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F Fernandes

Publications and source records attributed to F Fernandes.

At least 19 recordsLinked to original sources
PubMed2006

Binding assays of inhibitors towards selected V-ATPase domains.

The macrolide antibiotic bafilomycin and the related synthetic compound SB 242784 are potent inhibitors of the vacuolar H+ -ATPases (V-ATPase). It is currently believed that the site of action of these inhibitors is located on the membrane bound c-subunits of V-ATPases. To address the identification of the critical inhibitors binding domain, their specific binding to a synthetic peptide corresponding to the putative 4th transmembrane segment of the c-subunit was investigated using fluorescence resonance energy transfer (FRET), and for this purpose a specific formalism was derived. Another peptide of the corresponding domain of the c' isoform, was checked for binding of bafilomycin, since it is not clear if V-ATPase inhibition can also be achieved by interaction of the inhibitor with the c'-subunit. It was concluded that bafilomycin binds to the selected peptides, whereas SB 242784 was unable to interact, and in addition for bafilomycin, its interaction with the peptides either corresponding to the c- or the c'-subunit isoforms is identical. Since the observed interactions are however much weaker as compared to the very efficient binding of both bafilomycin and SB 242784 to the whole protein, it can be concluded that assembly of all V-ATPase transmembrane segments is required for an efficient interaction.

Amino Acid Sequence↗
PubMed2006

Interaction of the indole class of vacuolar H(+)-ATPase inhibitors with lipid bilayers.

The selective inhibitor of osteoclastic V-ATPase (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pentadienamide (SB 242784), member of the indole class of V-ATPase inhibitors, is expected to target the membrane-bound domain of the enzyme. A structural study of the interaction of this inhibitor with the lipidic environment is an essential step in the understanding of the mechanism of inhibition. In this work, a comprehensive study of the relevant features of this interaction was performed. Inhibitor partition coefficients to lipid vesicles as well as its transverse location, orientation (order parameters), and dynamics while bound to bilayers were determined through photophysical techniques, taking advantage of the intrinsic fluorescence of the molecule. To better evaluate the functionally relevant features of SB 242784, a second inhibitor, INH-1, from the same class and having a reduced activity was also examined. It is shown that regarding membrane interaction their properties remain very similar for both molecules, suggesting that the differences in inhibition efficiencies are solely a consequence of the molecular recognition processes within the inhibition site in the V-ATPase.

Indoles↗
PubMed2006

Morbidity and embolic potential of left atrial cardiac tumors.

BACKGROUND: The aim of the study was to correlate cardiac tumors with implantation site, embolic potential and long-term evolution in patients undergoing surgery. METHODS: From 1981 to 2004, 78 patients underwent surgery for cardiac tumors. 64 % were female, with a mean age of 44 years. 14 % had embolic episodes (91 % CVA). The sizes of the tumors ranged from 0.4 cm to 10 cm. The most frequent tumors were myxomas (70 %), papillary fibroelastomas and fibromas. The preferential location was the left atrium (72 %). Data were analyzed using chi (2) and Student's T-tests, and the Kaplan-Meyer method and curves were compared with the log-rank test. RESULTS: Hospital mortality was 6 % and 8.2 % in the follow-up period. Myxoma was predominantly found in the left atrium ( P < 0.0001; OR = 12.8 and 4 - 41 95 % CI). Left atrial tumors showed less mortality ( P = 0.1; OR = 3 and 0.7 - 11.6 95 % CI), with a lower mortality for myxomas ( P < 0.001), fewer recurrences ( P = 0.03; OR = 8.7 and 0.8 - 89 95 % CI), and a greater embolic potential than in other locations ( P = 0.03 % OR = 0.7 and 0.6 - 0.8 95 % CI). CONCLUSION: Left atrial tumors showed greater embolic potential, fewer recurrences and less mortality.

Adolescent↗
PubMed2001

Identification of an axonal determinant in the C-terminus of the sodium channel Na(v)1.2.

To obtain a better understanding of how hippocampal neurons selectively target proteins to axons, we assessed whether any of the large cytoplasmic regions of neuronal sodium channel Na(v)1.2 contain sufficient information for axonal compartmentalization. We show that addition of the cytoplasmic C-terminal region of Na(v)1.2 restricted the distribution of a dendritic-axonal reporter protein to axons. The analysis of mutants revealed that a critical segment of nine amino acids encompassing a di-leucine-based motif mediates axonal compartmentalization of chimera. In addition, the Na(v)1.2 C-terminus is recognized by the clathrin endocytic pathway both in non-neuronal cells and the somatodendritic domain of hippocampal neurons. The mutation of the di-leucine motif located within the nine amino acid sequence to alanines resulted in the loss of chimera compartmentalization in axons and of internalization. These data suggest that selective elimination by endocytosis in dendrites may account for the compartmentalized distribution of some proteins in axons.

