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1.
J Bacteriol ; 194(3): 553-60, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22123252

RESUMO

Fire blight is a devastating disease of rosaceous plants caused by the Gram-negative bacterium Erwinia amylovora. This pathogen delivers virulence proteins into host cells utilizing the type III secretion system (T3SS). Expression of the T3SS and of translocated and secreted substrates is activated by the alternative sigma factor HrpL, which recognizes hrp box promoters upstream of regulated genes. A collection of hidden Markov model (HMM) profiles was used to identify putative hrp boxes in the genome sequence of Ea273, a highly virulent strain of E. amylovora. Among potential virulence factors preceded by putative hrp boxes, two genes previously known as Eop3 and Eop2 were characterized. The presence of functionally active hrp boxes upstream of these two genes was confirmed by ß-glucuronidase (GUS) assays. Deletion mutants of the latter candidate genes, renamed hopX1(Ea) and hopAK1(Ea), respectively, did not differ in virulence from the wild-type strain when assayed in pear fruit and apple shoots. The hopX1(Ea) deletion mutant of Ea273, complemented with a plasmid overexpressing hopX1(E)(a), suppressed the development of the hypersensitivity response (HR) when inoculated into Nicotiana benthamiana; however, it contributed to HR in Nicotiana tabacum and significantly reduced the progress of disease in apple shoots, suggesting that HopX1(Ea) may act as an avirulence protein in apple shoots.


Assuntos
Proteínas de Bactérias/metabolismo , Erwinia amylovora/metabolismo , Regulação Bacteriana da Expressão Gênica , Malus/microbiologia , Doenças das Plantas/microbiologia , Fator sigma/metabolismo , Proteínas de Bactérias/genética , Erwinia amylovora/genética , Erwinia amylovora/patogenicidade , Dados de Sequência Molecular , Fator sigma/genética , Nicotiana/microbiologia , Virulência
2.
J Bacteriol ; 192(7): 2020-1, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20118253

RESUMO

Erwinia amylovora causes the economically important disease fire blight that affects rosaceous plants, especially pear and apple. Here we report the complete genome sequence and annotation of strain ATCC 49946. The analysis of the sequence and its comparison with sequenced genomes of closely related enterobacteria revealed signs of pathoadaptation to rosaceous hosts.


Assuntos
DNA Bacteriano/química , DNA Bacteriano/genética , Erwinia amylovora/genética , Genoma Bacteriano , Enterobacteriaceae/genética , Evolução Molecular , Dados de Sequência Molecular , Doenças das Plantas/microbiologia , Rosaceae/microbiologia , Análise de Sequência de DNA
3.
Int J Obes (Lond) ; 32(6): 967-74, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18268512

RESUMO

OBJECTIVE: Obesity promotes the development and progression of coronary heart disease (CHD), in part, through its association with hyperlipidemia, hypertension, clotting abnormalities and insulin resistance. We assessed whether these relationships persist in patients with established CHD treated with evidence-based preventive pharmacologic therapies. DESIGN AND SUBJECTS: We performed a cross-sectional study of 74 adults with CHD and a body mass index (BMI) of >27 kg m(-2) (mean 32+/-4). The mean age of subjects was 64+/-9 years (range 44-84 years). MEASUREMENTS: Obesity measures included weight, BMI, waist, fat mass, intra-abdominal fat and subcutaneous fat. Risk factor measures included insulin sensitivity, fasting insulin level, lipid profiles, blood pressure, C-reactive protein (hs-CRP), plasminogen activator inhibitor (PAI-1) and platelet reactivity. Medication use included aspirin (99%), statin (84%), beta-blocker (71%), ACE inhibitor or blocker (37%) and clopidogrel (28%). RESULTS: There was no direct relationship between obesity parameters and risk factor measures of lipid concentrations, blood pressure, clotting abnormalities or platelet reactivity except for a modest relationship between visceral fat and hs-CRP (r=0.30, P=0.02). However, increased BMI, waist circumference, fat mass, total abdominal fat and abdominal subcutaneous fat all correlated with insulin sensitivity (r-values -0.30 to -0.45, P-values 0.01 to <0.001) and insulin concentrations. Insulin sensitivity, in turn, was the best predictor of PAI-1, triglycerides, high-density lipoprotein (HDL) levels, cholesterol/HDL levels (all P<0.01) and platelet reactivity (R=0.34, P=0.02). CONCLUSIONS: Use of preventive pharmacologic therapies obviated the expected relationship between adiposity and CHD risk factors. However, a residual effect of insulin resistance is left untreated. Total adiposity and central adiposity were strong predictors of insulin sensitivity, which in turn predicted cardiac risk factors such as lipid concentrations, PAI-1 and platelet reactivity. Thus, while evidence-based pharmacologic treatments may diminish the statistical relationship between obesity and many cardiac risk factors, adiposity negatively impacts CHD risk by reducing tissue insulin sensitivity.


