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1.
J Cardiovasc Pharmacol Ther ; 23(6): 561-569, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29779420

RESUMO

In previous studies, it was demonstrated that lipid core nanoparticles (LDE) resemble the low-density lipoprotein structure and carrying the antiproliferative agent paclitaxel (PTX) strongly reduced atherosclerosis lesions induced in rabbits by cholesterol feeding. Currently, the aim was to verify whether combining LDE-PTX treatment with methotrexate (MTX) associated with LDE (LDE-MTX) could accelerate the atherosclerosis regression attained with single LDE-PTX treatment, after withdrawing the cholesterol feeding. Thirty-eight rabbits were fed 1% cholesterol chow for 8 weeks. Six of these rabbits were then euthanized for analyses of the aorta (controls). In the remaining rabbits, cholesterol feeding was withdrawn, and those 32 animals were allocated to 3 groups submitted to different 8-week intravenous treatments, all once/week: LDE-PTX (n = 10; 4 mg/kg), LDE-PTX + LDE-MTX (n = 11; 4 mg/kg), and LDE-alone (n = 11). Rabbits were then euthanized and aortas were excised for morphometric, immunohistochemical, and gene expression analyses. After cholesterol feeding withdrawal, in comparison with LDE-alone group, both LDE-PTX and LDE-PTX + LDE-MTX treatments had the ability to increase the regression of plaque areas: -49% in LDE-PTX and -59% for LDE-PTX + LDE-MTX. However, only LDE-PTX + LDE-MTX treatment elicited reduction in the intima area, estimated in -57%. Macrophage presence in aortic lesions was reduced 48% by LDE-PTX and 43% by LDE-PTX + LDE-MTX treatment. Matrix metalloproteinase 9 was reduced by either LDE-PTX (74%) or LDE-PTX + LDE-MTX (78%). Tumor necrosis factor α gene expression was reduced 65% by LDE-PTX and 79% by LDE-PTX + LDE-MTX. In conclusion, treatment with LDE-PTX indeed accelerated plaque reduction after cholesterol feeding; LDE-PTX + LDE-MTX further increased this effect, without any observed toxicity. These results pave the way for the use of combined chemotherapy to achieve stronger effects on aggravated, highly inflamed atherosclerotic lesions.


Assuntos
Aorta/efeitos dos fármacos , Doenças da Aorta/prevenção & controle , Aterosclerose/tratamento farmacológico , Fármacos Cardiovasculares/administração & dosagem , Colesterol na Dieta , Lipídeos/química , Metotrexato/administração & dosagem , Nanopartículas , Paclitaxel/administração & dosagem , Placa Aterosclerótica , Animais , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/sangue , Doenças da Aorta/patologia , Aterosclerose/sangue , Aterosclerose/patologia , Fármacos Cardiovasculares/química , Citocinas/metabolismo , Modelos Animais de Doenças , Composição de Medicamentos , Quimioterapia Combinada , Mediadores da Inflamação/metabolismo , Lipossomos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Metotrexato/química , Paclitaxel/química , Coelhos
2.
J Am Coll Cardiol ; 56(4): 278-87, 2010 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-20633819

RESUMO

OBJECTIVES: We sought to determine whether the quantitative assessment of myocardial fibrosis (MF), either by histopathology or by contrast-enhanced magnetic resonance imaging (ce-MRI), could help predict long-term survival after aortic valve replacement. BACKGROUND: Severe aortic valve disease is characterized by progressive accumulation of interstitial MF. METHODS: Fifty-four patients scheduled to undergo aortic valve replacement were examined by ce-MRI. Delayed-enhanced images were used for the quantitative assessment of MF. In addition, interstitial MF was quantified by histological analysis of myocardial samples obtained during open-heart surgery and stained with picrosirius red. The ce-MRI study was repeated 27+/-22 months after surgery to assess left ventricular functional improvement, and all patients were followed for 52+/-17 months to evaluate long-term survival. RESULTS: There was a good correlation between the amount of MF measured by histopathology and by ce-MRI (r=0.69, p<0.001). In addition, the amount of MF demonstrated a significant inverse correlation with the degree of left ventricular functional improvement after surgery (r=-0.42, p=0.04 for histopathology; r=-0.47, p=0.02 for ce-MRI). Kaplan-Meier analyses revealed that higher degrees of MF accumulation were associated with worse long-term survival (chi-square=6.32, p=0.01 for histopathology; chi-square=5.85, p=0.02 for ce-MRI). On multivariate Cox regression analyses, patient age and the amount of MF were found to be independent predictors of all-cause mortality. CONCLUSIONS: The amount of MF, either by histopathology or by ce-MRI, is associated with the degree of left ventricular functional improvement and all-cause mortality late after aortic valve replacement in patients with severe aortic valve disease.


