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1.
Scanning ; 2017: 4198519, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29109811

RESUMO

Nanocomposites physical properties unexplainable by general mixture laws are usually supposed to be related to interphases, highly present at the nanoscale. The intrinsic dielectric constant of the interphase and its volume need to be considered in the prediction of the effective permittivity of nanodielectrics, for example. The electrostatic force microscope (EFM) constitutes a promising technique to probe interphases locally. This work reports theoretical finite-elements simulations and experimental measurements to interpret EFM signals in front of nanocomposites with the aim of detecting and characterizing interphases. According to simulations, we designed and synthesized appropriate samples to verify experimentally the ability of EFM to characterize a nanoshell covering nanoparticles, for different shell thicknesses. This type of samples constitutes a simplified electrostatic model of a nanodielectric. Experiments were conducted using either DC or AC-EFM polarization, with force gradient detection method. A comparison between our numerical model and experimental results was performed in order to validate our predictions for general EFM-interphase interactions.

2.
Crit Rev Food Sci Nutr ; 55(10): 1406-24, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24915329

RESUMO

Regulation of food intake through modulation of gastrointestinal responses to ingested foods is an ever-growing component of the therapeutic approaches targeting the obesity epidemic. Alginates, viscous and gel-forming soluble fibers isolated from the cell wall of brown seaweeds and some bacteria, are recently receiving considerable attention because of their potential role in satiation, satiety, and food intake regulation in the short term. Enhancement of gastric distension, delay of gastric emptying, and attenuation of postprandial glucose responses may constitute the basis of their physiological benefits. Offering physical, chemical, sensorial, and physiological advantages over other viscous and gel-forming fibers, alginates constitute promising functional food ingredients for the food industry. Therefore, the current review explores the role of alginates in food intake and glycemic regulation, their underlying modes of action and their potential in food applications.


Assuntos
Alginatos/farmacologia , Glicemia/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Esvaziamento Gástrico/efeitos dos fármacos , Saciação/efeitos dos fármacos , Alginatos/administração & dosagem , Indústria Alimentícia , Humanos , Período Pós-Prandial/fisiologia
3.
Rev Mal Respir ; 31(9): 839-48, 2014 Nov.
Artigo em Francês | MEDLINE | ID: mdl-25433589

RESUMO

INTRODUCTION: The aim of this study was to evaluate the profile of skin prick-test reactivity to different aeroallergens in patients with rhinitis and asthma in Lebanon and its geographic variation within the country. It was also to suggest a minimal panel of allergens that should be used to detect sensitized patients. METHODS: All patients who underwent skin prick-testing, because of rhinitis and/or symptoms suggesting asthma, between 2004 to 2011 in the hôtel-Dieu de France university hospital of Beirut, were studied. The total number of patients was 2350 and all were tested with the same panel of 24 aeroallergens. A further series of 208 patients were added because Cupressaceae antigens were not included in the initial series. RESULTS: The overall rate of sensitization to any allergen was 75.6%. A battery of eleven allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia, Parietaria, grass, Salicaceae, oak, Oleaceae, dog, cat, and cockroaches) was found to identify sensitized patients with a sensitivity of 96% and a negative predictive value of 90%. Cupressaceae should be added to this battery in view of the results of the additional series. The Bekaa region had a unique profile of sensitization. CONCLUSION: Twelve allergens are able to detect almost all sensitized patients suffering from respiratory symptoms in Lebanon.


Assuntos
Alérgenos/imunologia , Asma/diagnóstico , Rinite Alérgica/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alérgenos/análise , Animais , Asma/epidemiologia , Asma/imunologia , Gatos , Criança , Pré-Escolar , Comportamento de Escolha , Cães , Humanos , Lactente , Líbano/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Rinite Alérgica/epidemiologia , Rinite Alérgica/imunologia , Testes Cutâneos/estatística & dados numéricos , Adulto Jovem
4.
Eur J Clin Nutr ; 68(5): 613-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24667749

