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1.
Sensors (Basel) ; 24(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38475225

RESUMO

In this study, we explore how the strategic positioning of conductive yarns influences the performance of plated knit strain sensors fabricated using commercial knitting machines with both conductive and non-conductive yarns. Our study reveals that sensors with conductive yarns located at the rear, referred to as 'purl plated sensors', exhibit superior performance in comparison to those with conductive yarns at the front, or 'knit plated sensors'. Specifically, purl plated sensors demonstrate a higher sensitivity, evidenced by a gauge factor ranging from 3 to 18, and a minimized strain delay, indicated by a 1% strain in their electromechanical response. To elucidate the mechanisms behind these observations, we developed an equivalent circuit model. This model examines the role of contact resistance within varying yarn configurations on the sensors' sensitivity, highlighting the critical influence of contact resistance in conductive yarns subjected to wale-wise stretching on sensor responsiveness. Furthermore, our findings illustrate that the purl plated sensors benefit from the vertical movement of non-conductive yarns, which promotes enhanced contact between adjacent conductive yarns, thereby improving both the stability and sensitivity of the sensors. The practicality of these sensors is confirmed through bending cycle tests with an in situ monitoring system, showcasing the purl plated sensors' exceptional reproducibility, with a standard deviation of 0.015 across 1000 cycles, and their superior sensitivity, making them ideal for wearable devices designed for real-time joint movement monitoring. This research highlights the critical importance of conductive yarn placement in sensor efficacy, providing valuable guidance for crafting advanced textile-based strain sensors.

2.
J Obes Metab Syndr ; 32(1): 1-24, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36945077

RESUMO

The goal of the 8th edition of the Clinical Practice Guidelines for Obesity is to help primary care physician provide safe, effective care to patients with obesity by offering evidence-based recommendations to improve the quality of treatment. The Committee for Clinical Practice Guidelines comprised individuals with multidisciplinary expertise in obesity management. A steering board of seven experts oversaw the entire project. Recommendations were developed as the answers to key questions formulated in patient/problem, intervention, comparison, outcomes (PICO) format. Guidelines underwent multi-level review and cross-checking and received endorsement from relevant scientific societies. This edition of the guidelines includes criteria for diagnosing obesity, abdominal obesity, and metabolic syndrome; evaluation of obesity and its complications; weight loss goals; and treatment options such as diet, exercise, behavioral therapy, pharmacotherapy, and bariatric and metabolic surgery for Korean people with obesity. Compared to the previous edition of the guidelines, the current edition includes five new topics to keep up with the constantly evolving field of obesity: diagnosis of obesity, obesity in women, obesity in patients with mental illness, weight maintenance after weight loss, and the use of information and communication technology-based interventions for obesity treatment. This edition of the guidelines features has improved organization, more clearly linking key questions in PICO format to recommendations and key references. We are confident that these new Clinical Practice Guidelines for Obesity will be a valuable resource for all healthcare professionals as they describe the most current and evidence-based treatment options for obesity in a well-organized format.

3.
Eur J Immunol ; 53(5): e2250048, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36815313

RESUMO

Keratinocytes are pivotal cells in the pathogenesis of atopic dermatitis (AD) as much as Th2 cells. In this sense, regulation of pro-inflammatory features of keratinocytes might be useful for AD patients. P2X7R-mediated activation of NLRP3 inflammasome (N3I) in keratinocytes and myeloid cells plays crucial roles in AD. Nonetheless, inhibition of P2X7R has not been feasible because of polymorphisms and ubiquitous expression of P2X7R. Here, we report that GPCR19 colocalizes with P2X7R, and a GPCR19 agonist (taurodeoxycholate [TDCA]) inhibits the activation of P2X7R. Noncistronically, TDCA inhibits NF-kB activation via the adenylate cyclase-PKA pathway and BzATP-mediated Ca++ mobilization. Cistronically, TDCA suppresses the expression of P2X7R and N3I components in keratinocytes. NLRP3 oligomerization and the production of mature IL-1ß and IL-18 was suppressed by TDCA treatment in keratinocytes. Topical TDCA treatment ameliorates proinflammatory features of AD in mice induced by DNCB, MC903, or oxazolone. Taken together, a GPCR19 agonist such as TDCA might inhibit P2X7R-mediated N3I activation of keratinocytes, which is crucial for the pathogenesis of AD.


