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J Barbosa

Publications and source records attributed to J Barbosa.

At least 19 recordsLinked to original sources
PubMed1999

Electrophoretic behaviour of quinolones in capillary electrophoresis. Effect of pH and evaluation of ionization constants.

Quinolones are a family of antibacterial agents that are used extensively in both human and veterinary clinics. Their antibacterial activity is pH-dependent, and therefore an examination of protonation equilibria in quinolone solution is essential. In this work, dissociation constants of quinolones in water were obtained using capillary electrophoresis (CE). The method is based on measuring the electrophoretic mobility of the solute as a function of pH. Mobility and pH data are fitted using different models. These developed equations have two advantages. They permit the determination of pKa of analytes with the advantages of CE and also permit the prediction of the effect of pH on the electrophoretic behaviour of substances and then the prediction of the pH optimum for the separation methods, using the minimum of experimental measurements.

Anti-Infective Agents↗
PubMed1999

Insulin-dependent diabetic sibling pairs are concordant for sodium-hydrogen antiport activity.

UNLABELLED: Insulin-dependent diabetic sibling pairs are concordant for sodium-hydrogen antiport activity. BACKGROUND: Recent findings of enhanced Na+/H+ antiport activity in cultured fibroblasts and immortalized lymphoblasts from type 1 diabetic patients with nephropathy support the view that a phenotypic or genotypic factor(s) underlies nephropathy risk. This study evaluated the kinetic properties of Na+/H+ antiporter in cultured fibroblasts from families with two siblings affected by type 1 (insulin-dependent) diabetes. METHODS: Seventeen diabetic sibling pairs were studied. The age was 38 +/- 10 years (mean +/- SD) in probands, the first to develop diabetes, and 39 +/- 7 in siblings; the duration of diabetes was, by definition, longer in probands (24 +/- 12 vs. 17 +/- 8 years in siblings). Na+/H+ antiport activity was determined using a microfluorometric technique with the pH sensitive dye 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in skin fibroblasts cultured for at least six passages. RESULTS: There were no significant differences between probands and siblings for the following parameters: glycated hemoglobin, 8.3 +/- 0.8% in probands and 8.6 +/- 1.4% in siblings; creatinine clearance, 103 +/- 24 ml/min/1.73 m2 in probands and 103 +/- 25 in siblings; albumin excretion rate, 6.8 (1 to 860) microgram/min (median and range) in probands and 4.9 (2 to 1334) in siblings. Intracellular pH and buffering capacity were superimposable in the sibling pairs. The Vmax for the antiport was 39.2 +/- 14.7 mmol/liter cell/min in probands and 40.3 +/- 17.6 in siblings. The internal pH for half-maximal activation (Km) and Hill coefficient was also similar in probands and siblings. There were correlations between probands and siblings in values for intracellular pH (r = 0.51, P < 0.04), Vmax (r = 0.84, P < 0.0001), and buffering capacity (r = 0.53, P < 0. 03). Glycated hemoglobin values over five years were not significantly correlated in the sibling pairs (r = 0.3, P > 0.1). Vmax was related with the albumin excretion rate (r = +0.49, P = 0. 005) and glycated hemoglobin (r = +0.41, P = 0.017) in the total cohort of sibling pairs. However, multiple regression analysis, using Vmax as the dependent variable, found no correlations between any of the subjects' clinical and demographic variables. CONCLUSIONS: Familial concordance for Na+/H+ antiport activity in long-term cultured skin fibroblasts from type 1 diabetic siblings suggests that at least some of the in vitro phenotypical characteristics of these cells are likely to be genetically determined and to be, at least in part, independent of in vivo metabolic control.

Adult↗
PubMed1999

Is diabetic nephropathy inherited? Studies of glomerular structure in type 1 diabetic sibling pairs.