RESUMO

BACKGROUND/OBJECTIVES: Sodium alginate reduces appetite and glycemia, when consumed in water- and sugar-based drinks. But, its effects when added to other commonly consumed beverages have not been reported. Because chocolate milk (CM) is criticized for raising blood glucose more than unflavored milk, the aim of our study was to investigate the effect of adding a strong-gelling sodium alginate to CM on glycemia, insulinemia, appetite and food intake. SUBJECTS/METHODS: In a randomized crossover design, 24 men (22.9±0.4 years; 22.5±0.3 kg/m(2)) were provided with isovolumetric (325 ml) treatments of CM, 1.25% alginate CM, 2.5% alginate CM or 2.5% alginate solution. Sodium alginate had a ratio of 0.78:1 of mannuronic acid (M) to guluronic acid (G) residues, and was block distributed. Treatments were standardized for lactose, sucrose and calcium content, and provided 120 min before an ad libitum pizza meal during which food intake was measured. Appetite and blood glucose and insulin were measured at baseline and at intervals pre- and post-meal. RESULTS: Addition of 2.5% alginate to CM reduced peak glucose concentrations, at 30 min, by an average of 6% and 13% compared with 1.25% alginate CM (95% confidence intervals (CIs): 0.02-1.08; P=0.037) and CM alone (95% CIs: 0.49-1.55; P=0.000) respectively. Insulin peaks at 30 min were lower by 46% after 2.5% alginate CM relative to CM (95% CIs: 3.49-31.78; P=0.009). Pre-meal appetite was attenuated dose dependently by alginate addition to CM; CM with 2.5% alginate reduced mean appetite by an average of 134% compared with CM alone (95% CIs: 8.87-18.98; P=0.000). However, total caloric intake at the pizza meal did not differ among treatments. CONCLUSIONS: The addition of a strong-gelling sodium alginate to CM decreases pre-meal glycemia, insulinemia and appetite, but not caloric intake at a meal 2 h later, in healthy adult men.


Assuntos
Alginatos/administração & dosagem , Apetite/efeitos dos fármacos , Glicemia/metabolismo , Laticínios/análise , Insulina/sangue , Adulto , Alginatos/análise , Bebidas/análise , Índice de Massa Corporal , Fenômenos Químicos , Estudos Cross-Over , Ingestão de Energia/efeitos dos fármacos , Ácido Glucurônico/administração & dosagem , Ácido Glucurônico/análise , Voluntários Saudáveis , Ácidos Hexurônicos/administração & dosagem , Ácidos Hexurônicos/análise , Ácidos Hexurônicos/química , Humanos , Masculino , Refeições , Período Pós-Prandial/efeitos dos fármacos , Método Simples-Cego , Adulto Jovem
5.
J Nutr Metab ; 2012: 703490, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22506105

RESUMO

The use of nutritional supplements among exercisers in gyms has been never investigated in the Middle East. The aim of the current study was to assess the prevalence intake of nutritional supplements and the potential influencing factors among people exercising in gyms in Beirut city. In this cross-sectional study, 512 exercisers, aged between 20 and 50 years, were randomly selected from gyms. The intake of nutritional supplements was reported among 36.3% (95% confidence interval 32.2-40.5) of participants, with a weak presence of medical supervision. Patterns of supplement use differed by gender and age. Men and younger exercisers were found to focus on supplements associated with performance enhancement and muscle building, while women and older exercisers were more concerned with health-promoting products such as vitamins, minerals, and herbal supplements. An appropriate dissemination of accurate and scientifically sound information regarding the benefits and side effects of nutritional supplements is highly recommended in the sports environment in Beirut city.

6.
J Nutr Metab ; 2012: 851362, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22187640

RESUMO

Despite the lack of international agreement regarding the definition and classification of fiber, there is established evidence on the role of dietary fibers in obesity and metabolic syndrome. Beta glucan (ß-glucan) is a soluble fiber readily available from oat and barley grains that has been gaining interest due to its multiple functional and bioactive properties. Its beneficial role in insulin resistance, dyslipidemia, hypertension, and obesity is being continuously documented. The fermentability of ß-glucans and their ability to form highly viscous solutions in the human gut may constitute the basis of their health benefits. Consequently, the applicability of ß-glucan as a food ingredient is being widely considered with the dual purposes of increasing the fiber content of food products and enhancing their health properties. Therefore, this paper explores the role of ß-glucans in the prevention and treatment of characteristics of the metabolic syndrome, their underlying mechanisms of action, and their potential in food applications.

