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1.
Diabetes Metab ; 47(3): 101195, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33039669

RESUMO

AIM: Despite the recognized association between type 2 diabetes (T2D) and Parkinson's disease (PD), the implications of glycaemic variability for patients with PD are as yet unknown. For this reason, our study assessed the future risk of incident PD according to visit-to-visit fasting plasma glucose (FPG) variability, as calculated by standard deviation (FPG-SD), coefficient variance (FPG-CV) and variability independent of the mean (FPG-VIM). METHODS: Using the Korean National Health Insurance Service Health Screening Cohort, 131,625 Korean adults without diabetes were followed. They were divided into a midlife group (age<65 years) and an elderly group (age≥65 years) throughout a median follow-up of 8.4 years. RESULTS: Adjusted hazard ratios (HRs) were calculated using multivariable Cox proportional-hazards analysis. In the midlife group, HRs for incident PD in the highest quartile of FPG variability (as measured by SD, CV and VIM) were 1.37 [95% confidence interval (CI): 1.09-1.73], 1.33 (95% CI: 1.06-1.68) and 1.35 (95% CI: 1.07-1.70), respectively, vs the lowest variability quartile group. However, while incident PD did not differ according to FPG variability in the elderly group, Kaplan-Meier curves of PD probability in the midlife group showed a progressively increasing risk of PD the higher the FPG variability. According to a multivariable adjusted model, every 1-SD unit increment in glycaemic variability was associated with a 9% higher risk of incident PD in the midlife group. CONCLUSION: Increased long-term glycaemic variability may be a precipitating risk factor for developing PD in the midlife population without diabetes.


Assuntos
Glicemia , Jejum , Doença de Parkinson , Idoso , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Jejum/sangue , Humanos , Pessoa de Meia-Idade , Doença de Parkinson/epidemiologia , Fatores de Risco
2.
Hong Kong Med J ; 26(6): 520-525, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33350964

RESUMO

Abnormal uterine bleeding in premenopausal women is a common gynaecological symptom and composes of abnormality in the frequency, duration, regularity, and flow volume of menstruation. It could constitute the presentation of various gynaecological malignancies. An appropriate history and physical examination are mandatory to ascertain the diagnosis. Depending on the clinical condition, a complete blood picture, thyroid function test, clotting profile, chlamydia test, cervical smear, and pregnancy test can be performed. Ultrasound should be performed in cases with a pelvic mass, unsatisfactory physical examination, persistent symptoms, or no response to medical treatment. In women aged ≥40 years, an out-patient endometrial biopsy with Pipelle should be performed. In women aged <40 years with risk factors for endometrial cancer, persistent symptoms, or no response to medical treatment, an endometrial biopsy should be performed to rule out endometrial cancer. Hysteroscopy or saline infusion sonohysterography is more sensitive than ultrasound for diagnosing endometrial pathology. Details of the above recommendations are presented.


Assuntos
Técnicas de Diagnóstico Obstétrico e Ginecológico/normas , Ginecologia/normas , Pré-Menopausa , Hemorragia Uterina/diagnóstico , Adolescente , Adulto , Biópsia/normas , Endométrio/diagnóstico por imagem , Feminino , Hong Kong , Humanos , Histeroscopia/normas , Ultrassonografia/normas , Adulto Jovem
3.
J Nutr Health Aging ; 22(10): 1275-1280, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30498837

RESUMO

OBJECTIVES: This study was conducted to determine the cutoff value and efficacy of the EuroQol Visual Analogue Scale (EQ-VAS) for predicting frailty. DESIGN: The EQ-VAS medians (Interquartile Range) were compared and analyzed against the FFI. PARTICIPANTS: The subjects were 1471 older adults aged 70 to 84 years who had completed both EQ-VAS and Fried Frailty index (FFI) in the first baseline year (2016) of the Korean Frailty and Aging Cohort Study. RESULTS: Of the 1471 subjects,600 were classified as robust, 716 as pre-frail, and 155 as frail. The median EQ-VAS scores were 80.00 (20.00) for robust, 75.00 (25.00) for pre-frail, and 60.00 (25.00) for frail subjects.The medians of all five components of the FFI, weight loss (70.00 vs. 80.00), grip strength (70.00 vs. 80.00), exhaustion (70.00 vs. 80.00), walking velocity (70.00 vs. 80.00), and physical activity (70.00 vs. 80.00), were lower in the abnormal groups. We tested the efficacy of EQ-VAS as a diagnostic tool to predict frailty, and the area under the curve of EQ-VAS was 0.71 withthe optimal cut-off value of 72. CONCLUSION: EQ-VAS presented negative correlation with FFI, and the optimal cut off value for frailty was 72. These results suggest that EQ-VAS is a valuable tool for assessing frailty andmay be a good predictor of frailty in Korean elderly population.