Assuntos
Estenose da Valva Aórtica/patologia , Imagem por Ressonância Magnética/métodos , Miocárdio/patologia , Índice de Gravidade de Doença , Adulto , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/fisiopatologia , Feminino , Fibrose/etiologia , Humanos , Imagem por Ressonância Magnética/normas , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto Jovem
3.
J Physiol ; 588(Pt 13): 2431-42, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20442263

RESUMO

Myocardial hypertrophy and dysfunction occur in response to excessive catecholaminergic drive. Adverse cardiac remodelling is associated with activation of proinflammatory cytokines in the myocardium. To test the hypothesis that exercise training can prevent myocardial dysfunction and production of proinflammatory cytokines induced by beta-adrenergic hyperactivity, male Wistar rats were assigned to one of the following four groups: sedentary non-treated (Con); sedentary isoprenaline treated (Iso); exercised non-treated (Ex); and exercised plus isoprenaline (Iso+Ex). Echocardiography, haemodynamic measurements and isolated papillary muscle were used for functional evaluations. Real-time RT-PCR and Western blot were used to quantify tumour necrosis factor alpha, interleukin-6, interleukin-10 and transforming growth factor beta(1) (TGF-beta(1)) in the tissue. NF-B expression in the nucleus was evaluated by immunohistochemical staining. The Iso rats showed a concentric hypertrophy of the left ventricle (LV). These animals exhibited marked increases in LV end-diastolic pressure and impaired myocardial performance in vitro, with a reduction in the developed tension and maximal rate of tension increase and decrease, as well as worsened recruitment of the Frank-Starling mechanism. Both gene and protein levels of tumour necrosis factor alpha and interleukin-6, as well as TGF-beta(1) mRNA, were increased. In addition, the NF-B expression in the Iso group was significantly raised. In the Iso+Ex group, the exercise training had the following effects: (1) it prevented LV hypertrophy; (ii) it improved myocardial contractility; (3) it avoided the increase of proinflammatory cytokines and improved interleukin-10 levels; and (4) it attenuated the increase of TGF-beta(1) mRNA. Thus, exercise training in a model of beta-adrenergic hyperactivity can avoid the adverse remodelling of the LV and inhibit inflammatory cytokines. Moreover, the cardioprotection is related to beneficial effects on myocardial performance.


Assuntos
Cardiomiopatias/prevenção & controle , Cardiomiopatias/fisiopatologia , Citocinas/metabolismo , Condicionamento Físico Animal/fisiologia , Receptores Adrenérgicos beta/fisiologia , Agonistas Adrenérgicos beta/farmacologia , Animais , Western Blotting , Cardiomegalia/induzido quimicamente , Cardiomegalia/fisiopatologia , Cardiomiopatias/induzido quimicamente , Cardiotônicos/farmacologia , Circulação Coronária/fisiologia , Ecocardiografia , Imuno-Histoquímica , Inflamação/metabolismo , Isoproterenol/farmacologia , Masculino , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , NF-kappa B/biossíntese , Ratos , Ratos Wistar , Receptores Adrenérgicos beta/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Necrose Tumoral alfa/metabolismo , Função Ventricular Esquerda/fisiologia
4.
BMC Microbiol ; 9: 194, 2009 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-19744321