7.
IEEE Pulse ; 2(5): 56-64, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-25372970

RESUMO

The authors presented a first application of 2-D contrast-enhanced ICE in localizing RF ablation lesions and, more importantly, accurately and reproducibly quantifying their extent and depth within the myocardium in the intact beating heart. Furthermore, the study extended this application and presented, for the first time, a novel method based on contrast-enhanced 3-D ICE to describe details of contiguous linear lesions.


Assuntos
Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/terapia , Ablação por Cateter/métodos , Ecocardiografia/métodos , Engenharia Biomédica , Humanos , Microbolhas , Terapia por Radiofrequência
8.
J Med Genet ; 43(8): 653-9, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16571646

RESUMO

BACKGROUND: Andersen-Tawil syndrome (ATS) is a rare inherited disorder, characterised by periodic paralysis, cardiac dysarrhythmias, and dysmorphic features, and is caused by mutations in the gene KCNJ2, which encodes the inward rectifier potassium channel, Kir2.1. This study sought to analyse KCNJ2 in patients with familial ATS and to determine the functional characteristics of the mutated gene. METHODS AND RESULTS: We screened a family with inherited ATS for the mutation in KCNJ2, using direct DNA sequencing. A missense mutation (T75R) of Kir2.1, located in the highly conserved cytoplasmic N-terminal domain, was identified in three affected members of this family. Using the Xenopus oocyte expression system and whole cell voltage clamp analyses, we found that the T75R mutant was non-functional and possessed a strong dominant negative effect when co-expressed with the same amount of wild type Kir2.1. Transgenic (Tg) mice expressing the mutated form of Kir2.1 in the heart had prolonged QTc intervals compared with mice expressing the wild type protein. Ventricular tachyarrhythmias were observed in 5 of 14 T75R-Tg mice compared with 1 of 7 Wt-Tg and none of 6 non-transgenic littermates. In three of five T75R-Tg mice with ventricular tachycardia, their ECG disclosed bidirectional tachycardia as in our proband. CONCLUSIONS: The in vitro studies revealed that the T75R mutant of Kir2.1 had a strong dominant negative effect in the Xenopus oocyte expression system. It still preserved the ability to co-assemble and traffic to the cell membrane in mammalian cells. For in vivo studies, the T75R-Tg mice had bidirectional ventricular tachycardia after induction and longer QT intervals.


Assuntos
Síndrome de Andersen/genética , Predisposição Genética para Doença , Mutação/genética , Canais de Potássio Corretores do Fluxo de Internalização/genética , Adolescente , Animais , Análise Mutacional de DNA , Eletrocardiografia , Eletrofisiologia , Feminino , Humanos , Camundongos , Camundongos Transgênicos , Miocárdio/citologia , Miocárdio/patologia , Miócitos Cardíacos/citologia , Xenopus
9.
Conf Proc IEEE Eng Med Biol Soc ; 2004: 3662-5, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-17271087

RESUMO

We tested the utility of intracardiac echocardiography (ICE) in measuring left ventricular (LV) volume. In 4 normal dogs, a 10-F percutaneous sheath was placed inside the LV along its major axis. An ICE catheter (9 F, 9 MHz) was then inserted through the sheath into the LV. The ICE catheter was pulled back in 1-mm intervals starting from the apex, and 2-D tomographic images were continuously acquired. Subsequently, the ICE catheter was replaced in the LV by a conductance catheter to measure single-beat volume signals. Stroke volume was determined by thermodilution for validation. All measurements were made in each dog while pacing the atrium at two different cycle lengths (range=300-500 ms). The endocardium was segmented in the ICE images throughout the cardiac cycle, and LV volume was computed by integrating multiple segments (range=55-70 mm). We found that ICE accurately reconstructed LV 3-D anatomy. Stroke volume by ICE was in excellent agreement with thermodilution (error = 3.8+/-3.0%, r = 0.99, n = 8). Morphology of LV volume signals correlated well with instantaneous volume signals derived by conductance (r=0.93, n=8). In conclusion, ICE accurately reconstructs LV anatomy and volume throughout the cardiac cycle in the normal heart. This approach could facilitate interventional diagnostic and therapeutic procedures.