Assuntos
Idoso Fragilizado/psicologia , Fragilidade/psicologia , Escala Visual Analógica , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , República da Coreia/epidemiologia
4.
Diabetes Metab ; 44(4): 361-367, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29752167

RESUMO

AIMS: This study examined whether dipeptidyl peptidase (DPP)-4 inhibitor use is beneficial or harmful to diabetic retinopathy (DR) compared with other glucose-lowering agents in patients with type 2 diabetes (T2D). METHODS: From a population-based cohort provided by the National Health Insurance Service in Korea, 67,743 adults with T2D were identified as having been treated with oral glucose-lowering agents between 2008 and 2013. Matching (1:1) was performed for two groups comparing ever-use (cases) and never-use (controls) of DPP-4 inhibitors (n=14,522 in each group). Cox regression analyses were used to assess risk of the following DR events: vitreous haemorrhage; vitrectomy or photocoagulation; intravitreal agent use; and blindness. RESULTS: During a median follow-up of 28.4 (14.0-45.2) months, there were 305 (in controls) and 342 (in cases) composite DR events. DPP-4 inhibitor ever-use was not associated with overall risk of composite DR events [adjusted hazard ratio (HR): 1.08, 95% CI: 0.93-1.26] compared with never-use, nor was the risk of each DR outcome increased with DPP-4 inhibitor therapy either. However, DPP-4 inhibitor administration for<12 months was associated with a greater risk of composite DR events (adjusted HR: 1.31, 95% CI: 1.09-1.57) compared with other glucose-lowering agents over the same treatment period. CONCLUSION: In comparison to other oral glucose-lowering agents, DPP-4 inhibitor treatment did not increase overall risk of DR. However, DPP-4 inhibitors may be associated with an increased risk of retinopathy events early in the treatment phase.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Retinopatia Diabética/induzido quimicamente , Retinopatia Diabética/epidemiologia , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fosfato de Sitagliptina/efeitos adversos , Fosfato de Sitagliptina/uso terapêutico , Adulto Jovem
5.
Vox Sang ; 111(4): 441-444, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27538125

RESUMO

A novel A subgroup allele (c.538C>T p.Arg180Cys) showing weak A phenotype was found in a 30-year-old Korean woman with ABO discrepancy. Using 3D structural analysis, protein stability prediction and flow cytometric analysis of ABO antigen expression on HeLa cells transfected with plasmids containing the p.Arg180Cys mutant, we found that the Arg180 residue in the loop region of the A glycosyltransferases (GTA) structure plays significant role in stabilizing its closed conformation, which is required for substrate binding and catalysis study.


Assuntos
N-Acetilgalactosaminiltransferases/genética , Sistema ABO de Grupos Sanguíneos/genética , Adulto , Estabilidade Enzimática , Feminino , Estudos de Associação Genética , Células HeLa , Humanos , Mutação de Sentido Incorreto , Fenótipo , Análise de Sequência de DNA
6.
Neurogastroenterol Motil ; 28(11): 1731-1740, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27283929

RESUMO

BACKGROUND: Therapeutic options for management of diabetic gastroparesis are limited. Failure to maintain upregulation of heme oxygenase (HO1) leads to loss of interstitial cells of Cajal and delayed gastric emptying (GE) in non-obese diabetic mice. Our hypothesis was that hemin upregulation of HO1 would restore normal GE in humans with gastroparesis. AIMS: To compare effects of hemin and placebo infusions on HO1 activity and protein, GE, autonomic function, and gastrointestinal symptoms in diabetic gastroparesis. METHODS: In a single-center, double-blind, placebo-controlled, randomized clinical trial, we compared intravenous hemin, prepared in albumin, or albumin alone (placebo) in 20 patients, aged 41 ± 5 (SEM) years with diabetic gastroparesis. After infusions on days 1, 3, and 7, weekly infusions were administered for 7 additional weeks. Assessments included blood tests for HO1 protein and enzyme activity levels, GE with 13 C-spirulina breath test, autonomic functions (baseline and end), and gastrointestinal symptoms every 2 weeks. KEY RESULTS: Nine of 11 patients randomized to hemin completed all study procedures. Compared to placebo, hemin increased HO1 protein on days 3 (p = 0.0002) and 7 (p = 0.008) and HO1 activity on day 3 (p = 0.0003) but not after. Gastric emptying, autonomic functions, and symptoms did not differ significantly in the hemin group relative to placebo. CONCLUSIONS & INFERENCES: Hemin failed to sustain increased HO1 levels beyond a week and did not improve GE or symptoms in diabetic gastroparesis. Further studies are necessary to ascertain whether more frequent hemin infusions or other drugs would have a more sustained effect on HO1 and improve GE.


