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1.
Hum Mol Genet ; 31(7): 1082-1095, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-34850884

RESUMO

Osteonecrosis of the femoral head (ONFH) involves necrosis of bone and bone marrow of the femoral head caused by ischemia with unknown etiology. Previous genetic studies on ONFH failed to produce consistent results, presumably because ONFH has various causes with different genetic backgrounds and the underlying diseases confounded the associations. Steroid-associated ONFH (S-ONFH) accounts for one-half of all ONFH, and systemic lupus erythematosus (SLE) is a representative disease underlying S-ONFH. We performed a genome-wide association study (GWAS) to identify genetic risk factors for S-ONFH in patients with SLE. We conducted a two-staged GWAS on 636 SLE patients with S-ONFH and 95 588 non-SLE controls. Among the novel loci identified, we determined S-ONFH-specific loci by comparing allele frequencies between SLE patients without S-ONFH and non-SLE controls. We also used Korean datasets comprising 148 S-ONFH cases and 37 015 controls to assess overall significance. We evaluated the functional annotations of significant variants by in silico analyses. The Japanese GWAS identified 4 significant loci together with 12 known SLE susceptibility loci. The four significant variants showed comparable effect sizes on S-ONFH compared with SLE controls and non-SLE controls. Three of the four loci, MIR4293/MIR1265 [odds ratio (OR) = 1.99, P-value = 1.1 × 10-9)], TRIM49/NAALAD2 (OR = 1.65, P-value = 4.8 × 10-8) and MYO16 (OR = 3.91, P-value = 4.9 × 10-10), showed significant associations in the meta-analysis with Korean datasets. Bioinformatics analyses identified MIR4293, NAALAD2 and MYO16 as candidate causal genes. MIR4293 regulates a PPARG-related adipogenesis pathway relevant to S-ONFH. We identified three novel susceptibility loci for S-ONFH in SLE.


Assuntos
Necrose da Cabeça do Fêmur , Lúpus Eritematoso Sistêmico , Esteroides , Carboxipeptidases/genética , Proteínas de Transporte/genética , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/complicações , Necrose da Cabeça do Fêmur/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Lúpus Eritematoso Sistêmico/genética , MicroRNAs/genética , Cadeias Pesadas de Miosina/genética , Polimorfismo de Nucleotídeo Único , Esteroides/efeitos adversos
2.
Int J Mol Sci ; 25(3)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38338667

RESUMO

mRNA vaccines have emerged as a pivotal tool in combating COVID-19, offering an advanced approach to immunization. A key challenge with these vaccines is their need for extremely-low-temperature storage, which affects their stability and shelf life. Our research addresses this issue by enhancing the stability of mRNA vaccines through a novel cationic lipid, O,O'-dimyristyl-N-lysyl aspartate (DMKD). DMKD effectively binds with mRNA, improving vaccine stability. We also integrated phosphatidylserine (PS) into the formulation to boost immune response by promoting the uptake of these nanoparticles by immune cells. Our findings reveal that DMKD-PS nanoparticles maintain structural integrity under long-term refrigeration and effectively protect mRNA. When tested, these nanoparticles containing green fluorescent protein (GFP) mRNA outperformed other commercial lipid nanoparticles in protein expression, both in immune cells (RAW 264.7 mouse macrophage) and non-immune cells (CT26 mouse colorectal carcinoma cells). Importantly, in vivo studies show that DMKD-PS nanoparticles are safely eliminated from the body within 48 h. The results suggest that DMKD-PS nanoparticles present a promising alternative for mRNA vaccine delivery, enhancing both the stability and effectiveness of these vaccines.


Assuntos
Lipossomos , Nanopartículas , Vacinas , Animais , Camundongos , RNA Mensageiro/química , Vacinas de mRNA , Transfecção , Células Apresentadoras de Antígenos , Nanopartículas/química
3.
Int J Mol Sci ; 25(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38892434

RESUMO

Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood-immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the lipid micellar structure capturing quantum dot (QD) for cancer theranosis. The QD/lipid micelles (QDMs) were prepared using a simple self-assembly procedure and then conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for tumor targeting. As a therapeutic agent, Bcl2 siRNA-cholesterol conjugates were loaded on the surface of QDMs. The EGFR-directed QDMs containing Bcl2 siRNA, so-called immuno-QDM/siBcl2 (iQDM/siBcl2), exhibited the more effective delivery of QDs and siBcl2 to target human colorectal cancer cells in cultures as well as in mouse xenografts. The effective in vivo targeting of iQDM/siBcl2 resulted in a more enhanced therapeutic efficacy of siBcl2 to the target cancer in mice. Based on the results, anti-EGFR QDM capturing therapeutic siRNA could be suggested as an alternative modality for tumor-targeted theranosis.


