sleep duration, more than 8 h, was significantly greater in the ICH group than in the control group (≥8 h, 30.4% vs. 22.6%, P = 0.002). After controlling for relevant confounding factors, longer sleep duration was found to be independently associated with the risk of ICH in a dose-response manner (8 h, OR 1.57, 95% CI 1.00-2.47; ≥9 h, OR 5.00, 95% CI 2.18-11.47). CONCLUSIONS: Our study suggested that long sleep duration is positively associated with an increased ICH risk in a dose-dependent manner. Further studies on the relationship linking long sleep duration with increased risk of ICH are required.
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Hemorragia Cerebral/etiología , Sueño/fisiología , Accidente Cerebrovascular/etiología , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , República de Corea , Factores de Riesgo , Factores de TiempoRESUMEN
OBJECTIVE: To investigate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DWI) in monitoring early therapeutic response to sorafenib in renal cell carcinoma (RCC) xenograft models. METHODS: Sorafenib (40 mg kg(-1)) was administered orally to BALB/c nude mice (n = 9) bearing subcutaneous tumours of human RCC ACHN xenografts. DCE-MRI and DWI were obtained 0, 1, 3 and 7 days after therapy, and DCE-MRI parameters (K(trans) and ve) and apparent diffusion coefficient (ADC) values were calculated. Tumour size and volume changes were correlated with changes in DCE-MRI parameters or ADC values after therapy. RESULTS: Following therapy, K(trans) showed a significant decrease over time (p = 0.005), whereas ve did not demonstrate significant changes between time points (p = 0.97). ADC values showed a progressive increase over time (p = 0.004). Compared with pre-therapy, K(trans) showed a significant decrease after 3 days of therapy (p = 0.039), and ADC values increased significantly after 7 days (p = 0.039). Tumour size and volume did not show significant changes during 7 days. Tumour size and volume changes were not associated with changes in DCE-MRI parameters or ADC values. CONCLUSION: DCE-MRI and DWI may show early physiological changes within 1 week after initiating sorafenib treatment on human RCC xenografts. ADVANCES IN KNOWLEDGE: The quantitative parameters of DCE-MRI and DWI may offer the potential for assessing early therapeutic response to sorafenib in clinical trials.
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Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Imagen por Resonancia Magnética/métodos , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Animales , Biomarcadores de Tumor/metabolismo , Medios de Contraste , Imagen de Difusión por Resonancia Magnética/métodos , Modelos Animales de Enfermedad , Estudios de Factibilidad , Masculino , Ratones , Ratones Desnudos , Niacinamida/uso terapéutico , Pronóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Sorafenib , Resultado del TratamientoRESUMEN
It is commonly assumed that creatine kinase (CK) activity in plasma is related to the state of an inflammatory response at 24-48 h, and also it has shown biphasic patterns after a marathon run. No information is available on CK isoenzymes after an ultra-marathon run. The purpose of the present study is to examine the CK isoenzymes after a 200 km ultra-marathon run and during the subsequent recovery. Blood samples were obtained during registration 1 2 h before the 200-km race and during the race at 100 km, 150 km and at the end of 200 km, as well as after a 24 h period of recovery. Thirty-two male ultra-distance runners participated in the study. Serum CPK showed a marked increase throughout the race and 24 h recovery period (p < 0.001). Serum CK during the race occurs mostly in the CK-MM isoform and only minutely in the CK-MB isoform and is unchanged in the CK-BB isoform. High-sensitivity C-reactive protein (hs-CRP), oestradiol, AST and ALT increased significantly from the pre-race value at 100 km and a further increase took place by the end of the 200 km run. The results of our study demonstrate a different release pattern of creatine kinase after an ultra-distance (200 km) run compared to the studies of marathon running and intense eccentric exercise, and changes in several biomarkers, indicative of muscle damage during the race, were much more pronounced during the latter half (100-200 km) of the race. However, the increases in plasma concentration of muscle enzymes may reflect not only structural damage, but also their rate of clearance.
