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1.
J Hum Hypertens ; 28(2): 85-91, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24048294

RESUMO

We examined the contribution of arterial wave reflection to early abnormalities in left ventricular relaxation, whether this association was modified by gender or hypertension and the role of reflected wave timing and amplitude. We studied a cohort of normotensive and untreated essential hypertensive Taiwanese participants (675 men, 601 women, mean age 52 years). Doppler flow and applanation tonometry were performed to assess carotid-femoral pulse wave velocity (PWV) and augmentation index (AI). Diastolic parameters including the ratio between the peak velocity of early and late diastolic mitral inflow (E/A), E-deceleration time and left atrial (LA) diameter were measured by echocardiography. In multivariate models predicting E/A, women were more likely to have lower E/A than men (ß=-0.08, P<0.001). AI was significantly associated with lower E/A in both men (ß=-0.09, P=0.005) and women (ß=-0.12, P<0.001) independent of PWV. Inclusion of AI in the overall model reduced the gender difference in E/A by 61% and rendered it nonsignificant. There was a significant interaction between AI and hypertension (P=0.02). The inverse association between AI and E/A was significant only in normotensive men and women, and only for the amplitude but not timing of the reflected wave. In conclusion, the contribution of wave reflection to left ventricular diastolic dysfunction was independent of arterial stiffness, more pronounced in normotensive individuals and explained a significant portion of the gender difference in diastolic function.


Assuntos
Pressão Sanguínea , Hipertensão/complicações , Hipertensão/fisiopatologia , Rigidez Vascular , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Adulto , Idoso , Distribuição de Qui-Quadrado , Estudos Transversais , Diástole , Feminino , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Análise de Onda de Pulso , Fatores de Risco , Fatores Sexuais , Volume Sistólico , Taiwan , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia
2.
Nutr Metab Cardiovasc Dis ; 23(12): 1263-70, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23809149

RESUMO

BACKGROUND AND AIMS: It is unclear whether subcutaneous and visceral fat are differentially correlated to the decline in left ventricular (LV) diastolic function with aging. This study sought to examine the hypothesis that age-related changes in the regional fat distribution account for changes in LV diastolic function and to explore potential mediators of this association. METHODS AND RESULTS: In this cross-sectional study, we evaluated 843 participants of the Baltimore Longitudinal Study of Aging with echocardiogram, dual-energy X-ray absorptiometry (DEXA), abdominal computed tomography (CT) and blood tests performed at the same visit. LV diastolic function was assessed by parameters of LV relaxation (E/A ratio, Em and Em/Am ratio) and LV filling pressures (E/Em ratio). Total body fat was computed by DEXA, while visceral and subcutaneous fat were determined from abdominal CT. In multivariate models adjusted for demographics, cardiovascular risk factors, antihypertensive medications, physical activity and LV mass, both visceral and subcutaneous fat were associated with LV diastolic dysfunction. When both measures of adiposity were simultaneously included in the same model, only visceral fat was significantly associated with LV diastolic dysfunction. Triglycerides and sex-hormone binding globulin, but not adiponectin and leptin, were found to be significant mediators of the relationship between visceral fat and LV diastolic function, explaining 28-47% of the association. Bootstrapping analyses confirmed the significance of these findings. CONCLUSIONS: Increased visceral adiposity is associated with LV diastolic dysfunction, possibly through a metabolic pathway involving blood lipids and ectopic fat accumulation rather than adipokines.


Assuntos
Adiposidade , Envelhecimento , Gordura Intra-Abdominal/fisiologia , Função Ventricular Esquerda/fisiologia , Absorciometria de Fóton , Adiponectina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Baltimore , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Leptina/sangue , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gordura Subcutânea/fisiologia , Triglicerídeos/sangue
3.
Artigo em Inglês | MEDLINE | ID: mdl-23872161

