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Biomedical subjects

S M Cardoso

Publications and source records attributed to S M Cardoso.

15 recordsLinked to original sources
PubMed2006

The key role of mitochondria in Alzheimer's disease.

Mitochondria are uniquely poised to play a pivotal role in neuronal cell survival or death because they are regulators of both energy metabolism and apoptotic pathways. This review is mainly focused in the discussion of evidence suggesting a clear association between amyloid-beta toxicity, mitochondrial dysfunction, oxidative stress and neuronal damage/death in Alzheimer's disease pathophysiology. The knowledge that mitochondrial dysfunction has a preponderant role in Alzheimer's disease opened a window for new therapeutic strategies aimed to preserve/ameliorate mitochondrial function. Based on recent developments in mitochondrial research, increased pharmacological and pharmaceutical efforts have lead to the emergence of 'Mitochondrial Medicine' as a whole new field of biomedical research being this topic discussed in the last section of this review.

Alzheimer Disease↗
PubMed2005

Protective effect of zinc on amyloid-beta 25-35 and 1-40 mediated toxicity.

Amyloid beta-peptide (Abeta) is widely held to be associated with Alzheimer's disease, the insoluble aggregates of the peptide being the major constituents of senile plaques. In this study, we evaluated the effect of Zn(2+) (5, 50 and 200 microM) on Abeta induced toxicity using the human teratocarcinome (NT2) cell line. Our results proved that 50 and 200 microM Zn(2+) protected NT2 cells from Abeta 25-35 toxicity. Zinc was also shown to be effective by preventing the loss of mitochondrial membrane potential (DeltaPsi(m)) induced by Abeta 25-35, not allowing cytochrome c release from mitochondria, and subsequently, caspase 3 activation. However, when the cells were treated with Abeta 1-40, only Zn(2+) 5 microM had a protective effect. We have further observed that 5 microM Zn(2+) prevented Abeta 1-40 aggregation into a beta-sheet structure. Considering the results presented, we argue that Zn(2+) has a concentration-dependent protective effect.

Amyloid beta-Peptides↗
PubMed2005

Organochlorine pesticide residues in European sardine, horse mackerel and Atlantic mackerel from Portugal.

This paper reports the results for the surveillance of nine organochlorine pesticides (HCH isomers (alpha, beta, e, gamma), p,p'-DDD, p,p'-DDT, p,p'-DDE, p,p'-DDD, HCB and aldrin) in muscle of three fish species, European pilchard (Sardina pilchardus), Atlantic horse mackerel (Trachurus trachurus) and Atlantic mackerel (Scomber scombrus). Analytical methodology included n-hexane extraction, clean-up with 2% deactivated Florisil, and quantification with gas chromatography-electron capture detection (GC-ECD). The highest mean concentrations were found for p,p'-DDT in sardine and mackerel at levels of 30.1 and 109.9 microg kg(-1), respectively, and for p,p'-DDD in horse mackerel at 51.9 microg kg(-1). Three species had higher levels for S-DDT than S-HCH. The estimated daily intake of organochlorine pesticides in the three species showed that in sardine, the highest EDIs were found for aldrin, at 1.8 ng kg(-1) bw day(-1), which represents 1.8% of the acceptable daily intake (ADI), and for ss-HCH, at 4.0 ng kg(-1) bw day(-1), representing 0.4% of ADI. Lowest values were found for Atlantic mackerel. Statistical analysis to determine the differences in mean concentrations of pesticides between species, and any correlation between groups of residues related with each one of the species, was undertaken.

Adipose Tissue↗
PubMed2005

Neurodegenerative pathways in Parkinson's disease: therapeutic strategies.

Parkinson's disease (PD), considered one of the major neurological disorders, is characterized by the loss of dopaminergic neurons in the pars compacta of the substantia nigra and by the presence of intraneuronal cytoplasmic inclusions called Lewy bodies. The causes for degeneration of PD neurons remain unclear, however, recent findings contributed to clarify this issue. This review will discuss the current understanding of the mechanisms underlying Parkinson's disease pathogenesis, focusing on the current and potential therapeutic strategies for human treatment.

Animals↗
PubMed2005

Alzheimer's disease-associated neurotoxic mechanisms and neuroprotective strategies.

The characteristic hallmarks of Alzheimer's disease (AD), the most common form of dementia in the elderly, include senile plaques, mainly composed of beta-amyloid (Abeta) peptide, neurofibrillary tangles and selective synaptic and neuronal loss in brain regions involved in learning and memory. Genetic studies, together with the demonstration of Abeta neurotoxicity, led to the development of the amyloid cascade hypothesis to explain the AD-associated neurodegenerative process. However, a modified version of this hypothesis has emerged, the Abeta cascade hypothesis, which takes into account the fact that soluble oligomeric forms and protofibrils of Abeta and its intraneuronal accumulation also play a key role in the pathogenesis of the disease. Recent evidence posit that synaptic dysfunction triggered by non fibrillar Abeta species is an early event involved in memory decline in AD. The current understanding of the molecular mechanisms responsible for impaired synaptic function and cognitive deficits is outlined in this review, focusing on oxidative stress and disturbed metal ion homeostasis, Ca(2+) dysregulation, mitochondria and endoplasmic reticulum dysfunction, cholesterol dyshomeostasis and impaired neurotransmission. The activation of apoptotic cell death as a mechanism of neuronal loss in AD, and the prominent role of neuroinflammation in this neurodegenerative disorder, are also reviewed herein. Furthermore, we will focus on the more relevant therapeutical strategies currently used, namely those involving antioxidants, drugs for neurotransmission improvement, hormonal replacement, gamma- and beta- secretase inhibitors, Abeta clearance agents (Abeta immunization, disruption of Abeta fibrils, modulation of the cholesterol-mediated Abeta transport), non-steroidal anti-inflammatory drugs (NSAIDs), microtubules stabilizing drugs and kinase inhibitors.

