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1.
Plant Biol (Stuttg) ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858861

ABSTRACT

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.

2.
eNeuro ; 7(3)2020.
Article in English | MEDLINE | ID: mdl-32376600

ABSTRACT

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.


Subject(s)
MicroRNAs , Base Sequence , Brain , MicroRNAs/genetics
3.
Eur J Neurol ; 27(5): 900-902, 2020 05.
Article in English | MEDLINE | ID: mdl-32064742

ABSTRACT

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.


Subject(s)
Atrial Fibrillation , Brain Ischemia , Stroke , Administration, Oral , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Brain Ischemia/complications , Brain Ischemia/drug therapy , Brain Ischemia/epidemiology , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Registries , Republic of Korea/epidemiology , Risk Assessment , Risk Factors , Stroke/complications , Stroke/drug therapy , Stroke/epidemiology
4.
Nat Commun ; 9(1): 5210, 2018 12 06.
Article in English | MEDLINE | ID: mdl-30523265

ABSTRACT

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.

5.
J Neuroendocrinol ; 30(2)2018 02.
Article in English | MEDLINE | ID: mdl-28514502

ABSTRACT

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.


Subject(s)
Aging/metabolism , Brain/metabolism , Estrogen Receptor beta/metabolism , Protein Isoforms/metabolism , Alternative Splicing/physiology , Animals , Estrogen Receptor beta/genetics , Estrogens/metabolism , Humans , Protein Isoforms/genetics
6.
Sci Rep ; 7(1): 4178, 2017 06 23.
Article in English | MEDLINE | ID: mdl-28646193

ABSTRACT

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.

7.
Eur J Neurol ; 24(1): 205-211, 2017 01.
Article in English | MEDLINE | ID: mdl-27766716

ABSTRACT

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.


Subject(s)
Fibrin Fibrinogen Degradation Products/analysis , Neoplasms/complications , Stroke/complications , Aged , Disease Progression , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neoplasms/blood , Neoplasms/diagnostic imaging , Risk Factors , Stroke/blood , Stroke/diagnostic imaging , Time Factors
8.
Eur J Neurol ; 23(6): 1036-43, 2016 06.
Article in English | MEDLINE | ID: mdl-26945678

ABSTRACT

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.


Subject(s)
Cerebral Hemorrhage/etiology , Sleep/physiology , Stroke/etiology , Adult , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Republic of Korea , Risk Factors , Time Factors
9.
Br J Radiol ; 88(1053): 20150163, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26133222

ABSTRACT

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.


Subject(s)
Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Magnetic Resonance Imaging/methods , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Animals , Biomarkers, Tumor/metabolism , Contrast Media , Diffusion Magnetic Resonance Imaging/methods , Disease Models, Animal , Feasibility Studies , Male , Mice , Mice, Nude , Niacinamide/therapeutic use , Prognosis , Reproducibility of Results , Sensitivity and Specificity , Sorafenib , Treatment Outcome
10.
Biol Sport ; 32(4): 357-361, 2015 Dec.
Article in English | MEDLINE | ID: mdl-28479667

ABSTRACT

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.

11.
Cell Death Dis ; 5: e1131, 2014 Mar 20.
Article in English | MEDLINE | ID: mdl-24651434

ABSTRACT

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.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Brain Neoplasms/enzymology , Class Ia Phosphatidylinositol 3-Kinase/metabolism , Glioma/enzymology , HSP70 Heat-Shock Proteins/metabolism , Nuclear Proteins/metabolism , Proteasome Endopeptidase Complex/metabolism , RNA-Binding Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism , Adaptor Proteins, Signal Transducing/genetics , Animals , Binding Sites , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Class Ia Phosphatidylinositol 3-Kinase/genetics , DNA-Binding Proteins , Glioma/genetics , Glioma/pathology , HEK293 Cells , HSP70 Heat-Shock Proteins/genetics , Humans , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Nude , Nuclear Proteins/genetics , PC12 Cells , Protein Isoforms , Protein Stability , Proteolysis , RNA Interference , RNA-Binding Proteins/genetics , Rats , Time Factors , Transfection , Tumor Burden , Ubiquitin-Protein Ligases/deficiency , Ubiquitin-Protein Ligases/genetics , src Homology Domains
12.
Anaesthesia ; 69(1): 53-7, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24320857

ABSTRACT

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.


Subject(s)
Bronchoscopes , Fiber Optic Technology/instrumentation , Intubation, Intratracheal/instrumentation , Oropharynx/anatomy & histology , Adult , Aged , Airway Obstruction/etiology , Airway Obstruction/prevention & control , Anthropometry/methods , Equipment Design , Female , Humans , Intubation, Intratracheal/adverse effects , Intubation, Intratracheal/methods , Male , Middle Aged , Prospective Studies , Sex Characteristics , Young Adult
13.
Int J Tuberc Lung Dis ; 17(9): 1212-6, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23823178

ABSTRACT

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 ∼10 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.