Assuntos
Receptores ErbB , Proteínas Proto-Oncogênicas c-bcl-2 , Pontos Quânticos , RNA Interferente Pequeno , Pontos Quânticos/química , Animais , Receptores ErbB/genética , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inibidores , Humanos , RNA Interferente Pequeno/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Camundongos , Linhagem Celular Tumoral , Nanopartículas/química , Lipídeos/química , Nanomedicina Teranóstica/métodos , Ensaios Antitumorais Modelo de Xenoenxerto , Micelas
4.
Int J Mol Sci ; 24(6)2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36982869

RESUMO

The nanoscale spatiotemporal resolution of single-particle tracking (SPT) renders it a powerful method for exploring single-molecule dynamics in living cells or tissues, despite the disadvantages of using traditional organic fluorescence probes, such as the weak fluorescent signal against the strong cellular autofluorescence background coupled with a fast-photobleaching rate. Quantum dots (QDs), which enable tracking targets in multiple colors, have been proposed as an alternative to traditional organic fluorescence dyes; however, they are not ideally suitable for applying SPT due to their hydrophobicity, cytotoxicity, and blinking problems. This study reports an improved SPT method using silica-coated QD-embedded silica nanoparticles (QD2), which represent brighter fluorescence and are less toxic than single QDs. After treatment of QD2 in 10 µg/mL, the label was retained for 96 h with 83.76% of labeling efficiency, without impaired cell function such as angiogenesis. The improved stability of QD2 facilitates the visualization of in situ endothelial vessel formation without real-time staining. Cells retain QD2 fluorescence signal for 15 days at 4 °C without significant photobleaching, indicating that QD2 has overcome the limitations of SPT enabling long-term intracellular tracking. These results proved that QD2 could be used for SPT as a substitute for traditional organic fluorophores or single quantum dots, with its photostability, biocompatibility, and superior brightness.


Assuntos
Nanopartículas , Pontos Quânticos , Humanos , Dióxido de Silício , Células Endoteliais da Veia Umbilical Humana , Linhagem Celular , Corantes Fluorescentes
5.
Ophthalmology ; 128(1): 110-119, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32553941

RESUMO

PURPOSE: To investigate the use of a retinal thickness deviation map generated from swept-source (SS) OCT images for hydroxychloroquine retinopathy screening. DESIGN: Retrospective cohort study. PARTICIPANTS: This study included 1192 Korean patients with a history of hydroxychloroquine treatment: 881 patients (1723 eyes) in the discovery set and 311 patients (591 eyes) in the validation set. Patients were screened for retinal toxicity using SS OCT, fundus autofluorescence, and standard automated perimetry. METHODS: According to the 2016 American Academy of Ophthalmology guidelines, hydroxychloroquine retinopathy was diagnosed by the presence of abnormalities on ≥1 objective structural tests alongside corresponding visual field defects. The 12 × 9-mm2 macular volume SS OCT scan was performed, and the retinal thickness deviation map was generated automatically using the built-in software. On this map, yellow (retinal thickness, <5% of the normative level) or red (<1% of the normative level) pixels were defined as abnormal. Abnormal findings were evaluated, and diagnostic criteria were developed based on the discovery set data; criteria were validated using the validation set data. MAIN OUTCOME MEASURES: The rate and patterns of abnormalities on the retinal thickness deviation map and sensitivity and specificity of the diagnostic criteria. RESULTS: The retinal thickness deviation map showed the following abnormal patterns in eyes with hydroxychloroquine retinopathy: pericentral (36.0%) or parafoveal (6.1%) ring, mixed-ring (34.2%), central island (13.2%), and whole macular thinning (10.5%). The criterion of ≥5 contiguous red pixels showing 1 of the 5 characteristic patterns in both eyes yielded the greatest diagnostic performance (sensitivity and specificity of 98.2% and 89.1% and of 100% and 87.5% in the discovery and validation set data, respectively). Moreover, the area of abnormal pixels on the map was correlated significantly with the mean deviation (P < 0.001) and pattern standard deviation (P < 0.001) on the Humphrey 30-2 test in eyes with hydroxychloroquine retinopathy. CONCLUSIONS: The retinal thickness deviation map may facilitate the objective evaluation of hydroxychloroquine retinopathy because it does not require subjective, morphologic evaluation of the outer retinal layers. The map has the potential to enhance hydroxychloroquine retinopathy screening when used in conjunction with conventional screening methods.