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The short isoform of ErbB3-binding protein 1 (Ebp1), p42, is considered to be a potent tumor suppressor in a number of human cancers, although the mechanism by which it exerts this tumor-suppressive activity is unclear. Here, we report that p42 interacts with the cSH2 domain of the p85 subunit of phosphathidyl inositol 3-kinase (PI3K), leading to inhibition of its lipid kinase activity. Importantly, we found that p42 induces protein degradation of the p85 subunit and further identified HSP70/CHIP complex as a novel E3 ligase for p85 that is responsible for p85 ubiquitination and degradation. In this process, p42 couples p85 to the HSP70/CHIP-mediated ubiquitin-proteasomal system (UPS), thereby promoting a reduction of p85 levels both in vitro and in vivo. Thus, the tumor-suppressing effects of p42 in cancer cells are driven by negative regulation of the p85 subunit of PI3K.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Neoplasias Encefálicas/enzimología , Fosfatidilinositol 3-Quinasa Clase Ia/metabolismo , Glioma/enzimología , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas Nucleares/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas de Unión al ARN/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Sitios de Unión , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Fosfatidilinositol 3-Quinasa Clase Ia/genética , Proteínas de Unión al ADN , Glioma/genética , Glioma/patología , Células HEK293 , Proteínas HSP70 de Choque Térmico/genética , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Desnudos , Proteínas Nucleares/genética , Células PC12 , Isoformas de Proteínas , Estabilidad Proteica , Proteolisis , Interferencia de ARN , Proteínas de Unión al ARN/genética , Ratas , Factores de Tiempo , Transfección , Carga Tumoral , Ubiquitina-Proteína Ligasas/deficiencia , Ubiquitina-Proteína Ligasas/genética , Dominios Homologos srcRESUMEN
Selecting the appropriate oropharyngeal airway for safe and effective airway management is important in clinical practice. In this prospective observational study, we examined the position of the distal end of oropharyngeal airways using a fibreoptic bronchoscope. We enrolled 149 adults (72 men and 77 women). The correct airway size was determined by inserting four adult sizes Guedel airway (Hudson RCI; Teleflex Medical, Research Triangle, Park, NC, USA) (sizes 8, 9, 10 and 11) sequentially in anaesthetised patients. The 'best fit' airway was size 10 in 45 (62%) men, and size 9 in 58 (75%) women. However, when these airways were inserted, the distal end of the airway either touched or passed beyond the epiglottis tip in 20 (27%) men and six (8%) women, respectively. When a size-9 airway was inserted in men and a size-8 airway inserted in women, the distal ends were obstructed by the tongue in three (2%) patients. In conclusion, a size-9 airway in men and a size-8 airway in women are the most acceptable sizes for adults of average height.
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Broncoscopios , Tecnología de Fibra Óptica/instrumentación , Intubación Intratraqueal/instrumentación , Orofaringe/anatomía & histología , Adulto , Anciano , Obstrucción de las Vías Aéreas/etiología , Obstrucción de las Vías Aéreas/prevención & control , Antropometría/métodos , Diseño de Equipo , Femenino , Humanos , Intubación Intratraqueal/efectos adversos , Intubación Intratraqueal/métodos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Caracteres Sexuales , Adulto JovenRESUMEN
SETTING: The Korean Institute of Tuberculosis, Seoul, Republic of Korea. OBJECTIVE: To develop a simple, direct drug susceptibility testing (DST) technique using Kudoh-modified Ogawa (KMO) medium. DESIGN: The critical concentrations of isoniazid (INH), rifampicin (RMP), kanamycin (KM) and ofloxacin (OFX) for KMO medium were calibrated by comparing the minimal inhibitory concentrations (MICs) against clinical isolates of Mycobacterium tuberculosis on KMO with those on Löwenstein-Jensen (LJ). The performance of the direct KMO DST technique was evaluated on 186 smear-positive sputum specimens and compared with indirect LJ DST. RESULTS: Agreement of MICs on direct vs. indirect DST was high for INH, RMP and OFX. KM MICs on KMO were â¼10 g/ml higher than those on LJ. The critical concentrations of INH, RMP, OFX and KM for KMO were therefore set at 0.2, 40.0, 2.0, and 40.0 g/ml. The evaluation of direct DST of smear-positive sputum specimens showed 100% agreement with indirect LJ DST for INH and RMP. However, the respective susceptible and resistant predictive values were 98.8% and 100% for OFX, and 100% and 80% for KM. CONCLUSION: Direct DST using KMO is useful, with clear advantages of a shorter turnaround time, procedural simplicity and low cost compared to indirect DST. It may be most indicated in resource-poor settings for programmatic management of drug-resistant tuberculosis.
