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Biomedical subjects

M Oliveira

Publications and source records attributed to M Oliveira.

At least 37 records · Page 2Linked to original sources
PubMed2003

Controlling hydrolysis and dispersion of AlN powders in aqueous media.

Aqueous suspensions of aluminum nitride (AlN) powders have been prepared in the presence of different surface-active agents, namely, H3PO4 and an anionic surfactant, to avoid the hydrolysis of AlN powders and to enhance dispersion. The most determinant parameters to the hydrolysis process (DeltapH and time of contact) and the stabilization of AlN particles in water (surface crystallinity, surface chemical modification, and surface ionic charge) were seen to be strongly dependent on the acidic agent. The H3PO4 treatment was effective against hydrolysis of AlN due to the formation of a phosphate-based protection layer on the particles' surface, and, although it keeps the pH of the suspension below 4, it does not guarantee a good dispersion. The individual adsorption of the anionic surfactant at the surface of AlN particles suspensions did not completely suppress the hydrolysis but it did enhance the degree of dispersion. A proper combination of the two types of surface-active agents enabled the preparation of AlN aqueous suspensions of relatively low viscosity and high AlN concentration, which can be a good starting point for aqueous-based colloidal shaping techniques or for freeze granulation or spray drying to obtain suitable granulate powder characteristics for dry-pressing technologies. An adsorption mechanism of the surface-active agents onto the particles' surface is proposed and supported by NMR and FT-IR analyses.

Journal Article↗
PubMed2002

RenaGel efficacy in severe secondary hyperparathyroidism.

BACKGROUND: Haemodialysis patients frequently have simultaneous hypercalcemia and hyperphosphatemia, posing a therapeutic dilemma for the traditional calcium--and aluminum--based binders. RenaGel (sevelamer hydrochloride) is an effective phosphate binder without changes in serum calcium or aluminum levels. However being an expensive medication it is currently used mainly for patients with moderate to severe secondary hyperparathyroidism. However most of the previous studies have not included patients with severe secondary hyperparathyroidism. METHODS: Our purpose is to determine RenaGel binder efficacy in haemodialysis patients with severe secondary hyperparathyroidism. As a secondary purpose we have followed the variations of parathyroid hormone, serum calcium, serum lipids [low- and high-density lipoprotein cholesterol, triglycerides and Lipoprotein(a)], uric acid and bicarbonate. All phosphate binders previously used were suspended one week before RenaGel prescription. Our study included 18 adult haemodialysis patients, with PTHi of 810 +/- 330 pg/ml after the "pre-treatment" washout. The binder was administered during 12 weeks, beginning with a mean dose of 2.4 +/- 0.4 g daily and adjusted to obtain serum phosphorus under 6.5 mg/dl (at the end of the study, the mean RenaGel dose was 2.8 +/- 0.6 g daily. RESULTS: The mean changes after RenaGel in serum phosphorus was -0.7 +/- 1.5. mg/dl (P < 0.05), in serum calcium was 0.5 +/- 1.0 mg/dl (P < 0.05) and in calcium x phosphate product of -4.0 +/- 12.4 mg/dl (P = NS). "Post-treatment" the PTHi levels remained stable (820 +/- 360 pg/ml vs 810 +/- 330) but serum alkaline phosphatase increased (14.3 +/- 14.4 U/l; P < 0.01). LDL cholesterol serum levels decreased by -35 +/- 10 mg/dl (P < 0.01), HDL cholesterol showed a trend to increase (3.0 +/- 8.1 U/l; P = NS), triglycerides decreased by 38 +/- 56 mg/dl (P < 0.05) and Lipoprotein(a) remained stable. Serum albumin increased by 0.1 +/- 0.2 g/L (P < 0.05), uric acid decreased -0.8 +/- 1.2 mg/dl (P < 0.05) and bicarbonate remained unchanged. CONCLUSIONS: RenaGel is an effective phosphate binder, even in haemodialysis patients with severe secondary hyperparathyroidism. The lipid profile improved with the treatment, with the exception of Lipoprotein(a) stabilization. Selection of patients with severe secondary hyperparathyroidism at the beginning of RenaGel disposal, for economic reasons is debatable, but could be correct.