Assuntos
Hidroxicloroquina/efeitos adversos , Retina/diagnóstico por imagem , Doenças Retinianas/diagnóstico , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Adulto , Idoso , Antirreumáticos/efeitos adversos , Feminino , Angiofluoresceinografia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Retina/efeitos dos fármacos , Doenças Retinianas/induzido quimicamente , Estudos Retrospectivos , Testes de Campo Visual , Campos Visuais
6.
Proc Natl Acad Sci U S A ; 115(45): E10730-E10739, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30348762

RESUMO

Impulsivity is closely associated with addictive disorders, and changes in the brain dopamine system have been proposed to affect impulse control in reward-related behaviors. However, the central neural pathways through which the dopamine system controls impulsive behavior are still unclear. We found that the absence of the D2 dopamine receptor (D2R) increased impulsive behavior in mice, whereas restoration of D2R expression specifically in the central amygdala (CeA) of D2R knockout mice (Drd2-/-) normalized their enhanced impulsivity. Inhibitory synaptic output from D2R-expressing neurons in the CeA underlies modulation of impulsive behavior because optogenetic activation of D2R-positive inhibitory neurons that project from the CeA to the bed nucleus of the stria terminalis (BNST) attenuate such behavior. Our identification of the key contribution of D2R-expressing neurons in the CeA → BNST circuit to the control of impulsive behavior reveals a pathway that could serve as a target for approaches to the management of neuropsychiatric disorders associated with impulsivity.


Assuntos
Núcleo Central da Amígdala/metabolismo , Comportamento Impulsivo , Vias Neurais/metabolismo , RNA Mensageiro/genética , Receptores de Dopamina D2/genética , Núcleos Septais/metabolismo , Animais , Núcleo Central da Amígdala/fisiopatologia , Comportamento de Escolha , Dopamina/metabolismo , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Knockout , Vias Neurais/fisiopatologia , Neurônios/metabolismo , Neurônios/patologia , Testes Neuropsicológicos , Optogenética , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Tempo de Reação , Receptores de Dopamina D2/deficiência , Núcleos Septais/fisiopatologia , Transdução de Sinais
7.
Ann Rheum Dis ; 79(11): 1438-1445, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32723749

RESUMO

OBJECTIVE: Genome-wide association studies (GWAS) in rheumatoid arthritis (RA) have discovered over 100 RA loci, explaining patient-relevant RA pathogenesis but showing a large fraction of missing heritability. As a continuous effort, we conducted GWAS in a large Korean RA case-control population. METHODS: We newly generated genome-wide variant data in two independent Korean cohorts comprising 4068 RA cases and 36 487 controls, followed by a whole-genome imputation and a meta-analysis of the disease association results in the two cohorts. By integrating publicly available omics data with the GWAS results, a series of bioinformatic analyses were conducted to prioritise the RA-risk genes in RA loci and to dissect biological mechanisms underlying disease associations. RESULTS: We identified six new RA-risk loci (SLAMF6, CXCL13, SWAP70, NFKBIA, ZFP36L1 and LINC00158) with pmeta<5×10-8 and consistent disease effect sizes in the two cohorts. A total of 122 genes were prioritised from the 6 novel and 13 replicated RA loci based on physical distance, regulatory variants and chromatin interaction. Bioinformatics analyses highlighted potentially RA-relevant tissues (including immune tissues, lung and small intestine) with tissue-specific expression of RA-associated genes and suggested the immune-related gene sets (such as CD40 pathway, IL-21-mediated pathway and citrullination) and the risk-allele sharing with other diseases. CONCLUSION: This study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA.


