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Liquid polymorphism is an intriguing phenomenon that has been found in a few single-component systems, the most famous being water. By supercooling liquid Te to more than 130 K below its melting point and performing simultaneous small-angle and wide-angle X-ray scattering measurements, we observe clear maxima in its thermodynamic response functions around 615 K, suggesting the possible existence of liquid polymorphism. A close look at the underlying structural evolution shows the development of intermediate-range order upon cooling, most strongly around the thermodynamic maxima, which we attribute to bond-orientational ordering. The striking similarities between our results and those of water, despite the lack of hydrogen-bonding and tetrahedrality in Te, indicate that water-like anomalies may be a general phenomenon among liquid systems with competing bond- and density-ordering.
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KEY MESSAGE: FKF1 dimerization is crucial for proper FT levels to fine-tune flowering time. Attenuating FKF1 homodimerization increased CO abundance by enhancing its COP1 binding, thereby accelerating flowering under long days. In Arabidopsis (Arabidopsis thaliana), the blue-light photoreceptor FKF1 (FLAVIN-BINDING, KELCH REPEAT, F-BOX 1) plays a key role in inducing the expression of FLOWERING LOCUS T (FT), encoding the main florigenic signal in plants, in the late afternoon under long-day conditions (LDs) by forming dimers with FT regulators. Although structural studies have unveiled a variant of FKF1 (FKF1 I160R) that disrupts homodimer formation in vitro, the mechanism by which disrupted FKF1 homodimer formation regulates flowering time remains elusive. In this study, we determined that the attenuation of FKF1 homodimer formation enhances FT expression in the evening by promoting the increased stability of CONSTANS (CO), a primary activator of FT, in the afternoon, thereby contributing to early flowering. In contrast to wild-type FKF1, introducing the FKF1 I160R variant into the fkf1 mutant led to increased FT expression under LDs. In addition, the FKF1 I160R variant exhibited diminished dimerization with FKF1, while its interaction with GIGANTEA (GI), a modulator of FKF1 function, was enhanced under LDs. Furthermore, the FKF1 I160R variant increased the level of CO in the afternoon under LDs by enhancing its binding to COP1, an E3 ubiquitin ligase responsible for CO degradation. These findings suggest that the regulation of FKF1 homodimerization and heterodimerization allows plants to finely adjust FT expression levels around dusk by modulating its interactions with GI and COP1.
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Proteínas de Arabidopsis , Arabidopsis , Dimerización , Luz Azul , Dominios Proteicos , ReproducciónRESUMEN
Understanding and mitigating filament formation, short-circuit and solid electrolyte fracture is necessary for advanced all-solid-state batteries. Here, we employ a coupled far-field high-energy diffraction microscopy and tomography approach for assessing the chemo-mechanical behaviour for dense, polycrystalline garnet (Li7La3Zr2O12) solid electrolytes with grain-level resolution. In situ monitoring of grain-level stress responses reveals that the failure mechanism is stochastic and affected by local microstructural heterogeneity. Coupling high-energy X-ray diffraction and far-field high-energy diffraction microscopy measurements reveals the presence of phase heterogeneity that can alter local chemo-mechanics within the bulk solid electrolyte. These local regions are proposed to be regions with the presence of a cubic polymorph of LLZO, potentially arising from local dopant concentration variation. The coupled tomography and FF-HEDM experiments are combined with transport and mechanics modelling to illustrate the degradation of polycrystalline garnet solid electrolytes. The results showcase the pathways for processing high-performing solid-state batteries.
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Suministros de Energía Eléctrica , Electrólitos , Electrólitos/química , Difracción de Rayos X , Microscopía , Tomografía Computarizada por Rayos XRESUMEN
Contouring surgery is an operation that makes a smooth, oval-shaped face by removing protruding parts of the face. In particular, mandibuloplasty is a procedure that softens the shape of the mandible and is a popular procedure among Asians with a dominant mesocephalic profile. In this study, we tried to discuss the considerations before surgery by dividing the mandibular shape into morphologic aspects in the lateral and frontal views and anatomic considerations. In the lateral view, it is essential to consider the posterior ramal height and mandibular body length of each patient. These factors are closely related to the postoperative outcomes. Consideration of the mandibular plane angle is also essential. In the frontal view, the position of the gonial angle relative to the ramal body should be considered because the position of the gonial angle can affect the difficulty of operation. Anatomic considerations include antero-posterior ramal width, bucco-lingual width of mandibular body, amount of mouth opening, and location of inferior alveolar nerve. These are important factors that determine the difficulty of the operation. In this study, classification according to the shape and shape of the mandible was presented, and considerations for each classification were discussed. Cosmetic surgery is a socio-psychologically meaningful procedure that not only improves the esthetics but also improves the mental well-being of the patients. Therefore, it will be possible to provide better medical services to patients if clinicians are fully aware of the factors that can increase the difficulty of the operation and the factors that affect the surgical outcome.