Assuntos
Dermatite Atópica , Camundongos , Animais , Dermatite Atópica/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Camundongos Endogâmicos BALB C , Queratinócitos/metabolismo , Inflamassomos/metabolismo , Citocinas/metabolismo
4.
J Prev Med Public Health ; 55(5): 492-497, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36229912

RESUMO

OBJECTIVES: Women experience more stress in middle age than in other periods of their lives. Therefore, health management programs that enable middle-aged women to cope with and manage stress are needed. This study investigated the psychological effects of a meditation-focused forest therapy program among 53 middle-aged women living in urban areas in Korea. METHODS: Participants were divided into 2 groups: one group underwent the program for 3 days in a forest, followed by 3 days in an urban environment, and the other group underwent the program for 3 days in the urban environment, followed by 3 days in the forest. The psychological effects of the forest therapy program were evaluated using the Profile of Mood States-Brief (POMS-B). Differences in mood state before and after the program conducted in the forest (experimental group) and in the urban environment (control group) were evaluated using the paired-samples t-test. RESULTS: The program in the forest significantly reduced tension, depression, anger, fatigue, and confusion among the domains of the POMS-B. The program in the urban area significantly reduced tension, but not depression, anger, fatigue, or confusion. CONCLUSIONS: Meditation-focused forest therapy programs are expected to contribute to promoting psychological health and enhancing the quality of life of middle-aged women.


Assuntos
Florestas , Qualidade de Vida , Fadiga , Feminino , Humanos , Saúde Mental , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , República da Coreia , Estresse Psicológico/terapia
5.
Drug Chem Toxicol ; 44(2): 161-169, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31215246

RESUMO

Sodium taurodeoxycholate (TDCA) has been investigated for various inflammatory disorders such as sepsis. We recently evaluated nonclinical safety profile of TDCA using rats infused intravenously. As a series of preclinical safety investigations, we further conducted toxicity studies with TDCA delivered to dogs via intravenous administration under Good Laboratory Practice regulation in this study. In dose range-finding study (dose escalation study), dogs given with TDCA at a dose of 150 mg/kg showed marked changes in clinical signs, hematology, and serum biochemistry. And biochemical markers of liver damage and local skin lesions were observed following intravenous infusion of 100 mg/kg TDCA, suggesting that 100 mg/kg was chosen as the highest dose of TDCA for 4-week repeated-dose toxicity study using dogs. Despite no treatment-related significant changes in body weight, food consumption, ophthalmoscopy, and urinalysis, skin lesions were observed at the injection site of animals administered with higher than 50 mg/kg of TDCA along with biochemical and histopathological changes associated with liver injury. However, most of off-target effects were found to be reversible since these were recovered after stopping TDCA infusion. These findings indicate that the no-observed-adverse-effect-level (NOAEL) for TDCA in dogs was considered to be 5 mg/kg/d. Taken together, our results provide important toxicological profiles regarding the safe dose of TDCA for drug development or clinical application.


Assuntos
Anti-Inflamatórios/toxicidade , Ácido Taurodesoxicólico/toxicidade , Animais , Anti-Inflamatórios/administração & dosagem , Cães , Relação Dose-Resposta a Droga , Feminino , Masculino , Nível de Efeito Adverso não Observado , Ácido Taurodesoxicólico/administração & dosagem , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda
6.
Drug Chem Toxicol ; 44(3): 268-276, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-31215257

RESUMO

Taurodeoxycholate (TDCA) inhibits various inflammatory responses suggesting potential clinical application. However, the toxicity of TDCA has not been evaluated in detail in vivo. We investigated the acute toxicity and 4-week repeated-dose toxicity of TDCA following intravenous infusion under Good Laboratory Practice regulations. In the sighting study of acute toxicity, one of two rats (one male and one female) treated with 300 mg/kg TDCA died with hepatotoxicity, suggesting that the approximate 50% lethal dose of TDCA is 300 mg/kg. Edema and discoloration were observed at the injection sites of tails when rats were infused with 150 mg/kg or higher amount of TDCA once. In 4-week repeated-dose toxicity study, no treatment-related mortality or systemic changes in hematology and serum biochemistry, organ weights, gross pathology, or histopathology were observed. However, the tail injection site showed redness, discharge, hardening, and crust formation along with histopathological changes such as ulceration, edema, fibrosis, and thrombosis when rats were infused with 20 mg/kg TDCA. Taken together, TDCA induced no systemic toxicity or macroscopic lesions at the injection site at a dose of 10 mg/kg/day, which is 33 times higher than the median effective dose observed in a mouse sepsis model. These findings suggest that TDCA might have a favorable therapeutic index in clinical applications.