Assuntos
Artrite Reumatoide/genética , Predisposição Genética para Doença/genética , Estudos de Casos e Controles , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único , República da Coreia
8.
Asia Pac J Clin Nutr ; 29(2): 404-413, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32674248

RESUMO

BACKGROUND AND OBJECTIVES: Koreans tend to have high sodium intake in restaurants. This study assessed the effect of the sodium reduction project in restaurants in Daegu Metropolitan City. METHODS AND STUDY DESIGN: A total of 156 sodium reduction menu items offered by 90 restaurants were categorized into 11 food groups to compare sodium content and salinity before and after the project. In total, 162 owners and staff members of the restaurants, as well as 727 of their customers, were surveyed on their perceptions of and satisfaction with the sodium reduction project. RESULTS: Average salinity of the menu items was significantly reduced from 0.70% prior to the project to 0.49% after the project (p<0.001), and average sodium content was also significantly reduced from 1,470 mg to 980 mg (p<0.001). The food groups with the highest sodium reduction rate were soups (46.0%) and grilled dishes (39.5%), with an average sodium reduction rate of 36.1%. The restaurant owners' average satisfaction score with the project was 39.6 points (out of 50). Customers responded that the sodium reduction menus were moderate (62.4%) and bland (27.9%), and the taste was good (48.9%) and excellent (25.0%). Approximately 52.0% and 18.6% of customers were satisfied and very satisfied, respectively, with the sodium reduction menu. CONCLUSIONS: Overall, the sodium reduction project in restaurants in Daegu had a positive effect because it successfully reduced the sodium content of food while also boosting the satisfaction of the restaurant owners and staff and their customers with the project.


Assuntos
Comportamento do Consumidor , Dieta Hipossódica , Rotulagem de Alimentos , Necessidades Nutricionais , Restaurantes , Humanos , República da Coreia , Inquéritos e Questionários
9.
Ecol Food Nutr ; 58(6): 560-574, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31327256

RESUMO

This study aimed to clarify the association between the frequency of dining out and the risk of obesity, diabetes mellitus, and dyslipidemia among Korean adults. This cross-sectional study surveyed 640 participants aged 20-69 years in Korea. Daily intake of energy, fat, protein, and cholesterol significantly increased as the frequency of dining out increased (P < .001). Energy derived from carbohydrates significantly decreased with the frequency of dining out, while that derived from fat and protein increased (P < .001). Among participants who rarely dined out, the fully adjusted odds ratios (ORs) for hyperglycemia were significantly lower at 0.35 (95% CI, 0.16-0.76). Decreased risk of being hyperglycemia among participants who rarely dined out suggests that the frequency of dining out can be related to diabetes risk.


Assuntos
Diabetes Mellitus/etiologia , Dislipidemias/etiologia , Comportamento Alimentar , Obesidade/etiologia , Restaurantes , Adulto , Idoso , Dislipidemias/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/epidemiologia , República da Coreia/epidemiologia , Fatores de Risco , Adulto Jovem
10.
Surg Endosc ; 32(4): 1708-1713, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28916891

RESUMO

BACKGROUND: Wire-guided cannulation has been widely accepted as a useful technique for achieving selective biliary access because it has significantly increased the success rate of biliary cannulation compared with conventional contrast-assisted cannulation. Unlike conventional guidewires with a straight tip, a loop-tip guidewire (LGW) has a closed distal loop that may facilitate less traumatic access through the epithelial folds of the intra-duodenal biliary segments. The aim of this study was to compare the performance of a LGW with a straight-tip guidewire (SGW) in achieving successful selective biliary cannulation. METHODS: From December 2014 to December 2015, we performed 192 wire-guided biliary cannulations for a naïve papilla in a randomized controlled trial. Patients were randomly assigned to the LGW group (n = 96) or the SGW group (n = 96). Our study protocol did not include crossover to the other guidewire arm if randomized wire-guided cannulation proved unsuccessful within the first 10 min. RESULTS: There was no significant difference in primary successful biliary cannulation between the two groups (LGW group: 86.5%; SGW group: 77.1%; p = 0.134). The rate and the mean number of unintentional pancreatic duct cannulations during wire-guided biliary cannulation were significantly lower in the LGW group than in the SGW group (LGW group: 14.6%; SGW group: 28.1%; p = 0.034; LGW group: 0.2 ± 0.5; SGW group: 0.6 ± 1.3; p = 0.007). Post-ERCP pancreatitis developed in 5.2% of patients in the LGW group and 8.3% of patients in the SGW group (p = 0.567). CONCLUSIONS: The biliary cannulation rate of the LGW was not significantly different from those of conventional guidewires. Use of the LGW was associated with a lower rate of unintentional pancreatic duct cannulation during wire-guided biliary cannulation than use of the SGW.