Assuntos
Diabetes Mellitus/sangue , Esvaziamento Gástrico/efeitos dos fármacos , Gastroparesia/sangue , Heme Oxigenase-1/sangue , Hemina/administração & dosagem , Adulto , Idoso , Diabetes Mellitus/tratamento farmacológico , Método Duplo-Cego , Feminino , Esvaziamento Gástrico/fisiologia , Gastroparesia/tratamento farmacológico , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
7.
J Nutr Health Aging ; 20(3): 248-55, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26892573

RESUMO

OBJECTIVE: Age-related declines in skeletal muscle mass may confer significant metabolic consequences for older adults. Associations of low muscle mass and metabolic syndrome (MetS) in Caucasians, and comparisons with associations observed in Asian populations, have not been reported. We examined associations of low muscle mass and metabolic syndrome (MetS) in Asian and Caucasian middle-aged and older men and women using criteria for low muscle mass. DESIGN, SETTING AND PARTICIPANTS: Two population-based studies of Australian (Tasmanian Older Adult Cohort Study; TASOAC; N=1005) and Korean (Korean Sarcopenic Obesity Study; KSOS; N=376) community-dwelling adults, mean age 62 and 58 years, respectively. MEASUREMENTS: Appendicular lean mass (aLM) determined by dual-energy X-ray absorptiometry and normalised to height squared (aLM/Ht2), weight (aLM/Wt) or body mass index (aLM/BMI). Participants in the lowest sex-specific 20% for aLM measures were defined as having low muscle mass. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: Although Australians demonstrated generally unfavourable anthropometric and metabolic characteristics compared to Koreans, prevalence of MetS was similar (29.5% in Australians and 31.4% in Koreans, respectively). Low aLM/Ht2 was associated with significantly reduced likelihood of MetS in both Australians (OR: 0.30, 95% CI 0.19 - 0.46) and Koreans (OR: 0.31, 95% CI 0.16 - 0.62). Conversely, low aLM/BMI was associated with increased odds for MetS in Australians (OR: 1.78, 95% CI 1.12 - 2.84), but not Koreans (OR: 1.33, 95% CI = 0.67 - 2.64). CONCLUSION: Low aLM/BMI is associated with significantly increased likelihood of MetS in Australian adults, but not Koreans, suggesting potential differences in effects of low muscle mass relative to body mass on cardiometabolic health in Caucasian and Asian middle-aged and older adults. Low muscle mass relative to height is associated with reduced likelihood of MetS in both populations.


Assuntos
Povo Asiático/estatística & dados numéricos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/fisiopatologia , Músculo Esquelético/fisiopatologia , População Branca/estatística & dados numéricos , Absorciometria de Fóton , Idoso , Antropometria , Austrália/etnologia , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/anatomia & histologia , Obesidade/epidemiologia , Prevalência , República da Coreia/etnologia , Sarcopenia/epidemiologia
8.
Skin Res Technol ; 22(2): 164-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26094640

RESUMO

BACKGROUND/PURPOSE: Many ingredients used in cosmetics evoke a comedogenic response. Rabbit ear model (REM) is a useful method that can replace human in examining materials and products in early developmental stage. However, a number of studies pointed out its disadvantage that it overreacts to comedogenic materials. The purpose of this study was to find the most appropriate region for evaluating comedogenicity in human skin. METHODS: Sixty-six female subjects (age 32.48 ± 10 years; range 20-52 years) with mild to moderate facial acne lesions were included in this study. The whole face, upper chest, and back of volunteers were photographed. Lesion (closed and open comedones) counting, instrumentation of sebum secretion level, and analysis of porphyrin number were performed. The entire study was performed under environmental conditions of specific relative temperature and humidity, controlled and maintained identically for each volunteer. RESULTS: In case of closed comedone, forehead showed a significant correlation with frontal cheek, lateral cheek, chin, and upper back. Meanwhile, significant correlations were observed between frontal cheek and chin as well as lateral cheek and chest. As for open comedone, forehead showed a significant correlation with chin site. A significant correlation was also observed between front cheek and lateral cheek as well as between upper chest and back. Analyzing the correlation between the occurrence of comedones and sebum in each region, a significant correlation between closed comedone and sebum was observed in frontal and lateral cheek. Analyzing the correlation between the occurrence of comedones and porphyrine in each region, a significant correlation between open comedone and porphyrin was observed in chin. CONCLUSION: When evaluating the comedogenicity of cosmetics ingredients or products, this study recommends using both of the methods of testing on back and directly testing on face according to the characteristics of the materials. In case of mild potent ingredients or products in particular, verification through usability test that the directly test on face will help securing reliability.


