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1.
J Clin Med ; 11(10)2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35628957

RESUMO

BACKGROUND: We investigated the prevalence of and the factors associated with a high risk of osteoporotic fractures in Korean patients with ankylosing spondylitis (AS). METHODS: This was a multicenter, retrospective study including 219 AS patients from five university hospitals; the control group was selected by matching age and sex with those of the AS patients. The fracture risk was evaluated based on bone mineral density (BMD) measured by dual-energy X-ray absorptiometry and the fracture risk assessment tool (FRAX) with/without BMD. RESULTS: The mean age of the patients was 47.6 years, and 144 (65.8%) patients were men. According to the WHO criteria and FRAX with/without BMD, the candidates for pharmacological treatment were 44 (20.1%), 20 (13.2%), and 23 (15.1%) patients, respectively, significantly more than those in the healthy control group. Among them, the proportion of patients receiving osteoporosis treatment was 39.1-75%. In logistic regression analysis, menopause was an independent factor for the high risk of fracture according to the WHO criteria and FRAX with/without BMD. C-reactive protein level (odds ratio (OR) 3.8 and OR 6) and glucocorticoid use (OR 1.5 and OR 1.7) were associated with a high risk of osteoporotic fracture based on FRAX without BMD and osteoporosis diagnosed according to the WHO criteria. CONCLUSIONS: Our study suggests that both FRAX and WHO criteria may be complementary for treatment decisions to reduce osteoporotic fractures in patients with AS.

2.
Clin Appl Thromb Hemost ; 27: 10760296211061148, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34786989

RESUMO

Although there is no age criterion for rivaroxaban dose reduction, elderly patients with atrial fibrillation (AF) are often prescribed an off-label reduced dose. We aimed to evaluate whether age is a necessary criterion for rivaroxaban dose reduction in Korean patients with AF. Among 2208 patients who prescribed warfarin or rivaroxaban, 552 patients over 75 years without renal dysfunction (creatinine clearance >50 mL/min) were compared based on propensity score matching. The rivaroxaban group was further divided into a 20 mg (R20; on-label) and a 15 mg (R15; off-label). Primary net clinical benefit (NCB) was defined as the composite of stroke, systemic embolism, major bleeding, and all-cause mortality. Secondary NCB was defined as the composite of stroke, systemic embolism, and major bleeding. Patients were followed for 1 year, or until the first outcome occurrence. Both rivaroxaban groups had comparable efficacy compared with warfarin. However, both R20 (0.9% vs 7.4%, p = .014) and R15 (2.3% vs 7.4%, p = .018) had a significant reduction in major bleeding. There were no differences in efficacy or safety outcomes between R20 and R15. R20 had significantly reduced primary (hazard ratio [HR] 0.33, 95% confidence interval [CI]: 0.12-0.93) and secondary (HR 0.31, 95% CI: 0.10-0.93) NCBs compared with warfarin. However, primary and secondary NCBs were not reduced in R15. In real-world practice with elderly patients with AF, off-label rivaroxaban dose reduction to 15 mg conferred no benefits. Therefore, guideline-adherent rivaroxaban 20 mg is favorable in elderly Korean patients with AF.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Rivaroxabana/uso terapêutico , Administração Oral , Idoso , Povo Asiático , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Rivaroxabana/farmacologia , Resultado do Tratamento
3.
Exp Mol Med ; 53(9): 1413-1422, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34584194

RESUMO

Doxorubicin is one of the most effective agents used to treat various cancers, including breast cancer, but its usage is limited by the risk of adverse effects, including cardiotoxicity. Melatonin, a natural hormone that functions as a major regulator of circadian rhythms, has been considered a supplemental component for doxorubicin due to its potential to improve its effectiveness. However, the mechanisms and biological targets of the combination of melatonin and doxorubicin with respect to cancer cell death are not well understood. In the present study, we found that melatonin synergized with doxorubicin to induce apoptosis of breast cancer cells by decreasing the expression of AMP-activated protein kinase α1 (AMPK α1), which acts as a critical survival factor for cancer cells. This cotreatment-induced reduction in AMPKα1 expression occurred at the transcriptional level via an autophagy-dependent mechanism. The synergistic effects of the combined treatment were evident in many other cancer cell lines, and melatonin was also highly effective in inducing cancer death when combined with other cancer drugs, including cisplatin, 5-fluorouracil, irinotecan, and sorafenib. AMPKα1 expression was decreased in all of these cases, suggesting that reducing AMPKα1 can be considered an effective method to increase the sensitivity of cancer cells to doxorubicin treatment.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Doxorrubicina/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Melatonina/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular Tumoral , Sinergismo Farmacológico , Técnicas de Silenciamento de Genes , Humanos
4.
Mol Ther Oncolytics ; 22: 166-179, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34514097