Adult↗
PubMed2001

Specific binding of the C-terminal Src homology 2 domain of the p85alpha subunit of phosphoinositide 3-kinase to phosphatidylinositol 3,4,5-trisphosphate. Localization and engineering of the phosphoinositide-binding motif.

Phosphoinositide second messengers, generated from the action of phosphoinositide 3-kinase (PI3K), mediate an array of signaling pathways through the membrane recruitment and activation of downstream effector proteins. Although pleckstrin domains of many target proteins have been shown to bind phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) and/or phosphatidylinositol 3,4-bisphosphate (PI(3,4)P(2)) with high affinity, published data concerning the phosphoinositide binding specificity of Src homology 2 (SH2) domains remain conflicting. Using three independent assays, we demonstrated that the C-terminal (CT-)SH2 domain, but not the N-terminal SH2 domain, on the PI3K p85alpha subunit displayed discriminative affinity for PIP(3). However, the binding affinity diminished precipitously when the acyl chain of PIP(3) was shortened. In addition, evidence suggests that the charge density on the phosphoinositol ring represents a key factor in determining the phosphoinositide binding specificity of the CT-SH2 domain. In light of the largely shared structural features between PIP(3) and PI(4,5)P(2), we hypothesized that the PIP(3)-binding site on the CT-SH2 domain encompassed a sequence that recognized PI(4,5)P(2). Based on a consensus PI(4,5)P(2)-binding sequence (KXXXXXKXKK; K denotes Arg, Lys, and His), we proposed the sequence (18)RNKAENLLRGKR(29) as the PIP(3)-binding site. This binding motif was verified by using a synthetic peptide and site-directed mutagenesis. More importantly, neutral substitution of flanking Arg(18) and Arg(29) resulted in a switch of ligand specificity of the CT-SH2 domain to PI(4,5)P(2) and PI(3,4)P(2), respectively. Together with computer modeling, these mutagenesis data suggest a pseudosymmetrical relationship in the recognition of the phosphoinositol head group at the binding motif.

Amino Acid Sequence↗
PubMed2001

Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis.

Familial hypertrophic cardiomyopathy (HCM) has been widely studied as a genetic model of cardiac hypertrophy and sudden cardiac death. HCM has been defined as a disease of the cardiac sarcomere, but mutations in the known contractile protein disease genes are not found in up to one-third of cases. Further, no consistent changes in contractile properties are shared by these mutant proteins, implying that an abnormality of force generation may not be the underlying mechanism of disease. Instead, all of the sarcomeric mutations appear to result in inefficient use of ATP, suggesting that an inability to maintain normal ATP levels may be the central abnormality. To test this hypothesis we have examined candidate genes involved in energy homeostasis in the heart. We now describe mutations in PRKAG2, encoding the gamma(2) subunit of AMP-activated protein kinase (AMPK), in two families with severe HCM and aberrant conduction from atria to ventricles in some affected individuals (pre-excitation or Wolff-Parkinson-White syndrome). The mutations, one missense and one in-frame single codon insertion, occur in highly conserved regions. Because AMPK provides a central sensing mechanism that protects cells from exhaustion of ATP supplies, we propose that these data substantiate energy compromise as a unifying pathogenic mechanism in all forms of HCM. This conclusion should radically redirect thinking about this disorder and also, by establishing energy depletion as a cause of myocardial dysfunction, should be relevant to the acquired forms of heart muscle disease that HCM models.

Amino Acid Sequence↗
PubMed2000

Selection of resistance-conferring mutations in HIV-1 by the nucleoside reverse transcriptase inhibitors (+/-)dOTC and (+/-)dOTFC.

The patterns of resistance-conferring mutations that are selected in HIV-1 reverse transcriptase (RT) by the racemates of 2'-dideoxy-3'-oxa-4'-thiocytidine (+/-)dOTC and its fluorinated derivative (+/-)dOTFC were characterized. Genotypic and phenotypic analyses of HIV-1 clinical isolates and HXB2D variants selected with (+/-)dOTC and (+/-)dOTFC were performed in primary cells and in the MT-2 T cell line. HIV-1 variants selected with (+/-)dOTC or (+/-)dOTFC displayed fivefold decreased susceptibility to the respective compounds. A substitution of methionine to valine was identified at position 184 (M184V) in variants selected with (+/-)dOTC. In contrast, a mutation of lysine to arginine at position 65 (K65R) was found in variants selected with (+/-)dOTFC. These patterns of selected mutations differ from those seen with the individual enantiomers. Studies with mutated recombinant HXB2D-M184V and -K65R confirmed that these mutations are important for phenotypic resistance in MT-2 cells. Clinical isolates that display resistance to (-)2'-deoxy-3'-thiacytidine (3TC) also showed cross-resistance to (+/-)dOTC and (+/-)dOTFC. These studies demonstrate that similar genotypes may be selected by the dOTC and dOTFC compounds to those with the structurally related drug 3TC.

