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Biomedical subjects

F S Machado

Publications and source records attributed to F S Machado.

At least 19 recordsLinked to original sources

Clinical significance of ostial great saphenous vein reflux.

PURPOSE: To evaluate anatomical and haemodynamic differences in patients with great saphenous vein (GSV) insufficiency by duplex scanning and air plethysmography. MATERIAL AND METHODS: Duplex scanning and air plethysmography examination were undertaken. One hundred and twenty-one limbs in 91 patients were selected prospectively and divided into three groups: group A consisted of 27 controls; group B consisted of 25 limbs with GSV reflux and normal saphenous femoral junction (SFJ) and group C consisted of 69 limbs of patients with GSV and SFJ reflux. The presence of reflux and GSV diameter (SFJ, proximal and medial thirds of the thigh, the knee and medial and distal thirds of the calf) were assessed by duplex scanning. Air plethysmography was used to evaluate haemodynamic parameters: total venous volume (VV), venous filling index (VFI), residual volume fraction (RVF) and ejection fraction (EF). RESULTS: There was a significant difference in GSV diameter among the three groups in almost all segments evaluated (e.g. medial thigh group A = 2.4 SD 0.3 mm; B = 3.2 SD 0.7 mm; C = 5.9 SD 2.2mm p<0.001, Anova). A significant difference in VFI was found among the groups (group A = 1.2 SD 0.5; B = 2.0 SD 1.4; C = 4.0 SD 2.5 p<0.05, Anova). VV was statistical different between groups A and C (p = 0.004) and B and C(p = 0.03). EF and RVF were comparable in all groups. The VFI was normal in 68% in group B comparing with only 14.5% in group C patients, finding a reflux more than 5ml/s (determined by VFI) in 26.1% of the group C patients, comparing with only 4% of group B patients (p<0.05). CONCLUSION: We have shown that in patients with GSV reflux those with incompetence of the ostial valve of the GSV show greater venous reflux and dilatation of the saphenous trunk than those in whom the ostial valve is competent.

Adult↗

Mitochondrial damage as an early event of monensin-induced cell injury in cultured fibroblasts L929.

The present study was designed to identify, submicroscopically, the primary organelle or target structure for monensin in cultured murine fibroblasts L929. In addition, the effect of the drug on cell size and surface membranes of the cells were analysed; cellular proliferation, collagen secretion, and necrosis and apoptosis were re-evaluated. At the lowest concentration of monensin the foremost ultrastructural alteration occurred in the mitochondria, characterized by increased matrix density with disorganized and less distinct crystae. Incubation with monensin at higher concentrations resulted in severe mitochondrial damage and marked dilatation of the Golgi apparatus and rough endoplasmic reticulum cisternae. Fibroblasts exposed to higher concentrations of monensin were enlarged with decreased number of filopodia and hollows in the surface membrane. Moreover, monensin inhibited the cell proliferation, increased immunohistochemical positiveness for collagen type I in a dose-dependent manner, and, at high concentrations, caused cell necrosis whereas apoptosis was not induced. Taken together, these results show that monensin induces early mitochondrial damage, possibly causing an energy deficit that led to inhibition of fibroblasts proliferation and accumulation of collagen causing dilatation of Golgi apparatus and rough endoplasmic reticulum. Moreover, the mitochondrial damage would also explain the monensin-induced necrosis.

Animals↗

Diastolic function in Chagas' disease: an echo and tissue Doppler imaging study.

AIMS: With the purpose of studying left ventricular filling in Chagas' disease (Chd), we evaluated 169 patients with Chd using echocardiography and Doppler and tissue Doppler imaging (TDI). METHODS AND RESULTS: The patients were divided into four groups according to the pattern of left ventricular filling: Group 0--normal filling pattern, Group 1--abnormal relaxation, Group 2--pseudonormal flow pattern, and Group 3--restrictive pattern. All patients were submitted to TDI of the basal portion of the left ventricle's walls. Diastolic dysfunction was found in 21.3% of the patients, with a strong correlation between the worsening of diastolic function and ejection fraction (r = 0.78, P < 0.001). TDI septal e' wave measurement was the best method for the detection of any kind of diastolic dysfunction. Considering a cut-off point of 11 cm/s, a reduced e' wave value has 97% sensitivity, 84% specificity, 62% positive predictive value, and 99% negative predictive value. The septal E/e' ratio was the best index for the detection of advanced diastolic dysfunction. Considering a cut-point of 7.2, an elevated E/e' ratio has 100% sensitivity, 88% specificity, 54.2% positive predictive value, and 100% negative predictive value. CONCLUSION: This study showed the characterization of the various patterns of left ventricle diastolic function by echocardiography and Doppler in Chagas' disease and the usefulness of TDI in the assessment of diagnosis of diastolic dysfunction in this disease.