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The purpose of this case report is to introduce a novel guided bone regeneration (GBR) technique that utilized bone harvested from previously grafted maxillary sinus with deproteinized bovine bone mineral (DBBM) 16 years ago. The patient is a 63-year-old male with hopeless maxillary right molars due to severe bone loss. Two months after the extraction, two bone blocks were harvested with a trephine drill from the lateral wall. One was used for histologic analysis and the other was crushed into particulate forms, which was used for a GBR procedure around an implant at the time of implant placement. The grafted site was then covered with a resorbable collagen membrane. The histological specimen showed newly-formed bone containing residual DBBM particles. The DBBM in the harvested bone was mostly resorbed; DBBM particles comprised only 3.6% of the total bone volume. The final prosthesis was delivered six months post-operatively. No change in crestal bone around the implant was observed throughout the 2 year follow-up period. Within the limitation of the present case report, previously grafted sinus can be a good donor site for further harvesting for a successful GBR procedure.
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Sustitutos de Huesos , Animales , Bovinos , Colágeno/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Prótesis e ImplantesRESUMEN
In the last two decades, far-field high-energy diffraction microscopy (FF-HEDM) and similar non-destructive techniques have been actively developed at synchrotron light sources around the world. As these techniques (and associated analysis tools) are becoming more available for the general users of these light sources, it is important and timely to characterize their performance and capabilities. In this work, the FF-HEDM instrument implemented at the 1-ID-E endstation of the Advanced Photon Source (APS) is summarized. The set of measurements conducted to characterize the instrument's repeatability and sensitivity to changes in grain orientation and position are also described. When an appropriate grain matching method is used, the FF-HEDM instrument's repeatability is approximately 5â µm in translation, 0.02° in rotation, and 2â ×â 10-4 in strain; the instrument sensitivity is approximately 5â µm in translation and 0.05° in rotation.
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The ability to store, organize, process and distribute experimental data effectively, efficiently and securely is particularly important for large user facilities like the Advanced Photon Source. In this article, the deployment of the APS Data Management System (DM) at the 1-ID and 6-BM beamlines of the APS is described. These two beamlines support a wide range of experimental techniques and generate data at relatively high rates, making them ideal candidates to illustrate the deployment and customization of the DM system and its tools. Using several usage examples at these beamlines, various capabilities of the DM system are described.
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Many cyanobacteria exhibit surface motility powered by type 4 pili (T4P). In the model filamentous cyanobacterium Nostoc punctiforme, the T4P systems are arrayed in static, bipolar rings in each cell. The chemotaxis-like Hmp system is essential for motility and the coordinated polar accumulation of PilA on cells in motile filaments, while the Ptx system controls positive phototaxis. Using transposon mutagenesis, a gene, designated hmpF, was identified as involved in motility. Synteny among filamentous cyanobacteria and the similar expression patterns for hmpF and hmpD imply that HmpF is part of the Hmp system. Deletion of hmpF produced a phenotype distinct from other hmp genes, but indistinguishable from pilB or pilQ. Both an HmpF-GFPuv fusion protein, and PilA, as assessed by in situ immunofluorescence, displayed coordinated, unipolar localization at the leading pole of each cell. Reversals were modulated by changes in light intensity and preceded by the migration of HmpF-GFPuv to the lagging cell poles. These results are consistent with a model where direct interaction between HmpF and the T4P system activates pilus extension, the Hmp system facilitates coordinated polarity of HmpF to establish motility, and the Ptx system modulates HmpF localization to initiate reversals in response to changes in light intensity.