Deoxycytidine↗
PubMed1999

Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154.

Reported effects of anti-CD154 treatment on autoimmunity, alloreactivity, and inflammatory events mediated by macrophages and endothelial cells indicated that it might be an ideal agent for the prevention of intrahepatic islet allograft failure. This hypothesis was tested in MHC-mismatched rhesus monkeys. Transplantation of an adequate number of viable islets resulted in engraftment and insulin independence in six of six recipients treated with anti-CD154 (hu5c8) induction plus monthly maintenance therapy (post-operative day >125, >246, >266, >405, >419, >476). Anti-CD154 (hu5c8) displayed no inhibitory effect on islet cell function. For monkeys followed for >100 days, continued improvement in graft function, as determined by first phase insulin release in response to intravenous glucose, was observed after the first 100 days post-transplant. No evidence of toxicity or infectious complications has been observed. All recipients treated with anti-CD154 became specifically nonresponsive to donor cells in mixed lymphocyte reactions. Furthermore, three monkeys are now off therapy (>113, >67, and >54 days off anti-CD154), with continued insulin independence and donor-specific mixed lymphocyte reaction hyporeactivity. In striking contrast to all previously tested strategies, transplantation of an adequate number of functional islets under the cover of anti-CD154 (hu5c8) monotherapy consistently allows for allogeneic islet engraftment and long-term insulin independence in this highly relevant preclinical model.

Animals↗
PubMed1999

Morphological and molecular analysis of a double-flowered mutant of the dioecious plant white campion showing both meristic and homeotic effects

Many double-flowered plants, in which petals replace stamens, are highly valued by the horticultural industry. These mutants exhibit a homeotic conversion of floral organs and frequently also a meristic increase in floral organ number. By gamma irradiation we generated a novel double-flowered mutant, Sl-dfl, in a male genetic background of the dioecious plant white campion (Silene latifolia). This mutant shows a homeotic conversion of stamens to petals, together with uncontrolled growth and division of second and third whorl floral organ primordia, causing a proliferation of petal and chimeric petal-stamen organs. We characterize this mutant developmentally by scanning electron microscopy and demonstrate that the effects of the mutation commence following the formation of a correctly partitioned floral meristem with a wild-type arrangement of organ primordia. We have commenced a molecular investigation of the Sl-dfl mutant by testing the expression and genomic organization of the known white campion putative MADS-box floral homeotic genes. These studies indicate four MADS-box genes to be unlikely to be mutated in the double-flowered mutant. The possibility that a putative C-function MADS-box gene may cause the mutant phenotype has not currently been excluded, though our morphological studies suggest that a C-function mutation is not involved in this case. We conclude that a number of different classes of double-flowered mutation exist, not all of which are currently known from model plant species. This may be indicative of important developmental differences between species and may also emphasize a need for comparative studies of floral development. Copyright 1999 Wiley-Liss, Inc.

Journal Article↗
PubMed1999

Sexual dimorphism in white campion: deletion on the Y chromosome results in a floral asexual phenotype.