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Antituberculosos , Países en Desarrollo/economía , Farmacorresistencia Bacteriana Múltiple , Pruebas de Sensibilidad Microbiana/métodos , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Pulmonar/diagnóstico , Antituberculosos/economía , Antituberculosos/uso terapéutico , Calibración , Análisis Costo-Beneficio , Relación Dosis-Respuesta a Droga , Costos de la Atención en Salud , Recursos en Salud/economía , Humanos , Pruebas de Sensibilidad Microbiana/economía , Pruebas de Sensibilidad Microbiana/normas , Mycobacterium tuberculosis/crecimiento & desarrollo , Valor Predictivo de las Pruebas , Pronóstico , Estándares de Referencia , Esputo/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/economía , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiologíaRESUMEN
Several reports have promoted the root-derived Korean red ginseng (KRG; Panax ginseng) as alternative treatment for erectile dysfunction (ED), and ginsenosides are known to be the principal active ingredients of ginseng. Recent studies showed that ginseng berries produce more ginsenosides than KRG; thus, we investigated the ability of the Korean ginseng berry extract GB0710 to relax the penile corpus cavernosum smooth muscle (CCSM) in this study. As a comparative control, the results were compared to those obtained using KRG. In addition, possible mechanisms of action for GB0710 were investigated. While KRG and GB0710 both displayed dose-dependent relaxation effects on precontracted rabbit CCSM in vitro, GB0710 was shown to be more potent than KRG. The GB0710-induced relaxation could be partially reduced by removing the endothelium. In addition, pre-treatment with several nitric oxide (NO) inhibitors significantly inhibited the relaxation of muscle strips. Furthermore, administration of GB0710 increased intracavernosal pressure (ICP) in a rat in vivo model in both a dose- and duration-dependent manner. Intracellular NO production in human microvascular endothelial cells could be induced by GB0710 and inhibited by N(G)-monomethyl-L-arginine. In conclusion, GB0710 had a greater relaxation effect on rabbit CCSM than did KRG extract, and increased ICP in a rat model in both a dose- and a duration-dependent manner. This relaxing effect might be mediated by NO production.
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Células Endoteliales/efectos de los fármacos , Frutas , Panax/química , Erección Peniana/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Relación Dosis-Respuesta a Droga , Células Endoteliales/citología , Inhibidores Enzimáticos/farmacología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Técnicas In Vitro , Masculino , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Óxido Nítrico/metabolismo , Erección Peniana/fisiología , Raíces de Plantas/química , Conejos , Ratas , Ratas Sprague-Dawley , República de Corea , omega-N-Metilarginina/farmacologíaRESUMEN
BACKGROUND AND PURPOSE: We investigated the effect of celecoxib, a selective inhibitor of cyclo-oxygenase 2, in patients with intracerebral hemorrhage (ICH). METHODS: We conducted a multicenter, randomized, controlled, and open with blinded end-point trial of 44 Korean patients 18 years or older with ICH within 24 h of onset. The intervention group (n = 20) received celecoxib (400 mg twice a day) for 14 days. The control group (n = 24) received the standard medical treatment for ICH. The primary end-point was the number of patients with a change in the volume of perihematomal edema (PHE) from the 1st to the 7th ± 1 day (cut-off value, 20%). RESULTS: The time from onset to computed tomography scan slightly differed between groups (177 ± 160 min for control vs. 297 ± 305 min for the celecoxib group; P = 0.10). In the primary end-point analysis using cut-off values, there was a significant shift to reduced expansion of PHE in the celecoxib group (P = 0.005). With respect to the secondary end-points, there was also a significant shift to reduced expansion of ICH in the celecoxib group (P = 0.046). In addition, the expansion rate of PHE at follow-up tended to be higher in the control group than in the celecoxib group (90.6 ± 91.7% vs. 44.4 ± 64.9%; P = 0.058). CONCLUSIONS: In our small, pilot trial, administration of celecoxib in the acute stage of ICH was associated with a smaller expansion of PHE than that observed in controls.
