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BACKGROUND: The lack of well-established operational definitions is a major limitation of Helicobacter pylori eradication studies that use secondary databases. We aimed to develop and validate operational definitions related to H. pylori eradication therapy. METHODS: Operational definitions were developed by analyzing a nationwide H. pylori eradication registry and validated using real-world data from hospital medical records. The primary endpoint was the sensitivity of the operational definitions in identifying individuals who received H. pylori eradication therapy. The secondary endpoint was the sensitivity and specificity of the operational definition in identifying successful H. pylori eradication therapy. RESULTS: H. pylori eradication therapy was defined as a prescription for one of the following combinations: 1) proton pump inhibitor (PPI) + amoxicillin + clarithromycin, 2) PPI + amoxicillin + metronidazole, 3) PPI + metronidazole + tetracycline, 4) PPI + amoxicillin + levofloxacin, 5) PPI + amoxicillin + moxifloxacin, or 6) PPI + amoxicillin + rifabutin. In the validation set, the sensitivity of the operational definition for identifying individuals who received H. pylori eradication therapy was 99.7% and 99.8% for the first- and second-line therapies, respectively. Operational definition to determine success or failure of the H. pylori eradication therapy was developed based on a confirmatory test and the prescription of rescue therapy. The sensitivity and specificity of the operational definition for predicting successful eradication were 97.6% and 91.4%, respectively, in first-line therapy and 98.6% and 54.8%, respectively, in second-line therapy. CONCLUSION: We developed and validated operational definitions related to H. pylori eradication therapy. These definitions will help researchers perform various H. pylori eradication-related studies using secondary databases.
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Helicobacter pylori , Humanos , Metronidazol/uso terapêutico , Projetos de Pesquisa , Antibacterianos/uso terapêutico , Amoxicilina/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêuticoRESUMO
The mRNA destabilizing factor tristetraprolin (TTP) functions as a tumor suppressor by down-regulating cancer-associated genes. TTP expression is significantly reduced in various cancers, which contributes to cancer processes. Enforced expression of TTP impairs tumorigenesis and abolishes maintenance of the malignant state, emphasizing the need to identify a TTP inducer in cancer cells. To search for novel candidate agents for inducing TTP in cancer cells, we screened a library containing 1019 natural compounds using MCF-7 breast cancer cells transfected with a reporter vector containing the TTP promoter upstream of the luciferase gene. We identified one molecule, of which the enantiomers are betamethasone 21-phosphate (BTM-21-P) and dexamethasone 21-phosphate (BTM-21-P), as a potent inducer of TTP in cancer cells. We confirmed that BTM-21-P, DXM-21-P, and dexamethasone (DXM) induced the expression of TTP in MDA-MB-231 cells in a glucocorticoid receptor (GR)-dependent manner. To identify potential pathways linking BTM-21-P and DXM-21-P to TTP induction, we performed an RNA sequencing-based transcriptome analysis of MDA-MB-231 cells at 3 h after treatment with these compounds. A heat map analysis of FPKM expression showed a similar expression pattern between cells treated with the two compounds. The KEGG pathway analysis results revealed that the upregulated DEGs were strongly associated with several pathways, including the Hippo signaling pathway, PI3K-Akt signaling pathway, FOXO signaling pathway, NF-κB signaling pathway, and p53 signaling pathway. Inhibition of the FOXO pathway using a FOXO1 inhibitor blocked the effects of BTM-21-P and DXM-21-P on the induction of TTP in MDA-MB-231 cells. We found that DXM enhanced the binding of FOXO1 to the TTP promoter in a GR-dependent manner. In conclusion, we identified a natural compound of which the enantiomers are DXM-21-P and BTM-21-P as a potent inducer of TTP in breast cancer cells. We also present new insights into the role of FOXO1 in the DXM-21-P- and BTM-21-P-induced expression of TTP in cancer cells.