Assuntos
Colagogos e Coleréticos/toxicidade , Ácido Taurodesoxicólico/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colagogos e Coleréticos/administração & dosagem , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Feminino , Infusões Intravenosas , Dose Letal Mediana , Masculino , Ratos , Ratos Sprague-Dawley , Ácido Taurodesoxicólico/administração & dosagem , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda
7.
Artigo em Inglês | MEDLINE | ID: mdl-32560522

RESUMO

Women experience more stress in middle age than in other life stages, and health in middle age is vital, because it influences the quality of life in old age. In this study, the effects of a forest therapy program on physiological changes in 53 middle-aged women (divided into two groups) who lived in the city were examined. One group participated in a three-day program in the forest, followed by three days in the city; the other group participated in a three-day program in the city, followed by three days in the forest. Forest experiments were conducted in a "healing forest," and urban experiments were conducted near a university campus. Blood tests were performed to evaluate the physiological effects of forest therapy. Differences in serotonin levels and vitamin D levels were verified before and after the forest (experimental group) and urban (control group) programs through paired t-tests. Statistically significant increases in serotonin levels were noted for participants in the forest program; vitamin D levels also increased, but not by statistically significant values. The findings of this study verify that forest therapy programs promote health among middle-aged women, and may prevent disease and improve quality of life.


Assuntos
Envelhecimento/fisiologia , Envelhecimento/psicologia , Florestas , Fadiga Mental , Terapias Mente-Corpo/métodos , Terapia de Relaxamento/métodos , Adaptação Psicológica/fisiologia , Adulto , Idoso , Envelhecimento/sangue , Cidades , Feminino , Promoção da Saúde/métodos , Envelhecimento Saudável/sangue , Envelhecimento Saudável/fisiologia , Envelhecimento Saudável/psicologia , Humanos , Massagem/psicologia , Meditação/psicologia , Fadiga Mental/sangue , Fadiga Mental/fisiopatologia , Fadiga Mental/psicologia , Pessoa de Meia-Idade , Terapias Mente-Corpo/psicologia , Angústia Psicológica , Qualidade de Vida/psicologia , Terapia de Relaxamento/psicologia , República da Coreia , Serotonina/sangue , Estresse Fisiológico/fisiologia , Saúde da População Urbana , População Urbana , Vitamina D/sangue , Caminhada/fisiologia , Caminhada/psicologia , Yoga/psicologia
8.
Ocul Immunol Inflamm ; 28(3): 370-378, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-30986119

RESUMO

Purpose: To evaluate the efficacy and safety of a novel topical cyclosporin A 0.05% nanoemulsion in comparison with a conventional emulsion in primary Sjögren's syndrome dry eyes.Methods: Prospective, randomized, double-blinded study was conducted.Results: Corneal and conjunctival staining score was improved in both groups, with a faster change noted in the nanoemulsion group at 12 weeks (p < 0.05). Tear film break-up time was significantly improved in the nanoemulsion group at 12 weeks (p < 0.05), while ocular surface disease index score was improved in both groups without a difference at 12 weeks. Schirmer I value and goblet cell grade did not change in both groups. IL-6 and MMP-9 were significantly decreased in both groups at 12 weeks.Conclusions: Both nanoemulsion and conventional cyclosporin A improved ocular signs, symptoms, and conjunctival inflammation. However, the novel cyclosporin A nanoemulsion showed faster improvement of ocular surface staining scores than the conventional emulsion.


Assuntos
Ciclosporina/administração & dosagem , Síndromes do Olho Seco/tratamento farmacológico , Síndrome de Sjogren/complicações , Administração Tópica , Contagem de Células , Túnica Conjuntiva/efeitos dos fármacos , Túnica Conjuntiva/patologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/etiologia , Emulsões , Feminino , Seguimentos , Células Caliciformes/efeitos dos fármacos , Células Caliciformes/patologia , Humanos , Pessoa de Meia-Idade , Nanopartículas , Estudos Prospectivos , Síndrome de Sjogren/diagnóstico , Resultado do Tratamento
9.
Front Immunol ; 9: 1984, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30279688

