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1.
J Nutr Health Aging ; 24(6): 619-626, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32510115

RESUMO

OBJECTIVES: Handgrip strength is an easy-to-assess indicator of overall muscle strength and can be used to evaluate health status. Although previous studies have reported an increase in grip strength due to aerobic exercise, such a study has not been conducted on Korean participants. This study aimed to investigate the effects of aerobic exercise on handgrip strength and examine the association between these two variables in Korean patients with hypertension or diabetes. DESIGN: Cross-sectional study. SETTING: This study used data from the 6th and 7th Korean National Health and Nutrition Examination Survey (2014-2017). PARTICIPANTS: A total of 19,650 individuals aged ≥19 years who had responded to questionnaires concerning aerobic exercise and handgrip strength were analyzed. MEASUREMENTS: The relationship between aerobic activity and handgrip strength was examined by logistic regression analysis. RESULTS: The mean age of individuals in the low muscle strength group was higher than that in the normal muscle strength group. The odds ratio for low handgrip strength was higher in individuals who did not perform aerobic exercise than in those who performed aerobic exercise. Following adjustment for covariates, the odds ratios (95% confidence intervals) for low handgrip strength were 1.415 (0.187-1.688) in the total sample, 1.799 (1.376-2.352) in patients with hypertension, and 1.811 (1.208-2.715) in patients with diabetes. CONCLUSION: The results of our study indicated a strong association between aerobic exercise and handgrip strength in the Korean population.


Assuntos
Exercício Físico/fisiologia , Força da Mão/fisiologia , Força Muscular/fisiologia , Inquéritos Nutricionais/métodos , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia
2.
Public Health ; 175: 1-3, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31362168

RESUMO

OBJECTIVE: The aim of the study is to examine associations between paternal age at childbirth and offspring cardiovascular risk factors in adolescence. STUDY DESIGN: This is a cross-sectional study. METHODS: Data from the 2007-2016 Korea National Health and Nutrition Examination Survey was used. A total of 4,096 adolescents were included in the final analysis, and their information on blood pressure, fasting glucose level, and lipid profile was collected. Multiple linear regression models were applied to evaluate the effect of paternal age on cardiovascular risk factors with adjustment for potential confounders. RESULTS: The median age of participants was 13 years, and 53.2% were male. Maternal and paternal ages were closely correlated with each other, and older parents had older offspring. Paternal age was positively associated with levels of total cholesterol (p = 0.033) and triglycerides (p = 0.042) after adjusting for confounders. CONCLUSION: This nationwide study shows that advanced paternal age is associated with a less favorable lipid profile in a dose-dependent manner.


Assuntos
Doenças Cardiovasculares/epidemiologia , Idade Paterna , Adolescente , Estudos Transversais , Feminino , Humanos , Lipídeos/sangue , Masculino , Inquéritos Nutricionais , República da Coreia/epidemiologia , Fatores de Risco
3.
Nutr Metab Cardiovasc Dis ; 25(8): 724-33, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26044516

RESUMO

BACKGROUND AND AIMS: This study evaluated the triglyceride (TG)-lowering effects of consuming dual probiotic strains of Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY1032 on the fasting plasma metabolome. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled study was conducted on 92 participants with hypertriglyceridemia but without diabetes. Over a 12-week testing period, the probiotic group consumed 2 g of powder containing 5 × 10(9) colony-forming units (cfu) of L. curvatus HY7601 and 5 × 10(9) cfu of L. plantarum KY1032 each day, whereas the placebo group consumed the same product without probiotics. Fasting plasma metabolomes were profiled using UPLC-LTQ-Orbitrap MS. After 12 weeks of treatment, the probiotic group displayed a 20% reduction (p = 0.001) in serum TGs and 25% increases (p=0.001) in apolipoprotein A-V (apoA-V). At the 12-week follow-up assessment, the following 11 plasma metabolites were significantly reduced in the probiotic group than the placebo group: palmitoleamide, palmitic amide, oleamide, and lysophosphatidyl choline (lysoPC) containing C14:0, C16:1, C16:0, C17:0, C18:3, C18:2, C18:1, and C20:3. In the probiotic group, changes (▵) in TG were negatively correlated with ▵ apoA-V, which was positively correlated with ▵ FFA. In addition, ▵ FFA was strongly and positively correlated with ▵ lysoPCs in the probiotic group but not the placebo group. CONCLUSIONS: The triglyceride-lowering effects of probiotic supplementation, partly through elevated apoA-V, in borderline to moderate hypertriglyceridemic subjects showed reductions in plasma metabolites, fatty acid primary amides and lysoPCs (NCT02215694; http://www.clinicaltrials.gov). Clinical trials: NCT02215694; http://www.clinicaltrials.gov.


