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The purpose of this study was to investigate the effects of dietary taurine-containing jelly supplementation on cognitive function and memory ability of the elderly. The jelly used in the study contained 3 g of taurine and was reprocessed in the soft state like pudding considering the safe intake and preference and provided for 4 weeks. The cognitive function and memory ability of subjects were assessed by MMSE-DS (Mini-Mental State Examination-Dementia Screening), DST (Digit Span Test), K-BNT (Korean version-Boston Naming Test), and K-SVLT (Korean version-Seoul Verbal Learning Test) and were conducted in a face-to-face survey. The subjective memory of subjects was assessed by a self-recording method. Statistical analysis was performed using SPSS 26.0. The results were compared before and after 4 weeks of dietary taurine-containing jelly supplementation. The subjects were 26 elderly Koreans (8 male, 18 female) with subjective cognitive decline with an average age of 72.3 years. The total average score of MMSE-DS in all subjects increased from 25.9 points before dietary taurine-containing jelly supplementation to 26.4 points 4 weeks after supplementation, but there was no significant difference. The total average scores of DST-F, K-BNT, and K-SVLT were significantly higher 4 weeks after supplementation (65.7, 51.7, and 17.8 points) than before supplementation (60.6, 46.5, and 15.2 points) (p < 0.01). In particular, the score of DST-F showed significant difference only in the female elderly (p < 0.001). The score for subjective memory showed significant difference 4 weeks after supplementation (3.0 points) than before supplementation (2.6 points) (p < 0.05). Especially, it increased significantly only in the female elderly (p < 0.01). These results show that dietary taurine-containing jelly supplementation has positive effects on the memory ability of the elderly with subjective cognitive decline. Therefore, it is suggested to supplement products for the elderly, such as pudding or jelly, with dietary taurine to improve memory ability and cognitive function of the elderly.
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Disfunção Cognitiva , Taurina , Idoso , Cognição , Disfunção Cognitiva/tratamento farmacológico , Suplementos Nutricionais , Feminino , Humanos , Masculino , Testes de Estado Mental e Demência , Taurina/farmacologia , Taurina/uso terapêuticoRESUMO
Significant improvements in the wettability and dissolution rate of celecoxib (CEL), a poorly soluble selective cyclooxygenase-2 (COX-2) inhibitor, have been shown by Huyn et al., 2019 by combining the binary pharmaceutical compositions including CEL and one of the two co-formers, adipic acid (ADI) and saccharin (SAC), into eutectic mixtures (EM). Purpose: In this study, we developed a therapeutic eutectic system for CEL which is a promising approach for oral delivery to enhance bioavailability. CEL EM were synthesized by novel techniques including supercritical CO2 techniques and new tablet formulations were purposed. Methods: CEL EM were synthesized by evaporation crystallization method, spray drying, supercritical fluid (SCF) techniques. The CEL EM particles were then characterized by differential scanning calorimetry, powder X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscope, and particle size analysis. Dissolution studies were carried out. With a quality by design approach, a statistical method through design of experiment and data analysis by JMP® (SAS institute) was applied to CEL EM immediate release tablet formulation development. Results: CEL EM produced by spray drying technique, supercritical fluid (SCF) techniques were identified and characterized. The enhancement of dissolution was observed for SCF processed samples. The design space for CEL-ADI EM IR tablet and control limits for individual parameters were determined.
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The mechanism of atopic dermatitis (AD) is modulated by the release of cytokines and chemokines through the mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway. Topical steroids are used to treat AD, but some people need safer anti-inflammatory drugs to avoid side effects. Mentha arvensis has been used as a herbal plant with medicinal properties, but its anti-inflammatory effects have not been elucidated in an AD model. In this study, we investigated the anti-inflammatory effects of M. arvensis essential oil (MAEO) and its underlying molecular mechanism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and HaCaT cells (human epidermal keratinocyte). Additionally, we examined the ameliorating effects of the MAEO in a dinitrochlorobenzene (DNCB)-induced murine model of AD. We found, in both RAW 264.7 cells and HaCaT cells, MAEO inhibited LPS-stimulated inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 and proinflammatory cytokines, including IL-1ß and IL-6, due to the suppression of COX-2 and iNOS expression. In LPS-stimulated macrophages, we also observed that MAEO inhibited the phosphorylation of ERK and P65. Furthermore, MAEO treatment attenuated AD symptoms, including the dermatitis score, ear thickness, epidermal thickness and infiltration of mast cells, in a DNCB-induced animal model of AD. Overall, our findings suggest that MAEO exerts anti-inflammatory and anti-atopic dermatitis effects via inhibition of the ERK/NF-κB signaling pathway.