RESUMO

Due to the lack of sensitivity in current methods for the determination of fenoterol (Fen), a rapid LC-MS/MS method was developed for the determination of (R,R')-Fen and (R,R';S,S')-Fen in plasma and urine. The method was fully validated and was linear from 50pg/ml to 2000pg/ml for plasma and from 2.500ng/ml to 160ng/ml for urine with a lower limit of quantitation of 52.8pg/ml in plasma. The coefficient of variation was <15% for the high QC standards and <10% for the low QC standards in plasma and was <15% for the high and low QC standards in urine. The relative concentrations of (R,R')-Fen and (S,S')-Fen were determined using a chirobiotic T chiral stationary phase. The method was used to determine the concentration of (R,R')-Fen in plasma and urine samples obtained in an oral cross-over study of (R,R')-Fen and (R,R';S,S')-Fen formulations. The results demonstrated a potential pre-systemic enantioselective interaction in which the (S,S')-Fen reduces the sulfation of the active (R,R')-Fen. The data suggest that a non-racemic mixture of the Fen enantiomers may provide better bioavailability of the active (R,R')-Fen for use in the treatment of cardiovascular disease.


Assuntos
Agonistas Adrenérgicos/sangue , Agonistas Adrenérgicos/urina , Cromatografia Líquida de Alta Pressão/métodos , Fenoterol/sangue , Fenoterol/urina , Espectrometria de Massas em Tandem/métodos , Agonistas Adrenérgicos/química , Fenoterol/química , Humanos , Sensibilidade e Especificidade , Estereoisomerismo
4.
J Intern Med ; 273(3): 253-62, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23061475

RESUMO

OBJECTIVES: The effects of vitamin D on the heart have been studied in patients with cardiac disease, but not in healthy persons. We investigated the relation between vitamin D status and left ventricular (LV) structure and function in community-dwelling subjects without heart disease. DESIGN: The relationship between concentrations of 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D reserve, and LV transthoracic echocardiography measures was analysed in 711 participants in the Baltimore Longitudinal Study of Aging who were without cardiac disease. RESULTS: Mean 25(OH)D in the study population was 32.3 ± 11.4 ng mL(-1) ; only 15.5% of subjects had moderate or severe vitamin D deficiency [25(OH)D < 20 ng mL(-1) ]. Adjusting for age, body mass index, cardiovascular disease risk factors, physical activity, calcium and parathyroid hormone, 25(OH)D was positively correlated with LV thickness (ß 0.095, SE 0.039, P < 0.05) and LV mass index (ß 7.5, SE 2.6, P < 0.01). A significant nonlinear relation between 25(OH)D and LV concentric remodelling was observed. LV remodelling was more likely in participants with 25(OH)D levels <30 ng mL(-1) [odds ratio (OR) 1.24; 95% confidence interval (CI) 0.83-1.85] or ≥38 ng mL(-1) (OR 1.73; 95% CI 1.13-2.65), compared with those with 30-37 ng mL(-1) 25(OH)D. Consistently, LV relative wall thickness was significantly lower (P for trend=0.05), and LV diastolic internal diameter index (P for trend<0.05) and end-diastolic volume index (P for trend<0.05) were significantly higher in subjects with 30-37 ng mL(-1) 25(OH)D compared to the rest of the study population. There was a significant interaction between 25(OH)D and hypertension on the risk of LV hypertrophy (P < 0.05). CONCLUSIONS: In a population-based sample of predominantly vitamin D-sufficient subjects without heart disease, LV geometry was most favourable at intermediate 25(OH)D concentrations.


Assuntos
Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia , Vitamina D/análogos & derivados , Vitaminas/sangue , Idoso , Envelhecimento/fisiologia , Baltimore , Índice de Massa Corporal , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertrofia Ventricular Esquerda , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Ultrassonografia , Vitamina D/sangue
6.
Nutr Metab Cardiovasc Dis ; 19(8): 532-41, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19321325

RESUMO

AIM: We investigated the gender-specific control of cardiovascular (CV) risk factors and subclinical vascular lesions in a founder population in Italy. METHODS AND RESULTS: 6148 subjects were enrolled (aged 14-102 years) from four towns. Hypertension (HT), diabetes mellitus (DM) and dyslipidemia (LIP) were defined in accordance with guidelines. A self-reported diagnosis defined awareness of these conditions, and the current use of specific medications as treatment. Prevalence was HT 29.2%, DM 4.8%, LIP 44.1% and was higher in men than in women. Disease prevalence increased with age for every CV risk factor. Men were less likely than women to take anti-HT drugs and to reach BP control (9.9% vs. 16%). Only 17.6% of HT > 65 years had a BP < or =140/90 mmHg, though 48.5% were treated. The use of statins was very low (<1/3 of eligible subjects > 65 years, those with the highest treatment rate). The ratio of control-to-treated HT was lower in subjects with, than in those without, thicker carotid arteries (31.5% vs. 38.8%, p < 0.05) or stiffer aortas (26.0% vs. 40.0%, p < 0.05) or carotid plaques (26.3% vs. 41.1%, p<0.05). CONCLUSION: A large number of subjects at high CV risk are not treated and the management of subclinical vascular lesions is far from optimal.