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Nostoc/genética , Proteínas Bacterianas/metabolismo , Movimiento Celular , Quimiotaxis/fisiología , Fimbrias Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica/genética , Locomoción , Nostoc/metabolismoRESUMEN
Most species of filamentous cyanobacteria are capable of gliding motility, likely via a conserved type IV pilus-like system that may also secrete a motility-associated polysaccharide. In a subset of these organisms, motility is achieved only after the transient differentiation of hormogonia, which are specialized filaments that enter a nongrowth state dedicated to motility. Despite the fundamental importance of hormogonia to the life cycles of many filamentous cyanobacteria, the molecular regulation of hormogonium development is largely undefined. To systematically identify genes essential for hormogonium development and motility in the model heterocyst-forming filamentous cyanobacterium Nostoc punctiforme, a forward genetic screen was employed. The first gene identified using this screen, designated ogtA, encodes a putative O-linked ß-N-acetylglucosamine transferase (OGT). The deletion of ogtA abolished motility, while ectopic expression of ogtA induced hormogonium development even under hormogonium-repressing conditions. Transcription of ogtA is rapidly upregulated (1 h) following hormogonium induction, and an OgtA-GFPuv fusion protein localized to the cytoplasm. In developing hormogonia, accumulation of PilA but not HmpD is dependent on ogtA Reverse transcription-quantitative PCR (RT-qPCR) analysis indicated equivalent levels of pilA transcript in the wild-type and ΔogtA mutant strains, while a reporter construct consisting of the intergenic region in the 5' direction of pilA fused to gfp produced lower levels of fluorescence in the ΔogtA mutant strain than in the wild type. The production of hormogonium polysaccharide in the ΔogtA mutant strain is reduced compared to that in the wild type but comparable to that in a pilA deletion strain. Collectively, these results imply that O-GlcNAc protein modification regulates the accumulation of PilA via a posttranscriptional mechanism in developing hormogonia.IMPORTANCE Filamentous cyanobacteria are among the most developmentally complex prokaryotes. Species such as Nostoc punctiforme develop an array of cell types, including nitrogen-fixing heterocysts, spore-like akinetes, and motile hormogonia, that function in dispersal as well as the establishment of nitrogen-fixing symbioses with plants and fungi. These symbioses are major contributors to global nitrogen fixation. Despite the fundamental importance of hormogonia to the life cycle of filamentous cyanobacteria and the establishment of symbioses, the molecular regulation of hormogonium development is largely undefined. We employed a genetic screen to identify genes essential for hormogonium development and motility in Nostoc punctiforme The first gene identified using this screen encodes a eukaryotic-like O-linked ß-N-acetylglucosamine transferase that is required for accumulation of PilA in hormogonia.
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N-Acetilglucosaminiltransferasas/metabolismo , Nostoc/enzimología , Nostoc/crecimiento & desarrollo , Proteínas Bacterianas/genética , Fimbrias Bacterianas/genética , Fimbrias Bacterianas/fisiología , Perfilación de la Expresión Génica , Regulación Bacteriana de la Expresión Génica , Movimiento , Mutación , N-Acetilglucosaminiltransferasas/genética , Nostoc/genética , SimbiosisRESUMEN
Protein tyrosine kinase 6 (PTK6; also known as Brk) is closely related to the Src family kinases, but lacks a membrane-targeting myristoylation signal. Sublocalization of PTK6 at the plasma membrane enhances its oncogenic potential. To understand the mechanism(s) underlying the oncogenic property of plasma---membrane-associated PTK6, proteins phosphorylated by membrane-targeted myristoylated PTK6 (Myr-PTK6) were enriched and analyzed using a proteomics approach. Eps8 which was identified by this method is phosphorylated by Myr-PTK6 in HEK293 cells. Mouse Eps8 expressed in HEK293 cells is phosphorylated by Myr-PTK6 at residues Tyr497, Tyr524, and Tyr534. Compared to wild-type Eps8 (Eps8 WT), the phosphorylation-defective 3YF mutant (Eps8 3YF) reverts the increased proliferation, migration, and phosphorylation of ERK and FAK mediated by Eps8 WT in HEK293 cells overexpressing PTK6. PTK6 knockdown in T-47D breast cancer cells decreased EGF-induced phosphorylation of Eps8. Endogenous PTK6 phosphorylates ectopically expressed Eps8 WT, but not Eps8 3YF mutant, in EGF-stimulated T-47D cells. The EGF-induced Eps8 phosphorylation enhances activation of ERK and FAK, cell adhesion, and anchorage-independent colony formation in T-47D cells, but not in the PTK6-knokdown T-47D cells. These results indicate that plasma-membrane-associated PTK6 phosphorylates Eps8, which promotes cell proliferation, adhesion, and migration and, thus, tumorigenesis. J. Cell. Biochem. 