White campion is a dioecious plant with heteromorphic X and Y sex chromosomes. In male plants, a filamentous structure replaces the pistil, while in female plants the stamens degenerate early in flower development. Asexual (asx) mutants, cumulating the two developmental defects that characterize the sexual dimorphism in this species, were produced by gamma ray irradiation of pollen and screening in the M1 generation. The mutants harbor a novel type of mutation affecting an early function in sporogenous/parietal cell differentiation within the anther. The function is called stamen-promoting function (SPF). The mutants are shown to result from interstitial deletions on the Y chromosome. We present evidence that such deletions tentatively cover the central domain on the (p)-arm of the Y chromosome (Y2 region). By comparing stamen development in wild-type female and asx mutant flowers we show that they share the same block in anther development, which results in the production of vestigial anthers. The data suggest that the SPF, a key function(s) controlling the sporogenous/parietal specialization in premeiotic anthers, is genuinely missing in females (XX constitution). We argue that this is the earliest function in the male program that is Y-linked and is likely responsible for "male dimorphism" (sexual dimorphism in the third floral whorl) in white campion. More generally, the reported results improve our knowledge of the structural and functional organization of the Y chromosome and favor the view that sex determination in this species results primarily from a trigger signal on the Y chromosome (Y1 region) that suppresses female development. The default state is therefore the ancestral hermaphroditic state.

Chromosome Deletion↗
PubMed1999

[Antitachycardia pacing in patients with left ventricular dysfunction and hemodynamically unstable arrhythmias].

UNLABELLED: The use of antitachycardia pacing (ATP) has shown itself to be an effective therapeutic option in the treatment of ventricular tachycardia (VT) in carriers of implantable cardioverter defibrillators (ICD). OBJECTIVE: To assess the safety and efficacy of ATP in ICD carriers with ischemic cardiopathy and systolic dysfunction of the left ventricle (LV) presenting VT badly tolerated hemodynamically. METHODS: We studied five patients (four male and one female), survivors of acute myocardial infarction, mean age 56.4 +/- 15.7 years and an ejection fraction < 35%, submitted to ICD implantation by VT inducible in the electrophysiological study (EPS) and refractory to pharmacologic therapy. In three cases the arrhythmia was syncopal and in two the patients felt palpitations and dizziness (systolic blood pressure < 90 mmHg during VT). The ICDs were implanted between March 1996 and October 1997 by transvenous approach in pectoral position. ATP was used as an initial therapeutic alternative (VT zone with a detection frequency of 160-220/min) according to an empirical programme (n = 3) or, whenever feasible, in accordance with the type of VT interruption during EPS (n = 2). During the follow-up of 11 +/- 6 months (2-18), a periodic assessment of the symptomatology and a detailed analysis of episodes of ventricular arrhythmia detected by ICD were made. RESULTS: Two hundred and fourteen episodes of VT were recorded with a post detection duration of > 2.5 sec treated by ICD. The ATP rate of efficacy was 93%. In 3% of the episodes the ATP did not alter VT; in 2% the rate of VT increased (reduction of the VT cycle > 20%) and in 2% therapeutic exhaustion was observed (after the application of ATP and the maximum number of shocks per episode). In 14 episodes with ATP inefficiency, two syncopes occurred (1% of the total number of episodes treated). CONCLUSION: In this study antitachycardia pacing has proven to be a therapeutic option with high rates of efficacy and safety despite its use in survivors of myocardial infarction with moderate to severe compromise of systolic function of the left ventricle and ventricular arrhythmias with hemodynamic instability.

Aged↗
PubMed1999

[The nonpharmacological treatment of atrial fibrillation].

The authors describe the main forms of nonpharmacological treatment of atrial fibrillation considering catheter ablation and surgical therapy. A new methodology to modify atrioventricular conduction is discussed as well its long-term results. All studies are non-randomised with selected patients, which makes the development of a therapeutical algorithm difficult. However, the results have shown that it is possible to recover sinus rhythm through surgery or catheter ablation and to control the ventricular rate either by His ablation or modification of atrioventricular conduction.

Aged↗
PubMed1999

[Pulmonary thromboembolism angiographically confirmed: clinical and prognostic aspects].