Amino Acid Motifs↗
PubMed2001

Selective inhibition of thapsigargin-induced contraction and capacitative calcium entry in mouse anococcygeus by trifluoromethylphenylimidazole (TRIM).

This study examined the effects of trifluoromethylphenylimidazole (TRIM) on tone, and calcium entry, in mouse anococcygeus stimulated by either thapsigargin (Tg; 100 nM) which activates capacitative calcium entry (CCE), or high K (60 mM) which activates voltage-operated calcium channels. TRIM (1 - 333 microM) produced concentration-related relaxation of Tg-induced tone (EC(50), 42 microM) but was much less effective against high K. In single smooth muscle cells loaded with FURA-2, TRIM reduced the increase in fluorescence ratio produced by Tg but had no effect on that produced by high K. The relaxations of Tg-induced tone, and reduction in fluorescence ratio, were obtained in the presence of L-N(G)-nitroarginine and were thus independent of nitric oxide synthase inhibition; further, TRIM had no discernible effect on nitrergic responses. TRIM provides a novel drug for the selective inhibition of CCE and a template for the development of more potent inhibitors.

Animals↗
PubMed2001

Primary neoplasms of the heart. Clinical and histological presentation of 50 cases.

OBJECTIVE: To analyze clinical and histologic findings of 50 patients with primary neoplasms of the heart in a tertiary referral center. METHODS: From 1980 to 1998, we retrospectively analyzed 50 patients, 32 of whom were females, whose ages ranged from 9 to 73 years (mean age = 44.16+/-18 years). RESULTS: Most tumors were located in the left side of the heart (72%), myxoma being the most common (84%) histologic type. The other histologic types found were as follows: fibroma (4%), lipoma (2%), rhabdomyosarcoma (2%), hemangioma (2%), sarcoma (2%), angiosarcoma (2%), and lymphoma (2%). Diagnosis was established by echocardiography in 94% of the cases. Clinical findings were as follows: dyspnea (36%), weight loss (20%), palpitations (18%), chest pain (16%), fever (8%), and arthralgia (6%). All patients with thromboembolic phenomena (10%) had left atrial myxoma. Approximately 20% of the patients were asymptomatic at the initial clinical assessment. CONCLUSION: Primary cardiac tumors are a rare entity with diverse clinical and histologic findings, requiring, therefore, a high level of clinical suspicion.

Adolescent↗
PubMed2001

Video-assisted pericardioscopy. How to improve diagnostic efficacy in pericardial effusions.

OBJECTIVE: To assess, in a prospective way, the experience with video-assisted pericardioscopy obtained in patients with pericardial effusion of unclear etiology in the preoperative period. METHODS: From January 1998 to June 2000, 20 patients were operated upon with the aid of video-assisted pericardioscopy. On echocardiography, 17 of these patients had significant pericardial effusion, and 3 had moderate pericardial effusion. Video-assisted pericardioscopy was performed through a small incision of the Marfan type. RESULTS: The diagnosis of pericardial effusion was established as follows: idiopathic in 9 (45%) patients, neoplastic in 4 (20%), resulting from hypothyroidism in 3 (15%), tuberculous in 2 (10%), due to cholesterol in 1 (5%), and chylopericardial in 1 (5%). The biopsy was positive in 30% of the patients, and the etiology could not be defined in 45% of the patients. CONCLUSION: Video-assisted pericardioscopy proved to be a method with low morbidity and a high index of diagnostic positivity. A high percentage of pericardial effusions are caused by viral infections, which are not diagnosed through current methods, being, therefore, classified as idiopathic.

Adolescent↗
PubMed1999

Non-coronary sinus of Valsalva aneurysm diagnosed after a road traffic accident.

A 38 year old man with a huge unruptured sinus of Valsalva aneurysm, complicated with severe valvar aortic regurgitation, is described. The aneurysm was detected by echocardiography in the asymptomatic patient who presented with an intense precordial diastolic rumble after a road traffic accident. The patient had successful surgery for the aneurysm and aortic valve replacement. Possible aetiologies for the aneurysm and a brief revision of clinical aspects and treatment are discussed.

Accidents, Traffic↗
PubMed1999

Neoplastic pericardial disease. Analysis of 26 patients.