Assuntos
Cateterismo/instrumentação , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Complicações Pós-Operatórias/cirurgia , Adulto , Idoso , Sistema Biliar , Cateterismo/métodos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
11.
J Korean Med Sci ; 32(11): 1814-1819, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28960034

RESUMO

Early post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) prediction may allow safe same-day outpatients discharge after ERCP and earlier proper management. This study aimed to assess the usefulness of the 4-hour post-ERCP serum amylase and lipase levels for PEP early prediction and to investigate predictive cut-off values for 4-hour post-ERCP serum amylase and lipase levels for safe discharge and urgent initiation of resuscitation. The data of 516 consecutive patients with native papilla who underwent ERCP between January 2013 and August 2014 were retrospectively reviewed. Serum amylase and lipase levels were measured before, and 4 and 24 hours after ERCP. PEP occurred in 16 (3.1%) patients. The receiver-operator characteristic curve for 4-hour post-ERCP serum amylase and lipase levels showed that the areas under the curve were 0.919 and 0.933, respectively, demonstrating good test performances as predictors for PEP (both P values < 0.001). The amylase level > 1.5 × the upper limit of reference (ULR) was found useful for PEP exclusion with a sensitivity of 93.8%, while 4 × ULR was found useful to guide preventive therapy with the best specificity of 93.2%. Similarly, the lipase level 2 × ULR showed best sensitivity, while 8 × ULR had the best specificity. Logistic regression analysis showed that 4-hour post-ERCP amylase level > 4 × ULR, lipase level > 8 × ULR, precut sphincterotomy, and pancreatic sphincterotomy were significant predictors for PEP. In conclusion, 4-hour post-ERCP amylase and lipase levels are useful early predictors of PEP that can ensure safe discharge or prompt resuscitation after ERCP.


Assuntos
Amilases/sangue , Colangiopancreatografia Retrógrada Endoscópica , Lipase/sangue , Pancreatite/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pâncreas/metabolismo , Pâncreas/patologia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Fatores de Tempo , Adulto Jovem
12.
J Gene Med ; 18(7): 112-23, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27191929

RESUMO

BACKGROUND: The effective delivery of therapeutic genes to target cells has been a fundamental goal in cancer gene therapy because of its advantages with respect to both safety and transfection efficiency. In the present, study we describe a tumor-directed gene delivery system that demonstrates remarkable efficacy in gene delivery and minimizes the off-target effects of gene transfection. METHODS: The system consists of a well-verified cationic O,O'-dimyristyl-N-lysyl glutamate (DMKE), Sendai virus fusion (F) protein and hemagglutinin-neuraminidase (HN) protein, referred to as cationic Sendai F/HN virosomes. To achieve tumor-specific recognition, anti-epidermal growth factor (EGF) receptor antibody was coupled to the surface of the virosomes containing interleukin-12 (IL-12) and/or salmosin genes that have potent anti-angiogenetic functions. RESULTS: Among the virosomal formulations, the anti-EGF receptor (EGFR) viroplexes, prepared via complexation of plasmid DNA (pDNA) with cationic DMKE lipid, exhibited more efficient gene transfection to tumor cells over-expressing EGF receptors compared to the neutrally-charged anti-EGFR virosomes encapsulating pDNA. In addition, the anti-EGFR viroplexes with IL-12 and salmosin genes exhibited the most effective therapeutic efficacy in a mouse tumor model. Especially when combined with doxorubicin, transfection of the two genes via the anti-EGFR viroplexes exhibited an enhanced inhibitory effect on tumor growth and metastasis in lungs. CONCLUSIONS: The results of the present study suggest that anti-EGFR viroplexes can be utilized as an effective strategy for tumor-directed gene delivery. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Venenos de Crotalídeos/genética , Receptores ErbB/genética , Interleucina-12/genética , Neoplasias/genética , Vírus Sendai/genética , Células A549 , Animais , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Venenos de Crotalídeos/metabolismo , Doxorrubicina/farmacologia , Receptores ErbB/metabolismo , Terapia Genética/métodos , Proteína HN/genética , Proteína HN/metabolismo , Humanos , Interleucina-12/metabolismo , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/metabolismo , Neoplasias/terapia , Vírus Sendai/metabolismo , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/metabolismo , Virossomos/genética , Virossomos/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
13.
Small ; 12(9): 1201-11, 2016 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-26573885