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The excessive synthesis of interleukin-6 (IL-6) is related to cytokine storm in COVID-19 patients. Moreover, blocking IL-6 has been suggested as a treatment strategy for inflammatory diseases such as sepsis. Sepsis is a severe systemic inflammatory response syndrome with high mortality. In the present study, we investigated the anti-inflammatory and anti-septic effects and the underlying mechanisms of Dracocephalum moldavica ethanol extract (DMEE) on lipopolysaccharide (LPS)-induced inflammatory stimulation in RAW 264.7 macrophages along with septic mouse models. We found that DMEE suppressed the release of inflammatory mediators NO and PGE2 and inhibited both the mRNA and protein expression levels of iNOS and COX-2, respectively. In addition, DMEE reduced the release of proinflammatory cytokines, mainly IL-6 and IL-1ß, in RAW 264.7 cells by inhibiting the phosphorylation of JNK, ERK and p65. Furthermore, treatment with DMEE increased the survival rate and decreased the level of IL-6 in plasma in LPS-induced septic shock mice. Our findings suggest that DMEE elicits an anti-inflammatory effect in LPS-stimulated RAW 264.7 macrophages and an anti-septic effect on septic mouse model through the inhibition of the ERK/JNK/NF-κB signaling cascades and production of IL-6.
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Interleucina-6/metabolismo , Lamiaceae/química , Lipopolissacarídeos/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Fator de Transcrição RelA/metabolismo , Animais , Etanol/química , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Extratos Vegetais/química , Células RAW 264.7RESUMO
To improve the dissolution behavior of telmisartan (TMS), a poorly water-soluble angiotensin II receptor blocker, TMS-phospholipid complex (TPC) was prepared by solvent evaporation method and characterized by differential scanning calorimetry and powder X-ray diffractometry. The crystalline structure of TMS was transited into an amorphous state by TPC formation. The equilibrium solubility of TPC (1.3-6.1 mg/mL) in various vehicles was about 100 times higher than that of TMS (0.009-0.058 mg/mL). TPC-loaded self-microemulsifying drug delivery system (SMEDDS) formulation was optimized using the D-optimal mixture design with the composition of 14% Capryol 90 (oil; X1), 59.9% tween 80 (surfactant; X2), and 26.1% tetraglycol (cosurfactant; X3) as independent variables, which resulted in a droplet size of 22.17 nm (Y1), TMS solubilization of 4.06 mg/mL (Y2), and 99.4% drug release in 15 min (Y3) as response factors. The desirability function value was 0.854, indicating the reliability and accuracy of optimization; in addition, good agreement was found between the model prediction and experimental values of Y1, Y2, and Y3. Dissolution of raw TMS was poor and pH-dependent, where it had extremely low dissolution (< 1% for 2 h) in water, pH 4, and pH 6.8 media; however, it showed fast and high dissolution (> 90% in 5 min) in pH 1.2 medium. In contrast, the dissolution of the optimized TPC-loaded SMEDDS was pH-independent and reached over 90% within 5 min in all the media tested. Thus, we suggested that phospholipid complex formation and SMEDDS formulation using the experimental design method might be a promising approach to enhance the dissolution of poorly soluble drugs.
