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Biomedical subjects

J Barbosa

Publications and source records attributed to J Barbosa.

At least 55 records · Page 3Linked to original sources
PubMed2000

Modelling retention in liquid chromatography as a function of solvent composition and pH of the mobile phase.

The aim of this work was to develop a model that accurately describes retention in liquid chromatography (LC) as a function of pH and solvent composition throughout a large parameter space. The variation of retention as a function of the solvent composition, keeping other factors constants, has been extensively studied. The linear relationship established between retention factors of solutes and the polarity parameter of the mobile phase, E(N)T, has proved to predict accurately retention in LC as a function of the organic solvent content. Moreover, correlation between retention and the mobile phase pH, measured in the hydroorganic mixture, can be established allowing prediction of the chromatographic behavior as a function of the eluent pH. The combination of these relationships could be useful for modelling retention in LC as a function of solvent composition and pH. For that purpose, the retention behavior on an octadecyl silica column of a group of diuretic compounds covering a wide range of physico-chemical properties were studied using acetonitrile as organic modifier. The suggested model accurately describes retention of ionizable solutes as concomitant effects of variables included and is applicable to all solutes studied. We also aimed to establish an experimental design that allows to reproduce to a good approximation the real retention surface from a limited number of experiments, that is from a limited number of chromatograms. Ultimately, our intention is to use the model and experimental design for the simultaneous interpretive optimization of pH and proportion of organic solvent of the mobile phase to be used in the proposed separation.

Chromatography, Liquid↗
PubMed2000

Decentralising the health sector: issues in Brazil.

The health sector in Brazil has undergone important changes, particularly with the development of the Unified Health System (SUS). Decentralisation is an important principle of SUS and advances have been made in transferring responsibilities and resources to the local government units, known as municipios. This article describes the changes introduced, focusing on the system of municipio classification and the funding mechanisms introduced through the basic operating rule (BOR) of 1996. The paper then moves on to analysing three key issues of decentralisation in Brazil that are related to the policy process, the system of decentralisation and the output of decentralisation. Firstly, the formal process by which decisions on health sector reform are made is discussed with particular attention being paid to the negotiated and relatively open policy space. Secondly, the role of the states is discussed within the decentralised system. Thirdly, the impact of decentralisation on equity is discussed with particular reference to the resourcing of the Municipal Health Funds. The article concludes by emphasising the political nature of health sector decentralisation and the need to develop the conditions for effectiveness in decentralisation programmes.

Brazil↗
PubMed2000

Visualization and trafficking of the vesicular acetylcholine transporter in living cholinergic cells.

The present experiments investigated the trafficking of the vesicular acetylcholine transporter (VAChT) tagged with the enhanced green fluorescent protein (EGFP) in living cholinergic cells (SN56). The EGFP-VAChT chimera was located in endosomal-like compartments in the soma of SN56 cells, and it was also targeted to varicosities of neurites. In contrast, EGFP alone in cells was soluble in the cytoplasm. The C-terminal cytoplasmic tail of VAChT has been implicated in targeting of VAChT to synaptic vesicles; thus, we have examined the role of the C-terminal region in the trafficking to varicosities. A C-terminal fragment tagged with EGFP appeared to be selectively accumulated in varicosities when expressed in SN56 cells. Interestingly, the protein was not freely soluble in the cytosol, and it presented a punctate pattern of expression. However, EGFP-C terminus did not present this peculiar pattern of expression in a nonneuronal cell line (HEK 293). Moreover, the C-terminal region of VAChT did not seem to be essential for VAChT trafficking, as a construct that lacks the C-terminal tail was, similar to EGFP-VAChT, partially targeted to endocytic organelles in the soma and sorted to varicosities. These experiments visualize VAChT for the first time in living cells and suggest that there might be multiple signals that participate in trafficking of VAChT to sites of synaptic vesicle accumulation.

Animals↗
PubMed2000

Dichotic listening and response inhibition in children with comorbid anxiety disorders and ADHD.

OBJECTIVE: To compare children with comorbid anxiety disorders (ANX) and attention-deficit hyperactivity disorder (ADHD) with children with either pure disorder and normal controls on 2 cognitive measures to elucidate the cognitive basis of this comorbidity. METHOD: Four groups of children aged 8 to 12 years (n = 64 total) were assessed: ANX, ADHD, both conditions (comorbid group), and neither condition (normal control group). Groups were compared on 2 cognitive measures: a measure of auditory emotional perception (dichotic listening task) and a measure of response inhibition (stop task), chosen for their relative specificity for ANX and ADHD, respectively, in previous studies. RESULTS: Multivariate analyses of variance revealed significant group differences on the dichotic listening task (p < .05), with the comorbid group differing from the control group on emotion targets (p < .01) and the ADHD group differing from the control group on word targets (p < .05). On the stop task, the ADHD group appeared slower than the other diagnostic groups on both go and stop-signal reaction times, but differences were not significant. CONCLUSIONS: In this study, children with comorbid ANX and ADHD showed reduced auditory emotion recognition relative to controls but did not show response inhibition deficits. Thus they appeared cognitively distinct from children with either pure disorder.