Assuntos
Acne Vulgar/induzido quimicamente , Bioensaio/métodos , Cosméticos/efeitos adversos , Porfirinas/análise , Sebo/química , Pele/patologia , Acne Vulgar/patologia , Adulto , Face/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Pele/efeitos dos fármacos , Pele/metabolismo , Adulto Jovem
9.
Skin Res Technol ; 21(1): 41-6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25216021

RESUMO

BACKGROUND/AIMS: The age-dependent changes in the optical reflection characteristics have been studied about skin hydration, melanin index, or skin color. However, the age-dependent changes in the optical reflection have little attention on inner skin structures. To control the factors affecting the optical reflection except for dermal matrix, subjects were selected as our guideline and we evaluated the optical reflection of subsurface on skin layers of two age groups. METHOD: Young and old healthy volunteers were recruited after signing a written informed consent form. Facial skin was measured by means of noninvasive measurements: skin hydration, color, epidermis and dermis thickness, dermal density, subsurface reflectance, and transmittance. RESULT: Compared to young group, old group showed that dermal density and thickness was decreased significantly although epidermis thickness was not changed. CONCLUSION: In conclusion, dermal density is one of the major factors which affects the subsurface reflectance in skin.


Assuntos
Luz , Refratometria/métodos , Espalhamento de Radiação , Fenômenos Fisiológicos da Pele , Pigmentação da Pele/fisiologia , Pele/química , Adulto , Face/anatomia & histologia , Face/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade , Pele/anatomia & histologia , Adulto Jovem
10.
J Clin Endocrinol Metab ; 98(7): 2897-901, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23633195

RESUMO

CONTEXT AND OBJECTIVE: Glypican-4 was identified as a novel adipokine capable of enhancing insulin signaling and modulating adipocyte differentiation. We investigated associations between glypican-4 and body composition, insulin resistance, arterial stiffness, and nonalcoholic fatty liver disease (NAFLD) in nondiabetic Asian subjects. DESIGN AND PARTICIPANTS: We analyzed baseline cross-sectional data from the Korean Sarcopenic Obesity Study, an ongoing prospective cohort study. NAFLD was diagnosed by unenhanced computed tomography using the liver attenuation index. We also examined the effects of a 3-month combined aerobic and resistance exercise program on glypican-4 levels and cardiometabolic risk factors. RESULTS: Circulating glypican-4 levels were higher in men than in women (1.83 [1.19, 2.78] ng/mL vs 1.17 [0.66, 2.00] ng/mL, P < .001) and had a significant positive relationship with the waist-to-hip ratio (WHR) (r = 0.20, P = .014) and the ratio of visceral to sc fat area (r = 0.30, P < .001). Furthermore, glypican-4 levels in women were correlated with cardiometabolic risk factors, including insulin resistance and arterial stiffness, and were independently associated with NAFLD by multiple logistic regression analysis (P = .017, R² = 0.33). The 3-month combined exercise training program significantly improved several cardiometabolic parameters and reduced retinol binding protein-4 levels. Changes in glypican-4 levels after the exercise program were significantly different between subjects with an increased WHR compared with those with a decreased WHR (P = .034). CONCLUSION: A gender-based difference in circulating glypican-4 levels was apparent as these were increased in women with NAFLD and related to body fat distribution, insulin resistance, and arterial stiffness.


Assuntos
Tecido Adiposo/metabolismo , Adiposidade , Distribuição da Gordura Corporal , Fígado Gorduroso/sangue , Glipicanas/sangue , Resistência à Insulina , Tecido Adiposo/patologia , Adulto , Idoso , Estudos de Coortes , Estudos Transversais , Exercício Físico , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/terapia , Feminino , Glipicanas/metabolismo , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , República da Coreia/epidemiologia , Fatores de Risco , Caracteres Sexuais , Rigidez Vascular
11.
Nutr Metab Cardiovasc Dis ; 23(8): 785-91, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22762845