Only a minority of patients with type 1 diabetes develop diabetic nephropathy (DN). Poor glycemic control cannot fully explain DN risk, and family studies suggest genetic susceptibility factors. To understand familial DN concordance, we evaluated glomerular structure in families with type 1 diabetic sibling pairs. Kidney function and biopsy studies were performed in 21 probands (P) (first to develop diabetes) and 21 siblings (S) (second to develop diabetes), most with normal urinary albumin excretion rates (UAER). Glomerular structure was measured by morphometry. Intrafamilial correlation was estimated by one-way random-effects ANOVA and by mixed-effects ANOVA, adjusting for age and duration of diabetes. Diabetes duration was, by definition, longer in P than in S, while age and sex were similar. HbA1c over 5 years and blood pressure were not different in P and S and were without familial effect. UAER was greater in P than in S (P < 0.05), with strong familial effect (P = 0.03). A strong concordance among siblings for mesangial fractional volume (P < or = 0.01) remained significant after adjustment for diabetes duration and age (P = 0.04). Results were similar for mesangial cell (P = 0.01; adjusted P = 0.04) and mesangial matrix fractional volumes (P < 0.01; adjusted P = 0.06). There was also clustering of the patterns of glomerular lesions. For example, if P had relatively marked glomerular basement membrane thickening compared with mesangial matrix expansion, S had a similar pattern (chi2, P < 0.025). Strong concordance in severity and patterns of glomerular lesions in type 1 diabetic siblings, despite lack of concordance in glycemia, supports an important role for genetic factors in DN risk.

Adult↗
PubMed1998

Retention behaviour of quinolone derivatives in high-performance liquid chromatography. Effect of pH and evaluation of ionization constants.

This paper examines the effect of solute ionisation on the retention behaviour of a series of quinolones and evaluates their pKa values using chromatographic data in acetonitrile-water mixtures with acetonitrile percentages of 30, 35, 40 and 50% (v/v). We also compare these pKa values with those previously obtained in acetonitrile-water mixtures from potentiometric measurements. In doing so, the pH values were measured in the hydroorganic mixture, which was used as the mobile phase, instead of in water, taking into account the effect of activity coefficients. The resulting equations permit the chromatographic determination of the pKa values of the quinolones in acetonitrile-water mixtures and also permit the prediction of the effect of pH on their chromatographic behaviour. These equations can be combined with those previously derived, which relate retention to the solvent composition of the mobile phase, to establish a general model that relates the elution behaviour of the solute to significant mobile phase properties: composition, pH and ionic strength.

Acetonitriles↗
PubMed1998

Fatal microcystin intoxication in haemodialysis unit in Caruaru, Brazil.

BACKGROUND: After a drought in February, 1996, all 126 patients in a haemodialysis unit in Caruaru, north-east Brazil, developed signs and symptoms of acute neurotoxicity and subacute hepatotoxicity following the use of water from a lake with massive growth of cyanobacteria (blue-green algae). 60 patients died. METHODS: Besides recording clinical details and outcome at follow-up, we arranged laboratory, radiological, and histological investigations on the patients and toxicological studies of serum and haemodialysis water filters. FINDINGS: The acute presentation was with malaise, myalgia and weakness, nausea and vomiting, and tender hepatomegaly, with a range of neurological symptoms from tinnitus, vertigo, headaches, and deafness to blindness and convulsions. Liver injury ranged from abnormal liver-function test results to rapidly progressive and fatal hepatic failure. Biochemical investigations revealed gross hyperbilirubinaemia, abnormal liver enzyme activities, and hypertriglyceridaemia, but there was no evidence of haemolysis or microangiopathy. Histology revealed a novel acute toxic hepatitis with diffuse panlobular hepatocyte necrosis, neutrophil infiltration, canalicular cholestasis, and regenerative multinucleate hepatocytes. Samples of serum, dialysis filters, and water-treatment columns contained microcystins, the highly toxic low-molecular-weight hepatotoxins produced by cyanobacteria. INTERPRETATION: Cyanobacteria present water-borne hazards to health via drinking water and recreational water. Haemodialysis presents an additional high-risk exposure route: when they enter directly into the circulation, microcystins can lead to fatal clinical syndromes ranging from acute neurotoxic illness to subacute liver failure.