Adult↗

Leukotriene B(4) induces nitric oxide synthesis in Trypanosoma cruzi-infected murine macrophages and mediates resistance to infection.

The production of nitric oxide (NO) by gamma interferon (IFN-gamma)-activated macrophages is a major effector mechanism during experimental Trypanosoma cruzi infection. In addition to IFN-gamma, chemoattractant molecules, such as platelet-activating factor (PAF) and CC chemokines, may also activate macrophages to induce NO and mediate the killing of T. cruzi in an NO-dependent manner. Here we investigated the ability of leukotriene B(4) (LTB(4)) to induce the production of NO by macrophages infected with T. cruzi in vitro and whether NO mediated LTB(4)-induced parasite killing. The activation of T. cruzi-infected but not naive murine peritoneal macrophages with LTB(4) induced the time- and concentration-dependent production of NO. In addition, low concentrations of LTB(4) acted in synergy with IFN-gamma to induce NO production. The NO produced mediated LTB(4)-induced microbicidal activity in macrophages, as demonstrated by the inhibitory effects of an inducible NO synthase inhibitor. LTB(4)-induced NO production and parasite killing were LTB(4) receptor dependent and were partially blocked by a PAF receptor antagonist. LTB(4) also induced significant tumor necrosis factor alpha (TNF-alpha) production, and blockade of TNF-alpha suppressed LTB(4)-induced NO release and parasite killing. A blockade of LTB(4) or PAF receptors partially inhibited IFN-gamma-induced NO and TNF-alpha production but not parasite killing. Finally, daily treatment of infected mice with CP-105,696 was accompanied by a significantly higher level of blood parasitemia, but not lethality, than that seen in vehicle-treated animals. In conclusion, our results suggest a role for LTB(4) during experimental T. cruzi infection. Chemoattractant molecules such as LTB(4) not only may play a major role in leukocyte migration into sites of inflammation in vivo but also, in the event of an infection, may play a relevant role in the activation of recruited leukocytes to kill the invading microorganism in an NO-dependent manner.

Animals↗

Doppler tissue imaging to evaluate early myocardium damage in patients with undetermined form of Chagas' disease and normal echocardiogram.

Chagas' disease can lead to severe and potentially lethal damage of cardiac function. Thus, the identification of contractile abnormalities in asymptomatic patients can be important for risk stratification in those patients. Doppler tissue imaging (DTI) is a new diagnostic modality for the study of regional and longitudinal contractility of the left ventricle. However, DTI has not been used for the assessment of Chagas' cardiopathy. The purpose of this study was to identify abnormalities related to longitudinal contractility by means of DTI in patients with an undetermined form of Chagas' disease and with normal echocardiogram and Doppler studies. Forty patients were studied, including 21 chagasic ones with normal electrocardiographic, radiologic, and echocardiographic studies, and 19 normal control individuals. All of the patients were submitted to DTI to evaluate longitudinal contractility in the various myocardial segments, including assessment of systolic and diastolic velocities and isovolumic contraction time (IVCT). Similar values were observed among the various systolic function rates in both groups, except for the IVCT along the septal wall, which was significantly higher in the chagasic group. DTI enabled the early detection of contractile abnormalities in patients with an undetermined form of Chagas' disease and with normal echocardiogram. Such abnormalities were particularly striking in the interventricular septum. The present study could be useful in risk stratification for those patients.

Adult↗

Tissue Doppler imaging enables the identification of diastolic dysfunction of pseudonormal pattern in Chagas' disease.