Assuntos
Doença das Coronárias/etiologia , Resistência à Insulina , Obesidade/complicações , Adiposidade/fisiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Índice de Massa Corporal , Doença das Coronárias/prevenção & controle , Estudos Transversais , Inibidores Enzimáticos/uso terapêutico , Medicina Baseada em Evidências , Feminino , Técnica Clamp de Glucose , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Fatores de Risco
4.
Minerva Pediatr ; 56(1): 1-28, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15249911

RESUMO

Pediatric interventional catheterization is an expanding specialty with a range of mature, emerging, and investigative procedures and technologies. Many dysfunctional obstructions and/or shunts caused by congenital heart defects may be treated or significantly palliated in the catheterization laboratory. These include valvar pulmonary or aortic stenosis, the patent ductus arteriosus, coarctation of the aorta, branch pulmonary stenosis, atrial septal defects and even ventricular septal defects. Valve replacement technology, approaches to complex heart diseases such as single ventricle, and fetal interventions are subjects of active investigations. A comprehensive review of the present and future of interventional pediatric cardiology is presented.


Assuntos
Cardiologia/tendências , Pediatria/tendências , Cateterismo Cardíaco , Procedimentos Cirúrgicos Cardíacos/métodos , Serviço Hospitalar de Cardiologia/tendências , Cateterismo de Swan-Ganz , Criança , Serviços de Saúde da Criança/tendências , Cardiopatias/congênito , Cardiopatias/diagnóstico por imagem , Comunicação Interventricular/cirurgia , Humanos , Radiografia
5.
J Oral Rehabil ; 31(1): 85-9, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15125603

RESUMO

There is current concern about bacterial contamination of dental unit waterlines. This research hypothesized that the presence of increasing concentrations of bacteria in water used to wash etched enamel would result in a corresponding decrease in both shear bond strength (SBS) and critical surface tension (gammaC) of enamel. A further hypothesis was made that there is a correlation between SBS and gammaC. The effect of 3.5 ppm iodine in the water as a bacteriostatic agent was also assessed. Five groups of 10 samples of bovine enamel were etched, washed, and a resin composite bonded to them. The control group was washed with distilled water. Another group was washed with the dilute iodine solution. The remaining three groups used a different concentration of Escherichia coli DH5alpha as follows (in cfu mL(-1)): group 1: 10(2); group 2: 10(4); group 3: 10(6). Shear bond strength data were measured on an Instron testing machine at a crosshead speed of 1 mm min(-1). Adhesion data were (MPa): control: 24.6 +/- 6.0; with iodine: 20.8 +/- 2.7; group 1: 19.8 +/- 2.7; group 2: 13.5 +/- 3.0; group 3: 13.9 +/- 3.6. The F-test yielded a highly significant difference between control group, iodine group and group 1, compared with groups 2 and 3 (P < 0.0001). Tukey's Studentized Range Test was used for pairwise comparison testing between groups. Using a Cahn dynamic contact angle analyzer and linear regression analysis, the plots of surface tension versus costheta were extrapolated to costheta = 1 to give gammaC data for the control group and groups 1-3. In all cases reasonable linearity was observed (r2 > or = 0.87). Data (mN m(-1)) were: control group: 50.8; group 1: 45.1; group 2: 43.2; group 3: 39.5. The SBS and gammaC were then plotted against each other and linear regression analysis performed. It was concluded that increasing concentrations of bacteria in wash water decreased both SBS and gammaC and that a linear correlation (R2 = 0.84) was found between the values of these two parameters.