Bacterial Toxins↗
PubMed1998

Modulation of receptor and receptor subtype affinities using diastereomeric and enantiomeric monosaccharide scaffolds as a means to structural and biological diversity. A new route to ether synthesis.

We show that carbohydrates constitute an attractive source of readily available, stereochemically defined scaffolds for the facile attachment of side chains contained in genetically encoded and other amino acids. beta-D- and beta-L-glucose, L-mannose, and the 6-deoxy-6-N-analogue of beta-D-glucose have been employed to synthesize peptidomimetics that bind the SRIF receptors on AtT-20 mouse pituitary cells, five cloned human receptor subtypes (hSSTRs), and the NK-1 receptor. The affinity profile of various sugar-based ligands at the hSSTRs is compared with that of SRIF. Compound 19 bound hSSTR4 with a Ki of 100 nM. Subtle structural changes affect affinities. Evidence is presented that suggests that one compound (8) binds both the AtT-20 cell receptors and the five hSSTRs via a unique mode. The SARs of the glycosides at SRIF receptors differ markedly from those at the NK-1 receptor. For example a 4-benzyl substituent is important for SRIF receptor binding, but the 4-desbenzyl analogue 27 was highly potent (IC50 of 27 nM) at the NK-1 receptor. A new, nonbasic method for the synthesis of base-sensitive ethers from primary and secondary alcohols is also described.

Animals↗
PubMed1998

The use of bovine pericardium for pulmonary valve reconstruction or conduit replacement: long-term clinical follow up.

BACKGROUND AND AIMS OF THE STUDY: This study aimed to determine the clinical performance of bovine pericardial aldehyde-treated material alone or in combination with aortic leaflets of porcine origin. These were the porcine aortic stentless pulmonary valved bovine pericardial conduit (PSPVC), and porcine aortic monocusp attached to pericardial patch (PAMC), used to correct right-sided heart lesions. METHODS: Between November 1985 and October 1995, 33 patients underwent corrective congenital surgery with PSPVC. Mean patient age was 5.7+/-4.3 years (range: 15 days to 18 years). Pulmonary atresia with ventricular septal defect (VSD) was the most frequent disease (16/33, 48%). For PAMC, 45 patients with various congenital heart malformations underwent implantation between June 1989 and April 1996. Mean patient age was 4.8+/-4.7 years (range: 2 weeks to 18 years). RESULTS: With PSPVC, hospital mortality rate was 18.2% and related to poor preoperative clinical condition in six cases. Four patients were lost to follow up; 23 (85%) were followed for 3 months to 10 years (mean 4.8+/-3.0 years). Distal anastomotic scarring in four patients was probably due to retraction of the pericardial tissue. With PAMC, hospital mortality rate was 11% and related to patients' preoperative clinical condition. Three patients were lost to follow up; 37 survivors have been followed for 6 to 88 months (mean 38.5+/-19.0 months). There were no late deaths. Two patients underwent reoperation; intra-operative observation showed well-preserved monocusps with no signs of tissue degeneration. The remaining 35 patients remain asymptomatic by clinical examination and Doppler echocardiography. The monocusps remained mobile in every case. CONCLUSION: PSPVCs have shown excellent performance and durability in young patients with a low mean age (5 years). The monocusp graft has remained functional with good leaflet motion for up to seven years.

Adolescent↗
PubMed1998

Use of bovine pericardial tissue for aortic valve and aortic root replacement: long-term results.

