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Biomedical subjects

C Pereira

Publications and source records attributed to C Pereira.

At least 37 records · Page 2Linked to original sources
PubMed2001

Obstetric and neonatal outcomes associated with maternal naltrexone exposure.

Poor maternal and neonatal outcomes are associated with the pregnant heroin user. These include increased antepartum haemorrhage, decreased neonatal birthweight and increased neonatal mortality Medically supervised withdrawal from heroin during pregnancy has, however, been discouraged due to possible risk to the fetus and because of the high incidence of return to regular illicit heroin use by the mother. In recent years, however, a number of withdrawal procedures using anaesthesia, oral sedation, or intravenous sedation, precipitated by naloxone and/or naltrexone have been developed and carried out successfully on pregnant heroin users. We have now collated information on 18 cases (19 detoxifications) from three countries (Portugal, Australia and the United Kingdom). These case study data, although limited, indicate that detoxification of the pregnant heroin user is possible without significant risk to the neonate or mother, with many women not returning to dependent heroin use following detoxification. Naltrexone maintenance has also been used in the non-pregnant heroin user to discourage illicit heroin use. Similarly to methadone, stabilisation on naltrexone may be associated with conception and pregnancy Over the past three years, 26 women have conceived while on the Western Australia naltrexone program. Due to the unknown teratogenic effects, most have ceased naltrexone intake at approximately seven or eight weeks gestation. In a number of instances, however, naltrexone maintenance has been recommenced following return to a dependent pattern of heroin use. As a consequence, neonates have had different periods of naltrexone exposure, building from the initial seven or eight weeks. We now report on seven women who have delivered and three who are well into their third trimester. Neonatal and obstetric features were unremarkable with good Apgar scores, birthweight and head circumference observed. In the three cases still in third-term gestation, normal fetal development has been observed at recent ultrasound examinations. These case data indicate that naltrexone maintenance may have a role in the management of the pregnant heroin user.

Adult↗
PubMed2001

Rapid genotyping of the major alleles at the Duffy (FY) blood group locus using real-time fluorescence polymerase chain reaction.

The Duffy blood group system has clinical importance due to involvement in transfusion reactions and hemolytic disease of the newborn. Recently, the molecular basis of the two alleles, FY*A and FY*B (125G>A), and the mutation situated in the promoter region of the FY gene (-33T>C), have been elucidated. In order to develop an accurate, easy, and rapid genotyping method, we describe a procedure using the LightCycler. Samples from 53 Caucasian Portuguese blood donors and 7 black, healthy, European individuals were phenotyped with commercial antisera. DNA was extracted from blood samples and the relevant sequences were amplified with the same cycling conditions, using real-time polymerase chain reaction. The melting point of the FY*A allele was 63 degrees C and of the FY*B allele, 55 degrees C. The allele without mutation at the promoter region had a melting point at 64 degrees C and the FY*B silent allele at 58 degrees C. The results in Caucasian individuals were similar to those found in European and American populations. When FY genotyping techniques are necessary, the methodology described is preferable to conventional methods as it is reliable, high speed, and uses small volumes, providing a highly competitive technology for use by a routine laboratory.

Journal Article↗
PubMed2000

Susceptibility to beta-amyloid-induced toxicity is decreased in goto-kakizaki diabetic rats: involvement of oxidative stress.

The response of synaptosomes isolated from Wistar non-diabetic rats and Goto-Kakizaki (GK) diabetic rats to the beta-amyloid fragment Abeta25-35 was compared. The synaptosomal redox activity, evaluated by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, was shown to be decreased in GK rats (72.8 +/- 7.45% of MTT reduction). However, the reduction of MTT was decreased in synaptosomes of Wistar rats upon Abeta25-35 treatment (84.47 +/- 3.73%), while in GK rats it was not affected. Abeta25-35 induced lipid peroxidation in synaptosomes of Wistar rats, but not in that of GK rats, leading to an 1.5-fold increase in thiobarbituric acid reactive substances (TBARS) levels. In the absence of Abeta25-35, basal TBARS levels were 1.6-fold higher in GK rats. In the former preparations, the content in vitamin E was also higher (2-fold). A decrease in ATP levels, of about 2-fold, was observed in synaptosomes of Wistar rats treated with Abeta25-35, while no significant changes were observed in synaptosomes of GK rats. No significant differences between the two groups were detected in the basal ATP levels. The extrasynaptosomal accumulation of aspartate and glutamate increased upon Abeta25-35 treatment, only in synaptosomes of Wistar rats (aspartate and glutamate accumulation increased by 1.1-fold and 1.5-fold, respectively), while the accumulation of glycine increased in both Wistar (by 1.8-fold) and GK (by 2.2-fold) rats. No statistical differences in the basal accumulation of aminoacids were observed. These results show that synaptosomes of GK diabetic rats have a lower redox activity, but are less susceptible to the Abeta25-35-induced toxicity. Data also suggest that oxidative stress occurs in this hyperglycemia animal model and that an increase in the antioxidant defense systems may exert protection against toxic insults. This mechanism, occuring in the early phases of diabetes, may correspond to an adaptive response.