Assuntos
Hipertrigliceridemia/sangue , Hipertrigliceridemia/dietoterapia , Lactobacillus plantarum/classificação , Lisofosfatidilcolinas/sangue , Probióticos/farmacologia , Adulto , Idoso , Apolipoproteína A-V , Apolipoproteínas A/sangue , Suplementos Nutricionais , Método Duplo-Cego , Jejum/sangue , Ácidos Graxos/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Probióticos/administração & dosagem , Resultado do Tratamento , Triglicerídeos/sangue
4.
Diabet Med ; 31(1): 24-30, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23819613

RESUMO

AIMS: While there is thought to be an association between glucose and lipid metabolism, it is largely unknown whether apolipoprotein B and non-high density lipoprotein (HDL) cholesterol are associated with the development of Type 2 diabetes. It is also unknown whether these atherogenic dyslipidaemic profiles have a stronger association with diabetes risk compared with conventional lipid measurements. METHODS: A total of 118 429 subjects without diabetes (70 980 men and 47 449 women), aged 17-90 years (mean age 39.6 years), were enrolled in this study and followed for a mean duration of 3.1 years. RESULTS: Apolipoprotein B and non-HDL cholesterol levels showed a strong association with the development of Type 2 diabetes compared with conventional lipid measurements and their ratios [hazard ratio per 1 sd; 1.39 (95% CI 1.37-1.42) and 1.38 (95% CI 1.35-1.40), respectively; both P < 0.001]. The Kaplan-Meier survival curve demonstrated that Type 2 diabetes developed more frequently as apolipoprotein B or non-HDL cholesterol levels increased across quartiles (both P < 0.001). In multivariate Cox regression analyses, both apolipoprotein B and non-HDL cholesterol were associated with the development of Type 2 diabetes, independent of other risk factor including age, sex, waist circumference, family history of diabetes, fasting serum glucose and insulin levels, HbA1c , systolic blood pressure and other conventional lipid measurements [hazard ratio per 1 sd; 1.14 (95% CI 1.11-1.18) and 1.13 (95% CI 1.10-1.16), respectively; both P < 0.001]. CONCLUSIONS: Atherogenic dyslipidaemia was more strongly associated with the development of Type 2 diabetes than conventional lipid measurements, and this effect was independent of other well-established risk factor for diabetes.


Assuntos
Apolipoproteínas B/sangue , Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Dislipidemias/sangue , Hemoglobinas Glicadas/metabolismo , Resistência à Insulina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Progressão da Doença , Dislipidemias/complicações , Dislipidemias/fisiopatologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Fatores de Tempo
5.
Diabetes Obes Metab ; 15(3): 284-6, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23061407

RESUMO

No clinical studies on the lipolytic effect of guanine nucleotide-binding protein ß3 subunit gene (GNB3) 825T polymorphism have been performed. This study was a subinvestigation of a 12-week randomized controlled trial (NCT01184560) for the additive effect of orlistat on sibutramine treatment. The analysis involved 101 obese females aged 18-49 years, genotyped at the GNB3 825 locus. To exclude any influence from potential confounders, we used an analysis of covariance model. After the intervention, fat mass proportion in total weight loss was significantly lower in subjects with a T allele than in those without a T allele (p = 0.034). GNB3 825T allele was associated with blunted fat mass reduction in obese females.