BACKGROUND AND AIMS OF THE STUDY: The study aimed to determine the clinical performance of bovine pericardial aldehyde-treated products alone or in combination with aortic leaflets of porcine origin. These included a composite porcine stentless aortic valve attached to a scalloped pericardial tube (BSAV), and valved and non-valved bovine pericardial conduits for use in left-sided heart lesions (BPG). METHODS: For BSAV grafts, between January 1990 and August 1996, 163 patients (119 males) had their aortic valves replaced by SJM Biocor BASV. Mean age was 37.9 +/- 17.6 years (range: 1 to 76 years). Rheumatic heart disease sequelae (n = 72) and replacement of a prosthetic heart valve (n = 46) were predominant. Preoperative NYHA functional class showed 90 patients (55.2%) in class III and 50 (30.7%) in class IV. BPVC and NVPC grafts were used in 166 patients: acute aortic dissection was the main indication in 52 (31.3%) and chronic in 36 (21/7%). The ascending aorta was involved in 141 patients (84.9%); grafts were seldom used at other sites. In most patients the graft implanted was either a non-valved (n = 79) or a valved (n = 75) pericardial conduit. Twelve patients had a localized lesion and required a patch repair. RESULTS: For BASV grafts, the non-valve-related hospital mortality rate was 4.9%. There were 14.7% non-fatal complications with full recovery of all patients. Mean follow up in 141 patients was 3.0 +/- 1.4 years (range: 1 month to 7.2 years); 14 patients were lost to follow up. Late, non-conduit-related, mortality occurred in seven patients (4.9%). Eight patients underwent reoperation. The current clinical follow up of 127 patients has shown 118 (92.9%) with competent valves and nine (7.0%) with mild stable aortic insufficiency. For BPVC and NVPC grafts, hospital mortality rate was 16.9%, death being related to poor preoperative clinical condition. Postoperative follow up was accomplished in 125 patients; reoperation was necessary in seven patients. Histology showed good tissue preservation up to five years; echocardiography revealed satisfactory findings. No valved conduit had to be reoperated for valve or pericardial tissue wear. CONCLUSIONS: Clinical results of left-sided heterologous pericardial grafts have shown excellent performance over time. The BASV (over seven years) and BPVC and NVPC (eight years) have demonstrated superior results as aortic valves alone or in combination with a pericardial conduit.

Adolescent↗
PubMed1997

Effect of protein kinase C activation on the release of [3H]acetylcholine in the presence of vesamicol.

The present work tested whether pharmacological activation of protein kinase C (PKC) influences the release of [3H]acetylcholine ([3H]ACh) synthesized in the presence of vesamicol, an inhibitor of the vesicular acetylcholine transporter (VAChT). Newly synthesized [3H]ACh was released from hippocampal slices by field stimulation (15 Hz) in the absence of vesamicol, but as expected [3H]ACh synthesized during exposure to vesamicol was not released significantly by stimulation. Treatment of slices with the PKC activator phorbol myristate acetate (PMA) decreased the inhibitory effect of vesamicol on [3H]ACh release. The effect of PMA was dose-dependent, was sensitive to calphostin C, a PKC-selective inhibitor, and could not be mimicked by alpha-PMA, an inactive phorbol ester. PMA did not alter the release of [3H]ACh in the absence of vesamicol, suggesting that the site of PKC action could be related to the VAChT. In agreement with this observation, immunoprecipitation of VAChT from 32P-labeled synaptosomes showed that phosphorylation occurs and that incorporation of 32P in the VAChT protein increases in the presence of PMA. We suggest that PKC alters the output of [3H]ACh formed in the presence of vesamicol and also provide circumstantial evidence for a role of phosphorylation of VAChT in this process.

Acetylcholine↗
PubMed1997

Production and characterization of a novel monoclonal antibody against phosphorylated T cell receptor zeta chain.

One of the earliest events following T cell receptor (TCR) triggering is the activation of the protein kinase Lck and induction of tyrosine phosphorylation of zeta, the major signal transduction subunit of the T cell receptor complex. Here we report the generation and characterization of a monoclonal antibody specific for human phosphozeta. The antibody was produced by immunizing mice with a truncated recombinant form of human zeta together with the Lck enzyme. The C415.9A antibody recognizes recombinant as well as cellular phosphozeta but is unreactive with unphosphorylated zeta or other tyrosine phosphorylated proteins. Using this antibody, we have demonstrated aberrant TCR-zeta tyrosine phosphorylation in Jurkat T cell transduction mutants. Therefore, this antibody can be used to elucidate T cell signal transduction mechanisms by analyzing and monitoring tyrosine phosphorylation of zeta in vitro and in vivo directly. Furthermore, this antibody could find application in the analysis of abnormal T cell signaling in autoimmune disease, cancer, and immunodeficiency disorders.

