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C Pereira

Publications and source records attributed to C Pereira.

At least 55 records · Page 3Linked to original sources
PubMed1998

The protective effect of vitamin E, idebenone and reduced glutathione on free radical mediated injury in rat brain synaptosomes.

In the present study the effect of ascorbate (0.8 mM)/iron (2.5 microM) on lipid and protein oxidation, in Synaptosomes isolated from rat brain cortex, was evaluated. Vitamin E, idebenone and reduced glutathione were used as free radicals scavengers, in order to analyze the mechanism involved in ascorbate/iron-induced oxidative stress. An increased formation of reactive oxygen species (ROS) in the cytosol and in the mitochondria was observed, in ascorbate/iron treated synaptosomes. Idebenone (50 microM) prevented the increased formation of ROS in both synaptosomal compartments, vitamin E (150 microM) protected partially this formation in mitochondria, whereas reduced glutathione (250 microM) (GSH) was ineffective. After ascorbate/iron treatment an increase in lipid peroxidation occurred as compared to control, which was completely inhibited by idebenone. A decrease in protein-SH content was also observed, and it was prevented by Vitamin E, idebenone and GSH. When synaptosomes were treated with ascorbate/iron the levels of GSH decreased, and the levels of oxidized glutathione (GSSG) increased as compared to controls under these conditions. Glutathione peroxidase activity was unchanged, whereas an inhibition of glutathione reductase activity was observed. These data suggest that the increased formation of free radicals in synaptosomes leads to lipid and protein oxidation, the role of the endogenous GSH being essential to protect protein thiol-groups against oxidative damage in order to maintain enzyme activity.

Adenine Nucleotides↗
PubMed1998

Regulation of the phosphorylation of glial fibrillary acidic protein (GFAP) by glutamate and calcium ions in slices of immature rat spinal cord: comparison with immature hippocampus.

The effect of glutamate and lack of external Ca2+ on the phosphorylation of the astrocyte cell marker glial fibrillary acidic protein (GFAP) was studied in slices of hippocampus and thoracic spinal cord from immature (P12-16) rats. Confirming previous work with immature hippocampal slices (Wofchuk, S.T. and Rodnight, R., Neurochem. Int., 24 (1994) 517-523; Wofchuk, S.T. and Rodnight, R., Dev. Brain Res., 85 (1995) 181-186), glutamate strongly stimulated GFAP phosphorylation in media with Ca2+ and in media lacking Ca2+ a quantitatively similar stimulation of basal GFAP phosphorylation was observed. By contrast in slices of immature thoracic spinal cord, glutamate had no effect on GFAP phosphorylation and in media lacking Ca2+ phosphorylation of GFAP was inhibited. Since GFAP phosphorylation is Ca2+-dependent and is not stimulated by glutamate in slices of adult hippocampus, the present results suggest that astrocytic functions in the rat spinal cord mature more rapidly than in the hippocampus. The possibility that the difference in the control of GFAP phosphorylation in the two structures is related to differences in the control of GFAP dephosphorylation was investigated by incubating spinal cord slices with the calcineurin inhibitor FK506 in the presence of Ca2+. In contrast to results obtained with hippocampal slices FK506 had no effect on the phosphorylation state of GFAP in spinal cord slices.

Animals↗
PubMed1998

Molecular dosimetry in fish: quantitative target organ DNA adduction and hepatocarcinogenicity for four aflatoxins by two exposure routes in rainbow trout.