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Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Fosfolipídeos/química , Telmisartan/química , Varredura Diferencial de Calorimetria , Concentração de Íons de HidrogênioRESUMO
BACKGROUND: RIPL peptide (IPLVVPLRRRRRRRRC)-conjugated nanostructured lipid carriers (RIPL-NLCs) can facilitate selective drug delivery to hepsin (Hpn)-expressing cancer cells, but they exhibit low stability in the blood. Generally, biocompatible and nontoxic poly(ethylene glycol) surface modification (PEGylation) can enhance NLC stability, although this may impair drug delivery and NLC clearance. To attain RIPL-NLC steric stabilization without impairing function, pH-sensitive cleavable PEG (cPEG) was grafted onto RIPL-NLCs (cPEG-RIPL-NLCs). METHODS: Various types of NLC formulations including RIPL-NLCs, PEG-RIPL-NLCs, and cPEG-RIPL-NLCs were prepared using the solvent emulsification-evaporation method and characterized for particle size, zeta potential (ZP), and cytotoxicity. The steric stabilization effect was evaluated by plasma protein adsorption and phagocytosis inhibition studies. pH-sensitive cleavage was investigated using the dialysis method under different pH conditions. Employing a fluorescent probe (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate [DiI]), in vitro drug delivery capacity of the cPEG-RIPL-NLCs under different pH conditions was also performed on Hpn-expressing SKOV3 cells and 3D-tumor spheroids. RESULTS: All prepared NLCs showed homogenous dispersion (<220 nm in size) with a negative ZP (-18 to -22 mV), except for positively charged RIPL-NLCs (~10 mV), revealing no significant cytotoxicity in either SKOV3 or RAW 264.7 cell lines. cPEG-RIPL-NLC protein adsorption was 1.75-fold less than that of RIPL-NLCs, and PEGylation significantly reduced the macrophage uptake. PEG detachment from the cPEG-RIPL-NLCs was pH-sensitive and time dependent. At 2 hours incubation, cPEG-RIPL-NLCs and PEG-RIPL-NLCs exhibited comparable cellular uptake at pH 7.4, whereas cPEG-RIPL-NLC uptake was increased over 2-fold at pH 6.5. 3D-spheroid penetration also demonstrated pH-sensitivity: at pH 7.4, cPEG-RIPL-NLCs could not penetrate deep into the spheroid core region during 2 hours, whereas at pH 6.5, high fluorescence intensity in the core region was observed for both cPEG-RIPL-NLC-and RIPL-NLC-treated groups. CONCLUSION: cPEG-RIPL-NLCs are good candidates for Hpn-selective drug targeting in conjunction with pH-responsive PEG cleavage.
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Portadores de Fármacos/química , Desenho de Fármacos , Lipídeos/química , Nanoestruturas/química , Neoplasias Ovarianas/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Polietilenoglicóis/química , Células Cultivadas , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Técnicas In Vitro , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Neoplasias Ovarianas/patologia , Fragmentos de Peptídeos/química , Fagocitose , Serina Endopeptidases/química , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/patologiaRESUMO
PURPOSE: To develop an immediate release-type tablet containing varenicline salicylate (VRC-S), a smoking cessation agent, formulation and stability studies were performed. The in vitro dissolution and in vivo pharmacokinetic (PK) behavior of the tablets were compared with those of the commercial product (Champix) as a reference. MATERIALS AND METHODS: The characteristics of the powder were investigated by particle morphology, size distribution, solubility, hygroscopicity, differential scanning calorimetry, and powder X-ray diffraction. Based on the drug-excipient compatibility test, different VRC-S tablets were prepared with the selected excipients through direct compression or wet granulation method and subjected to a dissolution test. The stability of the most promising VRC-S tablet (F4) was evaluated under accelerated conditions (40°C and 75% relative humidity). Further, the dissolution and human pharmacokinetic profiles of the F4 tablet and Champix were compared. RESULTS: VRC-S showed a positively skewed unimodal size distribution with a specific surface area of 2.02 m2/g, single endothermic peak of 225.2°C in differential scanning calorimetry, crystalline internal structure in powder X-ray diffraction, aqueous solubility of 244.7 mg/mL, and hygroscopicity of 0.256 mg/g. The wet granulation method was preferred for tablet preparation and employed the following excipients: microcrystalline cellulose and anhydrous dibasic calcium phosphate as diluents, croscarmellose sodium as a disintegrant, and colloidal silicon dioxide and magnesium stearate as lubricants. The F4 tablet was stable for 6 months under accelerated conditions. The dissolution of VRC was pH independent, revealing f 2 values of 76.49 and 68.38 at pH 1.2 and pH 6.8, respectively. After the oral administration of F4 tablet and Champix to healthy human volunteers, pharmacokinetic parameters, including time to reach the maximum plasma concentration (Tmax), maximum plasma concentration (Cmax), and area under the curve from 0 to infinity (AUCinf), were compared. The values of 90% CI were 0.972-1.035 for Cmax and 0.982-1.075 for AUCinf, which was indicative of the bioequivalence of both products. CONCLUSION: VRC-S-containing F4 tablet might be a good candidate for smoking cessation treatment.