Amino Acid Sequence↗
PubMed1997

Variation of acidity constants of peptides in acetonitrile-water mixtures with solvent composition: effect of preferential solvation.

The dissociation constant values of a series of peptides in 5.54, 10, 16.30, 25.03 and 50% (w/w) acetonitrile-water mixed solvents at 298.15 K were determined according to the criteria endorsed by IUPAC. A pronounced change in the acid-base pK values of carboxylic, phenol and thiol groups was observed as the solvent was enriched in acetonitrile. By contrast, pK values of protonated amino-terminal groups were influenced slightly as the solvent was enriched in acetonitrile, although continually increasing pK values were observed. The variation of the pK values obtained, over the whole composition ranged studies, was explained by taking into account the preferential solvation of electrolytes in acetonitrile-water mixtures. To obtain pK values in all possible binary solvent acetonitrile-water mixtures, relationships between pK values and different bulk properties were examined and the Linear Solvation Energy Relationships methodology was applied. The pKa values were then correlated with the Kamlet-Taft, phi, alpha and beta solvatochromic parameters of acetonitrile-water mixtures. The equations obtained allowed calculation of the pK values of peptides in acetonitrile-water mixtures up to 50% (w/w) and thus permitted the acid-base behavior of these substances in the widely used acetonitrile-water media to be known.

Acetonitriles↗
PubMed1997

Acid-base behavior of quinolones in aqueous acetonitrile mixtures.

Quinolones are a family of antibacterial agents that are used extensively in both human and veterinary clinics. Their antibacterial activity is pH-dependent, and therefore an examination of protonation equilibria in quinolone solutions is essential. pK-Values of nine quinolone antibacterials in acetonitrile-water mixtures containing 0, 10, 30, 40, 50 and 70%(w/w) acetonitrile were determined according to the rules and procedures endorsed by IUPAC. In order to obtain quinolone pK-values in any acetonitrile-water mixture up to 70%(w/w) acetonitrile, relationships between pK-values and different bulk properties (such as dielectric constant) and some microscopic parameters (such as solvatochromic parameters alpha, beta and pi*) were established. These relationships and the application of the preferential solvation theory of electrolytes in acetonitrile-water mixtures permit the interpretation of acid-base behaviour of these important antimicrobials in the widely used acetonitrile-water media.

Acetonitriles↗
PubMed1997

Determination of dissociation constants of loop diuretics in acetonitrile-water mixtures.

The dissociation pK values of the representative loop diuretics furosemide, bumetanide and ethacrynic acid in 10, 30, 40, 50 and 70% (w/w) acetonitrile-water mixtures at 298.15 K were determined, according to the rules and procedures endorsed by IUPAC. The variation in pK values over the whole composition range studied can be explained by tacking into account the preferential solvation of ionizable substances in acetonitrile-water mixtures. With a view to determining the pK values of the loop diuretics studied in any of the binary solvent acetonitrile-water mixtures, correlations of pK values and different bulk properties of the solvent were examined, and the linear solvation energy relationships method, LSER, has been applied. The pK values were then correlated with the pi*, alpha and beta solvatochromic parameters of acetonitrile-water mixtures. The resulting equations allowed us to calculate pK values for the loop diuretics in any acetonitrile-water mixture up to 70% (w/w) acetonitrile.

Acetonitriles↗
PubMed1997

[Cardiac changes in children with AIDS].