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Neoplasias , Tristetraprolina , Tristetraprolina/genética , Glucocorticoides/farmacologia , Fosfatidilinositol 3-Quinases , Receptores de Glucocorticoides/genéticaRESUMO
BACKGROUND: Using statins in combination with other drugs was reported to increase the risk of myopathy. However, there was a sparse number of studies on the incidence of adverse events (AEs) associated with the concomitant use of statin and contraindicated drugs in the real world. OBJECTIVES: This study aimed to identify the risk of concomitant use of statins with contraindicated drugs by exploring signals related to statin-drug interactions. METHODS: We performed a disproportionality analysis for drugs and AEs by applying the case/non-case study using the KIDS-KAERS database (KIDS-KD), 2016-2020. A case was defined as an individual case safety reports (ICSRs) including "rhabdomyolysis/myopathy." A non-case was defined as an ICSR, including all other AEs. We applied Ω shrinkage measure model, chi-square statics model, additive model, multiplicative model, and combination risk ratio model to detect signals of myopathy due to statin with concomitant drugs including antiviral agents, immunosuppressants, and antifungals. RESULTS: Among 1 011 234 ICSRs, 2708 were cases, with 861 cases of statin monotherapy and 1248 of concomitant uses of statin. The adjusted reporting odds ratios were 3.27 (95% confidence interval [CI]: 3.11-3.43), 8.70 (95% CI: 8.04-9.40), and 1.83 (95% CI: 1.73-1.94), respectively. Several combinations of signals were detected through an additive model or multiplicative model. CONCLUSION: Signals of an increased risk of myopathy associated with the use of statins with concomitant drugs, including contraindicated drugs, were confirmed in a real-world setting.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Musculares , Rabdomiólise , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doenças Musculares/induzido quimicamente , Doenças Musculares/diagnóstico , Doenças Musculares/epidemiologia , Rabdomiólise/induzido quimicamente , Rabdomiólise/diagnóstico , Rabdomiólise/epidemiologia , Interações MedicamentosasRESUMO
OBJECTIVES: This study developed an algorithm for identifying pregnancy episodes and estimating the last menstrual period (LMP) in an administrative claims database and applied it to investigate the use of pregnancy-incompatible immunosuppressants among pregnant women with systemic lupus erythematosus (SLE). METHODS: An algorithm was developed and applied to a nationwide claims database in Korea. Pregnancy episodes were identified using a hierarchy of pregnancy outcomes and clinically plausible periods for subsequent episodes. The LMP was estimated using preterm delivery, sonography, and abortion procedure codes. Otherwise, outcome-specific estimates were applied, assigning a fixed gestational age to the corresponding pregnancy outcome. The algorithm was used to examine the prevalence of pregnancies and utilization of pregnancy-incompatible immunosuppressants (cyclophosphamide [CYC]/mycophenolate mofetil [MMF]/methotrexate [MTX]) and non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy in SLE patients. RESULTS: The pregnancy outcomes identified in SLE patients included live births (67%), stillbirths (2%), and abortions (31%). The LMP was mostly estimated with outcome-specific estimates for full-term births (92.3%) and using sonography procedure codes (54.7%) and preterm delivery diagnosis codes (37.9%) for preterm births. The use of CYC/MMF/MTX decreased from 7.6% during preconception to 0.2% at the end of pregnancy. CYC/MMF/MTX use was observed in 3.6% of women within 3 months preconception and 2.5% during 0-7 weeks of pregnancy. CONCLUSIONS: This study presents the first pregnancy algorithm using a Korean administrative claims database. Although further validation is necessary, this study provides a foundation for evaluating the safety of medications during pregnancy using secondary databases in Korea, especially for rare diseases.