Adenine Nucleotides↗
PubMed2000

Detection of multiple sclerosis lesions using EPI-FLAIR images.

Fast fluid-attenuated inversion recovery (fast-FLAIR) sequences are very sensitive for detecting lesions of patients with multiple sclerosis (MS). Echo planar imaging allows to obtain FLAIR images (EPI-FLAIR) with significantly shorter scanning times. EPI-FLAIR images obtained with 10 measurements are as sensitive as fast-FLAIR for the detection of large MS lesions. Aim of this study was to compare the numbers of MS lesions seen on EPI-FLAIR images with fewer measurements (and, as a consequence, very short scanning times) with those seen on EPI-FLAIR images with 10 measurements. EPI-FLAIR scans with 2 (EPI-2), 4 (EPI-4), 6 (EPI-6), 8 (EPI-8) and 10 (EPI-10) measurements were obtained from 29 MS patients. Lesions seen using each of the five approaches were counted by agreement by two observers. EPI-10 images were used as the "gold standard" for pairwise comparisons. EPI-FLAIR scans with fewer measurements (EPI-2, -4, -6, -8) were all significantly less sensitive than EPI-10 for the detection of small, intermediate and large MS lesions. All the EPI-FLAIR scans, however, fulfilled MR diagnostic criteria for definite MS. When rapid MR scanning of uncooperative MS patients is needed, EPI-FLAIR images covering the entire brain in less than one minute may be considered.

Adult↗
PubMed2000

Vinpocetine attenuates the metabolic dysfunction induced by amyloid beta-peptides in PC12 cells.

The cytoprotective effect of vinpocetine [14-ethoxycarbonyl-(3alpha, 16alpha-ethyl)-14,15-eburnamine] was investigated on PC12 cells treated with the amyloid beta-peptides (Abeta) for 24 hours. Vinpocetine was shown to protect cells from the inhibition in redox status induced by exposure to Abeta25-35 and Abeta1-40, the maximal protection being achieved at a vinpocetine concentration of 40 microM. At this concentration, vinpocetine blocked the inhibition of the mitochondrial respiratory chain complexes II-III and IV and completely abolished the depletion of pyruvate levels induced by toxic concentrations of Abeta peptides. Furthermore, the accumulation of ROS in cells exposed to Abeta25-35 and Abeta1-40 evaluated using the fluorescent probe 2',7'-dichlorofluorescin (DCF), was reduced in the presence of 40 microM vinpocetine. Taken together, the data presented herein demonstrate that vinpocetine protects cells from Abeta toxicity, preventing the generation of oxidative stress due to the excessive accumulation of ROS. This study suggests that vinpocetine can exert neuroprotective properties which might be of importance and contribute to its clinical efficacy in the treatment of Alzheimer's disease or other neurodegenerative disorders in which oxidative stress is involved.

Amyloid beta-Peptides↗
PubMed2000

Effect of zinc ions on the cytotoxicity induced by the amyloid beta-peptide.

Insoluble aggregates of the amyloid beta-peptide (A beta) are a major constituent of senile plaques found in brains of Alzheimer's disease patients. The beta-amyloid fragment A beta(1-40) is toxic to rat pheochromocytoma PC12 cells, leading to a concentration-dependent decrease in the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The detrimental effects of A beta(1-40) are enhanced in the presence of 1 mM zinc, whereas 50 microM zinc exerts a protective effect against A beta(1-40)-induced toxicity. Exposure of PC12 cells to low zinc concentrations (50 microM) affords a decrease (1.4-fold) in the extent of lipid peroxidation, a decrement in protein oxidation (1.1-fold), and an increase in ATP levels (1.2-fold), although the differences were not statistically significant. However, treatment of cells with high concentrations of zinc (1 mM) led to significant increases in lipid peroxidation (3.7-fold) and protein oxidation (1.5-fold) and to depletion of the ATP pool (21-fold). These data suggest that zinc has a concentration-dependent dual effect, protective and toxic, thus playing an important role in the pathogenesis of Alzheimer's disease.