RESUMO

BACKGROUND: Chamydophila pneumoniae (CP) and/or Mycoplasma pneumoniae (MP) are two bacteria detected in vulnerable atheromas. In this study we aimed to analyze whether CP and/or MP aggravates atherosclerosis induced by cholesterol-enriched diet in C57BL/6 apoE KO male mice. Thirty male apoE KO mice aged eight weeks fed by a diet containing 1% cholesterol until 32 weeks of age were divided into four groups: the first was inoculated with CP (n = 7), the second with MP (n = 12), the third with both CP + MP (n = 5), and the fourth with saline (sham n = 6). The animals were re-inoculated at 36 weeks of age, and sacrificed at 40 weeks of age. Two ascending aorta and one aortic arch segments were sampled. In the most severely obstructed segment, vessel diameter, plaque height, percentage of luminal obstruction and the degree of adventitial inflammation were analyzed. The plaque area/intimal surface ratio was obtained by measuring all three segments. The adventitial inflammation was semiquantified (0 absent, 1 mild, 2 moderate, and 3 diffuse). RESULTS: The mean and standard deviation of plaque height, % luminal obstruction, external diameter, the plaque area/intimal surface ratio and the adventitial inflammation values are the following for each group: MP (0.20 +/- 0.12 mm, 69 +/- 26%, 0.38 +/- 0.11 mm, 0.04 +/- 0.04 and 0.22 +/- 0.67), CP (0.23 +/- 0.08 mm, 90 +/- 26%, 0.37 +/- 0.08 mm, 0.04 +/- 0.03, and 0.44 +/- 0.53), MP + CP (18 +/- 0.08 mm, 84 +/- 4.0%, 0.35 +/- 0.25 mm, 0.03 +/- 0.03 and 1.33 +/- 0.82) and sham (0.08 +/- 0.09 mm, 42 +/- 46%, 0.30 +/- 0.10 mm, 0.02 +/- 0.03 and 0.71 +/- 0.76). A wider area of plaque/intimal surface was observed in MP + CP inoculated groups (p = 0.07 and 0.06) as well as an increased plaque height in CP (p = 0.01) in comparison with sham group. There was also an increased luminal obstruction (p = 0.047) in CP inoculated group in comparison to sham group. Adventitial inflammation in MP + CP inoculated group was higher than MP, CP and the sham groups (p = 0.02). CONCLUSION: Inoculation of CP, MP or both agents in C57BL/6 apoE KO male mice caused aggravation of experimental atherosclerosis induced by cholesterol-enriched diet, with distinct characteristics. CP inoculation increased the plaque height with positive vessel remodeling and co-inoculation of MP + CP caused the highest adventitial inflammation measures.


Assuntos
Aterosclerose/complicações , Infecções por Chlamydophila/complicações , Pneumonia por Mycoplasma/complicações , Animais , Aorta/microbiologia , Aorta/patologia , Doenças da Aorta/complicações , Doenças da Aorta/microbiologia , Aterosclerose/microbiologia , Chlamydophila pneumoniae , Colesterol na Dieta , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mycoplasma pneumoniae
5.
Eur J Heart Fail ; 10(6): 534-9, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18502686

RESUMO

BACKGROUND: Sustained beta-adrenoreceptor activation promotes cardiac hypertrophy and cellular injury. AIMS: To evaluate the cardioprotective effect of exercise on damage induced by beta-adrenergic hyperactivity. METHODS: Male Wistar rats were randomised into four groups (n=8 per group): sedentary non-treated control (C), sedentary treated with isoproterenol 0.3 mg/kg/day administered subcutaneously for 8 days (I), exercised non-treated (E) and exercised plus isoproterenol administered during the last eight days of exercise (IE). Exercised animals ran on a treadmill for 1 h daily 6 times a week for 13 weeks. RESULTS: Isoproterenol caused increases in left ventricle (LV) wet and dry weight/body weight ratio, LV water content and cardiomyocyte transverse diameter. Additionally, isoproterenol induced severe cellular lesions, necrosis, and apoptosis, increased collagen content and reduced capillary and fibre fractional areas. Notably, all of these abnormalities were completely prevented by exercise. CONCLUSION: Our data have demonstrated that complete cardioprotection is possible through exercise training; by preventing beta-adrenergic hyperactivity-induced cardiac hypertrophy and structural injury.