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Lúpus Eritematoso Sistêmico , Nascimento Prematuro , Recém-Nascido , Gravidez , Humanos , Feminino , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/tratamento farmacológico , Resultado da Gravidez , Imunossupressores/uso terapêutico , Ciclofosfamida/efeitos adversos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Ácido Micofenólico/uso terapêutico , República da CoreiaRESUMO
Background/Aims: The efficacy of concurrent chemoradiotherapy (CCRT) or esophagectomy for locally advanced esophageal squamous cell carcinoma (ESCC) is unclear. This study compared the survival and recurrence of patients with locally advanced ESCC after definitive CCRT and surgery. Methods: A retrospective study was conducted on patients with locally advanced ESCC who underwent CCRT or esophagectomy at Kosin University Gospel Hospital from January 2010 to December 2016. The patients' baseline characteristics, pathology, recurrence rate, and three-year/five-year overall survival were obtained. Results: This study evaluated ESCC patients with cT1-T2, N+ or cT3-T4, or N, who were treated by definitive CCRT (n=14) or esophagectomy (n=32). No significant difference was noted between the two groups, except for the location of the cancer and performance state. The respective three- and five-year overall survival rates were 30.8% and 23.1% in the CCRT group and 40.2% and 22.5% in the esophagectomy group (p=0.685). In the CCRT group, three patients (21.4%) had a complete response, and two (66.7%) had a recurrence. In the esophagectomy group, an R0 resection was achieved in 28 (87.5%) patients, and a recurrence occurred in 18 (64.3%). The median disease-free survival in the CCRT and esophagectomy groups was 14 and 17 months, respectively (p=0.882). Conclusions: These results showed no significant difference in survival between the definitive CCRT and surgery as the initial treatment. Nevertheless, larger prospective studies will be needed because of the retrospective nature and small number of patients in this study.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/terapia , Estudos Retrospectivos , Esofagectomia , Estudos Prospectivos , Quimiorradioterapia/métodosRESUMO
BACKGROUND AND AIM: Corticosteroid use is a risk factor for avascular necrosis (AVN) and inflammatory bowel disease (IBD) patients are often exposed to higher corticosteroid usage. We investigated the epidemiology and risk factors of AVN in a nationwide population-based cohort of IBD patients. METHODS: Patients newly diagnosed with IBD were identified, and sex- and age-matched participants from the general population were selected in a 1:3 IBD:non-IBD ratio. We investigated newly diagnosed AVN and assessed the incidence rates and risk of AVN with multivariate Cox regression models. RESULTS: During the median follow-up period of 7.22±3.85 years, 357 (0.62â¯%) were newly diagnosed with AVN. The risk of AVN was higher in IBD (aHR = 1.42, 95â¯% CI: 1.25-1.62). Ulcerative colitis (UC) patients showed a particularly elevated risk of developing AVN. IBD patients with higher cumulative corticosteroid intake and exposed to a mean prednisolone-equivalent daily dose>20 mg for >1 month were at higher risk of AVN. In Crohn's disease (CD), longer exposure time to >20 mg prednisolone-equivalent presented a trend in increased risk. CONCLUSION: AVN risk was higher in IBD than in those without, particularly in UC and corticosteroid use in IBD could pose a crucial role. These underscore the importance of considering the AVN etiological factors, particularly corticosteroid use.
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The present study investigated the effects of glycyrrhizin (GRZ) on neuroinflammation and memory deficit in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of GRZ was orally administered (10, 30, or 50 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. At 24 h after the LPS injection, GRZ significantly reduced TNF-α and IL-1ß mRNA at doses of 30 and 50 mg/kg. COX-2 and iNOS protein expressions were significantly reduced by GRZ at doses of 30 and 50 mg/kg. In the Morris water maze test, GRZ (30 mg/kg) significantly prolonged the swimming time spent in the target and peri-target zones. GRZ also significantly increased the target heading and memory score numbers. In the hippocampal tissue, GRZ significantly reduced the up-regulated Iba1 protein expression and the average cell size of Iba1-expressing microglia induced by LPS. The results indicate that GRZ ameliorated the memory deficit induced by systemic LPS treatment and the effect of GRZ was found to be mediated through the inhibition of pro-inflammatory mediators and microglial activation in the brain tissue. This study supports that GRZ may be a putative therapeutic drug on neurodegenerative diseases associated with cognitive deficits and neuroinflammation such as Alzheimer's disease.