118: 2887-2895, 2017. © 2017 Wiley Periodicals, Inc.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Membrana Celular/metabolismo , Movimiento Celular , Proliferación Celular , Mutación Missense , Proteínas de Neoplasias/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Sustitución de Aminoácidos , Línea Celular Tumoral , Membrana Celular/genética , Femenino , Células HEK293 , Humanos , Proteínas de Neoplasias/genética , Fosforilación/genética , Proteínas Tirosina Quinasas/genéticaRESUMEN
BACKGROUND: To investigate the incidence and risk factors of glaucoma in normal-tension glaucoma (NTG) suspect patients who had been lost-to-follow-up for at least 24 months. METHODS: Seventy-two eyes of 72 NTG suspect patients who returned to the hospital after at least 24 months of follow-up loss were enrolled in this study between January 2009 and June 2013. The data were collected retrospectively. The incidence of glaucoma was investigated using a comprehensive glaucoma evaluation in lost-to-follow-up NTG suspect patients. The patients were classified into the glaucoma group, who developed glaucoma during the study period, and the glaucoma suspect group, who did not, to analyse the risk factors for glaucoma. RESULTS: The number of patients who developed glaucoma was 7 (9.7 %) out of the 72 NTG suspect patients who had been mean lost-to-follow-up for 44 months. The rate of progression from suspected to glaucoma was 2.6 %/year. In the glaucoma group, the baseline intraocular pressure (IOP) was 18.43 ± 2.44 mmHg, and the average retinal nerve fiber layer (RNFL) thickness was 78.14 ± 7.60 µm; in the glaucoma suspect group, the baseline IOP was 14.95 ± 2.47 mmHg, and the average RNFL thickness was 92.55 ± 7.65 µm. The study results showed that the glaucoma group had higher baseline IOP and a thinner average RNFL (p = 0.003; p < 0.001). The results of the multivariable logistic regression analysis showed that the risk factors for glaucoma were high baseline IOP (OR = 1.63; p = 0.037) and a thin average RNFL (OR = 0.841; p = 0.004). CONCLUSIONS: The incidence of glaucoma in the lost-to-follow-up NTG suspect patients was 9.7 % for approximately 44 months, at a rate of 2.6 %/year. The risk factors for glaucoma in these patients were high baseline IOP and a thin average RNFL.
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Glaucoma/epidemiología , Glaucoma de Baja Tensión/epidemiología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Glaucoma/etiología , Glaucoma/patología , Glaucoma/fisiopatología , Humanos , Incidencia , Presión Intraocular/fisiología , Modelos Logísticos , Perdida de Seguimiento , Masculino , Persona de Mediana Edad , Fibras Nerviosas/patología , Retina/patología , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
High-energy X-ray diffraction methods can non-destructively map the 3D microstructure and associated attributes of metallic polycrystalline engineering materials in their bulk form. These methods are often combined with external stimuli such as thermo-mechanical loading to take snapshots of the evolving microstructure and attributes over time. However, the extreme data volumes and the high costs of traditional data acquisition and reduction approaches pose a barrier to quickly extracting actionable insights and improving the temporal resolution of these snapshots. This article presents a fully automated technique capable of rapidly detecting the onset of plasticity in high-energy X-ray microscopy data. The technique is computationally faster by at least 50 times than the traditional approaches and works for data sets that are up to nine times sparser than a full data set. This new technique leverages self-supervised image representation learning and clustering to transform massive data sets into compact, semantic-rich representations of visually salient characteristics (e.g. peak shapes). These characteristics can rapidly indicate anomalous events, such as changes in diffraction peak shapes. It is anticipated that this technique will provide just-in-time actionable information to drive smarter experiments that effectively deploy multi-modal X-ray diffraction methods spanning many decades of length scales.