10.
Conf Proc IEEE Eng Med Biol Soc ; 2004: 1911-3, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-17272086

RESUMO

Intracardiac echocardiograpby (ICE) has been employed in guiding clinical interventional procedures. ICE could also be useful for 3-D anatomical and functional imaging of the heart. In this regard, we developed and tested a method to semi-automatically determine the endocardial boundary in multiple tomographic ICE images. Compared to manual segmentation, we found that semi-automatic segmentation of the endocardial boundary in ICE images was feasible and enabled accurate and efficient reconstruction of 3-D geometry of the heart cavity.

11.
Ann Biomed Eng ; 29(6): 493-500, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11459343

RESUMO

In the right atrium (RA) we globally investigated: (1) the properties of noncontact electrograms measured by multielectrode cavitary probes, (2) the features of endocardial electrograms computed from the noncontact probe electrograms, and (3) the impact of the probe size on both the noncontact and the computed electrograms. We deployed a custom catheter in the dog RA, which consisted of a cylindrical probe with 64 electrodes on its surface, for measuring noncontact cavitary electrograms, and a concentric endocardial basket carrying an additional array of 64 electrodes, for measuring contact endocardial electrograms (the "gold standard"). Both a 5-mm- and a 10-mm-diam probe (P5 and P10, respectively) were sequentially tested in the same RA of one dog. Unipolar electrograms from both the probe and the basket were simultaneously acquired during normal as well as during paced rhythms (n > or =24 protocols per probe). Boundary element method and numeric regularization were applied to compute endocardial electrograms at the basket electrode locations. We found that noncontact electrograms were attenuated and smoothed, and this effect was exaggerated with the small probe. Computed endocardial electrograms more accurately reconstructed important amplitude distribution and morphological features; peak-to-peak amplitude error, 35% for P5 and 34% for P10. Activation and spatial errors of computed endocardial electrograms were 8.8+/-6.8 ms and 5.1+/-6.1 mm for P5, respectively, and 6.0+/-5.5 ms and 3.2+/-4.4 mm for P10, respectively. In conclusion, global RA activation may be delineated directly from noncontact cavitary electrograms alone, but may be affected by volume attenuation, smoothing, and probe size. Accurate endocardial electrograms, however, can be successfully computed from noncontact electrograms acquired with small probes and be used to reconstruct both electrogram amplitude and detailed morphology.


Assuntos
Cateterismo Cardíaco/métodos , Animais , Função Atrial , Engenharia Biomédica , Cateterismo Cardíaco/instrumentação , Cateterismo Cardíaco/estatística & dados numéricos , Cães , Eletrodos , Eletrofisiologia , Endocárdio/fisiologia , Modelos Cardiovasculares
12.
J Immunol ; 166(9): 5464-72, 2001 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-11313384

RESUMO

Current data indicate that CD5 functions as an inhibitor of TCR signal transduction. Consistent with this role, thymocyte selection in TCR transgenic/CD5(-/-) mice is altered in a manner suggestive of enhanced TCR signaling. However, the impact of CD5 deletion on thymocyte selection varies depending on the transgenic TCR analyzed, ranging from a slight to a marked shift from positive toward negative selection. An explanation for the variable effect of CD5 on selection is suggested by the observation that CD5 surface expression is regulated by TCR signal intensity during development and CD5 surface levels on mature thymocytes and T cells parallel the avidity of the positively selecting TCR/MHC/ligand interaction. In this study, we generated mice that overexpress CD5 during thymocyte development (CD5-tg), and then examined the effect of CD5 overexpression or CD5 deletion (CD5(-/-)) on selection of thymocytes that express the same TCR transgenes. The results demonstrate that the effect on thymocyte selection of altering CD5 expression depends on the avidity of the selecting interaction and, consequently, the level of basal (endogenous) CD5 surface expression. Substitution of endogenous CD5 with a transgene encoding a truncated form of the protein failed to rescue the CD5(-/-) phenotype, demonstrating that the cytoplasmic domain of CD5 is required for its inhibitory function. Together, these results indicate that inducible regulation of CD5 surface expression during thymocyte selection functions to fine tune the TCR signaling response.