RESUMO

Immunotherapy has been well regarded as one of the safer and antigen-specific anti-cancer treatments compared to first-generation chemotherapy. Since Coley's discovery, researchers focused on engineering novel antibody-based therapies. Including artificial and modified antibodies, such as antibody fragments, antibody-drug conjugates, and synthetic mimetics, the variety of immunotherapy has been rapidly expanding in the last few decades. Genetic and chemical modifications to monoclonal antibody have been brought into academia, in vivo trials, and clinical applications. Here, we have looked around antibodies overall. First, we elucidate the antibody structure and its cytotoxicity mechanisms. Second, types of therapeutic antibodies are presented. Additionally, there is a summarized list of US Food and Drug Administration (FDA)-approved therapeutic antibodies and recent clinical trials. This review provides a comprehensive overview of both the general function of therapeutic antibodies and a few main variations in development, including recent advent with the proposed mechanism of actions, and we introduce types of therapeutic antibodies, clinical trials, and approved commercial immunotherapeutic drugs.

5.
Exp Mol Med ; 52(12): 2055-2068, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33339952

RESUMO

The clinical application of doxorubicin, one of the most effective anticancer drugs, has been limited due to its adverse effects, including cardiotoxicity. One of the hallmarks of doxorubicin-induced cytotoxicity is mitochondrial dysfunction. Despite intensive research over recent decades, there are no effective approaches for alleviating doxorubicin-induced cytotoxicity. Melatonin, a natural hormone that is primarily secreted by the pineal gland, is emerging as a promising adjuvant that protects against doxorubicin-induced cytotoxicity owing to its pharmaceutical effect of preserving mitochondrial integrity. However, the underlying mechanisms are far from completely understood. Here, we provide novel evidence that treatment of H9c2 cardiomyoblasts with doxorubicin strongly induced AMP-activated protein kinase α2 (AMPKα2), which translocated to mitochondria and interfered with their function and integrity, ultimately leading to cellular apoptosis. These phenomena were significantly blocked by melatonin treatment. The levels of AMPKα2 in murine hearts were tightly associated with cardiotoxicity in the context of doxorubicin and melatonin treatment. Therefore, our study suggests that the maintenance of mitochondrial integrity is a key factor in reducing doxorubicin-induced cytotoxicity and indicates that AMPKα2 may serve as a novel target in the design of cytoprotective combination therapies that include doxorubicin.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Doxorrubicina/efeitos adversos , Melatonina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Camundongos , Mitocôndrias/genética , Modelos Biológicos , Mioblastos Cardíacos/efeitos dos fármacos , Mioblastos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio
6.
Nutrients ; 12(7)2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32709000

RESUMO

Hypertension is affected by both genetic and dietary factors. This study aimed to examine the interaction between dietary sodium/potassium intake, sodium-potassium ratios, and FGF5 rs16998073 and link these with increased risk for developing hypertension. Using data from the Health Examinee (HEXA) Study of the Korean Genome and Epidemiologic Study (KoGES), we were able to identify a total of 17,736 middle-aged Korean adults who could be included in our genome-wide association study (GWAS) to confirm any associations between hypertension and the FGF5 rs16998073 variant. GWAS analysis revealed that the FGF5 rs16698073 variant demonstrated the strongest association with hypertension in this population. Multivariable logistic regression was used to examine the relationship between dietary intake of sodium, potassium, and sodium-potassium ratios and the FGF5 rs16998073 genotypes (AA, AT, TT) and any increased risk of hypertension. Carriers with at least one minor T allele for FGF5 rs16998073 were shown to be at significantly higher risk for developing hypertension. Male TT carriers with a daily sodium intake ≥2000 mg also demonstrated an increased risk for developing hypertension compared to the male AA carriers with daily sodium intake <2000 mg (adjusted odds ratio (AOR) = 2.41, 95% confidence intervals (CIs) = 1.84-3.15, p-interaction < 0.0001). Female AA carriers with a daily potassium intake ≥3500 mg showed a reduced risk for hypertension when compared to female AA carriers with a daily potassium intake <3500 mg (AOR = 0.75. 95% CIs = 0.58-0.95, p-interaction < 0.0001). Male TT carriers in the mid-tertile for sodium-potassium ratio values showed the highest odds ratio for hypertension when compared to male AA carriers in the lowest-tertile for sodium-potassium ratio values (AOR = 3.03, 95% CIs = 2.14-4.29, p-interaction < 0.0001). This study confirmed that FGF5 rs16998073 variants do place their carriers (men and women) at increased risk for developing hypertension. In addition, we showed that high daily intake of sodium exerted a synergistic effect for hypertension when combined with FGF5 rs16998073 variants in both genders and that dietary sodium, potassium, and sodium-potassium ratios all interact with FGF5 rs16998073 and alter the risk of developing hypertension in carriers of either gender among Koreans.