Adenosine Triphosphate↗
PubMed2000

Parotid nodular fasciitis in a mobile phone user.

We describe the first case of nodular fasciitis affecting the deep lobe of the parotid gland in a 39-year-old male telephone engineer and its possible association with the high usage of mobile phones.

Adult↗
PubMed2000

Immuno and cytochemical localization of Trypanosoma cruzi nitric oxide synthase.

The localization and subcellular distribution of Trypanosoma cruzi nitric oxide synthase was investigated in epimastigote cells by immunocytochemistry at electron and light microscope level, using a polyclonal antibody to neuronal nitric oxide synthase, and also, at light microscope level, by the nicotinamide adenine dinucleotide phosphate-diaphorase histochemical reaction. The immunoreactivity was ultrastructurally localized by electron microscopy in the inner surface of cell membranes and in free cytosolic clusters in the body, flagellum and apical extreme. Light microscopy showed that immunoprecipitates, specific for the Trypanosoma cruzi nitric oxide synthase, co-localized with the formazan precipitates generated by the diaphorase reaction in the same areas identified by electron microscopy. These results, taken together with previous finding from our laboratory could help to explain the involvement of the nitric oxide transduction pathway in T. cruzi epimastigote motility.

Animals↗
PubMed1999

Chlorophyllin chemoprevention in trout initiated by aflatoxin B(1) bath treatment: An evaluation of reduced bioavailability vs. target organ protective mechanisms.

Chlorophyllin (CHL) is known to inhibit DNA adduction and hepatocarcinogenesis in trout when administered at doses up to 4000 ppm in the diet with aflatoxin B(1) (AFB(1)). The principal protective mechanism is believed to involve CHL:AFB(1) complex formation, which may reduce systemic carcinogen absorption. However, mechanisms operative within the target organ in situ have not been ruled out. The present study used alternative CHL and AFB(1) exposures as well as hepatic metabolism studies to distinguish these mechanisms. Duplicate lots of 150 rainbow trout each were initiated by brief water bath exposure to 0.1 ppm AFB(1), with or without 500 ppm CHL in the water. The addition of 500 ppm CHL to the water bath, under conditions where AFB(1) is calculated to be >99% sequestered as the CHL:AFB(1) complex, reduced hepatic AFB(1)-DNA adduction by 95% and reduced hepatocarcinogenesis from 20.5% to 2%, compared with exposure to AFB(1) alone. Inclusion of 500 ppm CHL in the water bath also significantly reduced total body burden and hepatic levels of AFB(1) as well as AFB(2), a structural analogue of AFB(1) unable to directly form the 8,9-epoxide proximate electrophile but equally capable of complexing with CHL. By contrast, internal target organ CHL loading by pretreatment of trout with 4000 ppm dietary CHL for 7 days prior to (and 2 days following) AFB(1) waterbath exposure had no effect on AFB(1)-DNA adduction or tumorigenicity. Dietary CHL up to 8000 ppm had no effect on hepatic CYP2K1, CYP1A, glutathione transferase, UDP-glucuronosyl transferase, or, with one exception, the relative ratios among hepatic AFB(1) metabolites in vivo. These results support the hypothesis that CHL:AFB(1) complex formation and reduced systemic AFB(1) bioavailability is a principal mechanism for CHL chemoprevention in this model and that in situ target organ inhibitory mechanisms are relatively insignificant.

Aflatoxin B1↗
PubMed1999

Involvement of oxidative stress on the impairment of energy metabolism induced by A beta peptides on PC12 cells: protection by antioxidants.

Alzheimer's disease is widely held to be associated with oxidative stress due, in part, to the membrane action of amyloid beta-peptide (A beta) aggregates. In this study, the involvement of oxidative stress on A beta-induced energy metabolism dysfunction was evaluated on PC12 cells. It was shown that A beta peptides (A beta25-35 and A beta1-40) induce a concentration-dependent accumulation of reactive oxygen species (ROS), decrease the cellular redox activity, and lead to the depletion of ATP levels. The observed inhibition by A beta of mitochondrial function and of glycolysis is blocked by the antioxidants vitamin E, idebenone, and GSH ethyl ester. Taken together, these data suggest that exposure of PC12 cells to A beta results in an impairment of energy metabolism, leading to a deficit in ATP levels and to the compromise of cellular viability. Furthermore, the generation of ROS seems to be a crucial event responsible for the energetic metabolic dysfunction induced by A beta.