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Encefalite/tratamento farmacológico , Ácido Glicirrízico/farmacologia , Transtornos da Memória/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalite/induzido quimicamente , Encefalite/genética , Encefalite/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glicirrízico/administração & dosagem , Ácido Glicirrízico/química , Aprendizagem/efeitos dos fármacos , Lipopolissacarídeos/efeitos adversos , Masculino , Transtornos da Memória/induzido quimicamente , Camundongos , Microglia/efeitos dos fármacos , Microglia/imunologia , Microglia/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismoRESUMO
INTRODUCTION: Although messenger RNA (mRNA) vaccines have been developed and widely utilized to mitigate the coronavirus disease (COVID-19) pandemic, it is essential to describe the adverse events (AEs) following immunization. This study aimed to identify the patterns associated with serious AE reports after mRNA COVID-19 vaccination in the World Health Organization (WHO)'s global scale database (VigiBase). METHODS: This study performed a latent class analysis (LCA) of reports of serious AEs following mRNA COVID-19 vaccination from VigiBase between December 28, 2020 , and February 28, 2022 (N = 312878). The Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) terms were selected for LCA. The reporting characteristics in accordance with the cluster were described. We used a multinomial logistic regression model to estimate the association between potential factors and each cluster. RESULTS: Five clusters of AE reports were distinguished through LCA: infection AEs (cluster 1), cardiac AEs (cluster 2), respiratory/thrombotic AEs (cluster 3), systemic AEs (cluster 4), and nervous system AEs (cluster 5). Compared to cluster 4, cluster 2 had a higher proportion of males (OR 2.98; 95% confidence interval (CI) 2.87-3.09), and cluster 1 had a longer time to onset than other AEs (≥ 14 days) (OR 16.2; 95% CI 15.5-16.9). CONCLUSION: Using LCA, we found five clusters of serious AEs following mRNA COVID-19 vaccination. Each cluster was distinguished by potential factors such as age, gender, region, and time to onset. We suggest that monitoring should carefully consider the patterns of young males with cardiac AEs and elderly individuals with thrombosis after respiratory AEs. Our findings could contribute to enhancing understanding of safety profiles and establishing management strategies for serious AEs of special interest following mRNA COVID-19 vaccination.
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BACKGROUND AND OBJECTIVE: Despite several case reports, population-based studies on interstitial lung disease (ILD) following COVID-19 vaccination are lacking. Given the unprecedented safety issue of COVID-19 vaccination, it is important to assess the worldwide patterns of ILD following COVID-19 vaccination. This study aimed to investigate the signals of COVID-19 vaccine-associated ILD compared with other vaccinations using disproportionality analysis. METHODS: We analysed the VigiBase database during the period between 13 December 2020 and 26 January 2023. We adopted the case/non-case approach to assess the disproportionality signal of ILD for COVID-19 vaccines via 1:10 matching by age and sex. We compared COVID-19 vaccines with all other vaccines as the reference group. RESULTS: Among 1 233 969 vaccine-related reports, 679 were reported for ILD. The majority of ILD cases were related to tozinameran (376 reports, 55.4%), Vaxzevria (129 reports, 19.0%) and elasomeran (78 reports, 11.5%). The reporting OR of ILD following COVID-19 vaccination was 0.86 (95% CI 0.64 to 1.15) compared with all other vaccines. CONCLUSION: No significant signal of disproportionate reporting of ILD was observed for COVID-19 vaccines compared with all other vaccines. Moreover, when compared with the influenza vaccines that are known to cause ILD, no signal was observed. This study results might help decision-making on the subsequent COVID-19 vaccination strategy of ILD. Further large and prospective studies are required for more conclusive evidence.