Assuntos
Fator 5 de Crescimento de Fibroblastos/genética , Hipertensão/sangue , Hipertensão/genética , Idoso , Alelos , Antropometria , Povo Asiático , Estudos Transversais , Feminino , Fator 5 de Crescimento de Fibroblastos/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Polimorfismo de Nucleotídeo Único , Potássio/sangue , Potássio na Dieta/administração & dosagem , Estudos Prospectivos , República da Coreia , Sódio/sangue , Sódio na Dieta/administração & dosagem
7.
Biol Pharm Bull ; 43(3): 440-449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115502

RESUMO

There is significant cultivation of persimmon (Diospyros kaki) in East Asia, a plant whose fruit has abundant nutrients, including vitamins, polyphenols, and dietary fiber. Persimmon dietary supplements can benefit health by amelioration of diabetes, cardiovascular disease, and obesity. There are also persimmon-based beverages produced via fermentation, such as wines and vinegars, and increasing consumption of these products in East Asia. Although there is great interest in functional foods, the health effects of fermented persimmon extract (FPE) are completely unknown. We examined the effects of FPE on the metabolic parameters of mice fed a high-fat diet (HFD). Our results indicated that FPE supplementation led to an approx. 15% reduction of body weight, reduced abdominal and liver fat, and reduced serum levels of triglycerides, total cholesterol, and glucose. FPE also blocked the differentiation of murine 3T3-L1 pre-adipocyte cells into mature adipocytes. We suggest that gallic acid is a major bioactive component of FPE, and that AMP-activated protein kinase mediates the beneficial effects of FPE and gallic acid.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Diospyros/química , Obesidade/dietoterapia , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Células 3T3-L1/metabolismo , Gordura Abdominal/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Glicemia , Peso Corporal/efeitos dos fármacos , Fermentação , Frutas , Ácido Gálico/farmacologia , Gordura Intra-Abdominal/efeitos dos fármacos , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química
8.
J Bone Metab ; 26(3): 193-199, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31555616

RESUMO

BACKGROUND: Despite daily vitamin D recommendations, women with osteoporosis may not achieve optimal 25-hydroxy-vitamin D (25[OH]D) levels. We retrospectively evaluated the effect of education and vitamin D supplementation (1,000 IU/day) in Korean women with osteoporosis. METHODS: Sixty-one women with osteoporosis who were taking cholecalciferol (800-1,000 IU/day) were enrolled during 2011 to 2012. Forty patients (education only, Edu group) were educated on the importance of >30 min sunlight exposure daily while taking vitamin D. Twenty-one patients (education with vitamin D supplementation, Add group) were prescribed 1,000 IU/day cholecalciferol (total 1,800-2,000 IU/day) plus education. Patients were divided into 3 groups according to serum 25(OH)D status: deficiency (<20 ng/mL), insufficiency (20-30 ng/mL), and sufficiency (≥30 ng/mL). Furthermore, 25(OH)D levels were compared at baseline and after intervention for 3 months. RESULTS: The median (interquartile range) serum 25(OH)D concentration at baseline was 25.10 (18.95-33.60) ng/mL. The mean (±standard error) differences in 25(OH)D levels from baseline to post-intervention were 19.85±3.86 and 31.73±4.82 ng/mL in the Edu group and Add group, respectively. Eighteen patients (29.5%) had vitamin D deficiency, 25 (41.0%) had insufficiency, and 18 (29.5%) had sufficient levels. Optimal 25(OH)D (30 ng/mL or more) was achieved in 54.5% and 95.2% patients in the Edu group and Add group, respectively (P=0.003). CONCLUSIONS: We consider that vitamin D concentration should be measured on a regular basis in order to maintain an optimal level of vitamin D concentration, and education and supplementation is needed if not sufficient.