Assuntos
Antígenos CD5/fisiologia , Receptores de Antígenos de Linfócitos T/fisiologia , Transdução de Sinais/imunologia , Animais , Antígenos CD5/biossíntese , Antígenos CD5/genética , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Membrana Celular/genética , Membrana Celular/imunologia , Membrana Celular/metabolismo , Citoplasma/imunologia , Regulação para Baixo/genética , Regulação para Baixo/imunologia , Feminino , Humanos , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Ligação Proteica/genética , Ligação Proteica/imunologia , Estrutura Terciária de Proteína/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais/genética , Linfócitos T/citologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Timo/citologia , Timo/imunologia , Timo/metabolismo
13.
J Electrocardiol ; 34(1): 1-14, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11239365

RESUMO

Differences between conduction properties of interatrial conduits and their roles in initiation and maintenance of supraventricular arrhythmias remain unclear. Our objective was to determine details of interatrial activation in inferior atrial region and to correlate intra-atrial and interatrial activation patterns with the site of origin of atrial ectopic activation. In 9 dogs, basket-catheters carrying 64 electrodes were deployed into both the right atrium (RA) and left atrium (LA). A 10-electrode catheter was inserted into the coronary sinus (CS). Activation patterns of the RA, LA, and CS were compared during pacing in the CS, in RA inferoparaseptum posterior to Eustachian ridge-tendon of Todaro (TT), and in inferior RA near the CS ostium (anterior to TT). We found that pacing in proximal and middle CS resulted in a RA breakthrough invariably at the CS ostium, consistent with conduction through a CS-RA connection. Meanwhile, LA breakthrough emerged in inferoposterior region (inferior to mitral annulus), suggesting conduction through a CS-LA connection. While pacing in distal CS, LA breakthrough shifted to middle posterolateral wall. Whereas, the RA was activated by the LA directly through the septum. During pacing in RA inferoparaseptum posterior to TT, the LA was activated directly through the septum at 22 +/- 4 ms. Whereas, during pacing anterior to TT, the LA was activated through both the CS and the septum while earliest activation was delayed by 38 +/- 5 ms. In conclusion, both the interatrial septum and CS musculature form electrical conduits in inferior atrial region in canine. Differences in activation properties between the conduits in inferior interatrial region result in selective interatrial activation patterns during ectopic activation.


Assuntos
Função do Átrio Esquerdo/fisiologia , Função do Átrio Direito/fisiologia , Sistema de Condução Cardíaco/fisiologia , Animais , Complexos Atriais Prematuros/fisiopatologia , Cateterismo Cardíaco , Estimulação Cardíaca Artificial , Cães , Eletrocardiografia , Técnicas Eletrofisiológicas Cardíacas , Feminino , Septos Cardíacos/fisiopatologia , Masculino
14.
J Am Coll Cardiol ; 37(1): 278-85, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11153752