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Edema Encefálico/tratamiento farmacológico , Hemorragia Cerebral/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Anciano , Anciano de 80 o más Años , Edema Encefálico/patología , Edema Encefálico/cirugía , Celecoxib , Hemorragia Cerebral/patología , Hemorragia Cerebral/cirugía , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Progresión de la Enfermedad , Método Doble Ciego , Determinación de Punto Final , Femenino , Escala de Coma de Glasgow , Escala de Consecuencias de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Estudios Prospectivos , Pirazoles/efectos adversos , República de Corea , Sulfonamidas/efectos adversos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Montelukast sodium, cysteinyl leukotriene receptor 1 specific antagonist, has been marketed in Korea for the treatment of bronchial asthma and allergic rhinitis. The aim of this study was to compare the pharmacokinetics and relative bioavailability of a test and reference formulation of montelukast 5-mg chewable tablets in healthy Korean male volunteers to meet KFDA regulatory criteria for marketing of the new generic formulation. This study was designed as a single-dose, 2-treatment, and 2-period crossover trial with 32 healthy volunteers. Each subject was randomly assigned to receive the test (Dong-Kook Montelukast Sodium Chewable Tablet 5 mg®) or reference (Singulair Chewable Tablet 5 mg®) formulation. The tablet was chewed 20 times, and then swallowed with 240 mL of water. Plasma concentrations of montelukast up to 24 h after the dose were determined using a validated UPLC-MS/MS method, and the bioequivalence between the 2 formulations was assessed by statistical analysis of mean ratios of log-transformed AUC0-24 h and Cmax. No period or sequence effects were detected. The AUC0-24 h was 1 835 ng·h/mL for the test formulation, and 1 930 ng·h/mL for the reference formulation. The respective values of AUC0-∞ were 1 917 and 2 015 ng·h/mL. The Cmax of the test and reference products (247 and 283 ng/mL, respectively) reached at 2.25 and 2.72 h, respectively. Then, they gradually decreased with the mean terminal t1/2 of 5.25 and 5.30 h for the test and reference products, respectively. The 90% CIs for the ratio of log-transformed AUC0-24 h and Cmax for the test and reference formulations were 0.92-0.99 and 0.83-0.91, respectively. No adverse events were reported in this study. This single dose study found that the test and reference products met the regulatory criteria for bioequivalence in these fasting healthy Korean male volunteers.
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Acetatos/farmacocinética , Antiasmáticos/farmacocinética , Quinolinas/farmacocinética , Acetatos/administración & dosificación , Adulto , Antiasmáticos/administración & dosificación , Área Bajo la Curva , Pueblo Asiatico , Disponibilidad Biológica , Química Farmacéutica , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Ciclopropanos , Medicamentos Genéricos , Semivida , Humanos , Masculino , Espectrometría de Masas , Quinolinas/administración & dosificación , Reproducibilidad de los Resultados , Sulfuros , Comprimidos , Adulto JovenRESUMEN
The main determinant of muscle carnosine (M-Carn) content is undoubtedly species, with, for example, aerobically trained female vegetarian athletes [with circa 13 mmol/kg dry muscle (dm)] having just 1/10th of that found in trained thoroughbred horses. Muscle fibre type is another key determinant, as type II fibres have a higher M-Carn or muscle histidine containing dipeptide (M-HCD) content than type I fibres. In vegetarians, M-Carn is limited by hepatic synthesis of ß-alanine, whereas in omnivores this is augmented by the hydrolysis of dietary supplied HCD's resulting in muscle levels two or more times higher. ß-alanine supplementation will increase M-Carn. The same increase in M-Carn occurs with administration of an equal molar quantity of carnosine as an alternative source of ß-alanine. Following the cessation of supplementation, M-Carn returns to pre-supplementation levels, with an estimated t1/2 of 5-9 weeks. Higher than normal M-Carn contents have been noted in some chronically weight-trained subjects, but it is unclear if this is due to the training per se, or secondary to changes in muscle fibre composition, an increase in ß-alanine intake or even anabolic steroid use. There is no measureable loss of M-Carn with acute exercise, although exercise-induced muscle damage may result in raised plasma concentrations in equines. Animal studies indicate effects of gender and age, but human studies lack sufficient control of the effects of diet and changes in muscle fibre composition.