RESUMO

Recently, targeted delivery systems based on functionalized polymeric nanoparticles have attracted a great deal of attention in cancer diagnosis and therapy. Specifically, as neuroblastoma occurs in infancy and childhood, targeted delivery may be critical to reduce the side effects that can occur with conventional approaches, as well as to achieve precise diagnosis and efficient therapy. Thus, biocompatible poly(d,l-lactide-co-glycolide) (PLG) nanoparticles containing an imaging probe and therapeutic gene are prepared, followed by modification with rabies virus glycoprotein (RVG) peptide for neuroblastoma-targeting delivery. RVG peptide is a well-known neuronal targeting ligand and is chemically conjugated to PLG nanoparticles without changing their size or shape. RVG-modified nanoparticles are effective in specifically targeting neuroblastoma both in vitro and in vivo. RVG-modified nanoparticles loaded with a fluorescent probe are useful to detect the tumor site in a neuroblastoma-bearing mouse model, and those encapsulating a therapeutic gene cocktail (siMyc, siBcl-2, and siVEGF) significantly suppressed tumor growth in the mouse model. This approach to designing and tailoring of polymeric nanoparticles for targeted delivery may be useful in the development of multimodality systems for theranostic approaches.


Assuntos
Terapia Genética/métodos , Nanopartículas/química , Neuroblastoma/terapia , Imagem Óptica/métodos , Polímeros/química , Nanomedicina Teranóstica/métodos , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Inativação Gênica/efeitos dos fármacos , Humanos , Ácido Láctico/química , Masculino , Camundongos , Nanopartículas/ultraestrutura , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , RNA Interferente Pequeno/metabolismo , Vírus da Raiva/metabolismo , Distribuição Tecidual/efeitos dos fármacos , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Proteínas Virais/metabolismo
14.
Pediatr Int ; 57(1): 60-3, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25203556

RESUMO

BACKGROUND: The clavicle is the bone most frequently fractured during the delivery process. METHODS: A retrospective review was performed of all births with clavicular fractures from January 2003 to December 2012. Risk factors for fracture were determined and then compared to the control group. The data were compared and analyzed with previous studies. RESULTS: Three hundred and nineteen cases of clavicular fracture (0.41% of total live births, n = 77 543) were identified. Prior to discharge, 275 cases (86.2%) were detected, and 44 cases (13.8%) were not detected until after discharge. Physical examination identified 144 cases (45.1%), while 175 cases (54.9%) were identified on chest X-ray incidentally. All babies with fracture, including five (1.6%) with brachial plexus palsy, recovered without treatment. Vacuum delivery was associated with a significantly higher incidence of clavicular fracture, as were mothers of advanced age with relatively shorter height. High birthweight, low head to chest circumference ratio and low Apgar score were other variables also significantly associated with clavicular fracture. On logistic regression analysis vacuum delivery and birthweight were significant risk factors. When analyzing and comparing findings from previous studies, only birthweight was identified as common to the risk factors affecting clavicular fracture. CONCLUSION: Major risk factors for clavicular fracture were vacuum delivery and birthweight. Considering the previous studies together, neonatal clavicular fracture appears to be a transient event without sequelae and most probably not preventable during birth.


Assuntos
Traumatismos do Nascimento/complicações , Clavícula/lesões , Previsões , Fraturas Ósseas/epidemiologia , Vácuo-Extração/efeitos adversos , Traumatismos do Nascimento/epidemiologia , Feminino , Fraturas Ósseas/etiologia , Humanos , Incidência , Recém-Nascido , Masculino , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco
15.
J Korean Med Sci ; 30(3): 245-51, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25729245

RESUMO

Both immediate and delayed hypersensitivity reactions to iodinated contrast media (ICM) are relatively common. However, there are few data to determine the clinical utility of immunologic evaluation of ICM. To evaluate the utility of ICM skin testing in patients with ICM hypersensitivity, 23 patients (17 immediate and 6 delayed reactions) were enrolled from 3 university hospitals in Korea. With 6 commonly used ICM including iopromide, iohexol, ioversol, iomeprol, iopamidol and iodixanol, skin prick (SPT), intradermal (IDT) and patch tests were performed. Of 10 patients with anaphylaxis, 3 (30.0%) and 6 (60.0%) were positive respectively on SPTs and IDTs with the culprit ICM. Three of 6 patients with urticaria showed positive IDTs. In total, 11 (64.7%) had positive on either SPT or IDT. Three of 6 patients with delayed rashes had positive response to patch test and/or delayed IDT. Among 5 patients (3 anaphylaxis, 1 urticaria and 1 delayed rash) taken subsequent radiological examinations, 3 patients administered safe alternatives according to the results of skin testing had no adverse reaction. However, anaphylaxis developed in the other 2 patients administered the culprit ICM again. With 64.7% (11/17) and 50% (3/6) of the sensitivities of corresponding allergic skin tests with culprit ICM for immediate and delayed hypersensitivity reactions, the present study suggests that skin tests is useful for the diagnosis of ICM hypersensitivity and for selecting safe ICM and preventing a recurrence of anaphylaxis caused by the same ICM.