RESUMO

BACKGROUND AND AIM: Evidence of the relationship between serum vitamin D levels and cardiovascular risk factors in children is limited. We investigated the associations between serum vitamin D levels (25-hydroxyvitamin D [25(OH)D]) and obesity and metabolic syndrome and its components in Korean children. METHODS AND RESULTS: We recruited 1660, nine-year-old, Korean children (904 boys and 756 girls) who voluntarily participated in this study while being examined during school-based health examinations. We measured anthropometric variables (height and weight), metabolic parameters (blood pressure, fasting plasma glucose, triglyceride, and HDL cholesterol levels) and serum vitamin D levels. We analyzed the data using multivariate logistic regression models. Mean 25(OH)D levels were lower in children defined as obese or abdominally obese (P <0.001). When serum levels of 25(OH)D were divided into quartiles, BMI, waist circumference, and triglyceride levels were lower, and HDL cholesterol levels were higher, as vitamin D levels increased. Using children from the highest quartile of 25(OH)D levels as a referent, the adjusted ORs (95% CI) for obesity in those in the third, second, and lowest quartiles of 25(OH)D levels were 1.55 (1.01-2.40), 1.87 (1.22-2.85), and 2.59 (1.71-3.90), respectively (P for trend <0.001). For abdominal obesity the ORs (CI) were 2.08 (1.20-3.60), 2.32 (1.36-3.95), and 2.96 (1.75-5.00) (P for trend<0.001), and for metabolic syndrome they were 2.60 (1.08-6.30), 4.00 (1.73-9.26), and 4.25 (1.84-9.85), respectively (P for trend <0.05). CONCLUSIONS: We found low vitamin D levels in Korean children to be associated with obesity and metabolic syndrome. Insufficient serum vitamin D levels in children may be a risk factor of obesity and metabolic syndrome.


Assuntos
Síndrome Metabólica/sangue , Obesidade/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Povo Asiático , Glicemia/metabolismo , Índice de Massa Corporal , Peso Corporal , Criança , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos Transversais , Jejum , Feminino , Humanos , Modelos Logísticos , Masculino , Síndrome Metabólica/complicações , Análise Multivariada , Inquéritos Nutricionais , Obesidade/complicações , República da Coreia , Fatores de Risco , Triglicerídeos/sangue , Vitamina D/sangue , Deficiência de Vitamina D/complicações , Circunferência da Cintura
12.
Zoonoses Public Health ; 59(5): 303-13, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22332987

RESUMO

Laboratory and in vivo studies in primates, and serological evidence in humans, indicate that food animal oncogenic viruses show potential for causing cancer in humans. However, until fairly recently, supporting analytic epidemiologic studies have been lacking and have concentrated on lung cancer. We conducted an extensive Medline search and reviewed 60 studies investigating lung cancer risk in highly exposed workers in the meat and poultry industries. The overwhelming majority of studies of different designs (including all the cohort mortality and cancer incidence studies) indicate at least a 30% excess risk of lung cancer in meat and poultry plant workers, even after controlling for smoking. Evidence points to food animal oncogenic microorganisms as one of the main causes. This has important public health implications because the general population is also widely exposed. Studies carried out thus far have not had sufficient statistical power to investigate other potentially carcinogenic exposures within the industries. Thus, large studies that can adequately control for occupational and non-occupational confounding factors are needed, so that the possible role of food animal oncogenic viruses in the occurrence of human lung cancer can be clearly defined.


Assuntos
Transmissão de Doença Infecciosa/veterinária , Indústria de Processamento de Alimentos , Neoplasias Pulmonares/veterinária , Neoplasias Pulmonares/virologia , Doenças Profissionais/veterinária , Doenças Profissionais/virologia , Zoonoses , Animais , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Exposição Ocupacional , Aves Domésticas , Fatores de Risco
13.
J Clin Endocrinol Metab ; 96(8): E1325-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21677040