PURPOSE: To characterize patients with neoplastic pericardial disease diagnosed by clinical presentation, complementary test findings, and the histological type of tumor. METHODS: Twenty-six patients with neoplastic pericardial disease were retrospectively analyzed. RESULTS: Clinical manifestations and abnormalities in chest roentgenograms and electrocardiograms were frequent, but were not specific. Most patients underwent surgery. There was a high positivity of the pericardial biopsy when associated with the cytological analysis of the pericardial liquid used to determine the histological type of the tumor, particularly when the procedure was performed with the aid of pericardioscopy. CONCLUSION: The correct diagnosis of neoplastic pericardial disease involves suspicious but nonspecific findings during clinical examination and in screen tests. The suspicious findings must be confirmed through more invasive diagnostic approaches, in particular pericardioscopy with biopsy and cytological study.

Adult↗
PubMed1999

[Myocardial infarct without angiographic coronary atherosclerosis: study of a group of patients].

STUDY OBJECTIVES: Clinical characterization and aspects of subsidiary clinical tests in a group of patients with myocardial infarction with no visible angiographic atherosclerotic stenosis. Etiologic identification, therapeutic approach and prognostic assessment of non atherosclerotic myocardial infarction. PATIENTS: We studied patients admitted with myocardial infarction to coronary care unit over a 4 year period and in whom cardiac catheterism did not show atherosclerotic coronary stenosis (17 patients). METHODOLOGY: Retrospective study; Assessment of clinical characteristics, exercise test parameters, echocardiogram, hemodynamics, heart rate variability (HRV) and signal-averaged electrocardiogram (ECG) of this group of patients; Maximal follow-up of 44 months and minimal of 3 months (average: 19.9 +/- 12.7 months) for the occurrence of ischemic cardiac events (recurrent angina, reinfarction or sudden death). RESULTS: Non atherosclerotic coronary infarction was an unusual situation (2% of the totality of the infarction hospitalized during those 4 years--795 cases), occurring mainly among young men, with few vascular risk factors (except smoking), as small infarctions, without a preferential localization and with good evolution in the acute phase (Killip I). In the predischarge exercise test there was no residual ischemia and functional capacity was generally good. In the majority of cases left ventricular systolic function was preserved (82% of the cases). With cardiac catheterism, we observed two cases of "bridging" and four cases of slow contrast progression. In arrhythmic risk stratification with 24 hours ECG, HRV and high resolution ECG, we observed no adverse prognostic markers in the majority of the cases. The clinical observation of the patients and the tests permitted us to establish probable hypotheses for the etiological diagnoses in 10 of the cases (left main anterior descending artery "bridging"--2 cases; slow contrast progression in the coronary vessels--4 cases, severe aortic stenosis--1 case; left valvular mechanic prosthesis--1 case: probable coronary thrombosis with complete reperfusion after thrombolytic therapy--2 cases). The therapeutic approach in the acute phase was the same as that of atherosclerotic infarctions. Secondary prevention was individualized and according to each case etiology, maintaining the antiplatelet agents. In the follow-up there was unstable angina in 3 patients. There were no cases of reinfarction or sudden death. CONCLUSIONS: This study allowed the characterization of the group of non atherosclerotic myocardial infarction as a group of young men with few vascular risk factors, with small infarctions and good prognosis, without adverse arrhythmic risk markers. It also allowed to identify the probable infarction etiology in 10 patients and the secondary individual prevention for each situation. We noted a good prognosis of this situation at two years.

Adult↗
PubMed1999

[Pulmonary thromboembolism in a female with resistance to activated protein C].

Primary or acquired hypercoagulable states favour thrombotic events. The identification of prothrombotic states is of immediate practical usefulness in the orientation, prophylaxis and treatment of pulmonary embolism. Detection of individuals resistant to activated protein C. the most frequent laboratory anomaly in the study of patients with venous thromboembolism, offers a better approach for these patients as well as a better prophylaxis and orientation of their direct relatives concerning thromboembolic events. The authors describe the clinical case of a young woman, previously healthy, who developed serious pulmonary thromboembolism, the resolution of which was difficult and the evolution unusual. Later, a state of resistance to activated protein C (aPCr) was identified. Concerning the case described, the authors reflect on hypercoagulable situations, especially "aPCr" states.

Activated Protein C Resistance↗
PubMed1998

[Value of pericardial biopsy in the etiologic diagnosis of pericardial diseases].