Assuntos
Adiposidade/genética , Proteínas de Ligação ao GTP/genética , Proteínas Heterotriméricas de Ligação ao GTP/genética , Obesidade/genética , Redução de Peso/genética , Adiposidade/efeitos dos fármacos , Adulto , Alelos , Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/uso terapêutico , Ciclobutanos/uso terapêutico , Sinergismo Farmacológico , Feminino , Proteínas de Ligação ao GTP/efeitos dos fármacos , Genótipo , Humanos , Lactonas/uso terapêutico , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Orlistate , Polimorfismo Genético , Redução de Peso/efeitos dos fármacos
6.
Diabet Med ; 29(9): 1184-90, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22332964

RESUMO

AIMS: To determine whether there is a relationship between 1,5-anhydroglucitol (1,5-AG), a marker of postprandial hyperglycaemia and glycaemic variability, and the presence of diabetic retinopathy and albuminuria in patients with Type 2 diabetes. METHODS: Five hundred and sixty-seven patients with Type 2 diabetes (serum creatinine < 133 µmol/l), who were enrolled in the Seoul Metro-City Diabetes Prevention Program (SMC-DPP), were cross-sectionally assessed by multivariate logistic regression analysis. RESULTS: After controlling for age, sex, binary HbA(1c) levels, duration of diabetes, triglyceride, systolic blood pressure, smoking status, history of hypertension and dyslipidaemia, and the use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker medication, the odds ratios (95% CI) of diabetic retinopathy were 2.86 (1.12-7.25) for the first (lowest) quartile of 1,5-anhydroglucitol, 2.87 (1.25-6.61) for the second quartile and 0.88 (0.35-2.22) for the third quartile compared with the fourth quartile (P for trend = 0.010). Conversely, the associations between 1,5-anhydroglucitol and clinical albuminuria were non-significant after adjustment. Subjects with low 1,5-anhydroglucitol (< 10.0 µg/ml) were more likely to experience diabetic retinopathy than those with high 1,5-anhydroglucitol (≥ 10.0 µg/ml) under moderate glucose control (HbA(1c) < 8%, 64 mmol/mol) and there were no significant differences in the prevalence of diabetic retinopathy between the subgroup with HbA(1c) < 8% (64 mmol/mol) and low 1,5-anhydroglucitol and the subgroup with HbA(1c) ≥ 8% (64 mmol/mol). CONCLUSIONS: 1,5-Anhydroglucitol levels show close associations with diabetic retinopathy, especially among patients under moderate glucose control, but not with albuminuria. These results suggest that 1,5-anhydroglucitol might be a complementary marker for targeting higher risk group.


Assuntos
Desoxiglucose/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/sangue , Retinopatia Diabética/epidemiologia , Albuminúria/sangue , Albuminúria/epidemiologia , Biomarcadores/sangue , Estudos Transversais , Feminino , Seguimentos , Hemoglobinas Glicadas/metabolismo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia , Fatores de Risco
7.
Diabet Med ; 29(9): 1165-70, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22356423

RESUMO

AIMS: The aim of this study was to investigate whether increased apolipoprotein B/apolipoprotein A-I ratio is associated with Type 2 diabetes mellitus independent of other risk factors for Type 2 diabetes. METHODS: A total of 70,063 subjects (41,391 men and 28,672 women; mean age 41.5 years) who visited the Health Screening Center at Kangbuk Samsung Hospital for a routine medical check-up between January 2009 and December 2009 were enrolled in this study. RESULTS: The mean apolipoprotein B/apolipoprotein A-I ratio in the study subjects was 0.66 ± 0.18. The prevalence of Type 2 diabetes increased across the apolipoprotein B/apolipoprotein A-I ratio quartiles (1.0%, 1.6%, 2.9%, and 4.8% for the 1st through 4th quartiles, respectively, P < 0.001) and homeostasis model assessment-insulin resistance (HOMA2-IR) also showed an increasing tendency by quartile (P < 0.001). The apolipoprotein B/apolipoprotein A-I ratio was correlated with age, adiposity, blood pressure, HOMA2-IR value, fasting glucose levels, and other inflammatory marker, including high-sensitivity C-reactive protein, and lipoprotein (a) levels (all P < 0.001). In a multiple logistic regression model, the highest apolipoprotein B/apolipoprotein A-I ratio quartile was associated with Type 2 diabetes, even after controlling for other risk factors for diabetes, such as age, gender, BMI, systolic blood pressure, HOMA2-IR values, high-sensitivity C-reactive protein levels, family history of diabetes, presence of metabolic syndrome, and conventional lipid parameters (odds ratio 1.31; 95% confidence interval 1.17-1.46, P < 0.001). CONCLUSIONS: The apolipoprotein B/apolipoprotein A-I ratio was found to be associated with Type 2 diabetes independent of other risk factors for diabetes and conventional lipid parameters.