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Composição de Medicamentos , Salicilatos/química , Salicilatos/farmacocinética , Vareniclina/química , Vareniclina/farmacocinética , Adulto , Cromatografia Líquida , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Salicilatos/sangue , Solubilidade , Comprimidos , Espectrometria de Massas em Tandem , Equivalência Terapêutica , Vareniclina/sangue , Adulto JovemRESUMO
As a platform for hepsin-specific drug delivery, we previously prepared IPLVVPLRRRRRRRRC peptide (RIPL)-conjugated nanostructured lipid carriers (RIPL-NLCs) composed of Labrafil® M 1944 CS (liquid oil) and Precirol® ATO 5 (solid lipid). In this study, to prevent the recognition by the mononuclear phagocyte system, polyethylene glycol (PEG)-modified RIPL-NLCs (PEG-RIPL-NLCs) were prepared using PEG3000 at different grafting ratios (1, 5, and 10 mole %). All prepared NLCs showed a homogeneous dispersion (130â»280 nm), with zeta potentials varying from -18 to 10 mV. Docetaxel (DTX) was successfully encapsulated in NLCs: encapsulation efficiency (93â»95%); drug-loading capacity (102â»109 µg/mg). PEG-RIPL-NLCs with a grafting ratio of 5% PEG or higher showed significantly reduced protein adsorption and macrophage phagocytosis. The uptake of PEG(5%)-RIPL-NLCs by cancer cell lines was somewhat lower than that of RIPL-NLCs because of the PEG-induced steric hindrance; however, the uptake level of PEG-RIPL-NLCs was still greater than that of plain NLCs. In vivo biodistribution was evaluated after tail vein injection of NLCs to normal mice. Compared to RIPL-NLCs, PEG(5%)-RIPL-NLCs showed lower accumulation in the liver, spleen, and lung. In conclusion, we found that PEG(5%)-RIPL-NLCs could be a promising nanocarrier for selective drug targeting with a high payload of poorly water-soluble drugs.
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To overcome the poor dissolution of telmisartan (TMS) at weak acidic pH, amorphous alkalinized TMS (AAT) was prepared by introducing sodium hydroxide as a selective alkalizer. AAT-containing polymeric solid dispersions were prepared by a solvent evaporation method; these solid dispersions were AAT-PEG, AAT-PVP, AAT-POL, and AAT-SOL for the polymers of PEG 6000, PVP K30, Poloxamer 407, and Soluplus, respectively. The characteristics of the different formulations were observed by differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, and scanning electron microscopy. To compare the supersaturation behavior, a dissolution test was performed at 37 ± 0.5 °C either in 900 ml (plain condition) or 500 ml (limited condition) of pH 6.8-simulated intestinal fluid used as a medium. AAT-SOL exhibited enhanced dissolution, indicating the probability of extended supersaturation in the limited condition. AAT-SOL was further formulated into a tablet by introducing other excipients, Vivapur 105 and Croscarmellose, as a binder and superdisintegrant, respectively, using a direct compression method. The selected AAT-SOL tablet was superior to Micardis (the reference product) in the aspect of supersaturation maintenance during dissolution in the limited condition, suggesting that it is a promising candidate for practical development that can replace the commercial product in the future.