Assuntos
Agonistas Adrenérgicos beta/efeitos adversos , Cardiomegalia/patologia , Cardiomegalia/prevenção & controle , Isoproterenol/efeitos adversos , Condicionamento Físico Animal , Receptores Adrenérgicos beta/fisiologia , Animais , Cardiomegalia/etiologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Marcação In Situ das Extremidades Cortadas , Masculino , Ratos , Ratos Wistar , Receptores Adrenérgicos beta/efeitos dos fármacos
6.
Int J Cardiol ; 116(2): 279-80, 2007 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-16839625

RESUMO

Morphometric data obtained from the analysis of endomyocardial biopsy might be useful to evaluate prognosis of patients with dilated cardiomyopathy. We measured the myocyte diameter, its coefficient of variation and the fractional area of collagen in right ventricular endomyocardial biopsies of 35 outpatients with idiopathic dilated cardiomyopathy. None of the evaluated histological parameter was associated with the survival time of the patients (range: 2 to 5588; median: 706 days). Right ventricular endomyocardial biopsy should not be indicated to predict evolution or fatal outcome in patients with idiopathic dilated cardiomyopathy.


Assuntos
Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/patologia , Colágeno/metabolismo , Endocárdio/patologia , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Adolescente , Adulto , Biópsia , Tamanho Celular , Endocárdio/metabolismo , Feminino , Ventrículos do Coração , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Pacientes Ambulatoriais , Análise de Sobrevida , Distribuição Tecidual
7.
Clinics (Sao Paulo) ; 61(5): 473-8, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17072447

RESUMO

PURPOSE: Vulnerable plaques are characterized by a myxoid matrix, necrotic lipidic core, reactive oxygen species, and high levels of microorganisms. Aerobic microbes such as Chlamydophila pneumoniae and Mycoplasma pneumoniae usually do not survive in oxidative stress media. Archaea are anaerobic microbes with powerful anti-oxidative enzymes that allow detoxification of free radicals whose presence might favor the survival of aerobic microorganisms. We searched for archaeal organisms in vulnerable plaques, and possible associations with myxoid matrix, chlamydia, and mycoplasma bodies. METHODS: Twenty-nine tissue samples from 13 coronary artherectomies from large excentric ostial or bifurcational lesions were studied using optical and electron microscopy. Infectious agents compatible with archaea, chlamydia, and mycoplasma were semiquantified using electron micrographs and correlated with the amounts of fibromuscular tissue, myxoid matrix, and foam cells, as determined from semi-thin sections. Six of the cases were also submitted to polymerase chain reaction with archaeal primers. RESULTS: All 13 specimens showed archaeal-compatible structures and chlamydial and mycoplasmal bodies in at least 1 sample. There was a positive correlation between extent of the of myxoid matrix and archaeal bodies (r = 0.44, P = 0.02); between archaeal and mycoplasmal bodies (r = 0.41, P = 0.03), and between chlamydial bodies and foam cells (r = 0.42; P = 0.03). The PCR test was positive for archaeal DNA in 4 of the 6 fragments. DISCUSSION: DNA and forms suggestive of archaea are present in vulnerable plaques and may have a fundamental role in the proliferation of mycoplasma and chlamydia. This seems to be the first description of apparently pathogenic archaea in human internal organ lesions.


Assuntos
Archaea/isolamento & purificação , Chlamydophila pneumoniae/isolamento & purificação , Doença da Artéria Coronariana/microbiologia , Mycoplasma pneumoniae/isolamento & purificação , Idoso , Animais , Archaea/genética , Archaea/ultraestrutura , Chlamydophila pneumoniae/ultraestrutura , Doença da Artéria Coronariana/patologia , DNA Bacteriano , Feminino , Células Espumosas/ultraestrutura , Humanos , Lipídeos/análise , Masculino , Pessoa de Meia-Idade , Mycoplasma pneumoniae/ultraestrutura , Necrose/patologia , Reação em Cadeia da Polimerase , Espécies Reativas de Oxigênio/isolamento & purificação , Estatísticas não Paramétricas
8.
Clinics ; 61(5): 473-478, Oct. 2006. ilus, tab
Artigo em Inglês | LILACS | ID: lil-436773