RESUMO

CONTEXT AND OBJECTIVE: The dysregulation of hepatokines may be associated with the pathogenesis of insulin resistance and type 2 diabetes. A recent study has suggested that selenoprotein P (SeP), a novel hepatokine, may play a role in the regulation of glucose metabolism and insulin sensitivity. We examined the relationship between circulating SeP levels and clinical parameters associated with insulin resistance in humans. PARTICIPANTS AND METHODS: We compared serum SeP concentrations in 100 subjects with diverse glucose tolerance statuses. Furthermore, we evaluated the relationship between SeP and cardiometabolic risk factors including insulin resistance, high-sensitivity C-reactive protein, and carotid intima-media thickness. RESULTS: Serum SeP concentrations were significantly higher in patients with type 2 diabetes or prediabetes than those with normal glucose tolerance (all P < 0.01) and decreased in a stepwise manner [1032.4 (495.9-2149.4) vs. 867.3 (516.3-1582.7) vs. 362.0 (252.5-694.5), P = 0.004]. In addition, overweight and obese subjects had significantly increased SeP levels compared with lean subjects (P = 0.002). Spearman's partial correlation analysis adjusted for age and gender showed a significant relationship between SeP and cardiometabolic factors including body mass index, waist circumference, systolic blood pressure, triglycerides, glucose, hemoglobin A1c, aspartate aminotransferase, and insulin resistance. Furthermore, in multiple regression analyses, SeP showed an independent association with carotid intima-media thickness as well as high-sensitivity C-reactive protein, even after adjustment for other confounding factors. CONCLUSIONS: Circulating SeP concentrations were elevated in patients with glucose metabolism dysregulation and were related to various cardiometabolic parameters including insulin resistance, inflammation, and atherosclerosis.


Assuntos
Doenças das Artérias Carótidas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Inflamação/metabolismo , Resistência à Insulina/fisiologia , Estado Pré-Diabético/metabolismo , Selenoproteína P/sangue , Adulto , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/imunologia , Diabetes Mellitus Tipo 2/imunologia , Feminino , Humanos , Inflamação/imunologia , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/imunologia , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Ultrassonografia
14.
Cell Prolif ; 44(4): 320-9, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21645154

RESUMO

OBJECTIVES: Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti-cancer treatment have been sought from natural resources. Here, we have investigated anti-proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the de novo sphingolipid pathway, and its mechanism in B16F10 melanoma cells. MATERIAL AND METHODS: We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine-1-phosphate levels were analysed by HPLC. RESULTS: Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G(2) /M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21(waf1/cip1) was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine-1-phosphate in myriocin-treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells. CONCLUSIONS: Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21(waf1/cip1) , followed by inhibition of cyclin B1 and cdc2, resulting in G(2) /M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism-based therapy for this type of skin cancer.


Assuntos
Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Ácidos Graxos Monoinsaturados/farmacologia , Melanoma Experimental/tratamento farmacológico , Serina C-Palmitoiltransferase/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Animais , Proteína Quinase CDC2/biossíntese , Proteína Quinase CDC2/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ceramidas/biossíntese , Ceramidas/genética , Ciclina B1/biossíntese , Ciclina B1/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Lisofosfolipídeos/biossíntese , Lisofosfolipídeos/genética , Melanoma Experimental/genética , Camundongos , Proteínas Proto-Oncogênicas p21(ras)/biossíntese , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias Cutâneas/genética , Esfingomielinas/biossíntese , Esfingomielinas/genética , Esfingosina/análogos & derivados , Esfingosina/biossíntese , Esfingosina/genética , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/genética , Fosfatases cdc25/biossíntese , Fosfatases cdc25/genética
15.
Transplant Proc ; 42(10): 4648-50, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21168753

RESUMO

Xenotransplantation using porcine organs may resolve the chronic shortage of donor organs for clinical transplantation if significant immunologic barriers can be overcome. A xenograft can be rejected by T cells, especially CD8(+) cytotoxic T lymphocytes (CTL)-mediated responses, as these cells show cytotoxicity against xenografts by recognition of swine leukocyte antigen (SLA)-I. Peptide translocation is inhibited by the endoplasmic reticulum-resident human cytomegalovirus (HCMV) glycoprotein unique short (US) 6, due to alterations of the transporter associated with antigen processing loading onto MHC class I for antigen presentation to CD8(+) CTL. In this study we transfected the US6 gene into minipig fetal fibroblasts establishing three US6 clonal cell lines. Flow cytometry analysis of US6 clonal cell lines demonstrated a substantial reduction in SLA-I expression. The level of SLA-I expression in US6 clones was decreased to 56.3% compared with the control 42.7%. In CTL assays, the rate of CD8(+) CTL-mediated cytotoxicity was significantly reduced to 35.2% ± 11.7% compared with the control, 79.9% ± 6.5%, (P < .01). These results suggested that HCMV viral protein US6 suppresses the presentation of SLA-I on pig fetal fibroblast cells. This strategy might be used in transgenic pig production to protect porcine organs from CTL-mediated immune rejection.