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Antiácidos/química , Composição de Medicamentos/métodos , Telmisartan/química , Antiácidos/metabolismo , Anti-Hipertensivos/química , Anti-Hipertensivos/metabolismo , Varredura Diferencial de Calorimetria/métodos , Excipientes/química , Excipientes/metabolismo , Microscopia Eletrônica de Varredura/métodos , Polímeros/química , Polímeros/metabolismo , Solventes/química , Solventes/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Comprimidos , Telmisartan/metabolismo , Difração de Raios X/métodosRESUMO
BACKGROUND: To facilitate selective and enhanced drug delivery to hepsin (Hpn)-expressing cancer cells, RIPL peptide (IPLVVPLRRRRRRRRC, 16-mer)-conjugated nanostructured lipid carriers (RIPL-NLCs) were developed. METHODS: NLCs were prepared using a solvent emulsification-evaporation method and the RIPL peptide was conjugated to the maleimide-derivatized NLCs via the thiol-maleimide reaction. Employing a fluorescent probe (DiI), in vitro target-selective intracellular uptake behaviors were observed using fluorescence microscopy and flow cytometry. Separately, docetaxel (DTX) was encapsulated by pre-loading technique, then cytotoxicity and drug release were evaluated. In vivo antitumor efficacy was investigated in BALB/c nude mice with SKOV3 cell tumors after intratumoral injections of different DTX formulations at a dose equivalent to 10 mg/kg DTX. RESULTS: RIPL-NLCs showed positively charged nanodispersion, whereas NLCs were negatively charged. DTX was successfully encapsulated with an encapsulation efficiency and drug loading capacity of 95-98% and 44-46 µg/mg, respectively. DTX release was diffusion-controlled, revealing the best fit to the Higuchi equation. Cellular uptake of DiI-loaded RIPL-NLCs was 8.3- and 6.2-fold higher than that of DiI-loaded NLCs, in Hpn(+) SKOV3 and LNCaP cells, respectively. The translocation of RIPL-NLCs into SKOV3 cells was time-dependent with internalization within 1 h and distribution throughout the cytoplasm after 2 h. DTX-loaded RIPL-NLCs (DTX-RIPL-NLCs) revealed dose-dependent in vitro cytotoxicity, while drug-free formulations were non-cytotoxic. In SKOV3-bearing xenograft mouse model, DTX-RIPL-NLCs significantly inhibited tumor growth: the inhibition ratios of the DTX solution-treated and DTX-RIPL-NLC-treated groups were 61.4% and 91.2%, respectively, compared to those of the saline-treated group (control). CONCLUSION: RIPL-NLCs are good candidates for Hpn-selective drug targeting with a high loading capacity of hydrophobic drug molecules.
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Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/química , Peptídeos/química , Serina Endopeptidases/metabolismo , Animais , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Docetaxel , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lipídeos/química , Maleimidas/química , Camundongos Endogâmicos BALB C , Camundongos Nus , Tamanho da Partícula , Peptídeos/administração & dosagem , Taxoides/administração & dosagem , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The objective of this study was to formulate once-a-day extended-release (ER) pellet system of imidafenacin (IDN), a recently approved urinary antispasmodic agent with twice-a-day dosing regimen. The sugar sphere pellets were firstly layered with IDN and hypromellose and then coated with Eudragit RS (copolymers of acrylic and methacrylic acid esters), employed as a release modifier, using a fluid-bed coater. Solid-state characterizations using solid-state X-ray diffraction and differential scanning calorimeter indicated that the antispasmodic agent was homogeneously layered onto the pellets in an amorphous state. Drug release from multiple-unit ER system was effectively retarded in proportion to the amount of Eudragit RS in the outer layer, with a high correlation value above 0.86. In a pharmacokinetic evaluation in beagle dogs, the plasma concentration profile of IDN was markedly protracted by ER pellets, exhibiting delayed the time needed to reach the maximum drug concentration and the elimination half-life in plasma, compared to the commercial immediate release form (Uritos® tablet, Kyorin Pharmaceutical Co., Ltd., Japan). Therefore, the novel ER pellets can be a promising tool for oral IDN therapy, providing a once-a-day dosing regimen, and thus, improving patient compliance.
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Química Farmacêutica/métodos , Liberação Controlada de Fármacos , Imidazóis/sangue , Imidazóis/síntese química , Resinas Acrílicas/síntese química , Resinas Acrílicas/farmacocinética , Animais , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/farmacocinética , Cães , Liberação Controlada de Fármacos/fisiologia , Derivados da Hipromelose/síntese química , Masculino , Polímeros/síntese química , Polímeros/farmacocinética , SolubilidadeRESUMO
To develop a single-shot vaccine containing diphtheria toxoid (DT) with a sufficient immune response, poly(lactide-co-glycolide) (PLGA) microspheres were prepared by water-in-oil-in-water double emulsification and solvent extraction techniques using low or high-molecular-weight PLGA (LMW-MS or HMW-MS). Stearic acid (SA) was introduced to HMW-MS (HMW/SA-MS) as a release modulator. Mean particle sizes (dvs, µm) varied between the prepared microspheres, with LMW-MS, HMW-MS, and HMW/SA-MS having the sizes of 29.83, 110.59, and 69.5 µm, respectively; however, the protein entrapment and loading efficiency did not vary, with values of 15.2-16.8 µg/mg and 61-75%, respectively. LMW-MS showed slower initial release (~ 2 weeks) but faster and higher release of antigen during weeks 3~7 than did HMW-MS. HMW/SA-MS showed rapid initial release followed by a continuous release over an extended period of time (~ 12 weeks). Mixed PLGA microspheres (MIX-MS), a combination of HMW/SA-MS and LMW-MS (1:1), demonstrated a sufficient initial antigen release and a subsequent boost release in a pulsatile manner. Serum antibody levels were measured by ELISA after DT immunization of Balb/c mice, and showed a greater response to MIX-MS than to alum-adsorbed DT (control). A lethal toxin challenge test with MIX-MS (a DT dose of 18 Lf) using Balb/c mice revealed complete protection, indicating a good candidate delivery system for a single-shot immunization.