Assuntos
Conscientização , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Hipertensão/tratamento farmacológico , Síndrome Metabólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Aterosclerose/complicações , Aterosclerose/tratamento farmacológico , Aterosclerose/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/epidemiologia , Uso de Medicamentos , Dislipidemias/complicações , Dislipidemias/epidemiologia , Feminino , Efeito Fundador , Fidelidade a Diretrizes , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipertensão/complicações , Hipertensão/epidemiologia , Hipoglicemiantes/uso terapêutico , Itália/epidemiologia , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Prevalência , Medição de Risco , Fatores de Risco , Fatores Sexuais , Adulto Jovem
7.
Am J Physiol Heart Circ Physiol ; 280(2): H756-66, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11158975

RESUMO

Using adenovirus (Adv)-mediated overexpression of constitutively active (ca) and dominant-negative (dn) mutants, we examined whether protein kinase C (PKC)-epsilon, the major novel PKC isoenzyme expressed in the adult heart, was necessary and/or sufficient to induce specific aspects of the hypertrophic phenotype in low-density, neonatal rat ventricular myocytes (NRVM) in serum-free culture. Adv-caPKC-epsilon did not increase cell surface area or the total protein-to-DNA ratio. However, cell shape was markedly affected, as evidenced by a 67% increase in the cell length-to-width ratio and a 17% increase in the perimeter-to-area ratio. Adv-caPKC-epsilon also increased atrial natriuretic factor (ANF) and beta-myosin heavy chain (MHC) mRNA levels 2.5 +/- 0.3- and 2.1 +/- 0.2-fold, respectively, compared with NRVM infected with an empty, parent vector (P < 0.05 for both). Conversely, Adv-dnPKC-epsilon did not block endothelin-induced increases in cell surface area, the total protein-to-DNA ratio, or upregulation of beta-MHC and ANF gene expression. However, the dominant-negative inhibitor markedly suppressed endothelin-induced extracellular signal-regulated kinase (ERK) 1/2 activation. Taken together, these results indicate that caPKC-epsilon overexpression alters cell geometry, producing cellular elongation and remodeling without a significant, overall increase in cell surface area or total protein accumulation. Furthermore, PKC-epsilon activation and downstream signaling via the ERK cascade may not be necessary for cell growth, protein accumulation, and gene expression changes induced by endothelin.


Assuntos
Isoenzimas/metabolismo , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/enzimologia , Miocárdio/citologia , Miocárdio/enzimologia , Proteína Quinase C/metabolismo , Adenoviridae/genética , Sequência de Aminoácidos , Animais , Fator Natriurético Atrial/genética , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Tamanho Celular/fisiologia , Células Cultivadas , Endotelina-1/metabolismo , Regulação Enzimológica da Expressão Gênica , Ventrículos do Coração/citologia , Ventrículos do Coração/enzimologia , Isoenzimas/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Dados de Sequência Molecular , Mutagênese/fisiologia , Cadeias Pesadas de Miosina/metabolismo , Proteína Quinase C/genética , Proteína Quinase C-épsilon , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley
8.
J Mol Cell Cardiol ; 32(8): 1553-66, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10900180