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Vacinas contra COVID-19 , COVID-19 , Vacinas contra Influenza , Doenças Pulmonares Intersticiais , Humanos , Sistemas de Notificação de Reações Adversas a Medicamentos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacinas contra Influenza/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/epidemiologia , Farmacovigilância , Vacinação/efeitos adversosRESUMO
Although nanofibrous meshes are considered promising cultivation beds for maintaining cell differentiation, 3D cultivation is not possible because their nanoporous structures impede cell infiltration. To facilitate transverse cell migration across nanofibrous meshes, electrospun nanofibers are prepared with structures that vary in response to red laser light. Polyoxalate (POX), composed of oxalate linkers and oligomeric caprolactone, is synthesized and electrospun into fibrous meshes with a photosensitizer (chlorin e6, Ce6). These meshes exhibit morphological and chemical changes upon laser irradiation, and mass erosion rates of the meshes are faster after laser irradiation. Cell cultivation on POX meshes reveals that red laser effectively facilitates traverse migration of the cells without affecting cell viability. The use of light-triggered change of meshes is envisioned to promote the migration of cells during 3D matrix cultivation.
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Nanofibras , Diferenciação Celular , Linhagem Celular , Movimento Celular , Células Cultivadas , Nanofibras/química , Engenharia TecidualRESUMO
BACKGROUND: It is unclear whether depression is linked to nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to examine the association between depression and NAFLD and whether the association is partly explained by insulin resistance or inflammation. METHODS: Subjects consisted of 4,688 adults who participated in the 2016 Korea National Health and Nutrition Examination Survey. Depression was defined by Patient Health Questionnaire-9 score ≥ 10 or a previous diagnosis of depression. NAFLD was defined by hepatic steatosis index >36. Insulin resistance was assessed by triglycerides and glucose (TyG) index. Inflammation was measured with C-reactive protein (CRP). RESULTS: Depression had a significant association with TyG index (p = 0.005), but not with CRP. Depression was a significant predictor of NAFLD (OR = 1.63; 95% CI, 1.26-2.10; p < 0.001). Adjustment for sociodemographic features and waist circumference did not substantially affect the results. Further adjustment for comorbidities reduced the estimate for depression by 23% (OR = 1.56; 95% CI, 1.18-2.06; p = 0.002). Inclusion of CRP in a fully adjusted model did not affect the results. Addition of the TyG index decreased the estimate for depression by 28% (OR = 1.39; 95% CI, 0.88-2.19; p = 0.161), and the resulting estimate became no longer significant. The TyG index remained the independent predictor of outcome. LIMITATIONS: The absence of a structured diagnostic interview for depression and histological diagnosis of NAFLD. CONCLUSIONS: These data support an association of depression with NAFLD. Insulin resistance seems to play a major role in modulating the association between depression and NAFLD risk.
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Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Adulto , Depressão/epidemiologia , Humanos , Inflamação/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Inquéritos Nutricionais , República da Coreia/epidemiologiaRESUMO
Gold nanoparticles (AuNPs) were surface-engineered with a cationic corona to enhance the incorporation of photosensitizers for photodynamic therapy (PDT). The cationic corona composed of poly(2-(dimethylamino)ethyl methacrylate) was atom transfer radical-polymerized on the surface of the AuNPs. The cationic corona of the engineered surface was characterized by dynamic light scattering, electron microscopy, Raman spectroscopy, and mass spectroscopy. Chlorin-e6 (Ce6) incorporated onto the surface-engineered AuNPs exhibited higher cell incorporation efficiency than bare AuNPs. Ce6-incorporated AuNPs were confirmed to release singlet oxygen upon NIR irradiation. Compared to Ce6, Ce6-incorporated AuNPs exhibited higher cellular uptake and cytotoxicity against cancer cells in an irradiation time-dependent manner. Near-infrared-irradiated animals administered Ce6-incorporated AuNPs exhibited higher levels of tumor suppression without noticeable body weight loss. This result was attributed to the higher localization of Ce6 at the tumor sites to induce cancer cell apoptosis. Thus, we envision that engineered AuNPs with cationic corona can be tailored to effectively deliver photosensitizers to tumor sites for photodynamic therapy.