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X-ray diffraction based microscopy techniques such as high-energy diffraction microscopy (HEDM) rely on knowledge of the position of diffraction peaks with high precision. These positions are typically computed by fitting the observed intensities in detector data to a theoretical peak shape such as pseudo-Voigt. As experiments become more complex and detector technologies evolve, the computational cost of such peak-shape fitting becomes the biggest hurdle to the rapid analysis required for real-time feedback in experiments. To this end, we propose BraggNN, a deep-learning based method that can determine peak positions much more rapidly than conventional pseudo-Voigt peak fitting. When applied to a test dataset, peak center-of-mass positions obtained from BraggNN deviate less than 0.29 and 0.57 pixels for 75 and 95% of the peaks, respectively, from positions obtained using conventional pseudo-Voigt fitting (Euclidean distance). When applied to a real experimental dataset and using grain positions from near-field HEDM reconstruction as ground-truth, grain positions using BraggNN result in 15% smaller errors compared with those calculated using pseudo-Voigt. Recent advances in deep-learning method implementations and special-purpose model inference accelerators allow BraggNN to deliver enormous performance improvements relative to the conventional method, running, for example, more than 200 times faster on a consumer-class GPU card with out-of-the-box software.
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GLH8NDE, a derivative of eupatilin, is currently under development to treat dry eye disease. We conducted a randomized, double-masked, placebo-controlled, single- and multiple-day study to evaluate safety, tolerability, pharmacodynamics, and pharmacokinetics of ocular GLH8NDE in healthy male adults. Subjects randomly received topical ocular dosing of GLH8NDE or its matching placebo for a day, then for 7 consecutive days with a 62-h washout at one of the following daily doses: 9, 18, 36 (Koreans), and 36 mg (Whites). The study drug was administered in divided doses over 10 h with 2- or 5-h intervals. Thirty-nine (97.5%) out of 40 subjects completed the study. A total of 17 subjects experienced 31 treatment-emergent adverse events, all of which were mild in severity and recovered without sequelae. Neither pathological changes in eye compartments nor clinically significant systemic effects were observed. GLH8NDE was rapidly absorbed reaching the peak concentration within 0.25-0.75 h postdose. The systemic exposure as measured by area under the concentration-time curve from time of administration up to the time of the last quantifiable concentration (AUClast ) after single-day administration of the same dose was 109% higher in Koreans than in Whites. In conclusion, GLH8NDE was safe and well-tolerated in healthy Korean and White male adults at 9-36 mg/day after single- and multiple-day administrations.
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Pueblo Asiatico , Adulto , Área Bajo la Curva , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Voluntarios Sanos , Humanos , MasculinoRESUMEN
Purpose: Tomography using diffracted x-rays produces reconstructions mapping quantities such as crystal lattice parameter(s), crystallite size, and crystallographic texture, information quite different from that obtained with absorption or phase contrast. Diffraction tomography is used to map an entire blue shark centrum with its double cone structure (corpora calcerea) and intermedialia (four wedges). Approach: Energy dispersive diffraction (EDD) and polychromatic synchrotron x-radiation at 6-BM-B, the Advanced Photon Source, were used. Different, properly oriented Bragg planes diffract different x-ray energies; these intensities are measured by one of ten energy-sensitive detectors. A pencil beam defines the irradiated volume, and a collimator before each energy-sensitive detector selects which portion of the irradiated column is sampled at any one time. Translating the specimen along X , Y , and Z axes produces a 3D map. Results: We report 3D maps of the integrated intensity of several bioapatite reflections from the mineralized cartilage centrum of a blue shark. The c axis reflection's integrated intensities and those of a reflection with no c axis component reveal that the cone wall's bioapatite is oriented with its c axes lateral, i.e., perpendicular to the backbone's axis, and that the wedges' bioapatite is oriented with its c axes axial. Absorption microcomputed tomography (laboratory and synchrotron) and x-ray excited x-ray fluorescence maps provide higher resolution views. Conclusion: The bioapatite in the cone walls and wedges is oriented to resist lateral and axial deflections, respectively. Mineralized tissue samples can be mapped in 3D with EDD tomography and subsequently studied by destructive methods.