Assuntos
Meios de Contraste/efeitos adversos , Dermatite de Contato/diagnóstico , Dermatite de Contato/imunologia , Iodetos/imunologia , Testes Cutâneos/métodos , Anafilaxia/induzido quimicamente , Anafilaxia/diagnóstico , Anafilaxia/imunologia , Reações Cruzadas/imunologia , Hipersensibilidade a Drogas/diagnóstico , Feminino , Humanos , Iohexol/análogos & derivados , Iopamidol/análogos & derivados , Masculino , Pessoa de Meia-Idade , República da Coreia , Ácidos Tri-Iodobenzoicos , Urticária/diagnóstico , Urticária/imunologia
16.
J Korean Med Sci ; 30(7): 924-31, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26130956

RESUMO

The aim of this study was to observe the effects of prophylactic palivizumab on hospitalization secondary to respiratory syncytial virus (RSV) infection (RSVhospitalization) in former very low birth weight infants (VLBWI) with bronchopulmonary dysplasia (BPD). This study also sought to identify the risk factors of RSVhospitalizationin this particular infant population. A prospective observational study was conducted between September 2007 and April 2008 in seven Korean hospitals. Children with a history of very low birth weight, a diagnosis of BPD and who were <2 yr old at the onset of the RSV season were included in this study. Palivizumab injections were administered monthly for a maximum of five months during the RSV season. RSVhospitalization rates were reviewed, and RSVhospitalization rates between subgroups were categorized by gestational age, birth weight, and duration of ventilator care. A total of 90 subjects completed the follow-up interviews. The mean gestational age at birth was 26.1±1.7 weeks, and the mean birth weight was 889.4±222.2 g. The incidence of RSVhospitalization in the study population was 8.9% (8/90), and the mean hospital stay was 11.0±5.5 days, including one death. There were no statistically significant differences in the patients' demographic characteristics or risk factors for RSV hospitalization. When subgroup analyses were conducted, there were still no statistically significant differences. The administration of palivizumab prophylaxis during the entire RSV season is important in VLBWI with BPD, regardless of their gestational age and birth weight, or previous ventilator dependency.


Assuntos
Antibioticoprofilaxia/métodos , Antivirais/uso terapêutico , Displasia Broncopulmonar/complicações , Recém-Nascido de muito Baixo Peso , Palivizumab/uso terapêutico , Infecções por Vírus Respiratório Sincicial/epidemiologia , Peso ao Nascer , Feminino , Idade Gestacional , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Tempo de Internação , Masculino , Estudos Prospectivos , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Risco , Fatores de Risco
17.
Prenat Diagn ; 34(9): 831-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24691675

RESUMO

OBJECTIVES: Little is known on how the dose and timing of exposure co-influence the cumulative concentration of fatty acid ethyl esters (FAEEs) in meconium. The objective of the study was to assess the cumulative concentration of FAEEs in meconium as a biomarker of light, moderate, or heavy prenatal alcohol exposure occurring at either first, second, or third trimesters of pregnancy. METHODS: History of prenatal alcohol exposure was obtained in the 34th week of gestation from 294 pregnant women. Meconium was collected from their babies within the first 6 to 12 h after birth and examined for the presence of nine FAEEs. RESULTS: No significant differences were identified between the cumulative levels of FAEEs in the meconium from the babies born to abstainers and those born to mothers with history of light-to-moderate prenatal alcohol exposure during their pregnancy. CONCLUSIONS: Light-to-moderate prenatal alcohol exposure cannot be reliably predicted by the cumulative FAEE concentrations in meconium of exposed babies. A cumulative FAEE level of >10 nmol/g would be required to consider that prenatal alcohol exposure during the second to third trimesters occurred at risky levels in the absence of reliable maternal history of ethanol exposure.