Rainbow trout, a species highly sensitive to aflatoxins, was used to investigate the relative carcinogenicities of four structurally related aflatoxins in terms of their target organ DNA binding characteristics. Tritiated syntheses were carried out, DNA binding dose-response curves were established, and liver DNA binding indices were calculated for the four aflatoxins following a 2-week dietary fry exposure protocol. The results indicated that adduct levels increased linearly with dietary dose concentration, with relative DNA binding indices of 20.7, 20.3, 2.35, and 2.22 x 10(3) (pmoles aflatoxin mg-1 DNA)/(pmoles aflatoxin g-1 diet) for aflatoxin B1 (AFB1), aflatoxicol (AFL), aflatoxin M1 (AFM1), and aflatoxicol M1 (AFLM1), respectively. A similar protocol used over 7200 trout fry averaging 1.2 g initial body weight to establish full carcinogen dose-response curves for each aflatoxin, along with a single-dose estimate of DNA binding index within the tumor study animals. Owing to trout sensitivity a total of 180 micrograms or less of each aflatoxin was required. Data analyzed on logit incidence vs. Ln dose coordinates generated four curves which were modeled as parallel in slope over most or all dose ranges studied. By this analysis, relative tumorigenic potencies were: AFB1 1.00; AFL 0.936; AFM1 0.086; and AFLM1 0.041. When data were plotted as logit incidence vs. Ln adducts (effective dose received), all aflatoxin adducts described the same dose-response curve; that is, they were equally tumorigenic, except those from AFLM1, which were 2-3 fold less potent. Therefore, by these molecular dose studies, differences in tumorigenicity among the four dietary aflatoxins are largely or entirely accounted for by differences in uptake and metabolism leading to DNA adduction, rather than any inherent differences in tumor initiating potency per DNA adduct.

Aflatoxins↗
PubMed1998

Metabolic inhibition increases glutamate susceptibility on a PC12 cell line.

The effect of energetic metabolism compromise, obtained by chemical induction of hypoglycaemia (glucose deprivation), hypoxia (mitochondrial respiratory chain inhibition), and ischaemia (hypoglycaemia plus hypoxia), on glutamate toxicity was analyzed on PC12 cells. The respiratory status of these cells, measured by the MTT [3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide] assay, was significantly decreased after metabolic inhibition induced by ischaemia, but it was not affected by both hypoglycaemia and hypoxia. Under hypoglycaemia, but not under hypoxia, ATP levels were significantly reduced (from 12.67+/-0.48 to 5.38+/-1.41 nmol/mg protein). However, ischaemic-like conditions greatly potentiated the decline of ATP levels (95% decrease) observed after hypoglycaemia. The influence of metabolic inhibition on glutamate-induced cytotoxicity was also analyzed. When the cells were preincubated under conditions that deplete ATP (hypoglycaemia and ischaemia), the inhibition of MTT reduction, measured after glutamate incubation, was potentiated. This effect could be reverted when vitamin E and idebenone were present during the induction of metabolic inhibition. The ATP levels above which glutamate susceptibility was enhanced were also determined. These results indicate that glutamate toxicity on PC12 cells, which occurs by a mechanism independent of N-methyl-D-aspartate (NMDA) receptor activation, can be enhanced by the depletion of intracellular ATP upon metabolic stress; it is dependent on the extent of ATP depletion and seems to involve the generation of free radicals. It can be concluded that under ischaemic conditions, the deleterious effects of glutamate can be potentiated by the energetic compromise associated with this pathologic situation.

Adenosine Triphosphate↗
PubMed1998

Alterations in cytochrome-c oxidase expression between praziquantel-resistant and susceptible strains of Schistosoma mansoni.

The genetic differences between praziquantel-resistant (R) and susceptible (S) strains of Schistosoma mansoni (Fallon & Doenhoff, 1994) were explored using RAPD and by cloning differentially expressed mRNAs by subtractive PCR. No differences between the 2 strains were detectable by RAPD using 41 different primers indicating that no major genomic rearrangements were present. Subtractive PCR generated a number of fragments, 1 of which was shown to correspond to an over-expressed mRNA in the R strain and to encode a fragment of the subunit 1 of cytochrome-c oxidase (SCOX1). In the absence of a complete sequence for this gene, we used EST sequences to compile a consensus sequence for the 904 bp at the 3' end that enabled us to choose primers for semi-quantitative RT-PCR. This technique showed that SCOX1 was indeed over-expressed about 5 to 10-fold in the R strain whereas the genes encoding the 28 kDa glutathione S-transferase, glutathione peroxidase, NADH dehydrogenase subunit 5 and the ATP-binding cassette family protein SMDR2 were not. In contrast, cytochrome-c oxidase enzyme activity was 4-fold lower in the R strain than in the S strain.

Amino Acid Sequence↗
PubMed1998

Beta-receptors and stress protein 70 expression in hypoxic myocardium of rainbow trout and chinook salmon.