Assuntos
Condicionamento Ácido do Dente/métodos , Esmalte Dentário/microbiologia , Água , Animais , Bovinos , Resinas Compostas , Colagem Dentária/métodos , Escherichia coli/isolamento & purificação , Iodo/farmacologia , Tensão Superficial , Microbiologia da Água
6.
Acta Diabetol ; 41(1): 25-31, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15057551

RESUMO

Acute coronary syndromes are generally precipitated by rupture of lipid-laden, relatively acellular, vulnerable atherosclerotic plaques with thin fibrous caps. We investigated whether a high-fat diet alters insulin sensitivity and whether insulin sensitizers (troglitazone and rosiglitazone) alter the composition of otherwise lipidladen atherosclerotic plaques in mice deficient in apolipoprotein E (ApoE). ApoE-knockout mice were fed a high-fat (n=30) or standard chow (n=10) diet for two weeks. Thereafter, those fed the high-fat diet were treated with troglitazone (n=10), rosiglitazone (n=10) or no drug (n=10) for 16 weeks beginning at 8 weeks of age. Carbohydrate metabolism was assessed with intraperitoneal glucose tolerance tests and insulin tolerance tests. Plaque composition was characterised with confocal laser scanning microscopy. The high-fat diet induced insulin resistance in the absence of weight gain. Compared with control animals on the high-fat diet, animals given troglitazone (400 mg/kg/day) or rosiglitazone (4 mg/kg/day) had significantly less area under the curve (AUC) for insulin ( p<0.05) and glucose disposal ( p<0.05). Despite significant increases in insulin sensitivity with drug treatment, no change in HDL-cholesterol and triglyceride levels, nor reduction in atheroma size or lipid content was noted. Thus, improvement in insulin resistance induced by a high-fat diet in this animal model of vasculopathy did not alter plaque composition.


Assuntos
Apolipoproteínas E/sangue , Apolipoproteínas E/deficiência , Arteriosclerose/genética , Arteriosclerose/fisiopatologia , Hipoglicemiantes/farmacologia , Lipídeos/sangue , Animais , Arteriosclerose/patologia , Estenose das Carótidas/patologia , Estenose das Carótidas/fisiopatologia , Dieta Aterogênica , Suscetibilidade a Doenças , Resistência à Insulina , Camundongos , Camundongos Knockout , Microscopia Confocal
7.
Thromb Res ; 113(1): 27-34, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15081562

RESUMO

BACKGROUND: Patients with diabetes mellitus and acute coronary syndromes (ACS) derive enhanced benefit from treatment with glycoprotein (GP) IIb-IIIa inhibitors. To determine mechanisms potentially responsible we characterized the binding of fibrinogen to platelets from patients with and without diabetes in the presence and absence of GP IIb-IIIa antagonists. METHODS: GP IIb-IIIa antagonists (tirofiban, eptifibatide, and abciximab) were added in vitro to blood from patients with and without diabetes. Binding of fibrinogen to activated GP IIb-IIIa was assessed with the use of flow cytometry. The kinetics of binding of I(125)-abciximab and I(125)-fibrinogen to washed platelets from subjects with and without diabetes mellitus were determined. Glycation of platelet membrane proteins was measured with the fructosamine assay. RESULTS: In the presence of GP IIb-IIIa antagonists, activation-induced binding of fibrinogen to platelets was reduced to a greater extent (p<0.02) in blood from patients with diabetes. The greater inhibition in blood from patients with diabetes was seen with pharmacologic concentrations of tirofiban (50 ng/ml, by 27%), eptifibatide (1.5 microg/ml, by 24%), and abciximab (2 mg/ml, by 12%). Whereas the binding of I(125)-abciximab was similar to platelets from patients with diabetes and those without, the rate of binding of I(125)-fibrinogen was decreased with platelets from patients with diabetes. Binding after 5 min was reduced by 46% in those with diabetes (p<0.05). Platelet membrane proteins from patients with diabetes were glycated to a greater extent compared with those without diabetes. CONCLUSION: GP IIb-IIIa antagonists inhibit platelet activation to a greater extent in blood from patients with diabetes. The decreased rate of binding of fibrinogen early after activation of platelets appears to be a consequence of glycation and may promote inhibition by GP IIb-IIIa antagonists.