RESUMO

Bile acids (BAs) control metabolism and inflammation by interacting with several receptors. Here, we report that intravenous infusion of taurodeoxycholate (TDCA) decreases serum pro-inflammatory cytokines, normalizes hypotension, protects against renal injury, and prolongs mouse survival during sepsis. TDCA increases the number of granulocytic myeloid-derived suppressor cells (MDSCLT) distinctive from MDSCs obtained without TDCA treatment (MDSCL) in the spleen of septic mice. FACS-sorted MDSCLT cells suppress T-cell proliferation and confer protection against sepsis when adoptively transferred better than MDSCL. Proteogenomic analysis indicated that TDCA controls chromatin silencing, alternative splicing, and translation of the immune proteome of MDSCLT, which increases the expression of anti-inflammatory molecules such as oncostatin, lactoferrin and CD244. TDCA also decreases the expression of pro-inflammatory molecules such as neutrophil elastase. These findings suggest that TDCA globally edits the proteome to increase the number of MDSCLT cells and affect their immune-regulatory functions to resolve systemic inflammation during sepsis.


Assuntos
Células Supressoras Mieloides/imunologia , Sepse/imunologia , Linfócitos T/imunologia , Ácido Taurodesoxicólico/metabolismo , Animais , Contagem de Células , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Tolerância Imunológica , Elastase de Leucócito/genética , Elastase de Leucócito/metabolismo , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oncostatina M/genética , Oncostatina M/metabolismo
10.
J Neurogastroenterol Motil ; 20(2): 242-52, 2014 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-24840377

RESUMO

BACKGROUND/AIMS: Management of irritable bowel syndrome (IBS) imposes a heavy economic burden. This study was to estimate the epidemio-logic features of IBS and to report the IBS burden for the first time in the Korean population. METHODS: A cross-sectional study was conducted using the National Health Insurance (NHI) system database, which covers the entire pop-ulation of Korea. IBS was defined as diagnostic code -10 in adults with any outpatient clinic visits or hospitalization related to IBS. We excluded diseases that mimic IBS symptoms. RESULTS: A total of 2.42 million (58.2% female) individuals were identified as patients with IBS, yielding an age- and gender-adjusted prevalence of 5.1% in males and 6.9% in females. The prevalence of IBS increased proportionally with age, with higher medical costs in middle-aged patients. Outpatient clinics were visited by 98.6% of IBS patients, and 1.9% were treated upon admission. Of these patients, 87.6% were given a prescription. Co-morbidities that commonly accompanied IBS included upper gastro-intestinal (36.1%), respiratory (12.3%), musculoskeletal (8.0%) disease, somatoform (4.3%) and depression/anxiety disorders (3.1%). The NHI costs of IBS, which include the NHI covered cost and beneficiary copayment charges, were estimated to be 155 million USD, which accounts for 0.46% of the total NHI costs for the entire Korean population. CONCLUSIONS: According to the Korean national claims database, about 6% of the Korean population seeks medical care for IBS at least once per year. This high prevalence places a large economic burden on the Korean healthcare system, accounting for 0.46% of over-all national medical expenditure.

11.
Asian Pac J Cancer Prev ; 15(8): 3383-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24870726

RESUMO

BACKGROUND: Prostate cancer is rapidly increasing in Korea and professional societies have requested adding prostate specific antigen (PSA) testing to the National Cancer Screening Program (NCSP), but this started a controversy in Korea and neutral evidence on this issue is required more than ever. The purpose of this study was to provide economic evidence to the decision makers of the NCSP. MATERIALS AND METHODS: A cost-utility analysis was performed on the adoption of PSA screening program among men aged 50-74-years in Korea from the healthcare system perspective. Several data sources were used for the cost-utility analysis, including general health screening data, the Korea Central Cancer Registry, national insurance claims data, and cause of mortality from the National Statistical Office. To solicit the utility index of prostate cancer, a face-to-face interview for typical men aged 40 to 69 was conducted using a Time-Trade Off method. RESULTS: As a result, the increase of effectiveness was estimated to be very low, when adopting PSA screening, and the incremental cost effectiveness ratio (ICER) was analyzed as about 94 million KRW. Sensitivity analyses were performed on the incidence rate, screening rate, cancer stage distribution, utility index, and treatment costs but the results were consistent with the base analysis. CONCLUSIONS: Under Korean circumstances with a relatively low incidence rate of prostate cancer, PSA screening is not cost-effective. Therefore, we conclude that adopting national prostate cancer screening would not be beneficial until further evidence is provided in the future.