We examined the in vivo effect of acute hypoxemia on myocardial cell-surface (sarcolemmal) beta-adrenoreceptor density (Bmax) and binding affinity (KD) and on stress protein 70 (sp70) expression by exposing rainbow trout (Oncorhynchus mykiss; 2.1-2.7 kg) to hypoxic water (3 mg/l O2) at 15 degrees C for 6 h. This degree of hypoxia was the minimum O2 level that these trout could tolerate without losing equilibrium and struggling violently. Hypoxic exposure reduced arterial PO2 (PaO2) from 98 to 26 mmHg and arterial oxygen content (CaO2) from 10.8 to 7.4 vol/100 vol, but did not elevate epinephrine and norepinephrine levels above 10 and 30 nM, respectively. Despite the substantial reduction in blood oxygen status, the Bmax and KD of myocardial cell-surface beta-adrenoreceptors were unaffected by 6 h of hypoxic exposure. In addition, acute hypoxemia did not increase myocardial sp70 expression. The failure of short-term hypoxia to decrease trout myocardial beta-adrenoreceptor density clearly contrasts with the established hypoxia-mediated down-regulation shown for mammals. To further investigate the influence of low PO2 on salmonid myocardial beta-adrenoreceptors, binding studies were performed on the spongy (continuously exposed to deoxygenated venous blood) and compact (perfused by oxygenated blood supplied by the coronary artery) myocardia of chinook salmon. The spongy myocardium has adapted to its microenvironment of continuous low PO2 by having 14% more cell-surface beta-adrenoreceptors compared with the compact myocardium. There was no tissue-specific difference in KD and no evidence of sexual dimorphism in Bmax or KD. We conclude from our studies that the salmonid heart is well adapted for sustained performance under hypoxic conditions. We found that wild chinook salmon had 2.8 x more cell-surface beta-adrenoreceptors compared with hatchery-reared rainbow trout. This difference suggests a significant degree of plasticity exists for fish myocardial beta-adrenoreceptors. The signals underlying such differences await further study, but are not likely to include moderate hypoxia and sexual dimorphism.

Animals↗
PubMed1998

The effect of cross-talk on MRI lesion numbers and volumes in multiple sclerosis using conventional and turbo spin-echo.

We measured and compared lesion numbers and volumes present on brain magnetic resonance imaging (MRI) scans of patients with multiple sclerosis (MS) acquired with contiguous (scheme A) and interleaved (scheme B) slice acquisition, to evaluate whether there was a gain in sensitivity using the second pattern of acquisition and whether this counterbalanced the doubled acquisition time. Conventional spin-echo (CSE) sequences were performed for eight patients and turbo spin-echo (TSE) sequences for ten. Acquisition scheme B detected 3.8% more lesions than acquisition scheme A (the increase was 3.1% for CSE and 4.5% for TSE). These differences were not statistically significant. No significant difference in lesion numbers was found when different lesion locations were also considered. Lesions volumes were significantly higher when scheme B was used (P = 0.024). This was due to higher lesion volumes on TSE images (P = 0.006), especially on even-numbered slices (P = 0.008). Inter-slice cross-talk has a negligible effect on lesion numbers and volume estimates in MS for CSE sequence, whilst it cannot be neglected when TSE sequences are used to measure MS lesion volume.

Adult↗
PubMed1998

Evidence of genetic heterogeneity in a BALB/c mouse colony as determined by DNA fingerprinting.

A genetic monitoring of the BALB/c mouse foundation colony in our animal facility was carried out. The techniques of choice were skin grafting, coat colour test, flow cytometric analysis for H2 antigens (loci H2-D and H2-A), electrophoretic analysis of isoenzymes (loci Idh1, Pep3, Es3 and Mod1), PCR-amplified microsatellites (loci Igh-V, Ngfg, Plau, Crp, Igh, D16Mit5, D3Mit49 and D17Mit16) and DNA fingerprinting (multilocus probes 33.6, 33.15 and (CAC)5). No evidence of genetic contamination was found, ruling out the possibility of an outcross with AKR, the other albino strain maintained at the facility. Nevertheless, DNA fingerprint patterns revealed evidence of genetic heterogeneity in four out of nine lines of the nucleus colony, interpreted as minisatellite mutations favoured for a single line system with more than 40 generations of separation from the ancestral pair. These mice are mainly used in cancer and immunological research within the institute.