9.
Colloids Surf B Biointerfaces ; 179: 340-351, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30991214

RESUMO

Photothermal therapy using gold nanorods (AuNRs) has gained great attention for cancer therapy because AuNRs emit heat and induce tumor cell death responding to the near infrared light. However, the anticancer efficiency of AuNRs alone is undermined by its poor in vivo stability and potential toxicity. The prime purpose of this study was to send more AuNRs into tumors to more fully ablate them. For this, we fabricated hybrid albumin nanoparticles encapsulating small AuNRs (AuNRs-Alb-NPs), which take advantage of biocompatible albumin as a carrier, with better tumor targetability and high in vivo photothermal activity. The sizes of length/width of AuNRs were approximately 20.5 nm and 4.6 nm, respectively, showing a 4.5 aspect ratio, and the size of the resulting AuNRs-Alb-NPs was ˜130 nm, all of which are favorable for glomerular filtration and passive tumor targeting via extravasation. We chose the best formulation for AuNRs-Alb-NPs by in vitro cytotoxicity based on photothermal conversion efficiency considering the incorporated number of AuNRs. Visualized by a photothermal camera, the local tumor temperature of mice treated with AuNRs-Alb-NPs increased to 57℃, which was sufficient for the hyperthermal effect with 808 nm laser irradiation. Subsequently, AuNRs-Alb-NPs displayed remarkably better tumor ablation vs. naïve formulation of AuNRs (tumor volume: 73.8 ± 105.8 vs. 1455.3 ± 310.4 mm3 at day 8) in the glioblastoma N2a tumor-bearing mice. Most of all, we demonstrated, using photoacoustic imaging and inductively coupled plasma mass spectrometry, that this much better tumor ablation was due to enhanced tumor targeting with albumin nanoparticles. We believe our AuNRs-Alb-NPs should be considered promising photothermal agents that are safer, have good targetability, and exhibit excellent tumor ablation.


Assuntos
Ouro/química , Hipertermia Induzida , Nanopartículas/química , Nanotubos/química , Neoplasias/terapia , Fototerapia , Soroalbumina Bovina/química , Animais , Morte Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Endocitose , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Nanotubos/ultraestrutura , Neoplasias/patologia , Tamanho da Partícula , Esferoides Celulares/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Colloids Surf B Biointerfaces ; 176: 156-166, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30611939

RESUMO

Photothermal therapy (PTT) is an effective means of treating tumors because tumor cells are sensitive to heat. Gold and carbon nanoparticles are used as efficient PTT materials. However, development of a non-toxic biodegradable PTT agent remains a challenge. Here, we developed a hemoglobin (Hb) hydrogel that exhibited excellent PTT effects in vitro and in vivo. Unlike conventional PTT agents, which are toxic and do not decompose completely in the body, the Hb hydrogel was manufactured using only two components: (i) Hb, a natural substance derived from the human body, and (ii) PEG, an FDA-approved polymer. The gelation time of the Hb hydrogels could be controlled by changing the Hb concentration. Because Hb is present at a high concentration (150 mg/ml) in the body, the Hb hydrogel decomposed and was eliminated in vivo without toxicity. The Hb hydrogel showed an excellent PTT effect in response to 808 nm near-infrared (NIR) laser irradiation and had excellent anticancer effects against A549 lung cancer cells both in vitro and in vivo. Blood hematology and blood biochemical assay results from an animal model treated with Hb hydrogel were similar to those of the control group. Importantly, toxicity was not observed based on H&E staining of major organs (heart, liver, spleen, kidneys and lung). Tumors of A549 cell-xenografted mice treated with Hb hydrogel and 808 nm NIR laser irradiation were significantly smaller than those of the control group (23.1 mm3versus 746.5 mm3, respectively). This is a first report of a biocompatible photothermal hydrogel based on hemoglobin, and our overall results suggest that Hb hydrogels are commercially-promising PTT systems that have excellent anti-cancer effects.