RESUMO

PURPOSE: Vulnerable plaques are characterized by a myxoid matrix, necrotic lipidic core, reactive oxygen species, and high levels of microorganisms. Aerobic microbes such as Chlamydophila pneumoniae and Mycoplasma pneumoniae usually do not survive in oxidative stress media. Archaea are anaerobic microbes with powerful anti-oxidative enzymes that allow detoxification of free radicals whose presence might favor the survival of aerobic microorganisms. We searched for archaeal organisms in vulnerable plaques, and possible associations with myxoid matrix, chlamydia, and mycoplasma bodies. METHODS: Twenty-nine tissue samples from 13 coronary artherectomies from large excentric ostial or bifurcational lesions were studied using optical and electron microscopy. Infectious agents compatible with archaea, chlamydia, and mycoplasma were semiquantified using electron micrographs and correlated with the amounts of fibromuscular tissue, myxoid matrix, and foam cells, as determined from semi-thin sections. Six of the cases were also submitted to polymerase chain reaction with archaeal primers. RESULTS: All 13 specimens showed archaeal-compatible structures and chlamydial and mycoplasmal bodies in at least 1 sample. There was a positive correlation between extent of the of myxoid matrix and archaeal bodies (r = 0.44, P = 0.02); between archaeal and mycoplasmal bodies (r = 0.41, P = 0.03), and between chlamydial bodies and foam cells (r = 0.42; P = 0.03). The PCR test was positive for archaeal DNA in 4 of the 6 fragments. DISCUSSION: DNA and forms suggestive of archaea are present in vulnerable plaques and may have a fundamental role in the proliferation of mycoplasma and chlamydia. This seems to be the first description of apparently pathogenic archaea in human internal organ lesions.


PROPOSTA: Placas vulneráveis são caracterizadas por matriz mixomatosa, centro lipídico necrótico, espécies reativas de oxigênio e alto níveis de microorganismos. Micróbios aeróbicos como Chlamydophila pneumoniae e Mycoplasma pneumoniae usualmente não sobrevivem em meio de estresse oxidativo. Arquéias são microorganismos anaeróbicos com poderosas enzimas anti-oxidantes que permitem detoxificação de radicais livres e a presença delas poderia favorecer a sobrevivência de micróbios aeróbicos. Pesquisamos por elementos de arquéia em placas vulneráveis e sua possível associação com degeneração mixomatosa da matriz e aumento do número de clamídias e micoplasmas. MÉTODOS: Vinte e nove amostras de 13 produtos de aterotomia de lesões grandes e excêntricas de óstio ou bifurcação de coronárias foram estudadas pela microscopia óptica e eletrônica. Agentes compatíveis com arquéia, clamídia e micoplasma foram semiquantificados pela microscopia eletrônica e correlacionados com quantidade de tecido fibromuscular, matriz mixomatosa e células xantomatosas. Seis casos foram também submetidos à reação em cadeia da polimerase com oligonucleotídeos de arquéia. RESULTADOS: Os 13 casos foram positivos para estruturas sugestivas de arquéia, micoplasma ou clamídia, em pelo menos uma amostra. Houve correlação positiva entre intensidade de matriz mixomatosa versus arquéia (r=0.44, p=0.02); arquéia versus micoplasma (r=0.41, p=0.03) e clamídia versus células xantomatosas r=0,42; 0.03). PCR foi positiva para DNA de arqueia em 4 dos 6 fragmentos. DISCUSSÃO: DNA e formas compatíveis com arquéia estão presentes em placas vulneráveis e podem ter papel fundamental na proliferação de micoplasma e clamídia. Este parece ser o primeiro relato de arquéia aparentemente patogênica em lesões de órgãos internos humanos.


Assuntos
Humanos , Animais , Masculino , Feminino , Pessoa de Meia-Idade , Archaea/patogenicidade , Chlamydophila pneumoniae/isolamento & purificação , Doença da Artéria Coronariana/microbiologia , Mycoplasma pneumoniae/isolamento & purificação , Archaea/genética , Archaea/ultraestrutura , Chlamydophila pneumoniae/ultraestrutura , Doença da Artéria Coronariana/patologia , DNA Bacteriano , Células Espumosas/ultraestrutura , Lipídeos/análise , Mycoplasma pneumoniae/ultraestrutura , Necrose/patologia , Reação em Cadeia da Polimerase , Espécies Reativas de Oxigênio/isolamento & purificação , Estatísticas não Paramétricas
9.
APMIS ; 114(5): 338-44, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16725009