Adenosine Triphosphate↗
PubMed1999

A longitudinal study comparing the sensitivity of CSE and RARE sequences in detecting new multiple sclerosis lesions.

In this longitudinal study, we evaluated the sensitivities of dual-echo, conventional spin-echo (CSE), and rapid-acquisition relaxation-enhanced (RARE) scans for detecting the appearance of new lesions in multiple sclerosis (MS). Dual echo, CSE, and RARE scans were obtained on four occasions each separated by 28 days from five patients with relapsing-remitting MS using a 1.5-Tesla machine. A total of 44 new lesions were detected by the two sequences. Thirty-five lesions were seen on both sequences, three only on CSE and six only on FSE. This study indicates that CSE may be substituted by RARE when monitoring short-term disease activity in MS.

Brain↗
PubMed1999

Short-term evolution of individual enhancing MS lesions studied with magnetization transfer imaging.

We performed serial monthly magnetization transfer (MT) imaging to evaluate the prevalence and evolution of structural changes in individual enhancing lesions from patients with multiple sclerosis (MS). Every 4 weeks for 3 months, we obtained dual echo, magnetization transfer (MT) imaging and, 5 min after SD (0.1 mmol/kg) gadolinium-DTPA injection, T1-weighted scans from 10 patients with early relapsing-remitting MS. We measured the MT ratio (MTR) of enhancing lesions seen on the entry scans on co-registered quantitative MTR images at entry and during the follow up. Fourty-two enhancing lesions were identified on the entry scans. According to the "maximal random fluctuation" detected for the normal-appearing white matter MTR values, 16 (38%) lesions were classified as "increasing MTR" lesions, 21 (50%) as "stable MTR" lesions, and 5 (12%) as "decreasing MTR" lesions. The classification of the lesions after the first month of follow up strongly predicted the classification at the end of the follow up (chi squared = 20.35, p = 0.0004). These results indicate that the enhancing lesion population in MS is heterogeneous, and that reparative mechanisms occurring after blood-brain barrier opening are not efficient in only a minority of the enhancing lesions from patients with early relapsing-remitting MS.

Adult↗
PubMed1999

Mitochondrial function is differentially affected upon oxidative stress.

The mechanisms that lead to mitochondrial damage under oxidative stress conditions were examined in synaptosomes treated with ascorbate/iron. A loss of membrane integrity, evaluated by electron microscopy and by LDH leakage, was observed in peroxidized synaptosomes and it was prevented by pre-incubation with vitamin E (150 microM) and idebenone (50 microM). ATP levels decreased, in synaptosomes exposed to ascorbate/iron, as compared to controls. NADH-ubiquinone oxidoreductase (Cx I) and cytochrome c oxidase (Cx IV) activities were unchanged after ascorbate/iron treatment, whereas succinate-ubiquinone oxidoreductase (Cx II), ubiquinol cytochrome c reductase (Cx III) and ATP-synthase (Cx V) activities were reduced by 55%, 40%, and 55%, respectively. The decrease of complex II and ATP-synthase activities was prevented by reduced glutathione (GSH), whereas the other antioxidants tested (vitamin E and idebenone) were ineffective. However, vitamin E, idebenone and GSH prevented the reduction of complex III activity observed in synaptosomes treated with ascorbate/iron. GSH protective effect suggests that the oxidation of protein SH-groups is involved in the inhibition of complexes II, III and V activity, whereas vitamin E and idebenone protection suggests that membrane lipid peroxidation is also involved in the reduction of complex III activity. These results may indicate that the inhibition of the mitochondrial respiratory chain enzymatic complexes, that are differentially affected by oxidative stress, can be recovered by specific antioxidants.

Adenine Nucleotides↗
PubMed1999

A longitudinal MR study of the presymptomatic phase in a patient with clinically definite multiple sclerosis.

We describe the dynamics and the nature of the presymptomatic phase of multiple sclerosis (MS) in a patient for whom MR abnormalities suggestive of MS were found before the development of clinical symptoms. The patient was monitored with serial monthly MR imaging of the brain and spinal cord for 5 months. Disease activity during the presymptomatic phase showed imaging characteristics comparable to that of early relapsing-remitting MS in terms of enhancing lesions, duration of enhancement, and new lesions depicted by T2-weighted imaging. Measurements derived from magnetization transfer imaging suggested that the amount and degree of tissue destruction within and outside the lesions revealed by T2-weighted imaging were mild. This, together with the fact that only one of the 43 new lesions that developed during the presymptomatic phase was located in a neurologically eloquent area, may be the reason why, for a relatively long period, the patient had no clinical manifestations of MS despite the marked MR findings of disease activity.