Assuntos
Hemoglobinas/química , Temperatura Alta , Hidrogéis/química , Neoplasias Pulmonares/terapia , Fototerapia , Células A549 , Animais , Humanos , Raios Infravermelhos , Camundongos , Neoplasias Experimentais/terapia
11.
Transl Clin Pharmacol ; 27(2): 69-72, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32055584

RESUMO

A 60-year-old woman presented with polymorphic ventricular tachycardia secondary to hypokalemia, which necessitated dozens of DC cardioversions. She was not taking any other medication and denied any vomiting or diarrhea. Further investigation for hypokalemia suggested a hypermineralocorticoid state. Repeated inquiry prompted the patient to admit to taking herbal medicine containing licorice. She was treated with magnesium sulfate, potassium infusion, and intravenous lidocaine. A potassium-sparing diuretic was also prescribed. On the seventh day, the patient was discharged from the hospital with advice to discontinue taking herbal medicines containing licorice. She has been followed up at our outpatient clinic without further symptoms for 3 years. This case highlights the potential for cardiovascular complications associated with consumption of herbal medicines such as licorice. Clinicians should be aware that patients presenting to the emergency department with ventricular arrhythmia and uncertain hypokalemia should be questioned about licorice intake. Obtaining a detailed history from patients admitted to the hospital for electrical storm is essential.

12.
Br J Ophthalmol ; 103(10): 1361-1366, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30573498

RESUMO

BACKGROUND/AIM: The aim of this study was to estimate the nationwide incidence of clinically diagnosed exudative age-related macular degeneration (AMD) and associated use of ranibizumab and aflibercept in South Korea. METHODS: In this retrospective, population-based cohort study, claims data for 2010-2015 were analysed in a randomly selected sample of 519 661 adults aged ≥40 years. The incidence per 10 000 person-years was estimated, along with the 95% CI. Incident exudative AMD was defined based on the registration code for rare intractable diseases. Use of ranibizumab and aflibercept and the incidence of exudative AMD were recorded. RESULTS: Nine hundred and twelve patients were newly diagnosed with exudative AMD in 2010-2015. The 6-year incidence in the general population aged ≥40 years was 2.9 (95% CI 2.8 to 3.0) per 10 000 person-years. The incidence was highest in individuals aged 75-79 years (12.0, 95% CI 10.3 to 13.8). The incidence was higher in men than in women in all age groups. Six hundred and twenty-five (69%) of the 912 newly diagnosed patients started ranibizumab or aflibercept as a first-line treatment. The average number of injections administered was 6.1 (SD 3.9; minimum of 1 injection and maximum government-supported limit of 14) during 2010-2015; the number increased with increasing government funding support (from 5 to 10 and from 10 to 14 in 2013 and 2014, respectively). CONCLUSIONS: This study describes the incidence of exudative AMD in South Korea and its treatment under the national health insurance system in this country. Its findings could be used for reference purposes and be useful when planning treatment for exudative AMD.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Exsudatos e Transudatos , Feminino , Seguimentos , Humanos , Incidência , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/estatística & dados numéricos , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , República da Coreia/epidemiologia , Estudos Retrospectivos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/diagnóstico
13.
Int J Pharm ; 553(1-2): 363-374, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30385372

RESUMO

Gold nanoclusters (AuNCs) have been considered to be a promising candidate for hyperthermia-based anticancer therapy. Herein, we introduce albumin-assisted AuNCs composed of small gold nanoparticles (AuNPs, <6 nm) assembled with strands of polyallylamine (PAH), which exhibited strong surface plasmon resonance upon near-infrared (NIR, ∼808 nm) laser irradiation and good in vivo stability. Our albumin-assisted PAH-AuNCs (BSA/PAH-AuNCs) were facilely fabricated as a top-down process by a simple ultrasonication after the preparation of large nano-aggregates of PAH-AuNPs. Albumin played a critical role as a stabilizer and surfactant in making loosely associated large aggregates and thereby producing small gold nanoclusters (∼60 nm) of slightly negative charge upon ultrasonication. The prepared BSA/PAH-AuNCs displayed excellent hyperthermal effects (∼60 °C) in response to ∼808-nm NIR laser irradiation in a 4T1 cell system in vitro and in 4T1 cell tumor xenograft mice in vivo, indicating their remarkable potential to suppress breast cancer growth, without almost no significant toxicity in histology. Consequently, our gold nanoclusters should be considered as a promising photothermal agent that are easy to manufacture and exhibit marked anticancer effects in terms of tumor ablation.