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Antineoplásicos/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Clorofilídeos/síntese química , Clorofilídeos/efeitos da radiação , Clorofilídeos/uso terapêutico , Feminino , Ouro/química , Ouro/efeitos da radiação , Humanos , Raios Infravermelhos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Metacrilatos/síntese química , Metacrilatos/química , Metacrilatos/efeitos da radiação , Camundongos Endogâmicos BALB C , Camundongos Nus , Nylons/síntese química , Nylons/química , Nylons/efeitos da radiação , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Polimerização , Oxigênio Singlete/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: It is important to identify candidates who would benefit from target agent chemotherapy in advanced NSCLC patients. The purpose of this study is to evaluate the feasibility of DCE-MRI for early response evaluation in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) treatment in patients with NSCLC. METHODS: Seven patients were prospectively enrolled who have pathologically-proven NSCLC with EGFR mutations or at least 2 of the following factors; adenocarcinoma, female, or never-smokers. Patients were treated with gefitinib or erlotinib and the start of chemotherapy was denoted day 0. DCE-MRI was performed at day-1, day+7, and day+28. Longitudinal changes of perfusion parameters were quantified and compared to Response Evaluation Criteria in Solid Tumors (RECIST) results. RESULTS: Quantitative perfusion parameters; Ktrans, ve and vp of the lung cancer showed a significant decrease at day+7 (P=0.016), but no further significant decrease between day+7 and day+28 (P>0.05). Semiquantitative markers for tumor enhancement curve pattern; EA (enhancement amplitude), MS (maximum slope), and AUC (area under the curve) also showed a significant decrease at day+7 (P=0.016, 0.031, and 0.016, respectively), but no further significant decrease between day+7 and day+28 (P>0.05). When RECIST applied, all patient was in the stable disease at day+7 and three patients showed partial response (PR) at day+28. All seven patients showed PR by the 3-month follow-up. CONCLUSIONS: Perfusion parameters may be used as an early non-invasive imaging biomarker for the response evaluation of target agent treatment in NSCLC.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Imageamento por Ressonância Magnética , Projetos Piloto , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêuticoRESUMO
Charged phospholipids are employed to formulate liposomes with different surface charges to enhance the permeation of active ingredients through epidermal layers. Although 3D skin tissue is widely employed as an alternative to permeation studies using animal skin, only a small number of studies have compared the difference between these skin models. Liposomal delivery strategies are investigated herein, through 3D skin tissue based on their surface charges. Cationic, anionic, and neutral liposomes are formulated and their size, zeta-potential, and morphology are characterized using dynamic light scattering and cryogenic-transmission electron microscopy (cryo-TEM). A Franz diffusion cell is employed to determine the delivery efficiency of various liposomes, where all liposomes do not exhibit any recognizable difference of permeation through the synthetic membrane. When the fluorescence liposomes are applied to 3D skin, considerable fluorescence intensity is observed at the stratum cornea and epithelium layers. Compared to other liposomes, cationic liposomes exhibit the highest fluorescence intensity, suggesting the enhanced permeation of liposomes through the 3D skin layers. Finally, the ability of niacinamide (NA)-incorporated liposomes to suppress melanin transfer in pigmented 3D skin is examined, where cationic liposomes exhibit the highest degree of whitening effects.