Assuntos
Plaquetas/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Inibidores da Agregação Plaquetária/farmacologia , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Abciximab , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/metabolismo , Anticorpos Monoclonais/farmacocinética , Plaquetas/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/etiologia , Feminino , Fibrinogênio/metabolismo , Fibrinogênio/farmacocinética , Glicosilação , Humanos , Fragmentos Fab das Imunoglobulinas/metabolismo , Cinética , Masculino , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/fisiologia , Ligação Proteica/efeitos dos fármacos , Fatores de Tempo
8.
Nutr Metab Cardiovasc Dis ; 12(6): 325-30, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12669679

RESUMO

BACKGROUND AND AIM: Concentrations in blood of plasminogen activator inhibitor type 1 (PAI-1) and circulating free (non-esterified) fatty acids (FFA) are increased in diabetes and may accelerate atherosclerosis. We have shown that FFA increase expression of PAI-1 by activation of a transcription factor that binds to the repeated sequence 5'-TG(G/C) 1-2CTG-3'. This study was designed to determine whether FFA chain length, saturation, or both affect agonist properties and whether agonist properties are mediated by activated, thioesterified FFA (fatty acyl-CoA). METHODS AND RESULTS: Human hepatoma cells were exposed to selected FFA associated with bovine serum albumin (BSA). Triacsin C (5 microM) was used to inhibit production of fatty acyl-CoA. PAI-1 was assayed by enzyme linked immunosorbent assay. Maximal induction of PAI-1 was similar with medium and long chain FFA (fold induction of PAI-1 accumulated in conditioned media compared with control: C10 = 1.8 +/- 0.1, C12 = 2.0 +/- 0.1, C14 = 2.0 +/- 0.2, C16 = 1.4 +/- 0.1, C18 = 1.6 +/- 0.1, C20 = 1.32 +/- 0.1, p < 0.005 for each compared with control). Increased unsaturation did not alter the agonist properties of FFA (fold induction with C16: 0 = 1.4 +/- 0.1, C16: 1 = 1.4 +/- 0.1; C18: 0 = 1.6 +/- 0.1, C18: 1 = 1.5 +/- 0.1, C18: 2 = 1.6 +/- 0.1, C18: 3 = 1.4 +/- 0.1 and C20: 4 = 1.3 +/- 0.1, C20: 5 = 1.4 +/- 0.1, n = 6). However, maximal effects were seen with lower concentrations of longer chain FFA. Triacsin C consistently attenuated effects of FFA. CONCLUSIONS: Longer chain FFA exhibit maximal effects at lower concentrations. Augmented expression of PAI-1 is mediated by the fatty acyl-CoA derivative. These criteria identify targets for therapy designed to normalize expression of PAI-1 and retard progression of atherosclerosis in subjects with elevated concentrations of FFA in blood including those with insulin resistance.


Assuntos
Acil Coenzima A/metabolismo , Carcinoma Hepatocelular/genética , Ácidos Graxos não Esterificados/farmacologia , Neoplasias Hepáticas/genética , Palmitoil-CoA Hidrolase/farmacologia , Inibidor 1 de Ativador de Plasminogênio/genética , Acil Coenzima A/efeitos dos fármacos , Análise de Variância , Animais , Carcinoma Hepatocelular/patologia , Bovinos , Interações Medicamentosas , Regulação da Expressão Gênica , Hepatócitos/efeitos dos fármacos , Humanos , Neoplasias Hepáticas/patologia , Probabilidade , Sensibilidade e Especificidade , Células Tumorais Cultivadas/efeitos dos fármacos , Regulação para Cima
9.
J Thromb Thrombolysis ; 12(2): 171-6, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11729369

RESUMO

BACKGROUND: Optimal anti-thrombotic therapy for acute coronary syndromes (ACS) should suppress pro-thrombotic activity at the site of plaque rupture. We sought to determine whether platelet reactivity is increased in blood in the immediate vicinity of a ruptured plaque and is apparent even when blood is obtained by sampling from a catheter placed proximal to the lesion. METHODS: Blood was obtained from a catheter placed in the aorta and from the same catheter after engaging the culprit coronary artery. Platelet reactivity was determined with the use of flow cytometry by surface expression of P-selectin. RESULTS: In preliminary studies we demonstrated that a marker of thrombin activity, fibrinopeptide A, was similarly increased in blood taken from the coronary sinus and coronary arterial ostium of patients with ACS. Subsequently blood was obtained from the aorta and coronary arterial ostium through a coronary guide catheter for assessment of platelet reactivity in 23 subjects with ACS and 22 subjects with stable angina. The percentage of platelets expressing P-selectin in response to 0.2 microM adenosine diphosphate (ADP) was greater in coronary arterial samples from patients with ACS (aorta=6.1+/-1%, coronary artery=8.8+/-1.6%, p=0.02) compared with that in patients with stable symptoms (aorta=6.9+/-1.2, coronary artery=6.5+/-1.4, p=NS). CONCLUSIONS: Coronary arterial blood obtained from the ostium through a coronary guide catheter can be used to determine whether thrombin activity and platelet reactivity are increased in the immediate vicinity of a ruptured atherosclerotic plaque. The simplicity of the approach developed should facilitate its use in future studies designed to determine the impact of optimal suppression of platelet reactivity and the pro-thrombotic state before coronary interventions on short- and long-term clinical outcomes.