RESUMO

OBJECTIVES: Our goal was to identify the hemodynamic determinants of the mitral annulus (MA) diastolic velocities by tissue Doppler. BACKGROUND: The MA diastolic velocities are promising indexes of left ventricular (LV) diastolic function. However, their hemodynamic determinants have not yet been evaluated. METHODS: Ten adult mongrel dogs underwent left atrial (LA) and LV pressure measurements by Millar catheters while tissue Doppler was applied to record the MA diastolic velocities at the septal and lateral comers. Conventional transmitral flow was also obtained. Left atrial and LV pressures were modified utilizing fluid administration and caval occlusion, whereas dobutamine and esmolol were used to change LV and LA relaxation. Left ventricular filling pressures were altered during different lusitropic states to evaluate for the possible interaction of preload and LV relaxation on the early diastolic velocity (Ea). RESULTS: In the majority of dogs, a positive significant relation was observed between Ea and the transmitral pressure gradient (r = 0.57, p = 0.04). The Ea had strong correlations with tau (r = -0.83, p < 0.001), LV -dP/dt (r = 0.8, p < 0.001) and minimal LV pressure (r = -0.76, p < 0.01). However, there was no relation between Ea and the transmitral pressure gradient in experimental stages where tau >50 ms. Furthermore, the late diastolic velocity at both corners of the MA had significant positive relations with LA dP/dt (r = 0.67, p < 0.01) and LA relaxation (r = 0.73, p < 0.01) but an inverse correlation with LV end-diastolic pressure (r = -0.53, p = 0.01). CONCLUSIONS: Left ventricular relaxation, minimal pressure and preload determine Ea while late diastolic velocity determinants include LA dP/dt, LA relaxation and LV end-diastolic pressure.


Assuntos
Diástole/fisiologia , Ecocardiografia Doppler/métodos , Hemodinâmica/fisiologia , Valva Mitral/diagnóstico por imagem , Animais , Velocidade do Fluxo Sanguíneo/fisiologia , Cães , Contração Miocárdica/fisiologia , Função Ventricular Esquerda/fisiologia
15.
J Interv Card Electrophysiol ; 4(3): 501-9, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11046189

RESUMO

Medical therapy for managing atrial fibrillation remains less than satisfactory. Electrical therapy such as right atrial (RA) pacing was shown to reduce rate of recurrence of atrial fibrillation, while evidently dual-site pacing was more effective than single-site pacing. However, similarities and/or differences in the electrophysiological consequences of single-site and dual-site RA pacing are unclear. Our objective was to simultaneously map RA and left atrial (LA) activation patterns and compare intra-atrial and interatrial activation properties during single-site and dual-site RA pacing in the normal canine heart. Basket-shaped catheters carrying 64 electrodes were deployed under the guidance of fluoroscopy and echocardiography into both the RA and LA of 7 dogs. Basket unipolar electrograms were simultaneously recorded while pacing at high lateral RA (HRA) alone, at inferior RA septum (RAS) alone, and at both sites simultaneously. We found that pacing at HRA alone resulted in the longest interatrial conduction time (47+/-6 ms). Pacing at RAS alone significantly shortened interatrial conduction time (29+/-5 ms) and completely activated both the RA and LA simultaneously (70+/-6 ms and 69+/-8 ms, respectively). Dual-site pacing at HRA and RAS significantly abbreviated RA complete activation time (52+/-7 ms), but did not alter interatrial conduction time or LA activation pattern compared to pacing at RAS alone. In conclusion, single-site pacing at RAS shortened interatrial conduction time compared to HRA and completely activated both atria simultaneously in canines with normal atria. In addition to shortening interatrial conduction time, dual-site pacing at HRA and RAS abbreviated RA complete activation time.


Assuntos
Função Atrial/fisiologia , Estimulação Cardíaca Artificial/métodos , Sistema de Condução Cardíaco/fisiologia , Análise de Variância , Animais , Mapeamento Potencial de Superfície Corporal , Cateterismo Cardíaco , Cães , Feminino , Masculino , Modelos Animais , Probabilidade , Valores de Referência
16.
J Exp Med ; 192(6): 913-19, 2000 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-10993922

RESUMO

The T cell antigen receptor (TCR) and pre-TCR complexes are composed of multiple signal-transducing subunits (CD3 gamma, CD3 delta, CD3 epsilon, and zeta) that each contain one or more copies of a semiconserved functional motif, the immunoreceptor tyrosine-based activation motif (ITAM). Although biochemical studies indicate that individual TCR-ITAMs may bind selectively or with different affinity to various effector molecules, data from other experiments suggest that at least some ITAMs are functionally equivalent. In this study, we examined the role of CD3straightepsilon ITAM-mediated signals in T cell development by genetically reconstituting CD3 epsilon-deficient mice with transgenes encoding either wild-type or ITAM-mutant (signaling defective) forms of the protein. The results demonstrate that signals transduced by CD3 epsilon are not specifically required for T cell maturation but instead contribute quantitatively to TCR signaling in a manner similar to that previously observed for zeta chain. Unexpectedly, analysis of TCR-transgenic/CD3 epsilon-mutant mice reveals a potential role for CD3 epsilon signals in T cell survival.