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Lipossomos , Modelos Biológicos , Absorção Cutânea , Preparações Clareadoras de Pele/farmacocinética , Pigmentação da Pele , Pele/metabolismo , Cátions , Microscopia Crioeletrônica/métodos , Portadores de Fármacos , Células HEK293 , Humanos , Microscopia Eletrônica de Transmissão/métodosRESUMO
OBJECTIVE: The purpose of this study was to evaluate the usefulness of C-arm conebeam CT-guided percutaneous transthoracic lung biopsy of small (≤ 2 cm) lung nodules. MATERIALS AND METHODS: Twenty-seven patients who underwent C-arm cone-beam CT-guided percutaneous transthoracic lung biopsy of small (≤ 2 cm) lung nodules were enrolled in the study. The mean nodule size was 13 ± 4 mm in diameter. These lesions were divided into two groups according to size: 10 lesions 1 cm or smaller and 17 lesions larger than 1 cm. The diagnostic accuracy, sensitivity, and specificity in the two groups were compared by use of Fisher's exact test. Radiation dose in a female humanoid phantom was measured with radiophotoluminescent glass dosimeters. The average patient dose was calculated. RESULTS: Eighteen malignant (67%) and eight benign (30%) nodules and one (3%) indeterminate nodule were found. The overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 94%, 89%, 94%, 89%, and 92%. The sensitivity, specificity, and accuracy were 100%, 75%, and 90% for the lesions 1 cm or smaller and 91%, 100%, and 94% for the lesions larger than 1 cm. The accuracy, sensitivity, and specificity did not differ significantly between the groups (all p > 0.05, Fisher's exact test). The average radiation dose among 27 patients was 4.6 mSv (range, 2.19-9.37). CONCLUSION: C-arm cone-beam CT-guided percutaneous transthoracic lung biopsy is a useful diagnostic technique in the evaluation of small lung nodules.
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Biópsia por Agulha/métodos , Tomografia Computadorizada de Feixe Cônico , Neoplasias Pulmonares/patologia , Radiografia Intervencionista/métodos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Imagens de Fantasmas , Valor Preditivo dos Testes , Doses de Radiação , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: We conducted a review of serial high-resolution CT (HRCT) findings of cryptogenic organizing pneumonia (COP). MATERIALS AND METHODS: Over the course of 14 years, we saw 32 patients with biopsy-confirmed COP. Serial HRCT scans were available for only 22 patients (seven men and 15 women; mean age, 52 years; median follow-up period, 8 months; range, 5-135 months). Serial CT scans were evaluated by two chest radiologists who reached a conclusion by consensus. Overall changes in disease extent were classified as cured, improved (i.e., ≥ 10% decrease in extent), not changed, or progressed (i.e., ≥ 10% increase in extent). When there were remaining abnormalities, the final follow-up CT images were analyzed to express observers' ideas regarding what type of interstitial lung disease the images most likely suggested. RESULTS: The two most common patterns of lung abnormality on initial scans were ground-glass opacification (86% of patients [19/22]) and consolidation (77% of patients [17/22]), distributed along the bronchovascular bundles or subpleural lungs in 13 patients (59%). In six patients (27%), the disease disappeared completely; in 15 patients (68%), the disease was decreased in extent; and in one patient (5%), no change in extent was detected on follow-up CT. When lesions remained, the final follow-up CT findings were reminiscent of fibrotic nonspecific interstitial pneumonia in 10 of 16 patients (63%). CONCLUSION: Although COP is a disease with a generally good prognosis, most patients (73%) with COP have some remaining disease seen on follow-up CT scans, and, in such cases, the lesions generally resemble a fibrotic nonspecific interstitial pneumonia pattern.
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Pneumonia em Organização Criptogênica/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
LiCl is widely prescribed for bipolar disorder but adversely associated with a higher incidence of increased body weight. Here, we investigated effects and underlying mechanisms of LiCl on lipid accumulation. LiCl induced dose-dependent lipid accumulation in HepG2 and RAW264.7 cells under normal as well as high glucose conditions. LiCl exposure additionally promoted lipid accumulation in livers of zebrafish. SB216763, a specific GSK-3ß inhibitor, did not affect lipid accumulation in HepG2 cells. Expression of key lipogenic enzymes, such as FAS and aP2, as well as SR-B1 were increased in RAW264.7 cells. LiCl enhanced FAS, ACC and SCD-1 mRNA levels while suppressing CPT-1 in HepG2 cells. LiCl stimulated DNA binding activities of SREBP-1c and ChREBP. LiCl activated AMPK phosphorylation but the AMPK inhibitor, AICAR, did not suppress LiCl-induced lipid accumulation in RAW264.7. LiCl, but not SB216763, induced a significant increase in ROS in RAW264.7 and HepG2 cells. NOX activity was dose-dependently enhanced by LiCl. Furthermore, NOX-1, NOX-2 and DUOX-1 mRNA levels were upregulated at an early stage of LiCl stimulation. LiCl-induced lipid accumulation was suppressed by the antioxidant, NAC, and inhibitors of NOX, DPI and APO. Phosphorylation and transcriptional activity of CREB were enhanced by LiCl. The cell-permeable cAMP analog, di-butyryl cAMP, not only promoted lipid accumulation itself but also LiCl-induced lipid accumulation in RAW264.7 cells. H-89, a PKA inhibitor, suppressed CREB activation, lipid accumulation and NOX activity in RAW264.7 cells. Our results indicate that LiCl stimulates lipid accumulation in hepatocyte and macrophage cells potentially through increased PKA-dependent ROS production.