Assuntos
Apolipoproteína A-I/sangue , Apolipoproteínas B/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etnologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Homeostase/fisiologia , Humanos , Técnicas In Vitro , Resistência à Insulina/fisiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
8.
Eur J Vasc Endovasc Surg ; 41(6): 780-5, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21333559

RESUMO

OBJECTIVES: The treatment guidelines for isolated superior mesenteric artery dissection (SMAD) are not well established. The purpose of this study was to report a single-centre series of SMAD and propose treatment guidelines. MATERIALS AND METHODS: Between November 2004 and December 2009, 30 patients were diagnosed with SMAD. We retrospectively reviewed their medical records. RESULTS: The subjects included 26 men and four women, with a mean age of 55.1 years. The chief complaint was abdominal pain in 17 patients, whereas 13 patients were asymptomatic. The mean follow-up was 38.3 months. The radiographic findings included intimal flap with a false lumen in 20 patients and intramural haematoma in 10 patients. The treatments included observation in 18 patients, anticoagulation in five patients, stenting in six patients and surgery in one patient. During follow-up (mean 15.6 months), there was no change in the computed tomography scans of seven patients, improvement was observed in four patients and complete resolution was observed in four patients. All patients, including the symptomatic patients, remained asymptomatic during follow-up. CONCLUSIONS: Most patients with SMAD can be successfully managed with conservative treatment. Surgical treatment or percutaneous intervention can be reserved for patients with severe mesenteric ischaemia and those for whom the initial conservative treatment fails.


Assuntos
Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/terapia , Artéria Mesentérica Superior , Adulto , Idoso , Dissecção Aórtica/complicações , Anticoagulantes/uso terapêutico , Estudos de Coortes , Procedimentos Endovasculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
Gut ; 58(10): 1419-25, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19505882

RESUMO

OBJECTIVES: We performed a prospective study to determine whether weight gain predicts future ultrasonographically detected fatty liver (USFL) in a lean adult population. METHODS: Among 15,347 Korean male workers, aged 30-59 years, who participated in a health check-up programme in 2002, a USFL-free cohort of 4246 non-diabetic men was followed until September 2007. Alcohol consumption was assessed by a questionnaire. Weight change for each subject was calculated as the difference between baseline and subsequent measurements. Biochemical tests for liver and metabolic function were done. The primary outcome was ultrasound-diagnosed fatty liver. A standard Cox proportional hazards model and time-dependent Cox model were performed. RESULTS: During 16,829.7 person-years of follow-up, 622 participants developed USFL. After adjusting for age, the period from visit 1 to visit 2, BMI, HDL-C, triglyceride, uric acid, alanine aminotransferase, and HOMA-IR, the risk for USFL increased with increasing quartiles of weight change (p for trend <0.001). This association remained significant when weight change and covariates, except age and the period from visit 1 to visit 2, were modelled as time-dependent variables. Subjects in the fourth quartile (weight gain > or =2.3 kg) were at significantly elevated risk for USFL (adjusted hazard ratio (aHR), 1.26; 95% CI, 1.01 to 1.58). These associations did not change, even in normal weight men with a baseline BMI between 18.5 and 22.9 kg/m(2) (n = 2186). CONCLUSION: Weight gain per se appears to increase the risk for developing USFL. Thus, avoiding weight gain, even among lean adult individuals, can be helpful in preventing this disease.