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Carnosina/metabolismo , Ejercicio Físico/fisiología , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Carnosina/sangre , Dieta Vegetariana , Femenino , Humanos , Masculino , Músculo Esquelético/química , Caracteres Sexuales , beta-AlaninaRESUMEN
OBJECTIVE: The aim of our study was to determine if virtual unenhanced CT (VUCT) is equivalent to unenhanced CT (UCT) for detecting urinary stones. METHODS: Our institutional review board approved this retrospective study, which was compliant with the Health Insurance Portability and Accountability Act. A total of 80 stones were detected in 32 patients among 146 consecutive patients undergoing dual-energy CT urography. The number and size of stones were recorded on nephrographic VUCT (NVUCT) and excretory VUCT (EVUCT) images, respectively. UCT was a reference of standard for the number and size of stones. Image quality of VUCT was qualitatively assessed using a five-point scale. Repeated-measures analysis of variance with post-test was used for statistical analysis. RESULTS: 62 stones in 29 patients were detected on NVUCT and 59 stones in 27 patients were detected on EVUCT. The size of stones detected on NVUCT or EVUCT was significantly smaller compared with stones on UCT (p<0.05). The size of stones detected on UCT, NVUCT and EVUCT ranged from 1.4 to 19.2 mm (mean, 4.6 mm), 0 to 19.2 mm (mean, 3.6 mm) and 0 to 18.7 mm (mean, 3.6 mm), respectively. 18 stones were missed on NVUCT and 21 were missed on EVUCT. The sizes ranged from 1.4 to 3.2 mm (mean, 2.1 mm) and 1.4 to 3.2 mm (mean, 2.2 mm) on UCT, respectively. VUCT was inferior to UCT regarding image quality (p<0.05). CONCLUSION: VUCT missed a significant number of small stones probably owing to poor image quality compared with UCT. Subsequently, VUCT cannot replace UCT for detecting urinary stones.
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Tomografía Computarizada por Rayos X/métodos , Cálculos Urinarios/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Urografía/métodos , Adulto JovenRESUMEN
OBJECTIVE: The purpose of this study was to prospectively investigate differences of diffusion tensor imaging (DTI) using a different number of diffusion-encoding directions and to evaluate the feasibility of tractography in healthy prostate at 3 T. METHOD: 12 healthy volunteers underwent DTI with single-shot echo-planar imaging at 3 T using a phased-array coil. Diffusion gradients of each DTI were applied in 6 (Group 1), 15 (Group 2) and 32 (Group 3) non-collinear directions. For each group, the mean apparent diffusion coefficient (ADC), fractional anisotrophy (FA) and signal-to-noise ratio (SNR) were measured in the peripheral zone (PZ) and central gland (CG). The quality of diffusion-weighted and tractographic images were also evaluated. RESULTS: In all three groups, the mean ADC value of the CG was statistically lower than that of the PZ (p<0.01) and the mean FA value of the CG was statistically greater than that of the PZ (p<0.01). For the mean FA value of the CG, no statistical difference was seen among the three groups (p=0.052). However, the mean FA value of the PZ showed a statistical difference among the three groups (p=0.035). No significant difference in SNR values was seen among the three groups (p>0.05). Imaging quality of diffusion-weighted tractographic images was rated as satisfactory or better in all three groups and was similar among the three groups. CONCLUSION: In conclusion, prostate DTI at 3 T was feasible with different numbers of diffusion-encoding directions. The number of diffusion-encoding directions did not have a significant effect on imaging quality.
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Imagen de Difusión Tensora/métodos , Imagen Eco-Planar/métodos , Imagenología Tridimensional , Próstata/anatomía & histología , Adulto , Estudios de Factibilidad , Humanos , Masculino , Control de Calidad , Valores de Referencia , Muestreo , Sensibilidad y Especificidad , Relación Señal-RuidoRESUMEN
BACKGROUND: The present study was carried out to describe the epidemiologic characteristics of viral gastroenteritis and determine the phylogenetic composition of norovirus strains detected in hospitalized children with acute gastroenteritis in Seoul, Korea. METHODS AND RESULTS: In total, 10,603 stool samples were collected from 2004 to 2008 and tested by RT-PCR or ELISA. In 4,170 (39.3%) samples at least one viral pathogen was present. Rotavirus (RoV) (1,864, 17.5%) was found to be the causative agent followed by norovirus (NoV) (1,845, 17.4%), human adenovirus (HAdV) (266, 2.5%), human astrovirus (HAstV) (194, 1.8%), and sapovirus (SV) (1, 0.009%). Five GI genotypes (GI-1, GI-3, GI-4, GI-8, and GI-9) and eight GII genotypes (GII-2, GII-3, GII-4, GII-6, GII-7, GII-12, GII-16, and GII-17) of NoV were identified in acute gastroenteritis patients in 2008. CONCLUSIONS: The genetic characteristics of norovirus and the epidemiologic patterns of a viral pathogen from acute gastroenteritis patients may give potentially effective data for epidemiological studies in Seoul, Korea.