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Toxoide Diftérico/administração & dosagem , Poliglactina 910/química , Animais , Toxoide Diftérico/imunologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Microesferas , Tamanho da Partícula , VacinaçãoRESUMO
Ultrasound volume rendering is an efficient method for visualizing the shape of fetuses in obstetrics and gynecology. However, in order to obtain high-quality ultrasound volume rendering, noise removal and coordinates conversion are essential prerequisites. Ultrasound data needs to undergo a noise filtering process; otherwise, artifacts and speckle noise cause quality degradation in the final images. Several two-dimensional (2D) noise filtering methods have been used to reduce this noise. However, these 2D filtering methods ignore relevant information in-between adjacent 2D-scanned images. Although three-dimensional (3D) noise filtering methods are used, they require more processing time than 2D-based methods. In addition, the sampling position in the ultrasonic volume rendering process has to be transformed between conical ultrasound coordinates and Cartesian coordinates. We propose a 3D-mipmap-based noise reduction method that uses graphics hardware, as a typical 3D mipmap requires less time to be generated and less storage capacity. In our method, we compare the density values of the corresponding points on consecutive mipmap levels and find the noise area using the difference in the density values. We also provide a noise detector for adaptively selecting the mipmap level using the difference of two mipmap levels. Our method can visualize 3D ultrasound data in real time with 3D noise filtering.
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Gráficos por Computador , Imageamento Tridimensional/métodos , Ultrassonografia Pré-Natal/métodos , HumanosRESUMO
Recent results of corpus-based linguistics demonstrate that context-appropriate sentences can be generated by a stochastic constraint satisfaction process. Exploiting the similarity of constraint satisfaction and DNA self-assembly, we explore a DNA assembly model of sentence generation. The words and phrases in a language corpus are encoded as DNA molecules to build a language model of the corpus. Given a seed word, the new sentences are constructed by a parallel DNA assembly process based on the probability distribution of the word and phrase molecules. Here, we present our DNA code word design and report on successful demonstration of their feasibility in wet DNA experiments of a small scale.
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DNA/química , Modelos Moleculares , Sequência de Bases , Dados de Sequência MolecularRESUMO
PURPOSE: The purpose of this study was to determine the significant factors for risk estimate of aspiration and to evaluate the efficiency of the dysphagia assessment tool. METHODS: A consecutive series of 210 stroke patients with aspiration symptoms such as cough and dysphagia who had soft or regular diet without tube feeding were examined. The dysphagia assessment tool for aspiration was compared with videofluoroscopy using Classification and Regression Tree (CART) analysis. RESULTS: In CART analysis, of 34 factors, the significant factors for estimating risk of aspiration were cough during swallowing, oral stasis, facial symmetry, salivary drooling, and cough after swallowing. The risk estimate error of the revised dysphagia assessment tool was 25.2%, equal to that of videofluoroscopy. CONCLUSION: The results indicate that the dysphagia assessment tool developed and examined in this study was potentially useful in the clinical field and the primary risk estimating factor was cough during swallowing. Oral stasis, facial symmetry, salivary drooling, cough after swallowing were other significant factors, and based on these results, the dysphagia assessment tool for aspiration was revised and complemented.