Assuntos
Antígenos de Histocompatibilidade Classe II/imunologia , Proteínas de Ligação a RNA/genética , Proteínas Virais/genética , Animais , Animais Geneticamente Modificados , Linhagem Celular , Antígenos de Histocompatibilidade Classe I , Humanos , Suínos , Porco Miniatura , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/imunologia
16.
Clin Endocrinol (Oxf) ; 73(5): 588-94, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20618345

RESUMO

OBJECTIVE: A relationship between visceral fat accumulation and metabolic syndrome (MetS) has been established. However, the effect of a relative increase in visceral fat and a decrease in muscle mass on metabolic disorders has not been investigated. The aim of the present study was to examine the association between the ratio of visceral fat to thigh muscle area (VMR) and MetS in Korean adults. STUDY SUBJECT/MEASUREMENTS: A total of 264 age-and gender-matched subjects recruited from the Korean Sarcopenic Obesity Study (KSOS), an ongoing prospective observational cohort study, were categorized into four groups based on their body mass index (BMI) and VMR. We measured visceral fat area and thigh muscle area using computed tomography. RESULTS: Subjects with MetS showed a significantly higher VMR than those without MetS. In both obese and nonobese groups, the subjects with a higher VMR had a higher prevalence of MetS than those in the lower VMR groups. VMR was significantly related to components of the metabolic syndrome, especially in women, and was positively correlated with a number of MetS components in both men and women. In multiple logistic regression analysis, the odds ratio for MetS was 6·72 (highest vs lowest quartile, 95% confidence interval, 1·60-28·14) after an adjustment of potential confounders, including BMI and waist-to-hip ratio. CONCLUSION: VMR is significantly increased in subjects with MetS and independently associated with MetS. These results suggest that the VMR may be a potential indicator for MetS risk in Korean adults.


Assuntos
Gordura Intra-Abdominal/anatomia & histologia , Síndrome Metabólica/fisiopatologia , Músculo Esquelético/anatomia & histologia , Sarcopenia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Gordura Intra-Abdominal/metabolismo , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Obesidade/epidemiologia , Obesidade/metabolismo , Estudos Prospectivos , República da Coreia/epidemiologia
17.
Clin Pharmacol Ther ; 87(2): 187-90, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19956091

RESUMO

Heme oxygenase (HO)-1 degrades heme and protects against oxidative stress, but it has not been pharmacologically induced in humans. In this randomized study of 10 healthy volunteers, hemin (3 mg/kg intravenously in 25% albumin) was shown to increase plasma HO-1 protein concentration four- to fivefold and HO-1 activity ~15-fold relative to baseline at 24 and 48 h (placebo -56.41 +/- 6.31 (baseline), 69.79 +/- 13.00 (24 h), 77.44 +/- 10.62 (48 h) vs. hemin -71.70 +/- 9.20 (baseline), 1,126.20 +/- 293.30 (24 h), 1,192.20 +/- 333.30 (48 h)) in four of five subjects as compared with albumin alone (P

Assuntos
Heme Oxigenase-1/efeitos dos fármacos , Hemina/farmacologia , Albumina Sérica/química , Adolescente , Adulto , Ativação Enzimática/efeitos dos fármacos , Indução Enzimática/efeitos dos fármacos , Feminino , Heme Oxigenase-1/sangue , Heme Oxigenase-1/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Int J Obes (Lond) ; 33(8): 885-92, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19564878

RESUMO

OBJECTIVES: To examine the prevalence of sarcopenia and sarcopenic obesity (SO) as defined by different indices, including appendicular skeletal muscle mass (ASM)/height(2), skeletal muscle mass index (SMI) and residuals for Korean adults, and to explore the association between SO and metabolic syndrome. METHODS: Our study sample included 526 participants (328 women, 198 men) for whom complete data on body composition were collected using available dual X-ray absorptiometry. Modified National Cholesterol Education Program Adult Treatment Panel III criteria were used to identify the individuals with metabolic syndrome. RESULTS: The prevalence of sarcopenia and SO is higher in older adults. Using two s.d. of ASM/height(2) below reference values from young, healthy adults as a definition of sarcopenia, the prevalence of sarcopenia and SO was 6.3% and 1.3% in older (> or =60 years) men and 4.1% and 0.8% in older women, respectively. The prevalence of sarcopenia using the residuals method was 15.4% in older men and 22.3% in older women. In addition, using two s.d. of SMI, the prevalence of sarcopenia and SO was 5.1% and 5.1%, respectively, in older men and 14.2% and 12.5%, respectively, in older women. Among women, SO subjects defined by the SMI had three times the risk of metabolic syndrome (odds ratios (OR)=3.24, 95% confidence interval (CI)=1.21-8.66) and non-sarcopenic obese subjects had approximately twice the risk of metabolic syndrome (OR=2.17, 95% CI=1.22-3.88) compared with normal subjects. Similar trends were observed in men. CONCLUSION: The prevalence and cutoff values of sarcopenia and SO in the Korean population were evaluated using different methods. Among the different indices of sarcopenia and SO, SO only defined using the SMI was associated with the risk of metabolic syndrome. As the Korean population gets older and more obese, the problematics of SO need to be elucidated.