Alzheimer Disease↗
PubMed2003

Inhibition of NF-kB renders cells more vulnerable to apoptosis induced by amyloid beta peptides.

One of the mechanisms leading to neurodegeneration during Alzheimer's disease (AD) is amyloid beta peptide neurotoxicity. In response to a variety of stress insults, namely oxidative stress, the transcription factor NF-kB can be activated. We have previously shown that amyloid beta peptides 25-35 and 1-40 (A beta 25-35 and A beta 1-40) induces cell death. In response to A beta 25-35 or 1-40 treatment, we observed an increase in superoxide dismutase (SOD) activity in NT2 cells. Amyloid beta peptides also induced an increase in SOD expression levels. This could result from NF-kB activation, as determined by the expression of p65. We observed that the NF-kB inhibitor, PDTC, prevented SOD overexpression after A beta treatment. Previously we have shown that A beta peptides could activate caspases-mediated apoptotic cell death. In this study, we analyzed if NF-kB activation prevented cells from caspases-activation and we also observed that inhibition of NF-kB by PDTC induced an increase in caspase-3 and caspase-6 activation. Taken together, these data suggest that pharmacological induction of NF-kB can be a potential target in Alzheimer's disease treatment.

Alzheimer Disease↗
PubMed2000

[An evaluation of the impact of cardiovascular disease prevention in Portugal (1980-1996). A longitudinal Gompertzian analysis of mortality].

The behaviour of cardiovascular diseases has suffered important modifications in recent years. There have been increases in mortality and morbidity in some countries while others have seen stabilization and even reduction. In the countries where we have observed a reduction in cardiovascular mortality, the reasons are multiple: efficacy of prevention measures; improvement of environmental conditions; increase in survival; and competitiveness with other causes of death. In order to ascertain whether a certain tendency is real or fictitious, we need to use techniques that allow the evaluation of the true evolution, to study the effect of environmental factors (not genetic) and the variability of internal resistance (vitality) to disease. Based on the longitudinal Gompertzian analysis of mortality for ischemic heart disease (IHD) and cerebrovascular disease (CVD) between 1980 and 1996, it was possible to observe a reduction in mortality for both causes, which was more obvious in the case of CHD, and that the impact of the improvement in environmental conditions (not genetic) was higher in CVD versus IHD. The prevention of CVD was more efficient in men (42.8% vs 29.7%) than in women, while in IHD the most efficient prevention was 20.6% in women versus 14.9% in men, comparing the data of 1996 and 1980. During this period, the environmental influences (not genetic) were responsible for the reduction in mortality for IHD in 2.7% of men and 4.3% of women, while in CVD we observed a reduction in mortality of 7.5% in men and 4.5% in women.

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↗
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

[Measurement discrepancies (analysis of consistency between 2 methods)].

Our purpose was to study the agreement between two methods with clinical impact. Usually, many techniques are not correct for the analysis of concordance. Otherwise, it is normal to confuse association and concordance. We intend to prove that two methods can show a strong association and a weak concordance. Nowadays we must replace "old" methods with new ones, which are more correct and efficient for clinical and research goals.

Biometry↗
PubMed1998

[The spatial grouping of myocardial infarct in Portugal. The application of the methods of Grimson and of Moran].

OBJECTIVES: The objective of this study was to apply techniques of space grouping (clusters) to identify the existence of eventual clusters. The application of these techniques to illnesses, such as cardiovascular ones, may generate work hypotheses, in order to know the dynamics of the risk factors. MATERIAL AND METHODS: We used two techniques, Grimson's test and the Moran's I for the study of the behaviour of standardised mortality ratio (SMR) for myocardium infarction at a municipal level. The SMR had been calculated by municipalities, for men, women and both in the period of 1985-1989, based on the data of the INE. RESULTS: We verified that any of the two methods suggests the existence of clusters for the infarct of the myocardium, identifying regions in the country in which SMR are above that expected, implying the presence of "identical denominators" or other common ones. CONCLUSIONS: The use of these techniques for cardiovascular illnesses could be useful as a scientific form of identifying regions of high and low risk, making it possible for epidemiological studies to be made of the different known and unknown risk factors contributing to the implementation of preventive measures.

Cluster Analysis↗
PubMedDate not supplied

[The prevalence of cerebrovascular stroke in Coimbra].

The purpose of this study was to assess the prevalence of strokes in a community-based on a sample of the population of the county of Coimbra in 1992 (139,000 inhabitants). The study was made with the collaboration of local general practitioners who randomly selected a sample of 950 individuals over 50 years of age. These individuals were screened for the presence of vascular risk factors and strokes in the past, and submitted to clinical and laboratory examinations. There were 86 persons with strokes (crude prevalence 8%: 10.2% male, 6.6% female) the diagnosis being confirmed by neurological examination or analysis of hospital registers. Hypertension was significantly more frequent in patients with strokes (56.8%). Other risk factors had no significant differences. The magnitude of disability associated with stroke was assessed according to the modified Rankin scale. About fifty percent had no significant disability or a slight disability and 20% were severely disabled.

Age Distribution↗