OBJECTIVE: The aim of this study was to evaluate the clinical profile and prognosis of patients with an angiographically proven thromboembolism. METHODS: Data from 22 consecutive patients (13 males, 9 females; mean age 57.3 +/- 16.8 years) with pulmonary embolism confirmed by pulmonary angiography were reviewed. All our patients were previously submitted to non-invasive diagnostic procedures (blood examinations, EKG, chest x-ray, echocardiography). A V/Q scan was also performed in 5 patients. Fourteen patients were traditionally treated with heparin alone and the rest received thrombolytic therapy and heparin. Two patients had a thromboembolectomy. At discharge, all our patients were submitted to an oral anticoagulant therapy. The mean duration of the follow-up period was 26 +/- 12 months. RESULTS: The majority of the patients were in the 6th decade of life and it was possible to identify a hypercoagulable state in 82%. The most common symptom at the time of presentation was sudden chest pain (64%). The most specific sign in non-invasive procedures were right side cardiac dilatation seen echocardiographically (73%) and the mismatch in the V/Q scan (80%). The most common haemodynamic parameter (91%) observed in the right heart catheterization of these patients was the finding of a gradient between diastolic pulmonary artery and pulmonary capillary wedge pressures. Uneventful angiography was performed in all patients who showed massive pulmonary embolism (86%). Three patients (13.6%) died during the acute phase. At the end of the follow-up period, 10 patients were asymptomatic and 5 had heart failure. Four died, which corresponds to an overall mortality of 31.8% in 2.2 years of follow-up. None of the clinical or haemodynamic parameters analyzed (age, gender, arterial blood gases at presentation, hypercoagulable states, thrombolysis, pulmonary hypertension and extension of the embolism) were related to mortality. CONCLUSION: Angiographically confirmed pulmonary thromboembolism is still a poor outcome situation, even when a lot of diagnostic and therapeutic procedures are available.

Adult↗
PubMed1999

[Should all patients with ventricular pre-excitation of the Wolff-Parkinson-White syndrome type undergo catheter ablation?].

The authors make a concise review concerning clinical, electrocardiographic and electrophysiologic risk stratification in Wolff-Parkinson-White syndrome and present the results of radiofrequency catheter ablation of atrioventricular accessory pathways. The low sensitivity of electrophysiologic criteria for the identification of a high risk profile limits their use in asymptomatic patients with a low incidence of sudden death. The greater risk of ventricular fibrillation in symptomatic patients makes radiofrequency catheter ablation the treatment of choice for these patients. Therefore, the authors do not recommend an electrophysiologic risk stratification in Wolff-Parkinson-White syndrome, but emphasize that catheter ablation should be performed in all symptomatic patients.

Adolescent↗
PubMed1999

[Prevention of sudden death in congenital long-QT syndrome].

Congenital long QT syndrome (LQTS) is associated to an increased risk of ventricular arrhythmia, syncope and sudden cardiac death (SD). Four disease genes have been identified and different mutations described in each gene. This locus heterogenicity appears to have important functional and prognostic implications. Sympathetic imbalance has been invoked to explain an arrhythmogenic substrate. Prolonged repolarization is associated to increased dispersion of repolarization enhancing the propensity to develop early afterdepolarizations that may initiate polymorphic ventricular tachycardia (torsade de pointes). Syncope or cardiac arrest usually occur in young patients during exercise, possibly in association with relative bradycardia. The annual incidence of recurrent syncope and SD is 5% and 1%, respectively. Diagnostic criteria include clinical and electrocardiographic variables, family history of early SD and propensity for recurrent syncope. Careful assessment of clinical manifestations and ECG characteristics of family members is justified. Female gender, QTc interval > 500 ms, history of syncope or cardiac arrest are independent risk factors that predict arrhythmic events. Pharmacological agents known to be able to cause QT prolongation or beta-adrenergic stimulation must be avoided. Clinical management of asymptomatic persons with the LQTS is still controversial. Initial treatment of choice for the large majority of patients is administration of propranolol. This treatment is effective in 75-80% of cases. Other therapeutic options include left cervicothoracic sympathectomy, pacemakers, and the implantable cardioverter defibrillator. Risk stratification and efficacy of the subsequent treatment has significantly changed the clinical outcome of patients with LQTS. Recent molecular biology studies and data analysis from the International LQTS Registry may contribute to the definition of the best strategy for the future.

Cardiac Pacing, Artificial↗
PubMed1999

[Atrial fibrillation in Wolff-Parkinson-White syndrome].

The authors describe the main etiopathogenic factors and clinical importance of atrial fibrillation and analyse the results of catheter ablation of atrioventricular accessory pathways in Wolff-Parkinson-White syndrome. Atrial vulnerability is the principal mechanism and radiofrequency catheter ablation of atrioventricular accessory pathways seems to be useless to prevent atrial fibrillation.

Atrial Fibrillation↗