RESUMO

Mycoplasma pneumoniae (MP) and Chlamydophila pneumoniae (CP) antigens are encountered in complicated atheromas and may be implicated in the diversity of atherosclerotic lesions. Mycoplasma can downregulate the immune system, altering levels of inflammation, which may favor the proliferation of other co-infectious agents. In the present study we analyze whether initially stable human atheromas exhibit different ratios of MP/CP antigens compared to ongoing atheromatous lesions. Two groups were examined for the presence of inflammatory cells, macrophages, growth factors and infectious agents: Group I (GI), n=16, early stable atheromas, <4 CD68(+) macrophages/400 x field, showing a normal distribution and a fibrous cap; Group II (GII), n=14, growing atheromas, > or =4 CD68+ cells/400 x field, lacking a fibrous cap, showing a non-normal macrophage distribution. The amounts of CP (but not MP) antigens and lymphocytes in GI were significantly lower than in GII. MP/CP ratios were higher in GI. MP correlated with CP and PDGFB in GI (r=0.79 and r=0.83, p<0.001), but not in GII (r=-0.4 and r=-0.08, p=0.81). MP and CP antigens are already present in early atheromas, and a higher MP/CP ratio correlates with increased growth factors, lower inflammation and plaque stability.


Assuntos
Infecções por Chlamydophila/complicações , Chlamydophila pneumoniae/isolamento & purificação , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/microbiologia , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/análise , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Contagem de Células , Chlamydophila pneumoniae/imunologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/microbiologia , Vasos Coronários/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Inflamação/patologia , Macrófagos/citologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Mycoplasma pneumoniae/imunologia , Fator de Crescimento Derivado de Plaquetas/metabolismo
10.
Acta Cardiol ; 60(1): 33-7, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15779849

RESUMO

OBJECTIVE: The present work analysed endomyocardial biopsies of patients with acute Chagas' disease in order to evaluate the frequency and intensity of T. cruzi antigens, CD4+ and CD8+ T cells to determine the characteristics of this recurrent disease in Venezuela. MATERIAL AND METHODS: Twelve endomyocardial biopsies of patients with Chagas' disease, 12 to 51 years old, (7M and 5F) were analysed. T. cruzi antigens and CD4+ (helper) and CD8+ (cytotoxic-suppressor) T cells were detected by the immunoperoxidase technique. The presence and intensity of lymphocytic myocarditis was evaluated according to the degree of myocardial fibre injury caused by inflammatory infiltrate. RESULTS: Myocarditis was present in 100% of the cases. The mean numbers of CD4+ T cell and CD8+ T cell were 11.00 (+/- 10.29); 14.69 (+/- 13.08) and the CD4/CD8 T cell ratio was 0.75. T. cruzi antigens were detected in 58%. There was a good correlation between the numbers of CD4 and CD8 T cells of each case and a lack of correlation with the amount of T. cruzi antigens. CONCLUSION: All patients with acute Chagas' disease show some degree of myocarditis that seems to be directly related to the presence of parasitic antigens. Both CD4 and CD8 T cells participate in this process. We are following these patients to see if patients with severe myocarditis and more parasite antigens in the acute phase will develop chronic heart failure.


Assuntos
Antígenos de Protozoários/imunologia , Linfócitos T CD4-Positivos/imunologia , Cardiomiopatia Chagásica/prevenção & controle , Doença de Chagas/imunologia , Doença de Chagas/patologia , Trypanosoma cruzi/imunologia , Doença Aguda , Adolescente , Adulto , Análise de Variância , Animais , Antígenos de Protozoários/análise , Biópsia por Agulha , Relação CD4-CD8 , Linfócitos T CD4-Positivos/fisiologia , Cardiomiopatia Chagásica/imunologia , Doença de Chagas/epidemiologia , Criança , Estudos de Coortes , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prevalência , Probabilidade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Técnicas de Cultura de Tecidos , Trypanosoma cruzi/isolamento & purificação , Venezuela/epidemiologia
11.
Mod Pathol ; 16(5): 411-6, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12748246