The Doppler pseudonormal pattern of left ventricular (LV) diastolic function filling, characterized by apparent normal transmitral flow velocities, indicates advanced diastolic dysfunction with abnormal relaxation and compliance. Left ventricular diastolic dysfunction has been shown to occur in the early stages of the outcome of Chagas cardiopathy, and its identification may potentially contribute to the management of those patients. The aim of this study was to evaluate the usefulness of tissue Doppler imaging (TDI) in identifying LV diastolic dysfunction in patients with Chagas' disease with pseudonormal transmitral flow. For this purpose, 89 patients with Chagas' disease (48 men) who had no other pathology and showed normal (n = 79) or pseudonormal (n = 10) patterns of diastolic function by pulsed wave Doppler were submitted to TDI. A significant LV systolic impairment in terms of the dimensions (P = .00001), ejection fraction (P = .000001), and wall motion score (P = .000002) was observed in patients with diastolic dysfunction when compared with the group with normal LV diastolic function. Tissue Doppler imaging enabled the recognition of a pseudonormal type of transmitral flow velocity with high statistical significance through early (P = .000008) and late (P = .0003) expansion waves. The sensitivity and specificity in detecting LV diastolic dysfunction with TDI in the septal, anterior, inferior, posterior, and lateral walls were 90% and 87.3%, 87.3% and 90%, 87.3% and 90%, 84.8% and 90%, and 84.8 and 90%, respectively. In conclusion, TDI enabled the differentiation of patients with Chagas' disease with normal LV diastolic function and those with the pathologic LV pseudonormal pattern with high statistical significance. Moreover, this article shows the potential in demonstrating the occurrence of major alterations in the LV performance of patients with Chagas' disease with LV diastolic dysfunction, as well as the occurrence of signs of an increased LV filling pressure in those patients.

Chagas Cardiomyopathy↗

Trypanosoma cruzi-infected cardiomyocytes produce chemokines and cytokines that trigger potent nitric oxide-dependent trypanocidal activity.

BACKGROUND: The pathogenesis of myocarditis that occurs in Trypanosoma cruzi-infected mice is still poorly understood. Therefore, it is important to know the mediators that trigger leukocyte migration to the heart as well as the cellular source of these possible mediators. In this study, we investigated (1) NO synthase (NOS) induction, (2) NO synthesis, (3) trypanocidal activity, and (4) chemokine and cytokine mRNA expression by isolated cardiomyocytes infected with T cruzi. METHODS AND RESULTS: Mouse cardiomyocytes were isolated, infected with T cruzi, and evaluated for induction of inducible NOS (iNOS), nitrite production, trypanocidal activity, and cytokine and chemokine mRNA expression. We found that T cruzi-infected murine embryonic cardiomyocytes produced nitrite and expressed mRNAs for the chemokines chemokine growth-related oncogene, monokine induced by interferon-gamma, macrophage inflammatory protein-2, interferon-gamma-inducible protein, RANTES, and monocyte chemotactic protein, for iNOS, and for the cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta. Separate addition of IL-1beta, interferon-gamma, TNF-alpha or monocyte chemotactic protein, macrophage inflammatory protein-2, and interferon-gamma-inducible protein, to cultured cardiomyocytes resulted in NO production but low trypanocidal activity. However, simultaneous addition of IL-1beta, interferon-gamma, and TNF-alpha or the chemokines to cultures resulted in the induction of iNOS, high levels of nitrite, and a marked trypanocidal activity. The iNOS/L-arginine pathway mediated the latter activity, inasmuch as it was inhibited by treatment with N:(G)-monomethyl-L-arginine. CONCLUSIONS: These results indicate that iNOS activation and the proinflammatory cytokines and chemokines produced by cardiomyocytes are likely to control parasite growth and cell influx, thus contributing to the pathogenesis of chagasic cardiomyopathy seen in T cruzi-infected mice.

Animals↗

A narrow QRS does not predict a normal left ventricular function in Chagas' disease.

Left ventricular (LV) systolic dysfunction is a major prognostic determinant in Chagas' disease (ChD), a potentially fatal disorder which affects nearly 20 million individuals in Latin America. Therefore, reliable screening methods are needed to identify patients in need of a detailed evaluation of LV function. Since previous reports have suggested that a prolonged QRS duration may be an accurate predictor of LV dysfunction, the relationship between QRS duration and LV function was evaluated in ChD patients, in order to determine whether a narrow QRS on surface electrocardiogram (ECG) predicts a normal LV function. Ninety-eight patients with ChD and no other cardiac or systemic illness were underwent standard 12-lead ECG and Doppler echocardiogram (echo) examination. An investigator (blinded to the echo data) measured manually the QRS duration. LV dysfunction was defined by the presence of LV dilatation (LV diastolic dimension > 55 mm), depressed LV ejection fraction (LVEF < 0.50), segmental contractile abnormalities (SCA) or LV aneurysm. QRS duration was significantly correlated with LV diastolic dimension (r = 0.44, P = 0.000) and LVEF (r = 0.24, P = 0.016). A significant percentage of patients with QRS < 100 ms had abnormal systolic LV parameters, including LV dilatation (8.1%), reduced EF (10.2%), SCA (42.8%) and LV aneurysm (14.2%). A narrow QRS does not exclude the presence of significant global and segmental LV dysfunction in ChD patients. Since these abnormalities have prognostic and therapeutic implications, further evaluation of LV systolic performance is desirable in such patients.