Adult↗
PubMed1999

Comparison of three MR sequences for the detection of cervical cord lesions in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: Improving the sensitivity of MR imaging for the detection of multiple sclerosis (MS) lesions in the cord might be useful in the diagnostic workup and could lead to a better understanding of the evolution of the disease. The purpose of this study was to compare fast spin-echo (FSE) with magnetization transfer-prepared gradient-echo (MT-GE) and fast short-inversion-time inversion recovery (fast-STIR) MR sequences to determine which is best for imaging cervical cord lesions in MS patients. METHODS: FSE, MT-GE, and fast-STIR MR images were obtained in 56 MS patients and 10 healthy control subjects with a 1.5-T MR system and a phased-array coil. Cord lesions seen on images obtained with each sequence were counted by two observers in two stages (stage 1: random review of the complete sets of images from each technique; stage 2: side-by-side review with a retrospective count of lesions). RESULTS: At the end of stage 1, a mean of 1.16 cord lesions per patient were seen on FSE images, 1.57 on MT-GE images (35% more than on FSE), and 1.92 on fast-STIR images (66% more than on FSE). Two or more cervical cord lesions were found on 16 FSE images (29%), 23 on MT-GE images (46%), and 30 on fast-STIR images (54%). Differences were reduced after stage 2: MT-GE detected 22% more lesions and fast-STIR 36% more lesions than FSE. Considering the three sequences together, 113 cervical cord lesions were seen in 50 patients (89%). CONCLUSION: Both MT-GE and fast-STIR sequences depict more cervical cord MS lesions than the FSE sequence, with fast-STIR having the best sensitivity. Fast-STIR MR images may be useful for the diagnostic workup of patients with suspected MS and for improving our understanding of the evolution of MS.

Adult↗
PubMed1998

Quantitative volumetric analysis of brain magnetic resonance imaging from patients with multiple sclerosis.

We compared the volumes of the brain as a whole and of different cerebral structures from patients with multiple sclerosis (MS) and normal subjects. In the patients, we also correlated brain volumes with T2 and T1 lesion loads and disability. A magnetization-prepared rapid acquisition gradient echo (MP RAGE) sequence with subsequent reconstruction of axial 1-mm thick slices and a dual-echo sequence were obtained in 15 patients with relapsing-remitting or secondary progressive MS and 15 sex-, age-, height- and weight-matched normal subjects. The brains and the different cerebral structures studied (cerebral hemispheres, cerebellum and brainstem) were segmented manually by a single observer on the 1-mm MP RAGE scans. The hyperintense lesion volumes seen on dual-echo scans and the hypointense lesion volumes seen on the 1-mm MP RAGE scans were measured using a semi-automated segmentation technique based on local thresholding. Compared to the normal volunteers, patients had significantly lower cerebral (P = 0.008), hemispheric (P = 0.01) and brainstem (P = 0.03) volumes. Cerebral atrophy was detected in seven (47%) MS patients. Patients with brainstem signs had significantly lower mean brainstem volume than the others (P = 0.04). No significant correlations were found between the cerebral volumes and the EDSS scores, the hyperintense lesion volumes and the hypointense lesion volumes. We conclude that cerebral atrophy is a relatively frequent finding in MS, but its relationship with physical disability is modest.

Adult↗
PubMed1998

Mitochondrial function impairment induced by amyloid beta-peptide on PC12 cells.

The aim of the present study was to determine whether amyloid beta-peptide (A beta) induces mitochondrial dysfunction. Mitochondrial function was reported to be affected following A beta exposure, as demonstrated by depolarization of the mitochondrial membrane, decrease of oxygen consumption and by the inhibition of complexes I, III and IV of the mitochondrial respiratory chain. A beta25-35 and A beta1-40 peptides also inhibited MTT reduction in a dose-dependent manner in undifferentiated and differentiated PC12 cells. Several antioxidants prevented this inhibitory response, suggesting that oxidative stress is involved in A beta-induced cytotoxicity. These data suggest that mitochondrial dysfunction contributes to amyloid beta-protein cytotoxicity and may play a major role in the abnormalities of energy metabolism observed in Alzheimer's disease.

Amyloid beta-Peptides↗