Subject(s)
Antitubercular Agents , Developing Countries/economics , Drug Resistance, Multiple, Bacterial , Microbial Sensitivity Tests/methods , Mycobacterium tuberculosis/drug effects , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Pulmonary/diagnosis , Antitubercular Agents/economics , Antitubercular Agents/therapeutic use , Calibration , Cost-Benefit Analysis , Dose-Response Relationship, Drug , Health Care Costs , Health Resources/economics , Humans , Microbial Sensitivity Tests/economics , Microbial Sensitivity Tests/standards , Mycobacterium tuberculosis/growth & development , Predictive Value of Tests , Prognosis , Reference Standards , Sputum/microbiology , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/economics , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiology
14.
Asian J Androl ; 15(4): 503-7, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23708462

ABSTRACT

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.


Subject(s)
Endothelial Cells/drug effects , Fruit , Panax/chemistry , Penile Erection/drug effects , Plant Extracts/pharmacology , Animals , Dose-Response Relationship, Drug , Endothelial Cells/cytology , Enzyme Inhibitors/pharmacology , Human Umbilical Vein Endothelial Cells , Humans , In Vitro Techniques , Male , Muscle, Smooth/drug effects , Muscle, Smooth/physiology , Nitric Oxide/metabolism , Penile Erection/physiology , Plant Roots/chemistry , Rabbits , Rats , Rats, Sprague-Dawley , Republic of Korea , omega-N-Methylarginine/pharmacology
15.
Eur J Neurol ; 20(8): 1161-9, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23551657

ABSTRACT

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.


Subject(s)
Brain Edema/drug therapy , Cerebral Hemorrhage/drug therapy , Cyclooxygenase 2 Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Aged , Aged, 80 and over , Brain Edema/pathology , Brain Edema/surgery , Celecoxib , Cerebral Hemorrhage/pathology , Cerebral Hemorrhage/surgery , Cyclooxygenase 2 Inhibitors/adverse effects , Disease Progression , Double-Blind Method , Endpoint Determination , Female , Glasgow Coma Scale , Glasgow Outcome Scale , Humans , Male , Middle Aged , Neurosurgical Procedures , Prospective Studies , Pyrazoles/adverse effects , Republic of Korea , Sulfonamides/adverse effects , Tomography, X-Ray Computed , Treatment Outcome
16.
Arzneimittelforschung ; 62(3): 123-7, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22407900

ABSTRACT

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.


Subject(s)
Acetates/pharmacokinetics , Anti-Asthmatic Agents/pharmacokinetics , Quinolines/pharmacokinetics , Acetates/administration & dosage , Adult , Anti-Asthmatic Agents/administration & dosage , Area Under Curve , Asian People , Biological Availability , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Cross-Over Studies , Cyclopropanes , Drugs, Generic , Half-Life , Humans , Male , Mass Spectrometry , Quinolines/administration & dosage , Reproducibility of Results , Sulfides , Tablets , Young Adult
17.
Amino Acids ; 43(1): 5-12, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22327512

ABSTRACT

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.


Subject(s)
Carnosine/metabolism , Exercise/physiology , Muscle Fibers, Skeletal/metabolism , Muscle, Skeletal/metabolism , Carnosine/blood , Diet, Vegetarian , Female , Humans , Male , Muscle, Skeletal/chemistry , Sex Characteristics , beta-Alanine
18.
Br J Radiol ; 85(1014): e176-81, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21896665

ABSTRACT

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.


Subject(s)
Tomography, X-Ray Computed/methods , Urinary Calculi/diagnostic imaging , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Urography/methods , Young Adult
19.
Br J Radiol ; 85(1015): e279-83, 2012 Jul.
Article in English | MEDLINE | ID: mdl-21896666

ABSTRACT

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.


Subject(s)
Diffusion Tensor Imaging/methods , Echo-Planar Imaging/methods , Imaging, Three-Dimensional , Prostate/anatomy & histology , Adult , Feasibility Studies , Humans , Male , Quality Control , Reference Values , Sampling Studies , Sensitivity and Specificity , Signal-To-Noise Ratio
20.
Clin Lab ; 57(1-2): 59-65, 2011.
Article in English | MEDLINE | ID: mdl-21391466

ABSTRACT

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.


Subject(s)
Gastroenteritis/virology , Virus Diseases/virology , Child, Preschool , Enzyme-Linked Immunosorbent Assay , Feces/virology , Female , Gastroenteritis/epidemiology , Humans , Infant , Infant, Newborn , Male , Norovirus/genetics , Norovirus/isolation & purification , Phylogeny , Republic of Korea , Reverse Transcriptase Polymerase Chain Reaction
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