RESUMO

Previous studies from our laboratory and others indicate that contraction-induced mechanical loading of cultured neonatal rat ventricular myocytes produces many of the phenotypic changes associated with cardiomyocyte hypertrophy in vivo, and that these changes occur via the activation of serine-threonine protein kinases. These may include the extracellular regulated protein kinases (ERK1 and ERK2), the c-Jun N-terminal kinases (JNK1, JNK2, and JNK3), and one or more isoenzymes of protein kinase C. In this study, we assessed whether one or more of these kinases are activated by stimulated contraction, and whether activation was isoenzyme-specific. Low-density, quiescent cultures of neonatal rat ventricular myocytes were maintained in serum-free medium, or electrically stimulated to contract (3 Hz) for up to 48 h. ERK and JNK activation was assessed by Western blotting with polyclonal antibodies specific for the phosphorylated forms of both kinases. PKC activation was analysed by subcellular fractionation, detergent extraction, and Western blotting using isoenzyme-specific monoclonal antibodies. Stimulated contractile activity produced myocyte hypertrophy, as indicated by increased cell size, a 15+/-5% increase in total protein/DNA ratio, and induction of ANF and beta MHC gene transcription. Electrical pacing did not cause ERK1/2 or JNK1 activation, but increased JNK2 and JNK3 phosphorylation by;two-fold. Subcellular fractionation revealed a time-dependent increase in PKC delta, and to a much lesser extent PKC xi, in a Triton X-100-soluble membrane fraction within 5 min of the onset of stimulated contraction. PKC alpha was not activated by electrical pacing. These results indicate that contraction-induced mechanical loading acutely activates some but not all of the specific isoenzymes of JNKs and PKCs in cardiomyocytes.


Assuntos
Ventrículos do Coração/metabolismo , Isoenzimas/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteína Quinase C/metabolismo , Animais , Animais Recém-Nascidos , Fator Natriurético Atrial/genética , Western Blotting , Cardiomegalia , Células Cultivadas , Meios de Cultura Livres de Soro , Estimulação Elétrica , Eletroforese em Gel de Poliacrilamida , Eletrofisiologia , Ativação Enzimática , Proteínas Quinases JNK Ativadas por Mitógeno , Sistema de Sinalização das MAP Quinases , Proteína Quinase 10 Ativada por Mitógeno , Proteína Quinase 9 Ativada por Mitógeno , Cadeias Pesadas de Miosina/genética , Regiões Promotoras Genéticas , Proteínas Tirosina Quinases/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Frações Subcelulares , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Tempo , Transfecção
9.
Am J Physiol Heart Circ Physiol ; 278(5): H1695-707, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10775151

RESUMO

Endothelin-1 (ET) produces neonatal rat ventricular myocyte (NRVM) hypertrophy and activates focal adhesion kinase (FAK) in other cell types. In the present study, we examined whether ET activated FAK in NRVM and whether FAK was necessary and/or sufficient for ET-induced NRVM hypertrophy. Chronic ET-1 stimulation (100 nM, 48 h) increased protein-to-DNA and myosin heavy chain (MHC)-to-DNA ratios and stimulated the assembly of newly synthesized MHC into sarcomeres. ET-1 also induced the assembly of focal adhesions and costameres, as evidenced by increased phosphotyrosine, FAK, and paxillin immunostaining. Acutely, ET treatment rapidly increased tyrosine phosphorylation of FAK and paxillin. FAK was also activated by phorbol 12-myristate 13-acetate (2 microM, 5 min). Pretreatment with chelerythrine (5 microM) or rottlerin (10 microM) completely blocked ET-induced FAK phosphorylation, indicating that protein kinase C activation was upstream of ET-induced FAK activation. In contrast, ET-induced FAK activation was not affected by blocking calcium influx via L-type voltage-gated calcium channels. Adenoviruses (Adv) containing FAK and FAK-related nonkinase (FRNK) were used to specifically define the role of FAK in ET-induced hypertrophy. ET stimulation failed to increase total protein-to-DNA or MHC-to-DNA ratios or to stimulate sarcomeric assembly in myocytes infected with Adv-FRNK. However, Adv-FAK alone did not increase total protein-to-DNA or MHC-to-DNA ratios and failed to increase the number or size of myofibrils as evidenced by double immunofluorescence labeling for MHC and FAK. Thus, although FAK is necessary for ET-induced NRVM hypertrophy, other ET-generated signals are also required to elicit the hypertrophic phenotype.