Assuntos
Complexo CD3 , Cálcio/metabolismo , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais/imunologia , Linfócitos T/imunologia , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Sequência Conservada , Citocinas/análise , Linfonodos/imunologia , Ativação Linfocitária , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Subunidades Proteicas , Receptores de Antígenos de Linfócitos T/deficiência , Receptores de Antígenos de Linfócitos T/genética , Timo/imunologia , Tirosina
17.
Comput Biomed Res ; 33(4): 260-95, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10944405

RESUMO

A closed-loop model of cardiopulmonary circulation has been developed for the study of right-left ventricular interaction under physiologically normal and altered conditions. The core model provides insight into the effects of ventricular interaction and pericardial mechanics on hemodynamics. The complete model contains realistic descriptions of (a) the interacting ventricular free walls and septum, (b) the atria, (c) the pericardium, and (d) the systemic and pulmonary vascular loads. The current analysis extends previous work on ventricular interaction and pericardial influence under isolated heart conditions to loading conditions imposed by a closed-loop model of the circulation. A nonlinear least-squares parameter identification method (Levenberg-Marquardt algorithm) is used, together with parameter sensitivity analysis, to estimate the values of key parameters associated with the ventricular and circulation models. Pressure measurements taken at several anatomical locations in the circulation during open-chest experiments on dogs are used as data in the identification process. The complete circulatory model, including septal and pericardial coupling, serves as a virtual testbed for assessing the global affects of localized mechanical or hemodynamic alterations. Studies of both direct and series ventricular interaction, as well as the effect of the pericardium on cardiac performance, are accomplished with this model. Alterations in model parameter values are used to predict the impact of disease and/or clinical interventions on steady-state hemodynamic performance. Additionally, a software package titled CardioPV has been developed to integrate the complete model with data acquisition tools and a sophisticated graphical user interface. The complete software package enables users to collect experimental data, use the data to estimate model parameters, and view the model outputs in an online setting.


Assuntos
Fenômenos Fisiológicos Cardiovasculares , Simulação por Computador , Modelos Cardiovasculares , Animais , Cães , Hemodinâmica , Pericárdio/fisiologia , Circulação Pulmonar/fisiologia , Software , Função Ventricular
18.
IEEE Trans Biomed Eng ; 47(3): 327-37, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10743774

RESUMO

Numeric regularization methods for solving the inverse problem of electrocardiography in realistic volume conductor models have been mostly limited to uniform regularization in the spatial domain. A method of spatial regularization (SR) was developed and tested in canine, where each spatial spectral component of the volume conductor model was considered separately, and a SR operator was selected based on explicit a posteriori criterion at each time instant through the heartbeat. The inverse problem was solved in the left ventricle by reconstructing endocardial surface electrograms based on cavitary electrograms measured with the use of a noncontact, multielectrode probe. The results were validated based on electrograms measured in situ at the same endocardial locations using an integrated, multielectrode basket-catheter. A probe-endocardium three-dimensional model was determined from multiplane fluoroscopic images. The boundary element method was applied to solve the boundary value problem and derive the relationship between endocardial and probe potentials. Endocardial electrograms were reconstructed during both normal and paced rhythms using SR as well as standard, uniform, zeroth-order Tikhonov (ZOT) regularization. Compared to endocardial electrograms measured by the basket, electrograms reconstructed using SR [relative error (RE) = 0.32, correlation coefficient (CC) = 0.97, activation error = 3.3 ms] were superior to electrograms reconstructed using ZOT regularization (RE = 0.59, CC = 0.79, activation error = 4.9 ms). Therefore, regularization based on spatial spectral components of the model improves the solution of the inverse problem of electrocardiography compared to uniform regularization.