Assuntos
Hipertermia Induzida/métodos , Terapia a Laser/métodos , Neoplasias Mamárias Experimentais/terapia , Nanopartículas Metálicas , Albuminas/química , Animais , Feminino , Ouro , Masculino , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Poliaminas/química , Ressonância de Plasmônio de Superfície , Ensaios Antitumorais Modelo de Xenoenxerto
14.
JAMA Ophthalmol ; 136(10): 1164-1169, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30098167

RESUMO

Importance: Information on the incidence of central serous chorioretinopathy (CSC) in individuals who receive corticosteroids is scarce but clinically important because these agents are useful and widely used. Objective: To estimate the annual and 5-year incidence of CSC in South Korea in the overall population and in those who have used corticosteroid medications. Design, Setting, and Participants: A cohort study of a population-based random sample included East Asian adults for whom records are held in the Korean National Health Insurance Service database for calendar years 2011 through 2015. The data analysis was performed from July 1, 2017 to January 5, 2018. Exposures: Any type of corticosteroid use from 2002 through 2015. Main Outcomes and Measures: Incidence of CSC. Results: The data set contained data from 868 939 adults (4 117 768 person-years). From 2011 through 2015, 1423 individuals (among whom the mean [SD] age was 46.8 [16.4] years and 1091 [76.7%] were male) with newly diagnosed CSC were identified. From 2002 to 2015, 783 099 individuals in the data set (90.1%) had ever used corticosteroids. The incidence of CSC per 10 000 person-years was 3.5 (5.4 in men; 1.6 in women) among the total population, 2.5 (3.0 in men; 1.2 in women) in those who had never used corticosteroids, and 3.6 (5.7 in men; 1.6 in women) among those who had ever used corticosteroids. The risk of CSCR with individuals who had ever used corticosteroids was estimated as an adjusted hazard ratio of 1.81 (95% CI, 1.47-2.23) compared with those who have never used these drugs. Current or recent corticosteroid use showed a positive association with the incidence of CSC (depending on duration of use, adjusted hazard ratio ranged from 1.54 to 2.15). Corticosteroid use in 2006 through 2009 was associated with an increased incidence of CSC after 2011 (adjusted hazard ratio 1.57 [95% CI, 1.13-2.18]). Conclusions and Relevance: In 2002 through 2015, 90.1% of adults in Korea received corticosteroids at least once. Although there was a clear difference in relative risk, this data analysis could not replicate the more than 30-fold increase in the risk ratio of CSC that has been reported previously. The incidence of CSC in the most vulnerable group, middle-aged men, was estimated to be approximately 1 case per 1000 corticosteroid users in the year following medication use. The overall incidence among those who had ever used corticosteroids and those who had never used these drugs was 2.5 and 3.6 per 10 000 person-years, respectively. This study provides additional evidence to support the potential role of corticosteroids in CSC.


Assuntos
Coriorretinopatia Serosa Central/epidemiologia , Glucocorticoides/administração & dosagem , Adulto , Idoso , Coriorretinopatia Serosa Central/induzido quimicamente , Coriorretinopatia Serosa Central/diagnóstico , Estudos de Coortes , Bases de Dados Factuais , Formas de Dosagem , Feminino , Glucocorticoides/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/estatística & dados numéricos , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Adulto Jovem
15.
Br J Ophthalmol ; 102(3): 338-343, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28729368

RESUMO

BACKGROUND: Although several studies showed the association between stroke and open-angle glaucoma (OAG), there is still lack of longitudinal studies based on large populations. Therefore, in this study, we investigated the risk of stroke after OAG diagnosis over a 10-year follow-up period. METHODS: We performed a retrospective nationwide propensity score-matched cohort study. OAG and comparison groups were selected from a large database from the Korean National Health Insurance Service, comprising 1 025 340 random subjects. The OAG group comprised patients with an initial diagnosis of OAG between January 2004 and December 2007 (n=1520), and the comparison group comprised randomly selected patients (five per glaucoma patient; n=7570). Each cohort was tracked until 2013 for stroke development. Cox proportional hazard regression analysis was performed to determine possible association RESULTS: OAG was associated with increased stroke incidence (HR=1.20, 95% CI 1.03 to 1.40). Hypertension, diabetes mellitus, chronic renal failure, atrial fibrillation, hyperlipidaemia, increasing age and male gender also increased the incidences of stroke. Risk of stroke for patients with OAG was greater in the older age group (≥65 years, HR=1.23, 95% CI 1.02 to 1.47) than in the younger age group (<65 years, HR=1.12, 95% CI 0.86 to 1.46), and greater in males (HR=1.31, 95% CI 1.06 to 1.60) than in females (HR=1.10, 95% CI 0.88 to 1.38). CONCLUSIONS: Patients who were diagnosed with OAG were more likely to experience subsequent stroke than comparison group without OAG, and the risk was greater for older adults and males.