Assuntos
Envelhecimento/fisiologia , Músculo Esquelético/fisiologia , Obesidade/epidemiologia , Sarcopenia/epidemiologia , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Índice de Massa Corporal , Feminino , Humanos , Coreia (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Prevalência , Sarcopenia/fisiopatologia , Adulto Jovem
19.
Diabet Med ; 26(6): 628-35, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19538239

RESUMO

AIMS: The rapidly increasing prevalence of chronic diseases is an important challenge to healthcare systems worldwide. To improve the quality and efficiency of chronic disease care, we investigated the effectiveness and applicability of the Ubiquitous Chronic Disease Care (UCDC) system using cellular phones and the internet for overweight patients with both Type 2 diabetes and hypertension. METHODS: We conducted a randomized, controlled clinical trial over 3 months that included 123 patients at a university hospital and a community public health centre. RESULTS: After 12 weeks, there were significant improvements in HbA(1c) in the intervention group (7.6 +/- 0.9% to 7.1 +/- 0.8%, P < 0.001) compared with the control group (7.4 +/- 0.9% to 7.6 +/- 1.0%, P = 0.03). Furthermore, we observed a significant reduction in systolic and diastolic blood pressure, as well as improvements in total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels in the intervention group. Furthermore, there was a significant increase in adiponectin levels in the intervention group compared with the control group, although high-sensitivity C-reactive protein and interleukin-6 levels did not change in either group. CONCLUSIONS: The novel UCDC system presented in this paper improved multiple metabolic parameters simultaneously in overweight patients with both Type 2 diabetes and hypertension.


Assuntos
Automonitorização da Glicemia/métodos , Monitorização Ambulatorial da Pressão Arterial/métodos , Telefone Celular , Atenção à Saúde/métodos , Internet , Adulto , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso , Cooperação do Paciente , Educação de Pacientes como Assunto
20.
Int J Cardiol ; 132(1): 96-101, 2009 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-18190981

RESUMO

BACKGROUND: Advanced glycation end products (AGEs) and its receptor (RAGE) were known to play a pivotal role in the development of cardiovascular complications of diabetes. We investigated the association between circulating endogenous secretory RAGE (esRAGE) levels, inflammatory markers and arterial stiffness measured using brachial-ankle pulse wave velocity (baPWV). METHODS: The study subjects were composed of 76 type 2 diabetic patients and 78 age- and sex-matched non-diabetic subjects. RESULTS: Circulating esRAGE levels were significantly lower in subjects with type 2 diabetes (0.237+/-0.123 ng/ml vs. 0.307+/-0.177 ng/ml, p=0.005), and those levels were inversely correlated with body mass index (BMI), waist circumference, blood pressure, triglyceride, fasting glucose level and insulin resistance. Furthermore, esRAGE levels were significantly associated with adiponectin (r=0.164, p=0.044), interleukin-6 (IL-6) (r=-0.242, p=0.009) levels and baPWV (r=-0.296, p<0.001). Multiple regression analysis showed that fasting insulin, IL-6, glucose level and insulin resistance are major factor determining esRAGE (R(2)=0.186). Moreover, baPWV was found to be associated with age, systolic blood pressure, triglyceride, sex, BMI, fasting insulin and esRAGE level (R(2)=0.583). CONCLUSIONS: Circulating esRAGE levels were significantly lower in type 2 diabetic patients, and were associated with inflammation and arterial stiffness. These results suggest that esRAGE may play an important role on ligand-RAGE interaction propagated inflammation and atherosclerosis.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/diagnóstico , Produtos Finais de Glicação Avançada/sangue , Inflamação/diagnóstico , Doenças Vasculares Periféricas/diagnóstico , Receptores Imunológicos/sangue , Adiponectina/sangue , Adiposidade , Índice Tornozelo-Braço , Biomarcadores , Proteína C-Reativa/análise , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/fisiopatologia , Feminino , Humanos , Inflamação/etiologia , Inflamação/fisiopatologia , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/etiologia , Doenças Vasculares Periféricas/fisiopatologia , Receptor para Produtos Finais de Glicação Avançada , Análise de Regressão , República da Coreia , Fatores de Risco
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