Animals↗
PubMed1998

Outcome of 337 intracranial aneurysms patients operated in a public hospital.

Many recent series of surgery for intracranial aneurysms have been based on experience of developed countries with great resources and a state of art health care. The purpose of the current study is to correlate the outcome of patients operated for intracranial aneurysms, reported from intensive high technology neurosurgical centers with the results of low technology, environment, where we practice. Between January 1986 and December 1996, 337 patients with intracranial aneurysms were operated on at the Servidores do Estado Hospital. We retrospectively reviewed the medical and radiologic records and compared the outcome of this group with other series derived from developed countries. The overall mortality of this series was 6.9%. Of the 313 good grades surgical patients, the mortality was 4.7% and the successful results were obtained in 88.8% individuals. We conclude that patients harboring intracranial aneurysms can be satisfactory handled in less developed nations, if a meticulous intraoperative technique is employed, even though sophisticated technology and equipment are not available.

Adolescent↗
PubMed1998

Increased spatial resolution using a three-dimensional T1-weighted gradient-echo MR sequence results in greater hypointense lesion volumes in multiple sclerosis.

PURPOSE: Our goal was to evaluate whether improved spatial resolution of MR images results in the detection of higher volumes of hypointense lesions in patients with multiple sclerosis (MS). METHODS: A magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequence with subsequent reconstruction of axial sections with 5-, 3-, and 1-mm thickness and a dual-echo sequence were obtained in 16 patients with relapsing-remitting or secondary-progressive MS. The volumes of MR imaging abnormalities present on each of these studies were measured using a semiautomated segmentation technique based on local thresholding. The hypointense lesion volumes seen on the three reconstructed MP-RAGE sets of images were compared using the Friedman test and correlated with the hyperintense lesion volume on proton density-weighted images and with scores on the Expanded Disability Status Scale using Spearman's rank correlation coefficient. RESULTS: The median volume of hypointense lesions increased from 1.2 mL (range, 0 to 14.9 mL) on the 5-mm-thick MP-RAGE images to 1.7 mL (range, 0 to 15.8 mL) on the 3-mm-thick images, and to 1.9 mL (range, 0 to 16.2 mL) on the 1-mm-thick images. The hypointense lesion volumes measured on the three MP-RAGE images correlated significantly with the degree of disability, whereas this correlation was not significant with the T2-weighted lesion load. CONCLUSION: Our findings indicate that a significant increase in the volume of potentially disabling MS lesions is observed when obtaining MR images with thin sections.

Adult↗
PubMed1997

Handling stress does not affect the expression of hepatic heat shock protein 70 and conjugation enzymes in rainbow trout treated with beta-naphthoflavone.

A response in heat shock protein 70 (hsp 70) expression in the beta-naphthoflavone (BNF) treated rainbow trout (Oncorhynchus mykiss) corresponded to altered metabolic status of the liver as evidenced by the lower phosphoenolpyruvate carboxykinase (PEPCK), lactate dehydrogenase and 3-hydroxyacylcoA dehydrogenase activities. The BNF-induced increase in hsp70 levels and conjugation enzyme activities (phase I and phase II) were not modified by handling stress. Indeed handling stress did not affect either hsp 70 levels or conjugation enzyme activities in trout liver. The decrease in hepatic PEPCK activity in the BNF group may be responsible for the attenuation of the increase in liver glucose concentration after a 3 min handling stress in this species, suggesting that BNF affects liver gluconeogenic capacity in this species. Handling stress elicited a plasma cortisol and glucose response in both the sham and BNF group, however, the cortisol response with BNF was erratic compared with the sham, implying alterations in the cortisol dynamics post-stress. These results show for the first time that BNF affects cellular metabolic responses to stress and suggests the possibility of using hsp 70 as a biomarker for toxic effects in trout.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1997

A longitudinal magnetic resonance imaging study of the cervical cord in multiple sclerosis.