Assuntos
Análise Custo-Benefício , Detecção Precoce de Câncer/economia , Neoplasias da Próstata/diagnóstico , Adulto , Idoso , Custos de Cuidados de Saúde , Humanos , Calicreínas/sangue , Masculino , Programas de Rastreamento/economia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/economia , Neoplasias da Próstata/terapia , Anos de Vida Ajustados por Qualidade de Vida , República da Coreia
12.
J Chromatogr Sci ; 50(9): 803-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22744744

RESUMO

A simple, rapid and selective liquid chromatography method coupled with tandem mass spectrometry is developed and validated for the quantification of galantamine in human plasma using a commercially available compound, glimepride, as an internal standard (IS). Following simple one-step liquid-liquid extraction by ethyl acetate, the analytes are separated using an isocratic mobile phase consisting of acetonitrile and 0.01M ammonium acetate (95/5, v/v) on a reverse-phase C18 column and analyzed by tandem mass spectrometry in the multiple reaction monitoring mode using the transitions of respective (M + H)(+) ions, m/z 288.22 → 213.20 and m/z 491.17 → 352.30 for the quantification of galantamine and IS, respectively. The standard calibration curves show good linearity within the range of 4 to 240 ng/mL (r(2) = 0.9996, 1/x(2) weighting). The lower limit of quantification is 4 ng/mL. The retention times of galantamine and IS are 1.1 and 0.71 min, which showsthe high throughput potential of the proposed method. In addition, no significant metabolic compounds are found to interfere with the analysis. Acceptable precision and accuracy are obtained for the concentrations over the standard curve range. The validated method is successfully applied for pharmacokinetic and bioequivalence studies of 24 mg of a galantamine hydrobromide capsule in 32 healthy Korean subjects.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Galantamina/sangue , Compostos de Sulfonilureia/análise , Espectrometria de Massas em Tandem/métodos , Adulto , Disponibilidade Biológica , Cromatografia de Fase Reversa/métodos , Estudos Cross-Over , Galantamina/química , Galantamina/farmacocinética , Humanos , Análise dos Mínimos Quadrados , Extração Líquido-Líquido , Masculino , Reprodutibilidade dos Testes , República da Coreia , Sensibilidade e Especificidade , Compostos de Sulfonilureia/química , Equivalência Terapêutica
13.
J Chromatogr Sci ; 50(5): 396-400, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22451531

RESUMO

Nimesulide is a selective COX-2 inhibitor that is as effective as the classical non-acidic nonsteroidal anti-inflammatory drugs in the relief of various pain and inflammatory conditions, but is better tolerated with lower incidences of adverse effects than other drugs. After oral dose of 100 mg nimesulide to western subjects, a mean maximal concentration (C(max)) of 2.86 ∼ 6.5 µg/mL was reached at 1.22 ∼ 2.75 h and mean t(1/2ß) of 1.8 ∼ 4.74 h. This study developed a robust method for quantification of nimesulide for the pharmacokinetics and suitability of its dosage in Korea and compared its suitability with other racial populations. Nimesulide and internal standard were extracted from acidified samples with methyl tert-butyl ether and analyzed by high-performance liquid chromatography with ultraviolet detection (HPLC-UV). The 28 healthy volunteers took 2 tablets of 100 mg nimesulide and blood concentrations were analyzed during the 24 h post dose. Several pharmacokinetic parameters were represented: AUC(0-infinity) = 113.0 mg-h/mL, C(max) = 12.06 mg/mL, time for maximal concentrations (T(max)) = 3.19 h and t(1/2ß) = 4.51 h. These were different from those of western populations as follows: AUC was 14.5% and C(max) was 28% that of of Korean subjects and T(max) and t(1/2ß) were also different. The validated HPLC-UV method was successfully applied for the pharmacokinetic studies of nimesulide in Korean subjects. Because the pharmacokinetics of nimesulide were different from western populations, its dosage regimen needs to be adjusted for Koreans.


Assuntos
Anti-Inflamatórios não Esteroides/sangue , Cromatografia Líquida de Alta Pressão/métodos , Inibidores de Ciclo-Oxigenase/sangue , Sulfonamidas/sangue , Administração Oral , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Área Sob a Curva , Povo Asiático , Cromatografia Líquida de Alta Pressão/economia , Inibidores de Ciclo-Oxigenase/administração & dosagem , Humanos , Masculino , Sensibilidade e Especificidade , Sulfonamidas/administração & dosagem , Adulto Jovem
14.
Korean J Gastroenterol ; 58(6): 323-31, 2011 Dec.
Artigo em Coreano | MEDLINE | ID: mdl-22198230