Assuntos
Fígado Gorduroso/diagnóstico por imagem , Aumento de Peso/fisiologia , Adulto , Análise de Variância , Fígado Gorduroso/prevenção & controle , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Valores de Referência , Fatores de Risco , Ultrassonografia
10.
J Nanosci Nanotechnol ; 7(11): 3949-53, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18047094

RESUMO

LiFePO4 nanoparticles were synthesized in various polyol mediums without any further heating. The LiFePO4 samples synthesized in polyol mediums exhibited average sizes of 20, 20, 50, and 50 nm with orthorhombic-like shapes. The XRD patterns were indexed on the basis of an olivine structure (space group : Pnma) except for the sample prepared in EG polyol medium. The LiFePO4 samples prepared in EG, DEG, TEG, and TrEG polyol mediums show the reversible capacity of 120 mA h/g, 144 mA h/g, 159 mA h/g, and 167 mA h/g at current density of 0.1 mA/cm2 with no capacity fading and excellent cycle retentions during extended cycles. Especially, the samples showed the excellent performances at high rate of 30 C and 60 C with high capacity retention. It is a speculation that nanometer size materials (approximately 50 nm) and a uniform size-distribution with highly crystallined phase may affect the excellent performances at high rate current densities.


Assuntos
Cristalização/métodos , Eletroquímica/métodos , Compostos de Ferro/química , Compostos de Magnésio/química , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Nanotecnologia/métodos , Fosfatos/química , Silicatos/química , Impedância Elétrica , Fontes de Energia Elétrica , Eletroquímica/instrumentação , Substâncias Macromoleculares/química , Teste de Materiais , Conformação Molecular , Tamanho da Partícula , Propriedades de Superfície
12.
FEBS Lett ; 508(2): 277-81, 2001 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-11718730

RESUMO

Phospholipase D (PLD) has been associated with necrosis. However, it is not clear whether PLD plays a causative role in this cellular process. We investigated the role of PLD in oxidative stress-induced necrosis of vascular smooth muscle cells (VSMCs). Pervanadate (hydrogen peroxide plus orthovanadate) but not hydrogen peroxide alone activated PLD in a dose- and time-dependent manner. Exposure of VSMCs to pervanadate resulted in necrosis. Pretreatment with butan-1-ol, a PLD inhibitor, attenuated both pervanadate-induced necrosis and increase of intracellular Ca(2+). Removal of extracellular Ca(2+) inhibited pervanadate-induced necrosis by 50%. These results suggest that PLD activation mediates pervanadate-induced necrosis of VSMCs, which is at least partly due to Ca(2+) toxicity.


Assuntos
Músculo Liso Vascular/citologia , Músculo Liso Vascular/enzimologia , Estresse Oxidativo , Fosfolipase D/metabolismo , Animais , Aorta/citologia , Butanóis/farmacologia , Cálcio/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Citometria de Fluxo , Peróxido de Hidrogênio/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Necrose , Estresse Oxidativo/efeitos dos fármacos , Ratos , Fatores de Tempo , Vanadatos/farmacologia
13.
Protein Sci ; 9(8): 1497-502, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10975571

RESUMO

The native form of some proteins such as strained plasma serpins (serine protease inhibitors) and the spring-loaded viral membrane fusion proteins are in a metastable state. The metastable native form is thought to be a folding intermediate in which conversion into the most stable state is blocked by a very high kinetic barrier. In an effort to understand how the spontaneous conversion of the metastable native form into the most stable state is prevented, we designed mutations of alpha1-antitrypsin, a prototype serpin, which can bypass the folding barrier. Extending the reactive center loop of alpha1-antitrypsin converts the molecule into a more stable state. Remarkably, a 30-residue loop extension allows conversion into an extremely stable state, which is comparable to the relaxed cleaved form. Biochemical data strongly suggest that the strain release is due to the insertion of the reactive center loop into the major beta-sheet, A sheet, as in the known stable conformations of serpins. Our results clearly show that extending the reactive center loop is sufficient to bypass the folding barrier of alpha1-antitrypsin and suggest that the constrain held by polypeptide connection prevents the conversion of the native form into the lowest energy state.