RESUMO

The development and progression of pulmonary hypertension lesions involve continuous remodeling of the arterial wall, including the extracellular matrix components. The integrity of the internal elastic lamina may represent a barrier to cell migration and formation of intimal proliferative lesions. Some patients with congenital cardiac shunts develop precocious intimal occlusive lesions,whereas others evolve with isolated medial hypertrophy. We studied the 2-D and 3-D morphology of the internal elastic lamina of peripheral pulmonary arteries to search for any difference regarding the type of histological lesion. Fifteen lung biopsies collected for diagnostic purposes from patients with congenital shunts and 6 control lungs (mean ages, 15.8 and 14.7 mo) were studied using the confocal laser scanning microscope, under predetermined conditions of laser intensity, brightness and contrast. We measured the thickness of the internal elastic lamina and determined the number of gaps and projections of elastic tissue towards the medial and intimal layers. The mean internal elastic lamina thickness was significantly higher in arteries from cases with isolated medial hypertrophy when compared with controls and to those with proliferative lesions (P <.05). The number of gaps of the internal elastic lamina was higher in arteries >100 micro m in diameter from the group with intimal lesions when compared to the cases presenting with isolated hypertrophy, but did not differ from the controls. There was a positive linear correlation between the external arterial diameter and the thickness of the internal elastic lamina (r =.74, P <.001) in cases presenting isolated medial hypertrophy. The increased thickness and smaller number of gaps of the internal elastic lamina may act as a barrier that prevents smooth muscle cell migration in patients with pulmonary hypertension without intimal proliferative lesions. On the other hand, a greater number of gaps does not represent, by itself, unrestrained migration, because controls also showed fenestrated laminae.


Assuntos
Tecido Elástico/patologia , Cardiopatias Congênitas/patologia , Hipertensão Pulmonar/patologia , Artéria Pulmonar/patologia , Biópsia , Criança , Pré-Escolar , Feminino , Cardiopatias Congênitas/complicações , Humanos , Hipertensão Pulmonar/etiologia , Hipertrofia/patologia , Imagem Tridimensional , Lactente , Masculino , Microscopia Confocal , Túnica Íntima/patologia , Túnica Média/patologia
12.
Arq Bras Cardiol ; 79(1): 20-4, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12163942

RESUMO

OBJECTIVE: To verify the possible role of adventitial inflammation in atherosclerotic plaque vulnerability and coronary artery remodelling. METHODS: We compared the mean numbers of lymphocytes in the adventitia and in the plaque of ruptured thrombosed and stable equi-stenotic coronary segments of 34 patients who died due to acute myocardial infarction. We also analysed adventitial microvessels, adventitial fibrosis and the external elastic membrane. RESULTS: In the adventitia, the numbers of lymphocytes and microvessels/mm2 were 69.5+/-88.3 and 60.9+/- 32.1 in culprit lesions and 16.4 +/- 21.1 and 44.3+/-16.1 in stable lesions (p<0.05); within the plaques, the mean number of lymphocytes was 24+/-40.8 in culprit lesions and 10.9+/-13.2 in stable ones (p=0.17). The mean percent area of adventitial fibrosis/cross-sectional area of the vessel was significantly lower in unstable plaques (p<0.001). The confocal images showed holes in the external elastic membrane. CONCLUSION: Unstable plaques exhibit chronic pan-arteritis, accompanied by enlargement, medial thinning, and less fibrosis than in stable lesions, which is compatible with vessel aneurysm. Adventitial inflammation may contribute significantly to atheroma instability.


Assuntos
Arterite/patologia , Doença da Artéria Coronariana/patologia , Vasos Coronários/patologia , Endotélio Vascular/patologia , Cadáver , Humanos , Contagem de Linfócitos , Ruptura
13.
Arq. bras. cardiol ; 79(1): 20-24, July 2002. ilus, tab, graf
Artigo em Inglês | LILACS | ID: lil-316163