Adult↗

Platelet-activating factor induces nitric oxide synthesis in Trypanosoma cruzi-infected macrophages and mediates resistance to parasite infection in mice.

Trypanosoma cruzi replicates in nucleated cells and is susceptible to being killed by gamma interferon-activated macrophages through a mechanism dependent upon NO biosynthesis. In the present study, the role of platelet-activating factor (PAF) in the induction of NO synthesis and in the activation of the trypanocidal activity of macrophages was investigated. In vitro, PAF induced NO secretion by T. cruzi-infected macrophages and the secreted NO inhibited intracellular parasite growth. The addition of a PAF antagonist, WEB 2170, inhibited both NO biosynthesis and trypanocidal activity. The inducible NO synthase/L-arginine pathway mediated trypanocidal activity, since it was inhibited by treatment with L-N-monomethyl arginine (L-NMMA), an L-arginine analog. PAF-mediated NO production in infected macrophages appears to be dependent on tumor necrosis alpha (TNF-alpha) production, since the addition of a neutralizing anti-TNF-alpha monoclonal antibody mAb inhibited NO synthesis. To test the role of PAF in mediating resistance or susceptibility to T. cruzi infection, infected mice were treated with WEB 2170, a PAF antagonist. These animals had higher parasitemia and earlier mortality than did vehicle-treated mice. Taken together, our results suggest that PAF belongs to a group of mediators that coordinate the mechanisms of resistance to infections with intracellular parasites.

Animals↗

beta-Chemokines enhance parasite uptake and promote nitric oxide-dependent microbiostatic activity in murine inflammatory macrophages infected with Trypanosoma cruzi.

In the present study, we describe the ability of Trypanosoma cruzi trypomastigotes to stimulate the synthesis of beta-chemokines by macrophages. In vivo infection with T. cruzi led to MIP-1alpha, RANTES, and JE/MCP1 mRNA expression by cells from peritoneal inflammatory exudate. In addition, in vitro infection with T. cruzi resulted in expression of beta-chemokine MIP-1alpha, MIP-1beta, RANTES, and JE mRNA by macrophages. The expression of the beta-chemokine MIP-1alpha, MIP-1beta, RANTES, and JE proteins by murine macrophages cultured with trypomastigote forms of T. cruzi was confirmed by immunocytochemistry. Interestingly, macrophage infection with T. cruzi also resulted in NO production, which we found to be mediated mainly by beta-chemokines. Hence, treatment with anti-beta-chemokine-specific neutralizing antibodies partially inhibited NO release by macrophages incubated with T. cruzi parasites. Further, the addition of the exogenous beta-chemokines MIP-1alpha, MIP-1beta, RANTES, and JE/MCP-1 induced an increased T. cruzi uptake, leading to enhanced NO production and control of parasite replication in a dose-dependent manner. L-NMMA, a specific inhibitor of the L-arginine-NO pathway, caused a decrease in NO production and parasite killing when added to cultures of macrophages stimulated with beta-chemokines. Among the beta-chemokines tested, JE was more potent in inhibiting parasite growth, although it was much less efficient than gamma interferon (IFN-gamma). Nevertheless, JE potentiates parasite killing by macrophages incubated with low doses of IFN-gamma. Together, these results suggest that in addition to their chemotactic activity, murine beta-chemokines may also contribute to enhancing parasite uptake and promoting control of parasite replication in macrophages and may play a role in resistance to T. cruzi infection.

Animals↗

[Primary hyperaldosteronism--12 clinical cases].