PURPOSE: To determine the value of pericardial biopsy as a complementary exam in the etiology of pericardial effusion. METHODS: We analyzed retrospectively (from 1990 to 1997) 38 patients with pericardial effusion. The age ranged between 3 months and 79 years (mean 41.15 +/- 21.78 years). Pericardial biopsy was performed in all cases through a subxiphoid incision. RESULTS: In 4 patients (10.5%) the biopsy was able to define etiology, 2 had tuberculosis and 2 neoplasias (1 undetermined adenocarcinoma, 1 mesotelioma). In 34 patients the biopsy showed non-specific chronic pericarditis. CONCLUSION: Pericardial biopsy was not an effective method to determine the etiological diagnosis in pericardial effusion patients. We believe that we have to individualize the indication of pericardial biopsy especially if tuberculosis or neoplasia are suspected.

Adolescent↗
PubMed1998

[Cardiovascular diseases observed during follow-up of a group of patients with undetermined form of Chagas' disease].

PURPOSE: The aim of this study was to evaluate the cardiovascular outcome in patients with the undetermined form of Chagas' disease and whether or not it is related to the infectious disease in the long-term. METHODS: One hundred and sixty patients were prospectively followed-up at three month intervals for up to 177 months. RESULTS: Twenty and three (14.4%) patients developed hypertension complicated by ischemic stroke in two (1.2%) and symptomatic heart failure in one (0.6%). Cardiac arrhythmias occurred in four (2.4%) patients corresponding to isolated ventricular ectopic beats in two (1.2%), isolated supraventricular ectopic beats in one (0.6%) and an isolated episode of acute atrial fibrillation in another (0.6%). Two (1.2%) patients developed symptoms of coronary artery disease, one of them had one episode of acute chest pain diagnosed as myocardial infarction and the other had chronic chest pain diagnosed as angina. CONCLUSION: Hypertension is the most common cardiovascular disease occurring in the long-term follow-up of patients with the undetermined form of Chagas' disease. Cardiac rhythm disturbances and coronary artery disease were not more frequent than those generally found in a healthy population. These data confirm a favorable long-term prognosis in patients with the undetermined form of Chagas' disease.

Adolescent↗
PubMed1998

[Idiopathic chylopericardium].

We describe a case of a patient with idiopathic pericardial effusion that during investigation proved to be a chylopericardium. Lymphangiography showed the chylopericardium to be due to partial aplasia of the thoracic duct. A brief review the etiology, clinical feature, diagnostic procedures and therapeutic possibilities of chylopericardium is presented.

Adult↗
PubMed1998

Effect of quinupristin/dalfopristin alone or in combination with vancomycin on the structure of Enterococcus faecium.

Twenty strains of Enterococcus faecium susceptible to quinupristin/dalfopristin (< 2 mg/l) were DNA fingerprinted to exclude strain duplication. Ten strains were susceptible to vancomycin (minimal inhibitory concentration [MIC] < 2 mg/l) and 10 were resistant to vancomycin (MIC > 400 mg/l). Vancomycin at 1/2 MIC, quinupristin/dalfopristin at 1/4 MIC and their combination, except for a tube control, was added to 10 ml trypticase soy broth tubes which were planted with the respective 24-h trypticase soy broth cultures. The products of incubation were sampled periodically throughout 24 h for gram stain and electron microscopy. Cell size was measured on photographs at 20,000x final magnification and results were statistically analyzed. The cells of all strains of Enterococcus faecium exposed for 12 h to quinupristin/dalfopristin were comparable in size to the control, Most cells, however, showed areas of low density of ribosome in the center of the cells. The cells of Enterococcus faecium resistant to vancomycin exposed to vancomycin were larger than the controls with means of 1.96 micron -2.07 micron versus 1.16 micron (p < 0.001); these cells consisted of individual organisms connected by wide cross walls of abnormal fibrous structure. Enterococcus faecium sensitive to vancomycin exposed to vancomycin remained comparable to the control. The combination of quinupristin/dalfopristin plus vancomycin produced large cells with multiple abnormal cross walls in both vancomycin-resistant and vancomycin-sensitive Enterococcus faecium. The addition of quinupristin/dalfopristin to vancomycin appears to modify the vancomycin-susceptible strains to respond to vancomycin in the same manner as do the vancomycin-resistant organisms.

Anti-Bacterial Agents↗
PubMed1998

[Differential imaging diagnosis of left ventricular aneurysm and pseudoaneurysm in the course of a myocardial infarct].

Differential diagnosis between true and false left ventricular aneurysms is not always easy, despite the use of imaging techniques of great diagnostic accuracy. We report a case in which the distinction between these two situations offers some difficulty. Finally, we review the characteristics of ventricular aneurysms and that of pseudoaneurysms, focusing on the aspects that enable their differentiation.

Aneurysm, False↗