Assuntos
Etanol , Ácidos Graxos/análise , Exposição Materna , Mecônio/química , Teratogênicos , Adulto , Consumo de Bebidas Alcoólicas , Bebidas Alcoólicas , Biomarcadores/análise , Relação Dose-Resposta a Droga , Ésteres/análise , Feminino , Humanos , Recém-Nascido , Modelos Lineares , Comportamento Materno , Pessoa de Meia-Idade , Gravidez , Trimestres da Gravidez , Autorrelato , Fatores de Tempo
19.
Nutr Res Pract ; 18(2): 239-256, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38584808

RESUMO

BACKGROUND/OBJECTIVES: Over the past 10 yrs, the prevalence of diabetes in Korea has continued to incline, and the importance of lifestyle modification to manage diabetes has been highlighted. For patients with diabetes, carbohydrate intake reduction is effective in improving glycemic control; thus, we aimed to analyze the effect of carbohydrate intake ratio and suggest an appropriate carbohydrate intake ratio. SUBJECTS/METHODS: Using the 8th Korea National Health and Nutrition Examination Survey (2019-2021), we analyzed the data including participants aged 30 yrs or older with diabetes, and they were stratified into good and poor glycemic control groups. To analyze the correlation between the dietary behavior characteristics of participants with diabetes and the carbohydrate intake ratio, sociodemographic characteristics, dietary behavior, and health behavior were adjusted, and multivariate logistic regression analysis was conducted to present the adjusted odds ratio and 95% confidence interval (CI). RESULTS: In the unadjusted crude model, when carbohydrate intake ratio in total energy intake increased by 1%, the likelihood of poor glycemic control increased by 1.007-fold (95% CI, 0.998-1.016; P = 0.121). In model 1, which uses age and sex as adjustment variables, an increase of up to 1.011-fold was possible (95% CI, 1.001-1.021; P = 0.008). In model 2, which added variables such as diabetes duration, frequency of fruit consumption, frequency of lunch and, frequency of dinner, the risk of poor glycemic control increased by 1.010-fold as the carbohydrate intake ratio increased (95% CI, 0.998-1.022; P < 0.001). CONCLUSION: This study confirmed that as the ratio of carbohydrate intake to total energy intake increases the likelihood of poor glycemic control also increases in patients with diabetes. Therefore, to improve glycemic control in patients with diabetes, controlling the carbohydrate intake may be helpful.

20.
J Ultrasound Med ; 32(1): 45-52, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23269709

RESUMO

OBJECTIVES: The purpose of this study was to evaluate prenatal sonographic findings that could be helpful for diagnosis of congenital intrahepatic portosystemic venous shunts and the follow-up results. METHODS: Six neonates with congenital shunts between the portal vein and hepatic vein were enrolled in this study. Prenatal sonography was performed in 5 cases. We categorized the cases according to a previously published classification of intrahepatic portosystemic venous shunts and retrospectively reviewed the prenatal and postnatal sonographic examinations to identify findings that might be helpful for diagnosing shunts prenatally. Follow-up sonographic examinations were done until closure of the shunts. Clinical features were also determined. RESULTS: According to the original reports, intrahepatic portosystemic venous shunts were diagnosed by prenatal sonography in 2 of 5 cases. In the remaining 3 cases, there were suggestive abnormal findings on retrospective review, including an abnormal intrahepatic tubular structure, a prominent hepatic vein, and congestive heart failure. Postnatal sonography showed type 2 shunts in all 6 cases. In 1 case, there were 2 type 2 lesions between two branches of the left portal vein and the middle and left hepatic veins. On follow-up sonography, 5 of the 6 congenital shunts had spontaneously closed by 11 months of age. One case was treated with coil embolization during the neonatal period. Intrauterine growth restriction was the most commonly clinical feature prenatally. CONCLUSIONS: Findings such as an abnormal tubular structure, a prominent hepatic vein, and congestive heart failure can be important clues for identifying congenital intrahepatic portosystemic venous shunts on prenatal sonography. The use of prenatal and postnatal sonography is feasible for detection and evaluation of these shunts.


Assuntos
Veias Hepáticas/anormalidades , Veias Hepáticas/diagnóstico por imagem , Veia Porta/anormalidades , Veia Porta/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Fístula Vascular/congênito , Fístula Vascular/diagnóstico por imagem , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos Retrospectivos
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