Assuntos
Glaucoma de Ângulo Aberto/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/diagnóstico , Humanos , Incidência , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/estatística & dados numéricos , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Tonometria Ocular
16.
Europace ; 19(suppl_4): iv17-iv24, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29220423

RESUMO

AIMS: Prolonged Tpeak-Tend interval has been shown to be markers of arrhythmogenesis in various cardiac disorders. However, its dynamicity is one of the obstacles to predict fatal ventricular arrhythmia. This study investigated whether Tpeak-Tend interval during therapeutic hypothermia (TH) is associated with ventricular fibrillation (VF) inducibility and clinical arrhythmia in subjects with aborted arrhythmic sudden cardiac death (SCD). METHODS AND RESULTS: The study group included 31 patients (24 males, age 39.1 ± 17.6 years) presenting with arrhythmic SCD in whom Tpeak-Tend interval and J-wave amplitude were measured in electrocardiogram (ECG) of the earliest medical contact and during TH; these patients underwent programmed ventricular stimulation. The summation of J-wave amplitude and QTc interval increased during TH. However, it was not associated with VF inducibility. Patients with inducible VF showed a small Tpeak-Tend interval dispersion in the baseline 12-lead ECG (68.8 ± 24.7 vs. 94.0 ± 55.6 ms, P = 0.044) and a marked increase of the dispersion during the TH (36.2 ± 51.2 vs. -6.1 ± 45.5 ms, P = 0.039). Twenty-four patients underwent implantable cardioverter defibrillator (ICD) implantation. Among them, the patients with long QTc, Tpeak-Tend, and precordial Tpeak-Tend during the TH developed VF more frequently (QTc, 511.9 ± 53.71 ms vs. 566.5 ± 56.08 ms, P = 0.038; Tpeak-Tend interval, 145.6 ± 38.4 ms vs. 185.7 ± 49.95 ms, P = 0.048; precordial Tpeak-Tend interval, 139.3 ± 35.11 ms vs. 185.7 ± 49.95 ms, P = 0.018). The initial VF inducibility was not related with the VF development in follow-up. CONCLUSION: In patients with aborted arrhythmic SCD, long Tpeak-Tend interval and QTc interval during TH could predict VF development in their follow-up.


Assuntos
Arritmias Cardíacas/terapia , Morte Súbita Cardíaca/prevenção & controle , Eletrocardiografia , Hipotermia Induzida , Taquicardia Ventricular/diagnóstico , Fibrilação Ventricular/diagnóstico , Potenciais de Ação , Adulto , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Morte Súbita Cardíaca/etiologia , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Técnicas Eletrofisiológicas Cardíacas , Feminino , Frequência Cardíaca , Humanos , Hipotermia Induzida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Processamento de Sinais Assistido por Computador , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/terapia , Fatores de Tempo , Resultado do Tratamento , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/terapia , Adulto Jovem
17.
J Med Food ; 19(12): 1120-1129, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27982752

RESUMO

Krill oil is a novel, commercially available marine oil rich in long-chain polyunsaturated omega-3 fatty acids, particularly eicosapentaenoic acid and docosahexaenoic acid. Compared with fish oil, the effects of krill oil supplementation on human health and its underlying action mechanisms are currently poorly understood. In the present study, we examined the effect of krill oil supplementation on metabolic parameters of mice fed a high-fat diet (HFD). Krill oil supplementation in mice fed a HFD for 10 weeks resulted in an ∼15% lower body weight gain and a dramatic suppression of hepatic steatosis. These effects were associated with significantly lower serum triglyceride and low-density lipoprotein-cholesterol levels. We further uncovered a novel underlying mechanism, showing that AMP-activated protein kinase, a master regulator of glucose and lipid metabolism, mediates the beneficial effects of krill oil.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Dieta Hiperlipídica/efeitos adversos , Dislipidemias/tratamento farmacológico , Euphausiacea/química , Óleos/administração & dosagem , Aumento de Peso/efeitos dos fármacos , Gordura Abdominal/efeitos dos fármacos , Animais , LDL-Colesterol/sangue , Suplementos Nutricionais , Ativação Enzimática/efeitos dos fármacos , Ácidos Graxos/biossíntese , Ácidos Graxos Ômega-3/administração & dosagem , Fígado Gorduroso/prevenção & controle , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Triglicerídeos/sangue
18.
Artigo em Inglês | MEDLINE | ID: mdl-27818699