Assuntos
Eletrocardiografia , Endocárdio/fisiologia , Modelos Cardiovasculares , Animais , Mapeamento Potencial de Superfície Corporal , Simulação por Computador , Apresentação de Dados , Cães , Análise de Fourier , Processamento de Sinais Assistido por Computador
19.
Circulation ; 100(3): 312-9, 1999 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-10411858

RESUMO

BACKGROUND: The spread of activation between the right atrium (RA) and left atrium (LA), particularly along the right and left aspects of the interatrial septum, is not clear. METHODS AND RESULTS: Basket-shaped catheters carrying 64 electrodes were deployed into both the RA and LA of 10 dogs. Position and orientation of the baskets were determined by fluoroscopy and echocardiography. Basket unipolar electrograms were simultaneously recorded in each dog during sinus rhythm, right ventricular pacing, and pacing of the right septum through the basket in the superior and inferior regions. Isochrone maps depicting all aspects of the atria, including the septum, were compared. During sinus rhythm and superior right septal pacing, wave fronts propagated predominantly from superior to inferior regions on both the right and left septum. However, activation of the left septum was delayed compared with the right septum. During right ventricular pacing and inferior right septal pacing, activation of the septum was discordant; 1 wave front propagated rapidly on the right septum from inferior to superior regions, whereas 2 opposing wave fronts originated on the left septum in both the superior and inferior regions. The left septum was activated predominantly by the superior wave front. Activation of the left septum was completed in a significantly shorter time during pacing of the right septum in the inferior region compared with the superior region. CONCLUSIONS: In dogs, activation of the right and left aspects of the interatrial septum is discordant. Electrical connections are present between the RA and LA in regions superior as well as inferior to the septum.


Assuntos
Sistema de Condução Cardíaco/fisiologia , Septos Cardíacos/fisiologia , Animais , Estimulação Cardíaca Artificial , Cães , Ecocardiografia , Eletrodos , Eletrofisiologia , Feminino , Fluoroscopia , Átrios do Coração , Septos Cardíacos/anatomia & histologia , Masculino
20.
Pacing Clin Electrophysiol ; 21(11 Pt 2): 2500-5, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9825374

RESUMO

Cavitary electrograms previously were measured from multiple directions simultaneously in the canine left ventricle with the use of noncontact multielectrode probes. The objective of the present study was to measure cavitary electrograms in the canine right atrium (RA) and describe the corresponding global activation sequences during normal and abnormal atrial rhythms. A 64-electrode custom probe was inserted into the RA of six dogs. Probe position and orientation were guided by fluoroscopy. Probe unipolar electrograms were acquired simultaneously during sinus rhythm, RA pacing, and ventricular pacing. Vagally mediated atrial fibrillation (AF) was induced in four dogs. Probe electrograms were acquired during AF induced at baseline and after intravenous infusion of ibutilide (0.075 mg/kg followed by 0.075 mg/kg infusion over 10 minutes). Isochrone maps were derived from noncontact probe electrograms and were displayed on a beat-by-beat basis during normal and paced rhythms. During AF, maps were displayed for 10 consecutive 100-ms windows. Isochrone maps of normal and paced beats revealed regions of early activation that were consistent with sites of wavefront initiation. During AF, multiple varying activation wavefronts were observed. At baseline, AF cycle length was 110 +/- 15 ms and the number of wavefronts was 1.72 +/- 0.25 per 100-ms window. After ibutilide, AF cycle increased to 182 +/- 36 ms (P = 0.018) and the number of wavefronts decreased to 0.82 +/- 0.14 per 100-ms window (P = 0.009). In conclusion, global electrophysiological imaging with a noncontact multielectrode probe delineates RA anatomy. Furthermore, images of AF activation depict multiple wandering wavefronts. Ibutilide reduces the number of these wavefronts and organizes AF.


Assuntos
Fibrilação Atrial/diagnóstico , Eletrocardiografia , Animais , Antiarrítmicos/farmacologia , Função do Átrio Direito/fisiologia , Estimulação Cardíaca Artificial , Cães , Eletrocardiografia/instrumentação , Eletrocardiografia/métodos , Feminino , Masculino , Marca-Passo Artificial , Sulfonamidas/farmacologia
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