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In order to develop a preferable once-a-day oral tablet formulation, various formulations of three-layered tablets containing tamsulosin HCl as a hydrophilic model drug were evaluated and compared with a commercial reference, tamsulosin OCAS®. When the test tablet was exposed to a release medium, the medium quickly permeated to the mid-layer and the two barrier layers swelled surrounding the mid-layer rapidly. Volume expansion showed faster and enough swelling of the three-layered tablet up to 2 h. Larger amount of barrier layers caused reduced release kinetics and a high molecular weight polymer showed more resistance against agitation force. A formulation with water-soluble mid-layer showed fast erosion decreasing its volume significantly. On the pharmacokinetic study, the mean ratio of area under the curve (AUC) and C(max) for the test formulation to the reference was 0.69 and 0.84, respectively, showing that the absorption of the drug was less complete than the reference. Plasma concentration at 24 h of the test formulation was higher than the reference. The Wagner-Nelson method showed that decreased initial dissolution rate might be the cause of the less complete absorption. On considering in vitro-in vivo correlation (IVIVC), level A, the reference (R²=0.981) showed more linear relationship than the test (R²=0.918) due to the decreased dissolution and absorption rate of the formulation. This result suggests that the in vitro dissolution profiles and release kinetics might be useful in correlating absorption kinetics as well as overall plasma drug concentration-time profiles for formulation studies.
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Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Antagonistas de Receptores Adrenérgicos alfa 1/farmacocinética , Química Farmacéutica/métodos , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacocinética , Antagonistas de Receptores Adrenérgicos alfa 1/química , Animales , Área Bajo la Curva , Preparaciones de Acción Retardada , Perros , Esquema de Medicación , Peso Molecular , Solubilidad , Sulfonamidas/química , Comprimidos/administración & dosificación , Comprimidos/química , Comprimidos/farmacocinética , Tamsulosina , Factores de TiempoRESUMEN
A novel three-layered tablet consisting of a water-soluble mid-layer and two barrier layers with swellable polymers was investigated to develop a preferable once-a-day formulation containing terazosin HCl as a hydrophilic model drug. When the tablet was exposed to a release medium, the medium quickly permeated to the mid-layer and the two barrier layers swelled surrounding the mid-layer rapidly. It facilitated the tablet to absorb a lot of water compared with monolithic matrix. Moreover, formation of a lot of pores in the tablet during dissolution could be observed, suggesting significant water absorption in the inner matrix and swollen polymers of the tablet. Barrier layers influenced drug release profiles significantly, potentially due to differences in viscosity after swelling that produce different diffusion coefficients and mechanical strength. The drug in the mid-layer showed the sigmoid type of release pattern because a period of time might be needed to release the drug from the mid-layer through the barrier layers, but the drug in barrier layers showed the typical release pattern of monolithic matrix. As the amount of water-soluble excipient in the mid-layer increased, the degree of swelling also increased, suggesting that its amount in the layer may affect the overall swelling properties of the tablet. It was also shown that more hydrophilic mid-layer caused faster erosion rate, which was related to the results of swelling property. The three-layered tablets showed more consistent release kinetics than the matrix tablets. These results can give good information for the development of sustained drug delivery systems, especially once-a-day administration.
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Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Excipientes/química , Polímeros/química , Prazosina/análogos & derivados , Antagonistas de Receptores Adrenérgicos alfa 1/química , Preparaciones de Acción Retardada , Sistemas de Liberación de Medicamentos , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Prazosina/administración & dosificación , Prazosina/química , Solubilidad , Comprimidos , ViscosidadRESUMEN
BACKGROUND: Drug release from a solid form of self-emulsifying drug delivery system (SEDDS) has greatly been limited due to strong adsorption and physical interaction with carriers. To facilitate drug release process in the stomach, an acid-soluble powderizing carrier, Fujicalin(®) was evaluated together with different disintegrants and hydrophilic lubricants. METHOD: Immediate-release self-emulsifying tablets (IR-SETs) of ibuprofen (IBU) was prepared with solidified SEDDS of IBU, various disintegrants, and lubricants, and drug release was evaluated to develop IR-SET that can release IBU with a similar IBU release rate to that obtained with liquid SEDDS. RESULTS: The liquid SEDDS consisted of Capryol 90, Cremophor EL, Labrasol, and IBU at a ratio of 3:4:3:3, and was solidified with various adsorbents. The powderized SEDDS was tabletted by a direct compression. Fujicalin(®)-based SEDDS tablets demonstrated remarkably higher dissolution rate of IBU compared with Neusilin(®) and Neosyl(®)-based SEDDS tablets. The IR-SET formula of IBU prepared with Fujicalin(®) as an adsorbent, Polyplasdone(®) as a disintegrant, and sodium bicarbonate as a co-disintegrant showed over 90% of initially loaded dose of IBU released within 5 min in a stimulated gastric juice (pH 1.2), exhibiting almost equivalent rate of IBU release to that shown by liquid SEDDS. The particle size analysis revealed no significant differences in droplet sizes of the microemulsions formed from liquid (116 nm) and IR-SET (110 nm). CONCLUSION: The novel IR-SET can be promising as a fast-releasing SEDDS tablet of IBU for fast onset of action.