RESUMO

Purpose. This study aims to verify the effects of electroacupuncture treatment on osteoarthritis of the knee. Methods. MEDLINE/PubMed, EMBASE, CENTRAL, AMED, CNKI, and five Korean databases were searched by predefined search strategies to screen eligible randomized controlled studies meeting established criteria. Any risk of bias in the included studies was assessed with the Cochrane Collaboration's tool. Meta-analysis was conducted using RevMan version 5.3 software. Results. Thirty-one randomized controlled studies of 3,187 participants were included in this systematic review. Meta-analysis was conducted with eight studies including a total of 1,220 participants. The electroacupuncture treatment group showed more significant improvement in pain due to knee osteoarthritis than the control group (SMD -1.86, 95% CI -2.33 to -1.39, I2 75%) and in total WOMAC score than the control group (SMD -1.34, CI 95% -1.85 to -0.83, I2 73%). Compared to the control group, the electroacupuncture treatment group showed more significant improvement on the quality of life scale. Conclusion. Electroacupuncture treatment can relieve the pain of osteoarthritis of the knees and improve comprehensive aspects of knee osteoarthritis and the quality of life of patients with knee osteoarthritis.

19.
J Bone Metab ; 21(4): 257-62, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25489574

RESUMO

BACKGROUND: The aim of this study is to evaluate whether the optimal vitamin D level is achieved after taking recommended dose in vitamin D deficient patients. METHODS: This was a retrospective study. Women (n=52) first diagnosed with osteoporosis were recruited in outpatient clinic. They were recommended to be exposed to sun light for more than 30 min a day. Subjects were divided into 3 groups according to serum 25-hydroxy-vitamin D3 (25-[OH]D3) status: deficiency (less than 20 ng/mL), insufficiency (20-30 ng/mL) and sufficiency (30 ng/mL or more). Insufficient and sufficient patients received the recommended dose (1,000 IU/day) but deficient patients received recommended or double dose (1,800-2,000 IU/day). We compared 25-(OH)D levels at baseline and after vitamin D supplementation for 3 months. RESULTS: Median (interquartile range) serum 25-(OH)D concentration at baseline was 15.10 (13.30-16.97) ng/mL and the proportion of deficient, insufficient and sufficient groups were 69.2%, 23.1%, and 7.7% respectively. The optimal 25-(OH)D level (30 ng/mL or more) was achieved in 83.3% of insufficient patients with the recommended dose and was did in 55.6% of deficient patients with recommended dose (P=0.117). However, 88.9% of the deficient patient with double dose achieved optimal level (P=0.030). CONCLUSIONS: About 44% of vitamin D deficient patients did not attain the optimal level of serum 25-(OH)D despite recommended daily intake of vitamin D to 1,000 IU in patients with osteoporosis. Follow-up of serum 25-(OH)D levels may be required for vitamin D supplementation in vitamin D deficient patients with osteoporosis.

20.
J Diabetes Investig ; 5(5): 525-32, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25411620

RESUMO

AIMS/INTRODUCTION: Sasang constitutional medicine (SCM) has existed in traditional Korean medicine for more than 100 years. SCM consists of four different types: So-Eum (SE), So-Yang (SY), Tae-Eum (TE) and Tae-Yang (TY). It is of great importance that the Sasang constitution type (SCT) be evaluated accurately and recognized by medical communities. MATERIALS AND METHODS: From the Ansung-Ansan prospective cohort study, 10,038 participants were recruited from the years 2001-2002. Of 10,038 original participants, 2,460 participants underwent SCT evaluation. The Cox proportional hazard model was used to predict diabetes during the 10-year follow-up period. RESULTS: During 10 years of follow up (22,007 person-years), 472 incidence cases (215/10,000 Incidence Density) of type 2 diabetes mellitus were documented. We identified that the TE group was significantly older, more obese, and had higher blood pressure, glucose metabolic values and lipid profiles levels. Relative risk (RR) and 95% confident intervals (CI) for type 2 diabetes were 1.696 (95% CI 1.204-2.39, P = 0.003) for TE when compared with the SE type. After controlling all potential confounders, the Cox proportional hazard model showed that RR was 1.635 (95% CI 1.111-2.406) in non-obese (body mass index <25) TE, and RR was 1.725 (95% CI 1.213-2.452) in obese (body mass index ≥25) TE when compared with the SE type. We did not find any differences when comparing SE and SY types. The findings shows that TE is a higher risk factor for type 2 Diabetes, independent of obesity level. CONCLUSIONS: The present study suggests that the TE type, independent of obesity level, is a strong risk factor of type 2 diabetes.

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