This study was performed to evaluate the correlation between changes of cross-sectional cord area and disability in multiple sclerosis. Axial magnetic resonance images at the C-5 spinal level were obtained at entry and 12 months later for 29 patients with clinically definite multiple sclerosis. The degree of disability was inversely correlated at entry and follow-up with the cross-sectional area and the transverse diameter of the spinal cord. In addition, changes in disability correlated inversely with changes in cross-sectional area (r = -0.4, p = 0.04). These findings suggest that cross-sectional cord area at C-5 might be a useful marker of disease evolution.

Adult↗
PubMed1997

Serial contrast-enhanced MR in patients with multiple sclerosis and varying levels of disability.

PURPOSE: To compare the rates of enhancement and changes in lesion burden in patients with multiple sclerosis (MS) and varying levels of disability. METHODS: Monthly enhanced MR images of the brain were obtained for 6 months from seven patients with mildly disabling relapsing-remitting MS and from seven patients with secondary progressive MS and severe disability. At entry and 1 year later, two unenhanced T2-weighted images of the brain were also obtained. RESULTS: Despite the fact that both groups had clinically active disease and had similar increases in unenhanced MR lesion load, the total number of enhancing lesions was 239 in patients with relapsing-remitting MS (42 on the baseline images, 151 new and 46 persistent during follow-up) (average number of lesions per patient per year was 68) and 21 in those with secondary progressive MS (five on the baseline images, 13 new, and three persistent during follow-up) (average number of lesions per patients per year was seven). CONCLUSION: Our data indicate that the rate of enhancement significantly decreases in the more advanced phases of MS. This is important when planning clinical trials, and suggests that mechanisms underlying lesion formation might be dissimilar in different MS patient groups.

Activities of Daily Living↗
PubMed1996

Contribution of plasma membrane and endoplasmic reticulum Ca(2+)-ATPases to the synaptosomal [Ca2+]i increase during oxidative stress.

In the present study we analyzed the effect of ascorbate (0.8 mM)/Fe2+ (2.5 microM)-induced membrane lipid peroxidation on the levels of intracellular free calcium,[Ca2+]i and on the possible mechanisms involved in the perturbation of intracellular calcium homeostasis during oxidative stress. For this purpose, the influence of the ascorbate/iron oxidant system on the plasma membrane and endoplasmic reticulum Ca(2+)-dependent ATPases of brain cortical synaptosomes was studied. In addition, the influence of the peroxidative process on the uptake of calcium (45Ca2+) and on the Na+/Ca2+ exchange activity at the plasma membrane was evaluated. After ascorbate/Fe(2+)-induced membrane lipid peroxidation of the order of 18.05 +/- 4.20 nmol TBARS/mg protein, an increase in [Ca2+]i occurred, under basal or depolarizing conditions (30 mM KCl), which was dependent on the extracellular calcium concentration. Thus, for 1 and 3 mM extracellular calcium concentration, an increase of the resting [Ca2+]i values of 19.8% and 33.7% was observed, while after the K(+)-depolarization the enhancement of the [Ca2+]i was 18.4% and 29.5%, respectively. The Na+/Ca2+ exchange activity and the time-dependent influx of 45Ca2+ observed in basal conditions and after the 30 mM K(+)-depolarization, were not affected under the peroxidative conditions. The Ca(2+)-dependent ATPase activity of the synaptosomal plasma membrane was significantly depressed following peroxidation of membrane lipids, decreasing the V(max) by 48.1%, without significant changes in the affinity of the enzyme for calcium (K(m) for Ca2+ was 0.54 +/- 0.04 microM in control conditions and 0.56 +/- 0.034 microM in peroxidized conditions). The Ca(2+)-ATPase activity of the endoplasmic reticulum was also affected during ascorbate/iron-induced oxidative stress; thus, an inhibition of 45.2% was observed 5 min after adding ATP. These data suggest that the increase in synaptosomal [Ca2+]i due to oxidative stress may result from the inhibition of the plasma membrane and the endoplasmic reticulum membrane Ca(2+)-ATPase activities, probably as a result of the alteration of the lipid environment required for the maximal activity of these membrane enzymes. The consequent increase in [Ca2+]i may be responsible for the injury of the nervous tissue observed during several pathological conditions in which free radical generation seems to be involved.