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Fosfatos de Calcio/química , Emulsionantes/química , Emulsiones/química , Ibuprofeno/química , Antiinflamatorios no Esteroideos/química , Disponibilidad Biológica , Sistemas de Liberación de Medicamentos , Tamaño de la Partícula , Solubilidad , ComprimidosRESUMEN
Oral montelukast (MTK) is prescribed to treat asthma or rhinitis, and is clinically investigated as new medication in the treatment of Alzheimer's dementia. Herein, in order to better patient's compliance, microsuspensions (MSs)-based oral liquid preparations of montelukast (MTK) were formulated with polymeric suspending agents including hypromellose (HPMC), and those drug-polymer interaction, physicochemical stability, dissolution, and in vivo pharmacokinetic profile was evaluated. When amorphous MTK particle was suspended in aqueous vehicle, it was readily converted into crystalline form and grown into aggregates, drastically lowering dissolution rate. However, the addition of HPMC polymer markedly suppressed the crystal growth, providing both improved drug stability and profound dissolution profile. Raman spectrometry denoted the inter-molecular hydrogen boding between MTK particle and HPMC polymer. The crystal growth or dissolution profile of MSs was markedly affected by pharmaceutical additives (sucrose or simethicone) in the preparations or storage temperature. The optimized HPMC-based MS exhibited over 80% higher bioavailability, compared to marketed granule (Singulair®) in rats. Therefore, novel MTK-loaded MS can be a promising liquid preparation, bettering oral absorption and patient's compliance.
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Acetatos/administración & dosificación , Ciclopropanos/administración & dosificación , Derivados de la Hipromelosa/química , Quinolinas/administración & dosificación , Sulfuros/administración & dosificación , Acetatos/química , Acetatos/farmacocinética , Administración Oral , Animales , Cristalización , Ciclopropanos/química , Ciclopropanos/farmacocinética , Liberación de Fármacos , Estabilidad de Medicamentos , Enlace de Hidrógeno , Masculino , Quinolinas/química , Quinolinas/farmacocinética , Ratas , Solubilidad , Sulfuros/química , Sulfuros/farmacocinética , SuspensionesRESUMEN
Oral and maxillofacial infection is a common complication in patients undergoing chemotherapy. The treatment of oral diseases in such patients differs from that administered to healthy patients. This paper reports a case of acute osteomyelitis of odontogenic origin following a recent chemotherapy session. The patient's condition was life-threatening because of neutropenic fever and sepsis that developed during the inpatient supportive care. However, the patient showed prompt recovery within 40 days following the use of appropriate antibiotics and routine dressing, without the requirement for surgical treatment, except tooth extraction. As seen in this case, patients undergoing chemotherapy are more susceptible to rapid progression of infections in the oral and maxillofacial areas. Therefore, accurate diagnosis through prompt clinical and radiological examination, identification of the extent of infection, and assessment of the patient's immune system are crucial for favorable outcomes. It is also necessary to eliminate the source of infection through appropriate administration of antibiotics. In particular, a broad-spectrum antibiotic with anti-pneumococcal activity is essential. Proper antibiotic administration and wound dressing are essential for infection control. Furthermore, close consultation with a hemato-oncologist is necessary for effective infection management based on the professional evaluation of patients' immune mechanisms.