Assuntos
Antimaníacos/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Cloreto de Lítio/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Aumento de Peso/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Transtorno Bipolar/tratamento farmacológico , Glicogênio Sintase Quinase 3 beta/metabolismo , Células Hep G2 , Humanos , Indóis/farmacologia , Isoquinolinas/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Maleimidas/farmacologia , Camundongos , Células RAW 264.7 , Sulfonamidas/farmacologia , Peixe-ZebraRESUMO
To facilitate cell sheet formation of human dermal fibroblasts, gelatin moieties were chemically decorated onto the surface of electrospun nanofibrils (NFs). Poly(caprolactone) [PCL] was electrospun onto fibrous meshes and then fragmented into nanofibrils by optimized milling and hydrolysis. After aminolysis of the NFs, methacrylated gelatin (GelMA) was reacted via Michael-type addition with the surface-exposed amines of the aminolyzed NFs (ahPCL NFs). GelMA was immobilized on the ahPCL NFs. Analysis of ahPCL NFs and native NFs conducted using X-ray photoelectron spectroscopy confirmed that gelatin was chemically conjugated onto the NFs. Human dermal fibroblasts (HDF) and the decorated NFs were self-assembled into cell sheets, and cells in the matrix showed highly spreading morphology by confocal microscopy. Our results indicate that the degree of cell spreading and cellular viability was much higher in the presence of GelMA immobilized in ahPCL NFs.
RESUMO
The present study was to evaluate the effects of Huang Bai, Zhi Mu, Mai Ya, and Xia Ku Cao on hormone using the GT1-7 and GH3 cells. The GT1-7 and GH3 cell lines were incubated with DW; DMSO; and 30, 100, or 300 µg/mL of one of the four extract solutions in serum-free media for 24 hours. The MTT assay was performed to determine the cytotoxicity of the four herbs. The GT1-7 and GH3 cells were incubated in DW, estradiol (GT1-7 only), or noncytotoxic herb solutions in serum-free medium for 24 hours. A quantitative RT-PCR and western blot were performed to measure the GnRH expression in GT1-7 cells and GH expression in GH3 cells. Huang Bai, Zhi Mu, Xia Ku Cao, and Mai Ya inhibited the GnRH mRNA expression in GT1-7 cells, whereas Huang Bai enhanced GH mRNA expression in GH3 cells. Additionally, Xia Ku Cao inhibited GnRH protein expression in GT1-7 cells and Huang Bai promoted GH protein expression in GH3 cells. The findings suggest that Huang Bai can delay puberty by inhibiting GnRH synthesis in the hypothalamus while also accelerating growth by promoting GH synthesis and secretion in the pituitary.
RESUMO
We report two cases of pathologically proven pulmonary metastases presenting as pulmonary infarction with tumour emboli. In two cases, high-resolution CT showed multiple small subpleural consolidations in both lungs. The patients had breast cancer and uterine cervix cancer, respectively. Although various pulmonary diseases show subpleural consolidations on CT, pulmonary metastases by tumour emboli should be primarily considered in differential diagnosis especially when the patient has known malignancy.