Assuntos
Doença da Artéria Coronariana/complicações , Circulação Coronária , Ativação Plaquetária , Ruptura Espontânea/sangue , Doença Aguda , Idoso , Aorta , Estudos de Casos e Controles , Doença da Artéria Coronariana/patologia , Vasos Coronários , Fibrinolíticos/administração & dosagem , Fibrinopeptídeo A/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Ativação Plaquetária/efeitos dos fármacos , Ruptura Espontânea/etiologia , Trombofilia/sangue , Trombofilia/etiologia
10.
Circulation ; 104(2): 181-6, 2001 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-11447083

RESUMO

BACKGROUND: Platelet activation is pivotal in the pathogenesis of complications after percutaneous coronary interventions (PCI). We previously reported substantial interindividual variability in activation of glycoprotein (GP) IIb/IIIa in response to a low concentration of ADP. We assessed GP IIb/IIIa activation prospectively to determine whether this could differentiate patients at low risk from those at high risk for complications early and late after PCI. Methods and Results-- A total of 112 patients undergoing PCI were studied. Platelet reactivity was determined with the use of flow cytometry. Patients were classified into high and low platelet reactivity groups on the basis of extent of activation of GP IIb/IIIa in response to 0.2 micromol/L ADP. The median value was used for differentiation. The incidence during 90-day follow-up interval of a composite end point (myocardial infarction, urgent revascularization, or repeat revascularization) was determined in each group. Follow up was completed in all 112 patients. The 2 groups were similar with respect to diverse clinical characteristics. Nevertheless, the incidence of the composite end point occurred in 26.8% of the high and 7.1% in the low platelet reactivity group (P=0.01). The difference in the composite end point was most striking during the 30- to 90-day interval after PCI (16.7% versus 1.9%; P=0.02). Repeat revascularization was more frequent in those with increased platelet reactivity (17.9% versus with 3.6%, P=0.029). CONCLUSIONS: Prospective assessment of platelet GP IIb/IIIa activation permits stratification of patients into low- and high-risk groups with respect to adverse events after PCI.


Assuntos
Angioplastia Coronária com Balão , Doença das Coronárias/metabolismo , Doença das Coronárias/terapia , Ativação Plaquetária , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Angioplastia Coronária com Balão/efeitos adversos , Determinação de Ponto Final , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Complicações Pós-Operatórias/etiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Reoperação , Medição de Risco , Resultado do Tratamento
11.
Coron Artery Dis ; 12(3): 245-53, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11352081

RESUMO

BACKGROUND: After exposure of platelets to abciximab and tirofiban in vitro, we have observed variable inhibition of fibrinogen binding and a lack of inhibition of alpha-granule degranulation. DESIGN: To determine whether such changes occur with treatment, platelet reactivity was assayed in blood from 50 patients receiving abciximab or tirofiban. METHODS: Platelet reactivity was determined before and during steady-state infusions of abciximab (0.125 microg/kg/min) or tirofiban, with either the PRISM-PLUS dosage (0.1 microg/kg/min) or the RESTORE dosage (0.15 microg/kg/min). Fibrinogen binding and P-selectin expression were determined by flow cytometry after stimulation of platelets with ADP (0.2 or 1 microM) or thrombin-receptor agonist peptide (TRAP, 25 microM). RESULTS: Both dosages of tirofiban and abciximab reduced fibrinogen binding in response to 0.2 microM ADP comparably. However, fibrinogen binding in response to 1.0 microM ADP or 25 microM TRAP was inhibited to a greater extent by the RESTORE dosage of tirofiban and abciximab than by the PRISM-PLUS dosage of tirofiban (P< 0.05). Furthermore, only the RESTORE dosage of tirofiban and abciximab reduced P-selectin expression in response to ADP. Inhibition with each regimen varied markedly between patients. CONCLUSIONS: The RESTORE dosages of tirofiban and abciximab each inhibit fibrinogen binding and alpha-granule degranulation similarly. However, substantial interindividual variation in inhibition of fibrinogen binding is evident.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/uso terapêutico , Tirosina/uso terapêutico , Abciximab , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Feminino , Fibrinogênio/efeitos dos fármacos , Citometria de Fluxo , Humanos , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Tirofibana , Tirosina/administração & dosagem , Tirosina/análogos & derivados
12.
J Invasive Cardiol ; 13(4): 306-9, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11287718