Anxiety Disorders↗
PubMed1999

Synthesis and biological activity of cyclic peptide inhibitors of ribonucleotide reductase.

[formula: see text] A series of lactam-bridged peptide inhibitors (2-6) of mammalian ribonucleotide reductase (mRR) has been designed and synthesized on the basis of the heptapeptide N-AcFTLDADF (1), corresponding to the C-terminus of the R2 subunit of mRR. Inhibition studies revealed a direct relation between ring size and activity, with peptide 5 being 2.5 times more potent than peptide 1.

Enzyme Inhibitors↗
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

Separation and identification of peptide mixtures in a synthesis crude of carbetocin by liquid chromatography/electrospray ionization mass spectrometry.

In order to separate and characterize the target peptide and the side-product peptide compounds of a synthesis crude of the peptide hormone carbetocin, liquid chromatography coupled to high-flow electrospray ionization mass spectrometry (LC/eS-MS) has been used. Carbetocin is an important drug with recognized therapeutical application for stimulation of uterine contractions to facilitate parturition. Stepwise solid phase peptide synthesis (SPPS) commonly results in unwanted side products associated with incomplete peptide chains. Consequently, this procedure requires extensive purification and characterization of the final synthesis crude. The linear solvation energy relationship (LSER) method has been applied to optimize the proportion of organic modifier of the mobile phase used in the established LC method. On the other hand, ES-MS has allowed rapid and reliable identification of the target peptide and the other impurities present in the carbetocin synthesis products.

Amino Acid Sequence↗
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

[Intravenous lysine clonixinate for the treatment of migraine: an open pilot study].

Several oral nonsteroidal anti-inflammatory drugs (NSAID) are effective to treat migraine attacks. Despite its efficacy to treat migraine and other pain, there are a few commercial NSAIDs available for intravenous (i.v.) administration. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid that has been proven effective in various algic syndromes such as renal colic, nerve compression, muscular pain and odontalgias. The aim of this study was to evaluate the efficacy of the i.v. LC in the treatment of severe attacks of migraine. We studied prospectively 19 patients, 17 women and 2 men, ages from 18 to 57 years, with the diagnosis of migraine according to the International Headache Society criteria. The patients were oriented to proceed to the clinic once the headache has started, and were placed under an i.v. infusion of LC and saline in a superficial vein of the forearm, once the intensity reached severe. Evaluating the headache intensity after 30, 60 and 90 minutes, as well as the presence of side effects, we observed that all of the 19 patients were headache free after 90 minutes. Some patients presented mild adverse effects and the vital signs were not significantly affected. We then concluded that the i.v. infusion of the NSAID LC (2-3-chloro-o-toluidin)piridin-3-lysine carboxilate), a derived from the nicotinic acid with a chemical structure that resembles the flufenamic acid, was efficient abolishing a severe migraine attack after 90 minutes in 19 patients. Controlled studies with a double-blind and randomized design, and treating a greater number of patients and attacks are necessary to confirm these initial observations.

Acute Disease↗
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↗
PubMed1999

Expression of the vesicular acetylcholine transporter, proteins involved in exocytosis, and functional calcium signaling in varicosities and soma of a murine septal cell line.

The expression and localization of the vesicular acetylcholine transporter in a septal cell line, SN56, were investigated. Immunoprecipitation and immunoblot analysis of postnuclear supernatants indicated that this cell line expresses reasonable amounts of the transporter. Immunofluorescence and confocal microscopy experiments showed that the vesicular transporter is present in varicosities and also in the cell body of differentiated cells. Varicosities have the potential to be functional sites of transmitter release because they responded to depolarization with calcium influx through voltage-gated calcium channels and expressed the synaptic proteins synaptotagmin, SV2, synaptophysin, and a subunit of P/Q calcium channels. In the soma of SN56 cells, the transporter immunoreactivity was similar to that for synaptotagmin, and it colocalized with synaptophysin, but it did not colocalize with SV2. Labeling for SV2 appeared prominently in a defined perinuclear structure, whereas the two former proteins were widely distributed in the soma, where several endocytic compartments could be identified with the vital dye FM4-64. These data suggest that distinct synaptic vesicle proteins exist in different subcellular compartments, and consequently they may follow distinct pathways in neurites before reaching sites of transmitter storage and release in SN56 cells.

Animals↗
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↗