STUDY OBJECTIVES: To show clinical, biochemical, and morphological data of 12 patients with primary hyperaldosteronism: eight with an aldosterone-producing adenoma and four with adrenal hyperplasia. To compare clinical and biochemical parameters of the patients with adenoma and hyperplasia. For those with adenoma, to verify clinical and biochemical modifications after adrenalectomy. PATIENTS AND METHODS: In the 12 patients with hyperaldosteronism, retrospective analysis of clinical (age, sex, blood pressure), biochemical (plasmatic and urinary potassium, plasmatic aldosterone, plasma renin activity, and plasmatic aldosterone/renin activity ratio), and morphological (computed tomography, magnetic resonance, and norcholesterol scintigraphy) data was performed. RESULTS: 1--In the 12 patients with hyperaldosteronism (seven female), the age was 51.0 +/- 10.2 years (mean +/- standard deviation), the systolic pressure 200.9 +/- 34.5 mm Hg and the diastolic pressure 120.0 +/- 12.3 mm Hg. Hypertension was diagnosed 12.0 +/- 10.1 years before. As biochemical evidence, we found kalaemia of 3.06 +/- 0.28 and urinary potassium of 63.4 +/- 16.5 mEq/l, renin activity 0.98 +/- 1.02 ng/ml/h, plasmatic aldosterone of 49.4 +/- 36.0 ng/dl, aldosterone/renin activity > 30 in 83% of the cases. As morphological evidence, computed tomography allowed diagnosis in nine patients, suggested it in two, being doubtful in one. Performed on four patients, resonance confirmed the tomography in three and was not contributive in one. The scintigraphy performed in four patients visualized two adenomas, was negative in one adenoma and in one hyperplasia. 2--In the eight patients with adenoma (six female), the youngest age and the highest diastolic pressure compared with patients with hyperplasia were statistically significant (p < 0.01 and 0.05). In the adenomas, the biochemical changes were more pronounced, but not statistically significant. The plasmatic aldosterone/renin activity ratio was also higher in the adenoma cases. 3--After the adrenalectomy, blood pressure became normal in five patients and was more easily therapeutically controlled in three. The average systolic and diastolic pressures decreased and the biochemical parameters became normal in all patients. The pre/post surgical modification of these parameters had statistical significance (systolic pressure decrease, p < 0.01; diastolic pressure decrease, p < 0.01; kalaemia increase, p < 0.001; renin activity increase, p < 0.01; aldosterone decrease, p < 0.02). The plasmatic aldosterone/renine activity ratio normalized in all patients. CONCLUSIONS: In diagnosing primary hyperaldosteronism, biochemical (kalaemia, urinary potassium, plasmatic aldosterone, renin activity, aldosterone plasmatic/renin activity) and tomography studies were important. On comparing the patients with hyperplasia with those with adenoma, we found that the latter are younger and exhibit higher diastolic pressure, both findings with statistical significance. After adenoma surgery, blood pressure became normal in five patients and improved in three, these findings, and the improvement of the kalaemia, plasmatic aldosterone, and renin activity parameters were statistically significant.

Adenoma↗

[Renovascular arterial hypertension. Importance of subtraction digital angiography in its diagnosis].

The objective of this study is to contribute to the positioning of the intravenous digital subtraction angiography (IVDSA) in the detection of morphologic abnormalities of renal arteries (RAs), susceptible to originate renovascular hypertension (RVH). The authors focus on the prevalence of RVH in the broad spectrum of systemic arterial hypertension. The definition of RVH is given and its diagnostic criteria are revisited. The angiography methods used in the evaluation of RAs morphologic abnormalities are described.

Angiography, Digital Subtraction↗

Takayasu's arteritis and pregnancy: a case of deleterious association.

The association of pregnancy with Takayasu's arteritis is almost always uneventful. A case with high values of maternal blood pressure (BP) and severe intra-uterine growth retardation (IUGR), submitted to aggressive management with the delivery of a live fetus at 30 weeks, is presented.

Adult↗

[Endocrine arterial hypertension. Pheochromocytoma].

The authors emphasize some embryologic features of the chromaffin tissue as a basis of understanding of both the physiopathologic and clinical aspects of Pheochromocytoma. The appropriate sequence of diagnostic procedures was established in order to obtain clinical, biochemical and anatomical evidence of the tumor. It was concluded that an early diagnosis is mandatory in order to plan a curative surgical therapeutic approach. The embryologic and biochemical understanding of the Pheochromocytoma, in the context of the neuroendocrine tumors, allows a better rationale both for the diagnosis and therapy of this condition.

Adrenal Gland Neoplasms↗

[Endocrine arterial hypertension. Primary hyperaldosteronism].

The authors emphasize some adrenal embryologic features, mainly the cortex and medulla relationships. After brief considerations both on the biosynthesis and physiologic actions of aldosterone, the Primary Hyperaldosteronism physiopathology is described. The clinical, biochemical and anatomic evidences are presented as a basis for both the Syndrome diagnosis and its subtypes. The theoretical and practical aspects of the diagnostic tests are also referred as a basis for the rationale of the medical and surgical therapeutic approach. Some clinical and biochemical similar aspects between the Syndrome of Hyperaldosteronism and Essential Hypertension with low renin, are put forward as a possible physiopathologic link that could eventually contribute for a better understanding of the pathogenesis of Essential Hypertension.

Aldosterone↗