RESUMO

A patient with d-transposition of the great arteries who underwent the Mustard operation at one year of age developed intermittent symptomatic cyanosis as a young adult. Evaluation demonstrated a large baffle leak with bidirectional flow and stenosis of the intra-atrial IVC baffle channel. Initially, a single stent was placed to relieve the obstruction, followed by placement of an Amplatzer septal occluder device which assumed suboptimal position after release. Placement of additional stents securely repositioned the ASD device into excellent position, resulting in complete occlusion of the baffle leak and no residual obstruction in the IVC channel.


Assuntos
Complicações Pós-Operatórias/terapia , Próteses e Implantes , Stents , Transposição dos Grandes Vasos/cirurgia , Veia Cava Inferior , Adulto , Cateterismo Cardíaco , Procedimentos Cirúrgicos Cardíacos/métodos , Feminino , Humanos
13.
Thromb Haemost ; 85(2): 309-13, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11246553

RESUMO

Aspirin and abciximab independently decrease the incidence of cardiac events. To identify potential interactions, antiplatelet effects of abciximab were characterized in blood from healthy subjects given aspirin. Platelet activation was determined in whole blood with and without abciximab (2 microg/ml) added in vitro. Flow cytometry was used to quantify fibrinogen binding (glycoprotein IIb-IIIa activation). Binding of fluorochrome-labeled and 125I-labeled abciximab was determined before and after exposure to aspirin. In blood from subjects given aspirin for 5 days, abciximab-induced inhibition of the capacity to bind fibrinogen in response to 1 microM ADP was greater when the daily dose had been 325 mg compared with 81 mg (% inhibition: no aspirin 53 +/- 6; 81 mg daily 62 +/- 5; 325 mg daily 69 +/- 6). The effect of 5 daily doses of aspirin was greater than that of one. Larger single doses elicited larger effects (% inhibition 2 h after 325 mg 59 +/- 6; 2 h after 650 mg 78 +/- 5). Neither salicylsalicylic acid nor naproxen sodium potentiated the effect of abciximab. Exposure of platelets to 14C-acetylsalicylic acid led to acetylation of glycoprotein IIb and IIIa. Binding of 125I-abciximab to platelets was increased after 30 and 60 min. Acetylation of glycoprotein IIb-IIIa by aspirin augments inhibitory effects of abciximab in a dose- and time-dependent manner by increasing binding of abciximab to platelets.


Assuntos
Anticorpos Monoclonais/farmacologia , Aspirina/farmacologia , Fragmentos Fab das Imunoglobulinas/farmacologia , Ativação Plaquetária/efeitos dos fármacos , Abciximab , Acetilação , Anticorpos Monoclonais/farmacocinética , Aspirina/administração & dosagem , Aspirina/farmacocinética , Radioisótopos de Carbono , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Fibrinogênio/metabolismo , Humanos , Radioisótopos do Iodo , Inibidores da Agregação Plaquetária/farmacocinética , Inibidores da Agregação Plaquetária/farmacologia , Testes de Função Plaquetária , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Ligação Proteica/efeitos dos fármacos , Fatores de Tempo
14.
J Interv Cardiol ; 14(2): 231-7, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12053311

RESUMO

The successful employment of embolization coils for transcatheter occlusion of the patent ductus arteriosus (PDA) has resulted in acceptance of transcatheter occlusion as the treatment of choice for small to medium-sized PDAs. The Duct-Occlud device was developed to further improve the technique by utilizing a controlled release mechanism and coil shape specifically designed for the geometry of the ductus arteriosus. Clinical studies have demonstrated excellent efficacy with low embolization rates and low incidences of complications. Newer modifications have been designed for occlusion of larger PDAs and subaortic ventricular septal defects, and preliminary clinical results have been promising.