RESUMO

BACKGROUND/AIMS: Gastrointestinal (GI) diseases impose a heavy economic burden. We aimed to provide the first report on the health care utilization and costs of GI diseases in Korea. METHODS: We collected the data from all insurance claims database of National Health Insurance Corporation in Korea and the cause of death database in 2007 of Korea National Statistical Office. We compiled information about all digestive disease as a primary diagnosis on clinic visits, hospitalization, and cause of death from these databases. RESULTS: Seventeen million people (35.6%) had a diagnosis of GI diseases during the year 2007. Among them, the proportion of patients with upper GI diseases was prevalent in 54.9% (9.5 million patients/year). The 1/4 patients in out-patients clinic had any one of gastroesophageal reflux disease, irritable bowel syndrome and constipation. Thirteen percent of the total direct cost in 2007 was attributed to all GI diseases, which was 3,649 billion won (0.4% of GDP). The patients with hospitalization occupied by 5% of all patients with GI diseases, however, attributed to 58.9% of GI-related direct costs. GI malignancy was the major cause of medical expenses in hospitalization. Stomach cancer continues to be the leading cause of GI-related death in Korea. CONCLUSIONS: GI diseases causes a heavy socioeconomic burden with high morbidity of functional GI disorders in outpatients care and high mortality of GI malignancy in inpatient care. This report highlights the healthcare utilization burden of GI diseases for researchers and public health policy maker to create new directions of integrated researches and health care plan.


Assuntos
Gastroenteropatias/economia , Custos de Cuidados de Saúde , Bases de Dados Factuais , Neoplasias Gastrointestinais/economia , Neoplasias Gastrointestinais/mortalidade , Hospitalização/economia , Humanos , Programas Nacionais de Saúde/economia , República da Coreia , Análise de Sobrevida
15.
Int J Toxicol ; 28(3): 151-61, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19546254

RESUMO

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been associated with diabetes in several epidemiological studies. However, the diabetogenic action of TCDD on pancreatic cells is unclear. Here, we investigated the direct toxic effects of TCDD on a rat insulin-secreting beta cell line. We found that TCDD enhances exocytosis of MTT formazan and lysosomal proteins such as beta-hexosaminindase and Lamp-1. This TCDD-induced exocytosis was abrogated by T-type calcium channel blockers (mibefradil, flunarizine) but not by an aryl hydrocarbon receptor antagonist (alpha-naphtoflavone). Indeed, cytosolic calcium levels were increased by TCDD. Furthermore, TCDD stimulated insulin secretion, which was inhibited by flunarizine. Taken together, our results suggest that TCDD-induced calcium influx via T-type channels regulates vesicular trafficking, such as lysosomal and secretory granule exocytosis, and that TCDD might exert adverse effects on beta cells by continuous insulin release followed by beta cell exhaustion. This could contribute to the link between TCDD exposure and the risk of developing diabetes.


Assuntos
Canais de Cálcio Tipo T/metabolismo , Cálcio/metabolismo , Poluentes Ambientais/toxicidade , Exocitose/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Dibenzodioxinas Policloradas/toxicidade , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Lisossomos/efeitos dos fármacos , Lisossomos/enzimologia , Ratos , Receptores de Hidrocarboneto Arílico/antagonistas & inibidores , Via Secretória/efeitos dos fármacos
16.
Neuroreport ; 17(18): 1871-5, 2006 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-17179861

RESUMO

Clusterin, a secretory glycoprotein, has been shown to be up-regulated in the reactive astrocytes in response to brain injury and neurodegenerative diseases, but its function has not been clearly elucidated. In this study, we investigate whether clusterin has growth-stimulatory activity in astrocytes. Suppression of clusterin with antisense oligonucleotide induced growth arrest, whereas transient overexpression of clusterin by cDNA transfection or exogenous treatment with purified clusterin promoted proliferation of the primary astrocytes in culture. This clusterin-stimulated proliferation was abrogated by PD98059, an inhibitor of mitogen-activated protein kinase kinase. These results suggest that clusterin might play an important role in astrogliosis by stimulating the proliferation of astrocytes through activation of the extracellular signal-regulated kinase 1/2 signaling pathway.


Assuntos
Astrócitos/fisiologia , Proliferação de Células , Clusterina/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Animais , Animais Recém-Nascidos , Astrócitos/efeitos dos fármacos , Western Blotting/métodos , Contagem de Células/métodos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Clusterina/química , Clusterina/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Citometria de Fluxo/métodos , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Oligodesoxirribonucleotídeos Antissenso/farmacologia , Ratos , Ratos Sprague-Dawley , Timidina/metabolismo , Transfecção , Trítio/metabolismo
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