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Transtornos de Deglutição/diagnóstico , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Tosse , Deglutição , Transtornos de Deglutição/complicações , Assimetria Facial , Feminino , Fluoroscopia/métodos , Humanos , Inalação , Masculino , Pessoa de Meia-Idade , Medição de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapiaRESUMO
Inflammation of the tubulointerstitial compartment, leading to fibrosis, is a major factor in the progressive loss of renal function in a wide variety of kidney diseases. In order to develop a therapeutic approach for nephropathy, we examined the simultaneous inhibition of transcription factor nuclear factor-kappaB (NF-kappaB), which is responsible for a wide range of cellular processes, especially inflammation, in a mouse model of unilateral ureteral obstruction. In this study, we employed a ring-type NF-kappaB (R-NF-kappaB) decoy oligodeoxynucleotide (ODN), containing consensus promoter sequences of NF-kappaB. This R-NF-kappaB decoy ODN is more highly resistant to degradation by nucleases than is the current phosphothiolated double stranded NF-kappaB decoy ODN. The inhibitory effect of R-NF-kappaB decoy ODN on nephropathy was confirmed by molecular and histological examinations. In addition, treatment with R-NF-kappaB decoy ODN reduced the activities of inflammatory cytokines, such as tumor necrosis factor-alpha and interleukin-1beta. Interestingly, the treatment with R-NF-kappaB decoy ODN also suppressed the gene expression of transforming growth factor-beta1 and fibronectin, resulting in the inhibition of fibrotic changes. These results suggest that the inhibition of NF-kappaB using R-NF-kappaB decoy ODN has potential therapeutic application in the prevention of renal fibrosis.
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Nefropatias/genética , NF-kappa B/genética , Oligodesoxirribonucleotídeos/farmacologia , Transcrição Gênica/efeitos dos fármacos , Animais , Sequência de Bases , Nitrogênio da Ureia Sanguínea , Modelos Animais de Doenças , Fibronectinas/genética , Fibronectinas/metabolismo , Fibrose/complicações , Fibrose/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Glomerulonefrite/complicações , Glomerulonefrite/genética , Imuno-Histoquímica , Inflamação/complicações , Interleucina-1beta/sangue , Nefropatias/patologia , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos/genética , Ratos , Soro , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/sangueRESUMO
To verify the changes of mesopic and photopic contrast sensitivity function of sound eye whose visual acuity was kept the same after occlusion therapy in the amblyopic children. Fourteen sound eyes of amblyopic children (mean; 7.67 years; S.D., 1.50 years) who kept their visual acuity the same after the occlusion therapy were tested. The children had 6 hours of part-time patch therapy for 3 months prior to this examination. Among 14 amblyopic children, 8 were anisometric and 6 were strabismic amblyopes. Using the visual capacity analyzer which measures the minimal contrast level at from low to high spatial frequencies, the contrast sensitivity of sound eye was measured, under both photopic and mesopic condition, before and after 3 months of occlusion therapy. Comparing the contrast sensitivity of sound eye after the occlusion therapy to that before the occlusion, there was no statistical difference in photopic condition. When it comes to mesopic condition, the contrast sensitivity decreased at the intermediate spatial frequency level (3-13 c.p.d, p=0.028) after the occlusion therapy. The occlusion caused statistically significant decrease in mesopic contrast sensitivity, when the visual acuity was not changed after the occlusion therapy. It may indicate that mesopic contrast sensitivity can be considered as a useful tool for early detection of hidden occlusion amblyopia.
Assuntos
Ambliopia/fisiopatologia , Ambliopia/terapia , Sensibilidades de Contraste , Criança , Humanos , Ortóptica , Acuidade VisualRESUMO
Unique starlike CdS particles were prepared from the lyotropic triblock copolymer solution system. The starlike CdS consists of a spherical core and dozens of the attached conical nanolobes. From the comparative studies with the spherical and rod-shaped CdS nanoparticles, the unique photophysical property is presented for the starlike CdS particle. The experimental results suggest that the photogenerated charge carriers at the tip-edge region of the conical nanolobe in the starlike CdS system diffuse into the thicker inner part including the core region, which is possibly due to the decreasing excited state potential gradient from the tip edge to the thicker inner part. This type of charge carrier diffusion dynamics from the surrounding to the thicker inner part in this anisotropic morphology of the starlike CdS semiconductor closely resembles the energy transfer dynamics in the organic dendrimers.