Assuntos
Cateterismo Cardíaco , Permeabilidade do Canal Arterial/terapia , Embolização Terapêutica , Ensaios Clínicos como Assunto , Desenho de Equipamento , Humanos , Próteses e Implantes
15.
Arterioscler Thromb Vasc Biol ; 20(12): 2696-701, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11116074

RESUMO

The increased expression of plasminogen activator inhibitor type-1 (PAI-1) is associated with increased concentrations of fatty acids in blood and may accelerate atherogenesis in diabetes. The present study was designed to define mechanisms by which nonesterified (free) fatty acids (FFAs) augment the expression of PAI-1. FFAs increased PAI-1 protein and mRNA expression by HepG2 cells. To identify potential regulatory elements, we constructed chimeric genes by fusing 1313, 853, 610, or 328 bp of human PAI-1 5'-flanking DNA to a luciferase reporter (PAI-LUC). A 2-fold increase in luciferase activity was seen when cells were transfected with PAI-LUC 1313, 863, or 610 and exposed to FFAs. No response to FFAs was seen with PAI-LUC 328 and after deletion of a 72-bp (-599 to -528) fragment from PAI-LUC 1313. This 72-bp fragment conferred FFA responsiveness to a different (simian virus 40) promoter. Two footprinted regions were demonstrated by DNase I analysis. Gel mobility shift assays indicated specific binding of extracted proteins to an FFA response element: 5'-TG(G/C)(1-2)CTG-3'. This sequence is repeated 4 times and is similar to an Sp1-binding site. Sp1 consensus oligonucleotides inhibited binding of extracted proteins to the regulatory elements. Accordingly, FFA-induced increased expression of PAI-1 in HepG2 cells is mediated by the binding of a transcription factor or factors to the repeated fatty acid response element, 5'-TG(G/C)(1-2)CTG-3', that is highly homologous to an Sp1-binding site.


Assuntos
Ácidos Graxos/farmacologia , Inibidor 1 de Ativador de Plasminogênio/genética , Sítios de Ligação , Quimera , Sequência Consenso , Meios de Cultivo Condicionados , Pegada de DNA , Regulação da Expressão Gênica/efeitos dos fármacos , Genes Reporter , Humanos , Luciferases/genética , Inibidor 1 de Ativador de Plasminogênio/biossíntese , Ligação Proteica , Proteínas/isolamento & purificação , Proteínas/metabolismo , RNA Mensageiro/biossíntese , Fator de Transcrição Sp1/metabolismo , Transcrição Gênica , Transfecção , Células Tumorais Cultivadas
17.
Circulation ; 102(17): 2051-7, 2000 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-11044419

RESUMO

BACKGROUND: Because optimal use of combinations of antiplatelet and antithrombotic drugs requires improved methods for assessment of therapeutic efficacy, we developed an assay designed to increase sensitivity that is based on initiation of clotting by tissue factor in minimally altered whole blood. METHODS AND RESULTS: Blood samples were obtained from healthy subjects, and the contact pathway of coagulation was inhibited with corn trypsin inhibitor (a specific factor XIIa inhibitor without effect on other coagulation factors). Clotting was initiated with relipidated tissue factor and detected with a Hemochron ACT instrument. Results were reproducible with samples from 25 healthy volunteers (mean time to clot, 125+/-17 seconds). Blood was also exposed to pharmacological concentrations of antithrombotic and antiplatelet agents in vitro. Heparin (0.25 anti-IIa/Xa U/mL) prolonged the time to clot by 2.4-fold (172 seconds, P:<0.05); hirudin (1.0 anti-IIa U/mL), by 3-fold (250 seconds P:<0.05); and enoxaparin (0.6 anti-Xa U/mL), by 2 -fold (123 seconds, P:<0.05). Additive effects of antiplatelet agents were readily detectable with both heparin and hirudin. Thus, addition of 3 microg/mL abciximab to 1.0 anti-IIa/Xa U/mL heparin and to 1.0 anti-IIa U/mL hirudin further prolonged the times to clot by 140 and 67 seconds, respectively (P:<0.05 for each). Addition of abciximab to enoxaparin did not further prolong the time to clot (increment, 13 seconds; P:=NS). CONCLUSIONS: The assay developed should facilitate improved dose selection, titration, and monitoring of combination antithrombotic and antiplatelet treatment regimens.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Fibrinolíticos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Tromboplastina/fisiologia , Enoxaparina/farmacologia , Heparina/farmacologia , Hirudinas/farmacologia , Humanos , Técnicas In Vitro , Tempo de Tromboplastina Parcial , Tempo de Coagulação do Sangue Total
18.
J Bone Joint Surg Am ; 82(8): 1096-101, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10954098