PURPOSE: To describe the cardiac findings in children with AIDS, the follow-up with treatment and the correlation between clinical and pathological features. METHODS: We studied prospectively 25 children with clinical-laboratorial diagnosis of AIDS, ages between 3 months and 11 years, even those without cardiac symptoms. We classified the signs of AIDS following that of CDC-Atlanta 1994. Eight children died and it was done necropsy in six with macro and microscopic examinations. RESULTS: Fifteen cases had already complications of AIDS and were classified as C2 and C3, 5 as B2, 3 B1 and 2 as A1. Beside the symptoms related to the disease and infections we found signs of congestive heart failure III and IV (NYHA) in 5 children, pericardial effusion in 5, (one of them had cardiac tamponade). In the electrocardiogram (EKG), 8 children had repolarization abnormalities. In 1st echocardiogram (ECHO) we found some features of dilated myocardiopathy in 8 (6 were asymptomatic) 5 of those had pericardial effusion, one child had huge amount of pericardial liquid and also increased measures of intraventricular septum and posterior wall of left ventricle by ECHO and confirmed by necropsy examination. All cases of diagnosis of myocardiopathy received treatment with captopril and 4 also received furosemide and digoxina. Even under oral treatment three of them had deterioration of heart failure but after combined anti-retroviral drugs they showed better cardiac functions. From the six necropsied cases, two had increased heart weight without myocarditis, one had toxoplasma pancarditis and other one had fibrocalcic vasculopathy. CONCLUSION: We found several assymptomatic cases already with decreased ventricular function. Some worsened of heart failure even under apropriate treatment and showed better cardiac index after combined anti-retroviral drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Solvatochromic parameter values and pH in acetonitrile-water mixtures. Optimization of mobile phase for the separation of peptides by high-performance liquid chromatography.

The proportion of the organic modifier and the pH of the mobile phase were optimized in order to separate a series of low-molecular-mass peptides by HPLC. The composition of the mobile phase was optimized by establishing relationships between retention parameters and Reichardt's ENT scale of solvent polarity, and between retention and the Kamlet-Taft multiparameter solvent scale of the eluent, using linear solvation energy relationships (LSER). The pH of the mobile phase was also successfully optimized by establishing relationships between the retention and the pH measured in the aqueous-organic mixture used as eluent.

Acetonitriles↗
PubMed1996

Direct determination of anabolic steroids in human urine by on-line solid-phase extraction/liquid chromatography/mass spectrometry.

A fully automated method is presented for the determination of anabolic steroids in human urine. On line solid-phase extraction with automatic cartridge exchange is used for sample clean-up followed by an high-performance liquid chromatographic isocratic separation. A narrow-bore 5 microns reversed-phase column (250 x 2.1 mm i.d.) at a flow rate of 0.2 ml min-1 is connected to a particle beam interface linked to a single-quadrupole mass spectrometer. No derivatization is needed and normal electron impact mass spectra are obtained for a series of up to 28 steroids and metabolites. Urine samples collected following the ingestion of therapeutic doses of some of the steroids were analysed and the detection and confirmation of excreted compounds accomplished. A dramatic reduction in human intervention and overall analysis time was achieved compared with other common approaches.

Anabolic Agents↗
PubMed1996

Nd-YAG laser as a palliative treatment for malignant dysphagia.

Two hundred and twenty-four patients with histologically-confirmed carcinoma of the oesophagus received palliative Nd-YAG laser therapy for malignant dysphagia between January 1986 and December 1994. The results are appraised in terms of the degree of relief obtained, its relation to the macroscopic type and the size of the tumour, peri-operative complications, duration of hospitalization and survival after treatment. Recannulation of the oesophageal lumen was obtained in 98.2% of the patients, after which 93.7% were able to ingest at least semi-solids. Although the lumen was permeable for a 9.8 mm endoscope, the remainder could only ingest liquids. The only complication was a perforation is six cases (2.7%). After treatment, 14.8% survived more than 1 year and 3.4% more than 2 years. After discussing the role of lasers in the palliative treatment of malignant dysphagia, the authors conclude that it can be considered effective in that it relieves the dysphagia and improves the patients' quality of life.

Adult↗