Assuntos
Dobramento de Proteína , Inibidores de Serino Proteinase/química , Serpinas/química , Sítios de Ligação , Dicroísmo Circular , Cristalografia por Raios X , Escherichia coli/enzimologia , Guanidinas/farmacologia , Concentração de Íons de Hidrogênio , Cinética , Modelos Moleculares , Mutagênese , Conformação Proteica , Estrutura Secundária de Proteína , Inibidores de Serino Proteinase/metabolismo , Serpinas/metabolismo
14.
Gen Pharmacol ; 35(6): 341-7, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11922965

RESUMO

This study was designed to determine whether the relaxant effect of apigenin was endothelium dependent and to examine the possible antiproliferative effect of apigenin. Apigenin relaxed the phenylephrine-precontracted endothelium-intact aortic rings with IC(50) value of 3.7+/-0.5 microM and removal of a functional endothelium significantly attenuated this relaxation (IC(50)=8.2+/-0.9 microM). However, apigenin did not affect the 0.1 microM phorbol 12,13-dibutyrate-induced contraction (IC(50)=34.6+/-1.2 microM) within the concentration range that relaxed the phenylephrine-contracted arteries, suggesting that apigenin did not influence protein kinase C-mediated contractile mechanisms in rat aorta. Pretreatment of apigenin significantly potentiated the relaxant effect of acetylcholine on phenylephrine-induced contraction. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) or methylene blue reduced the relaxant effect of apigenin. Apigenin (10 microM) increased the guanosine 3',5'-cyclic monophosphate (cGMP) content of endothelium-intact tissues. Pretreatment with L-NAME (100 microM) or removal of endothelium significantly suppressed the effect of apigenin on cGMP production. In addition, apigenin significantly inhibited [3H]thymidine incorporation into DNA of primary cultured rat aortic smooth muscle cell in a dose-dependent manner. These findings suggest that besides influx and release of Ca(2+), nitric oxide (NO) and cGMP may account for the apigenin-induced endothelium-dependent relaxation and hypotensive activity. Both vasorelaxant and antiproliferative activities may contribute to a benefit of apigenin in the vascular system.


Assuntos
Endotélio Vascular/fisiologia , Flavonoides/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Animais , Aorta Torácica/citologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Apigenina , Divisão Celular/efeitos dos fármacos , Células Cultivadas , GMP Cíclico/metabolismo , Endotélio Vascular/citologia , Contração Isométrica/efeitos dos fármacos , Masculino , Azul de Metileno/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Dibutirato de 12,13-Forbol/farmacologia , Ratos , Ratos Sprague-Dawley , Timidina/metabolismo
15.
Mol Biol Cell ; 10(4): 1093-104, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10198059

RESUMO

Enhanced activity of receptor tyrosine kinases such as the PDGF beta-receptor and EGF receptor has been implicated as a contributing factor in the development of malignant and nonmalignant proliferative diseases such as cancer and atherosclerosis. Several epidemiological studies suggest that green tea may prevent the development of cancer and atherosclerosis. One of the major constituents of green tea is the polyphenol epigallocathechin-3 gallate (EGCG). In an attempt to offer a possible explanation for the anti-cancer and anti-atherosclerotic activity of EGCG, we examined the effect of EGCG on the PDGF-BB-, EGF-, angiotensin II-, and FCS-induced activation of the 44 kDa and 42 kDa mitogen-activated protein (MAP) kinase isoforms (p44(mapk)/p42(mapk)) in cultured vascular smooth muscle cells (VSMCs) from rat aorta. VSMCs were treated with EGCG (1-100 microM) for 24 h and stimulated with the above mentioned agonists for different time periods. Stimulation of the p44(mapk)/p42(mapk) was detected by the enhanced Western blotting method using phospho-specific MAP kinase antibodies that recognized the Tyr204-phosphorylated (active) isoforms. Treatment of VSMCs with 10 and 50 microM EGCG resulted in an 80% and a complete inhibition of the PDGF-BB-induced activation of MAP kinase isoforms, respectively. In striking contrast, EGCG (1-100 microM) did not influence MAP kinase activation by EGF, angiotensin II, and FCS. Similarly, the maximal effect of PDGF-BB on the c-fos and egr-1 mRNA expression as well as on intracellular free Ca2+ concentration was completely inhibited in EGCG-treated VSMCs, whereas the effect of EGF was not affected. Quantification of the immunoprecipitated tyrosine-phosphorylated PDGF-Rbeta, phosphatidylinositol 3'-kinase, and phospholipase C-gamma1 by the enhanced Western blotting method revealed that EGCG treatment effectively inhibits tyrosine phosphorylation of these kinases in VSMCs. Furthermore, we show that spheroid formation of human glioblastoma cells (A172) and colony formation of sis-transfected NIH 3T3 cells in semisolid agar are completely inhibited by 20-50 microM EGCG. Our findings demonstrate that EGCG is a selective inhibitor of the tyrosine phosphorylation of PDGF-Rbeta and its downstream signaling pathway. The present findings may partly explain the anti-cancer and anti-atherosclerotic activity of green tea.