Adenosine Triphosphatases↗
PubMed1996

A spinal cord MRI study of benign and secondary progressive multiple sclerosis.

This study was performed to achieve a better definition of the nature of the disability in multiple sclerosis (MS). Axial spinal cord magnetic resonance imaging (MRI) at C5 was obtained in 15 patients with benign MS, 17 patients with secondary progressive MS and 10 healthy controls. Patients with secondary progressive MS had smaller spinal cord cross-sectional area (P = 0.01) and transverse diameter (P = 0.006) than patients with benign MS. The degree of disability was inversely correlated with both the cross-sectional area (r = -0.6, P = 0.0018) and transverse diameter (r = -0.5, P = 0.0032) of the cord. Spinal cord atrophy was found in 7 (41%) patients with secondary progressive MS and in 2 (13%) with benign MS. These findings suggest that destructive pathology within MS lesions might play a relevant role in the development of disability in MS.

Adult↗
PubMed1996

Pharmacokinetic and pharmacodynamic interactions between diltiazem and quinidine.

OBJECTIVES: To examine the pharmacokinetic and pharmacodynamic interactions between quinidine and diltiazem because both drugs can inhibit drug metabolism. METHODS: Twelve fasting, healthy male volunteers (age, 24 +/- 5 years; weight, 75 +/- 10 kg) received a single oral dose of diltiazem (60 mg) or quinidine (200 mg), alone and on a background of the other drug, in a crossover study. Background treatment consisted of 100 mg quinidine twice a day or 90 mg sustained-release diltiazem twice a day for 2 day before the study day. RESULTS: Pretreatment with diltiazem significantly (p < 0.05) increased the area under the curve of quinidine from 7414 +/- 1965 to 11,213 +/- 2610 ng.hr/ml and increased its terminal elimination half-life (t1/2) from 6.8 +/- 1.1 to 9.3 +/- 1.5 hours. Its oral clearance was decreased from 0.39 +/- 0.1 to 0.25 +/- 0.1 L/hr/kg, whereas the maximal concentration was not significantly affected. Diltiazem disposition was not significantly affected by pretreatment with quinidine. Diltiazem pretreatment increased QTc and PR intervals and decreased heart rate and diastolic blood pressure. No significant pharmacodynamic differences were shown for diltiazem alone versus quinidine pretreatment. CONCLUSION: Diltiazem significantly decreased the clearance and increased the t1/2 of quinidine, but quinidine did not alter the kinetics of diltiazem with the dose used. No significant pharmacodynamic interaction was shown for the combination that would not be predicted from individual drug administration.

Adult↗
PubMed1996

A comparative study of caesarean deliveries by assistant medical officers and obstetricians in Mozambique.

OBJECTIVE: To evaluate the outcome of caesarean delivery performed by assistant medical officers and specialists in obstetrics and gynaecology with particular attention to post-operative complications. DESIGN: We performed a nonrandomised analysis of 2071 consecutive caesarean deliveries at Maputo Central Hospital. Of these, 958 (46.3%) were performed by assistant medical officers (medical assistants trained for surgery) and the rest (53.7%) by specialists in obstetrics and gynaecology. The age and parity distributions of women in the two groups were almost identical. SETTING: University Hospital in Maputo, covering all emergency obstetrics with about 48,000 deliveries per year. POPULATION: Two thousand and seventy-one consecutive caesarean deliveries. MAIN OUTCOME MEASURES: Post-operative complications and the duration of post-operative hospital stay. RESULTS: There were no differences in the indications for caesarean delivery. The surgical interventions associated with caesarean delivery did not differ in the two groups. The only significant difference was in the group of superficial wound separation due to haematoma, which was slightly more common (0.35% vs 0.05%) in the group operated on by assistant medical officers (Odds Ratio 2.2; 95% Confidence Interval 1.3-3.9). CONCLUSION: Training selected medical assistants to perform caesarean delivery, even on women in poor general condition, is justified in settings in which doctors are scarce.

Adult↗