RESUMO

OBJECTIVE: To verify the possible role of adventitial inflammation in atherosclerotic plaque vulnerability and coronary artery remodelling. METHODS: We compared the mean numbers of lymphocytes in the adventitia and in the plaque of ruptured thrombosed and stable equi-stenotic coronary segments of 34 patients who died due to acute myocardial infarction. We also analysed adventitial microvessels, adventitial fibrosis and the external elastic membrane. RESULTS: In the adventitia, the numbers of lymphocytes and microvessels/mm² were 69.5±88.3 and 60.9± 32.1 in culprit lesions and 16.4 ± 21.1 and 44.3±16.1 in stable lesions (p<0.05); within the plaques, the mean number of lymphocytes was 24±40.8 in culprit lesions and 10.9±13.2 in stable ones (p=0.17). The mean percent area of adventitial fibrosis/cross-sectional area of the vessel was significantly lower in unstable plaques (p<0.001). The confocal images showed holes in the external elastic membrane. CONCLUSION: Unstable plaques exhibit chronic pan-arteritis, accompanied by enlargement, medial thinning, and less fibrosis than in stable lesions, which is compatible with vessel aneurysm. Adventitial inflammation may contribute significantly to atheroma instability


Assuntos
Humanos , Doença da Artéria Coronariana , Inflamação , Cadáver , Contagem de Linfócitos , Ruptura
14.
Rev. bras. cir. cardiovasc ; 16(4): 275-288, out.-dez. 2001. tab, graf
Artigo em Português | LILACS | ID: lil-304830

RESUMO

OBJETIVO: Nesta investigaçäo, os resultados tardios da ventriculectomia parcial esquerda, associada à correçäo da insuficiência das valvas atrioventriculares, foram estudados em 43 pacientes portadores de cardiomiopatia dilatada. CASUíSTICA E MÉTODOS: Os pacientes estavam em classe funcional III (18) ou IV (25) no pré-operatório, sendo que 7 pacientes foram operados na vigência de choque cardiogênico. A reduçäo cirúrgica do volume do ventrículo esquerdo (VE) foi associada à anuloplastia mitral em 32 pacientes e à substituiçäo daquela valva em 3. Em 10 pacientes, também foi realizada plastia de valva tricúspide. Doze pacientes foram submetidos ao implante de desfibriladores automáticos. RESULTADOS: Ocorreram 9 (20,9 por cento) óbitos hospitalares. O tempo de seguimento pós-operatório variou entre dois e 68 meses, com média de 34,2 meses. Aos seis meses de seguimento, 8 pacientes estavam em classe funcional I, 13 em classe II, 3 em classe III e 1 em classe IV (p<0,001). Por outro lado, outros 19 pacientes faleceram no seguimento tardio, sendo observados índices de sobrevida de 58 (?7 por cento em um ano, de 48 (?7 por cento aos dois anos e de 32?(?8 por cento aos cinco anos. A regressäo logística mostrou que a sobrevida nos primeiros seis meses foi influenciada pelo diâmetro das fibras miocárdicas. A análise da sobrevida tardia através do modelo proporcional de Cox mostrou que a classe funcional IV e o nível elevado de nor-adrenalina sérica no pré-operatório estavam relacionados a maior mortalidade. Quando a análise também incluiu variáveis anatomopatológicas, a existência de apoptose das células miocárdicas e o maior diâmetro das fibras miocárdicas no pré-operatório foram identificados como únicos fatores independentes de pior prognóstico tardio. Pacientes operados em classe funcional III ou IV apresentaram índices de sobrevida de 60,6?(?11,6 por cento e de 14,4?(?8,2 por cento em cinco anos, respectivamente. Na presença de apoptose das células miocárdicas, a sobrevida dos pacientes foi de 8,3?(?7,9 por cento no mesmo período, contra 63,1?(?11 por cento na ausência dessa alteraçäo. Em relaçäo à funçäo ventricular, os benefícios observados após a ventriculectomia parcial näo se mantiveram tardiamente. Houve redilataçäo progressiva do ventrículo esquerdo, associada à queda concomitante dos valores de sua fraçäo de ejeçäo. CONCLUSÄO: A ventriculectomia parcial esquerda, associada, quando necessário, à correçäo da insuficiência das...


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Cardiomiopatia Dilatada , Função Ventricular Esquerda/fisiologia , Ventrículos do Coração/cirurgia , Apoptose , Arritmias Cardíacas , Morte Súbita Cardíaca , Seguimentos , Insuficiência Cardíaca/mortalidade , Fibras Musculares Esqueléticas , Miocárdio , Norepinefrina , Prognóstico , Estudos Prospectivos , Intervalo Livre de Doença
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