Assuntos
Antineoplásicos/farmacologia , Catequina/análogos & derivados , Proteínas Quinases Ativadas por Mitógeno , Músculo Liso Vascular/fisiologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Proteínas Oncogênicas de Retroviridae/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células 3T3 , Animais , Aorta , Becaplermina , Neoplasias Encefálicas , Cálcio/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Catequina/farmacologia , Transformação Celular Neoplásica , Células Cultivadas , Glioblastoma , Humanos , Cinética , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno , Músculo Liso Vascular/citologia , Músculo Liso Vascular/efeitos dos fármacos , Proteínas Oncogênicas v-sis , Fosforilação , Fosfotirosina/metabolismo , Proteínas Proto-Oncogênicas c-sis , Ratos , Ratos Endogâmicos WKY , Proteínas Recombinantes/metabolismo , Proteínas Oncogênicas de Retroviridae/genética , Transdução de Sinais/fisiologia , Chá , Transfecção , Células Tumorais Cultivadas
16.
J Ethnopharmacol ; 58(2): 117-23, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9406900

RESUMO

Comparative studies of the effects of tetrandrine (TET) and fangchinoline (FAN), two major components of the Radix of Stephannia tetrandrae, on vasodilations and on calcium movement in vascular smooth muscle, and studies of hypotensive effects on stroke-prone spontaneously hypertensive rats (SHRSP) were performed in the following experiments. TET and FAN inhibited high K+ (65.4 mM) and induced sustained contraction in the rat aorta smooth muscle strips. IC50 values for TET and FAN were 0.27 +/- 0.05 microM (n = 6) and 9.53 +/- 1.57 microM (n = 6), respectively, and this inhibition was antagonized by increasing the Ca2+ concentration in the medium. The IC50 of TET for norepinephrine (NE)-induced contraction (0.86 +/- 0.04 g) was 3.08 +/- 0.05 microM (n = 4), and the IC50 of FAN for NE-induced contraction (0.88 +/- 0.07 g) was 14.20 +/- 0.40 microM (n = 4). At the molecular level, radiolabelled 45Ca2+ uptake tests revealed that TET and FAN also inhibited high K+ (65.4 mM) and 1 microM NE-stimulated Ca2+ influx in rat aorta strips at the maximal concentration was needed to inhibit the contraction. TET (3 mg/kg) and FAN (30 mg/kg) administered by intravenous (i.v.) bolus injection also lowered the mean arterial pressure (MAP) significantly during the period of observation in conscious SHRSP, respectively. These results showed that TET was more potent than FAN in blocking calcium channels and antihypertensive activity.


Assuntos
Alcaloides/farmacologia , Benzilisoquinolinas , Bloqueadores dos Canais de Cálcio/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Animais , Aorta/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Norepinefrina/antagonistas & inibidores , Potássio/antagonistas & inibidores , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley
17.
Life Sci ; 60(25): 2333-40, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9194689

RESUMO

This study was designed to test the hypothesis that 8-Br-cAMP and 8-Br-cGMP dependent relaxation of phorbol dibutyrate stimulated contractions of intact rat aorta are independent of changes in the level of myosin light chain phosphorylation. Phorbol dibutyrate stimulated contraction with a concomitant increase in myosin light chain phosphorylation in normal tissues and without an increase in myosin light chain phosphorylation in calcium-depleted tissues. Phorbol dibutyrate stimulated contractions in normal CaCl2-containing physiological salt solution were relaxed in a concentration-dependent manner by 8-Br-cAMP and 8-Br-cGMP. Phorbol dibutyrate-induced contractions in the absence of Ca2+ were only relaxed by 8-Br-cGMP; 8-Br-cAMP had no effect. The relaxation induced by 8-Br-cGMP was associated with a decrease in myosin light chain phosphorylation suggesting that cGMP-dependent protein kinase may alter the activity of either the myosin light chain kinase or phosphatase. The relaxation induced by 8-Br-cAMP was not associated with a decrease in phosphorylation suggesting that cAMP-dependent protein kinase may uncouple myosin light chain phosphorylation from force.