RESUMO

BACKGROUND: Notching of the anterior femoral cortex during total knee arthroplasty has been implicated as a cause of subsequent periprosthetic supracondylar femoral fracture. However, other than observational clinical data, no reliable association between these events has been established, to our knowledge. The purpose of the present study was to investigate the biomechanical effects of notching of the anterior femoral cortex. METHODS: The femoral component of a total knee replacement was implanted in twelve matched pairs of human cadaveric femora; one specimen in each pair had preservation of the anterior femoral cortex, and the other had a full-thickness cortical defect created just proximal to the anterior flange of the femoral component. The pairs were then subjected to either bending or torsional loading to failure. Both the fracture pattern and the quantitative load to failure were analyzed. Two matched pairs were excluded from the analysis because of inadvertent fracture during placement of the component. RESULTS: Following the application of a bending load, femora with notching of the anterior femoral cortex sustained a short oblique fracture that originated at the cortical defect proximal to the femoral component and femora without notching had a midshaft fracture. In contrast, notching of the anterior femoral cortex had no effect on the fracture pattern that was observed after the application of a torsional load. The mean load to failure was significantly reduced by notching in both testing modes. Notching decreased bending strength from 11,813 to 9690 newtons (18 percent; p = 0.0034), and it decreased torsional strength from 134.7 to 81.8 newton-meters (39.2 percent; p = 0.01). CONCLUSIONS: Biomechanical testing demonstrated that notching of the anterior femoral cortex significantly lessens the load to failure following total knee arthroplasty and influences the subsequent fracture pattern. These effects are manifested in different ways under the two loading conditions: the fracture pattern is altered under bending load, and there is a greater quantitative decrease in load to failure with torsional loading. CLINICAL RELEVANCE: Weakening of the femur by notching of the anterior cortex after total knee arthroplasty may warrant alteration in the customary postoperative regimen for these patients. Manipulation of a total knee replacement with a notched anterior femoral cortex should probably be avoided.


Assuntos
Artroplastia do Joelho/efeitos adversos , Fraturas do Fêmur/etiologia , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/métodos , Fenômenos Biomecânicos , Cadáver , Humanos
19.
Clin Orthop Relat Res ; (377): 265-71, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10943210

RESUMO

The presence of the ossific nucleus and its role in reducing the risk of ischemic necrosis in developmental dysplasia of the hip remains a matter of controversy. Ischemic necrosis of the pre-osseous capital femoral epiphysis, defined as chondronecrosis, was evaluated in a rabbit model. Histologic evidence of chondronecrosis after casting in maximum abduction was greater in 1-day-old New Zealand White rabbits before the radiographic appearance of the ossific nucleus, compared with 16-day-old New Zealand White rabbits with an ossific nucleus already present. This preliminary study supports the hypothesis that the ossific nucleus may decrease the risk of intracapsular compressive ischemic injury to the developing capital femoral epiphysis in a rabbit model.


Assuntos
Cartilagem/fisiologia , Necrose da Cabeça do Fêmur/etiologia , Luxação Congênita de Quadril/complicações , Animais , Cartilagem/anatomia & histologia , Coelhos
20.
Eur J Obstet Gynecol Reprod Biol ; 91(2): 197-8, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10869795

RESUMO

Factor V Leiden mutation is a risk factor for the development of thrombo-embolic episodes in pregnancy. A case is presented of a pregnant woman with repeated episodes of venous thrombosis with a complicated clinical course.


Assuntos
Fator V/genética , Mutação , Complicações Cardiovasculares na Gravidez , Trombose Venosa/genética , Adulto , Antitrombina III/análise , Feminino , Idade Gestacional , Heparina/administração & dosagem , Heparina/uso terapêutico , Humanos , Gravidez , Fatores de Risco , Trombose Venosa/tratamento farmacológico , Varfarina/administração & dosagem , Varfarina/uso terapêutico
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