Assuntos
Cardiomegalia/induzido quimicamente , Cardiomegalia/enzimologia , Endotelinas , Coração/efeitos dos fármacos , Miocárdio/enzimologia , Proteínas Tirosina Quinases/metabolismo , Adenoviridae/genética , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Cardiomegalia/patologia , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Proteínas do Citoesqueleto/metabolismo , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Quinase 1 de Adesão Focal , Proteína-Tirosina Quinases de Adesão Focal , Miocárdio/química , Miocárdio/citologia , Cadeias Pesadas de Miosina/análise , Paxilina , Fosfoproteínas/metabolismo , Fosforilação , Proteína Quinase C/antagonistas & inibidores , Proteínas Tirosina Quinases/genética , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Acetato de Tetradecanoilforbol/farmacologia , Transfecção , Tirosina/metabolismo
11.
J Toxicol Environ Health ; 36(4): 411-23, 1992 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1507271

RESUMO

Carbaryl, a carbamate insecticide, exerts its toxic effect in animals by inhibiting the activity of neural acetylcholinesterase. Differences in sensitivity of this enzyme to inhibition were studied after intraperitoneal administration to chickens and rats. A dose of 900 mg/kg to chickens and 70 mg/kg to rats caused equivalent inhibition of brain cholinesterase activities (57% +/- 6 and 47% +/- 4, respectively) 60 min after administration, which was the time of maximal cholinergic signs. Signs of toxicity (salivation, respiratory distress, muscle tremors and weakness) were more pronounced in rats than in chickens when brain acetylcholinesterase was inhibited to the same extent in both species. Carboxylesterase activities in brain, liver, and plasma were also inhibited 60 min after administration of carbaryl to chickens and rats. Activities of enzymes associated with hepatic microsomes were unaffected. Specific activities of brain esterases, including acetylcholinesterase, carboxylesterase and neurotoxic esterase, were higher in untreated chickens than in untreated rats. Specific activities of liver esterases (carboxylesterase, A-esterase) were, however, 4- and 10-fold lower in untreated chickens than in untreated rats. Total clearance of carbaryl in the chicken, determined after intravenous administration of 5 mg/kg, was 0.26 +/- 0.02 l/kg/min. This value is 5.7 times higher than that reported for the rat, indicating that the relatively lower activities of esterases in the liver of chickens did not affect the clearance of this chemical in the avian species.


Assuntos
Carbaril/farmacocinética , Animais , Carbaril/toxicidade , Galinhas , Inibidores da Colinesterase/farmacocinética , Inibidores da Colinesterase/toxicidade , Relação Dose-Resposta a Droga , Esterases/antagonistas & inibidores , Feminino , Masculino , Ratos , Ratos Endogâmicos , Especificidade da Espécie
12.
Opt Lett ; 15(4): 209-11, 1990 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-19759759

RESUMO

We present the theory for photorefractive two-beam coupling without optical activity in cubic crystals rotated around the [110] axis. We also describe two-beam coupling experiments in InP:Fe that fit the theory closely. The 15.5% gain enhancement for grating wave vectors aligned along the <111> directions is demonstrated explicitly.

13.
Am J Vet Res ; 48(4): 586-9, 1987 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-3592356

RESUMO

Radioimmunoassay for parathyroid hormone (PTH) in equids was performed on blood samples from healthy equids and equids with hypercalcemia and hypophosphatemia. The assay was validated for equine carboxy-terminal PTH. Manipulation of serum ionized Ca in healthy equids by infusing Na2 EDTA and CaCl2 produced an expected increase and decrease, respectively, in measurable immunoreactive PTH. Intra-assay and interassay coefficients of variation were 2.6% and 11.7%, respectively. The range of PTH valves for healthy mature horse mares and geldings maintained on pasture was less than 0.27 ng/ml to 0.92 ng/ml and for horse colts fed grain was 0.61 to 1.25 ng/ml. Serum PTH values were measured on 2 equine patients with hypercalcemia, 1 pony with primary hyperparathyroidism and 1 horse with pseudohyperparathyroidism. Both patients had increased serum PTH values.


Assuntos
Doenças dos Cavalos/sangue , Cavalos/sangue , Hiperparatireoidismo/veterinária , Hormônio Paratireóideo/sangue , Animais , Feminino , Hipercalcemia/sangue , Hipercalcemia/veterinária , Hiperparatireoidismo/sangue , Masculino , Radioimunoensaio
14.
Appl Opt ; 25(3): 338-9, 1986 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-20445693
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