Assuntos
8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Aorta Torácica/efeitos dos fármacos , GMP Cíclico/análogos & derivados , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Dibutirato de 12,13-Forbol/farmacologia , Animais , Aorta Torácica/fisiologia , AMP Cíclico/fisiologia , GMP Cíclico/farmacologia , GMP Cíclico/fisiologia , Técnicas In Vitro , Masculino , Músculo Liso Vascular/fisiologia , Cadeias Leves de Miosina/metabolismo , Fosforilação , Proteína Quinase C/fisiologia , Ratos , Ratos Sprague-Dawley , Estimulação Química
19.
Can J Physiol Pharmacol ; 72(11): 1420-6, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7767888

RESUMO

Agonist activation enhances smooth muscle myofilament Ca2+ sensitivity. The increased force accompanying receptor stimulation (over Ca2+ alone) requires GTP and is reversed by GDP beta S, demonstrating a G-protein dependence. Protein kinase C (PKC) activators, such as phorbol esters, mimic and PKC inhibitors block the agonist-induced increase in Ca2+ sensitivity, suggesting a role for PKC in the regulation of Ca2+ sensitivity. Myosin light chain (MLC) phosphorylation levels are transiently increased by agonist stimulation, but steady-state levels of MLC phosphorylation are similar to those in response to Ca2+ alone. Thus, G-protein-mediated inhibition of MLC phosphatase may account for the initial increase in force development but not the increase in steady-state force. In contrast to MLC, calponin phosphorylation levels are maintained during agonist stimulation of intact vascular smooth muscle. We propose that stimulation of smooth muscle by membrane depolarization increases MLC phosphorylation, but as a result of inhibition by unphosphorylated calponin only a portion of the phosphorylated cross bridges attach to actin. Agonist stimulation produces the same steady-state level of MLC phosphorylation but also leads to calponin phosphorylation via a PKC-dependent pathway. Thus, during agonist stimulation, all phosphorylated cross bridges can interact with actin, thereby generating significantly greater levels of force.


Assuntos
Citoesqueleto de Actina/metabolismo , Cálcio/fisiologia , Proteínas de Ligação ao GTP/metabolismo , Músculo Liso Vascular/metabolismo , Receptores de Superfície Celular/metabolismo , Citoesqueleto de Actina/fisiologia , Animais , Humanos , Músculo Liso Vascular/fisiologia
20.
J Chromatogr B Biomed Appl ; 653(2): 163-9, 1994 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-8205243

RESUMO

In this study, an indirect diastereomeric method and a direct method utilizing a chiral stationary phase (CSP) were investigated for the resolution of ibuprofen enantiomers. In the indirect method, ethylchloroformate (ECF) and 2-ethoxy-1-1-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) were utilized as first-step derivatizing reagents in acetonitrile or toluene. In the direct CSP method, ibuprofen enantiomers were derivatized to p-nitrobenzyl ureides and then resolved on an (R)-(-)-(1-naphthyl)ethylurea CSP column. The derivatization procedure took place in 10 min with an overall inversion efficiency of 90.3%. Racemization was not observed under the derivatization conditions used. The HPLC-CSP method was utilized to study the pharmacokinetics of ibuprofen enantiomers in dog plasma after a single oral administration of 200 mg of ibuprofen racemate.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ibuprofeno/isolamento & purificação , Animais , Cães , Ésteres do Ácido Fórmico , Ibuprofeno/química , Ibuprofeno/farmacocinética , Indicadores e Reagentes , Quinolinas , Estereoisomerismo
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