1,720,977 research outputs found
Effect of homocysteine and nitric oxide levels on specific computed axial tomography measurements in Alzheimer disease
Full text linkThe present study was undertaken to examine the effect of Homocysteine (Hcy) and nitric oxide (NO) levels on specific Computed Axial Tomography (CAT) measurements, as global brain atrophy and brain vascular lesion in Alzheimer Disease (AD) and in Vascular Dementia (VD) patients. We have analysed serum Hcy and NO levels in AD patients and compared the findings with those in VD patients and control subjects. Moreover we have studied the correlation of Hcy and NO levels with cognitive impairment and brain atrophy determined by Computed Axial Tomography. Hcy serum levels significantly increased in all demented patients compared to control group, independently from the dementia type. On the contrary, no differences were observed in NO serum levels between groups. Moreover, we found significant correlation between Hcy and brain atrophy in both demented groups; whereas NO levels correlated only in AD, but not in VD patients. The pathogenic effect of Hcy either in AD and VD patients appears to confirm a definitive vascular component in AD. As regards NO, our results highlight the role of NO as a beneficial molecule in AD and support the use of NO mimetics as an antineurodegenerative therapy for AD patients. (c) Versita Warsaw and Springer-Verlag Berlin Heidelberg. All rights reserved
Caspase-8 activation and oxidative stress are involved in the cytotoxic effect of beta-amyloid on rat brain microvascular endothelial cells
No full textSeveral studies have demonstrated that cerebrovascular dysfunction and damage play a significant role in the pathogenesis of Alzheimer disease (AD). In fact, beta-amyloid peptides (A beta s), the major component of the senile plaques and cerebrovascular amyloid deposits in AD, were shown to be cytotoxic to endothelial cells. We have recently observed that A beta s exert a toxic effect on neuromicrovascular endothelial cells (NECs) in a time- and concentration-dependent manner, apoptosis playing a pivotal role in this process. Hence, it seemed worthwhile to investigate the A beta-mediated apoptosis mechanism in NECs. A beta s were found to induce, after a short incubation period, apoptosis throughout caspase-8 activation. Moreover, A beta s elicited a highly significant (p < 0.001) increase in superoxide dismutase (SOD) levels after a 3-h exposure period, while SOD concentration was not affected after a 24-h incubation. The time-dependent increase in SOD concentration is probably correlated with the production of all excess of reactive oxygen species. Collectively, our findings allow Lis to conclude that: i) A beta s may induce apoptosis via the activation of caspase-8, presumably by cross-linking and activating receptors of the death-receptor family; ii) oxidative stress is possibly involved in the A beta-induced cytotoxic effect; and iii) these two mechanisms do not act sequentially but, probably, are independent of each other
Comparative effects of A beta((1-42))-Al complex from rat and human amyloid on rat endothelial cell cultures
No full textMetal ions are widely recognized as a key factor for the conformational changes and aggregation of the Alzheimer's disease amyloid (Abeta). So far Al(3+) has received much less attention than other biometals in terms of interaction with Abeta. Brain endothelial cells have been identified as important regulators of the neuronal microenvironment, including Abeta levels. The purpose of this study is to compare the effects of the complex amyloid (Abeta(1-42))-Al, from human and rat, with the effects produced by metal-free Abeta on rat neuroendothelial cells (NECs). To establish Abeta and Abeta-Al toxicity on NECs, survival, vitality, and angiogenesis are evaluated. Cell survival is reduced by human and rat Abeta in a time-dependent manner. This toxic effect is remarkably pronounced in the presence of human Abeta-Al. Moreover, rat Abeta has anti-angiogenic properties on NECs, and this effect is aggravated dramatically by using both human and rat Abeta-Al complexes. The data and arguments presented herein clearly demonstrate the involvement of Al(3+) in Abeta aggregation and, consequently, increasing endothelial cell toxicity
Structural characterisation and cell response evaluation of electrospun PCL membranes: micrometric vs sub-micrometric fibers
No full textElectrospinning is a valuable technique to fabricate fibrous scaffolds for tissue engineering. The typical nonwoven architecture allows cell adhesion and proliferation, and supports diffusion of nutrients and waste products. Poly(epsilon-caprolactone) (PCL) electrospun membranes were produced starting from 14% w/v solutions in (a) mixture 1:1 tetrahydrofuran and N,N-dimethylformamide and (b) chloroform. Matrices made up of randomly arranged uniform fibers free of beads were obtained. The average fiber diameters were (a) 0.8 +/- 0.2 microm and (b) 3.6 +/- 0.8 microm. PCL matrices showed the following tensile mechanical properties: tensile modulus (a) 5.0 +/- 0.7 MPa (b) 6.4 +/- 0.2 MPa, yield stress (a) 0.55 +/- 0.06 MPa (b) 0.43 +/- 0.02 MPa, and ultimate tensile stress (a) 1.7 +/- 0.2 MPa and (b) 0.8 +/- 0.1 MPa. The ultimate strain ranged between 300% and 400%. Cytotoxicity of electrospun membranes was continuously evaluated by means of electric cell-substrate impedance sensing technique using human umbilical vein endothelial cells (HUVEC). PCL matrices resulted free of toxic amounts of contaminants and/or process by-products. In vitro studies performed by culturing HUVEC on micrometric and submicrometric fibrous mats showed that both structures supported cell adhesion and spreading. However, cells cultured on the micrometric network showed higher vitality and improved interaction with the polymeric fibers, suggesting an increased ability to promote cell colonization
Involvement of the receptor for advanced glycation-end products (RAGE) in beta-amyloid-induced toxic effects in rat cerebromicrovascular endothelial cells cultured in vitro.
No full textTo ascertain whether the potential biological effects of beta amyloid (beta A) on the endothelium are partly mediated by the receptor for advanced glycation-end products (RAGE), we performed a series of experiments which analyzed the effects of the beta A((1-42)) peptide on in vitro cerebromicrovascular endothelial cells (CECs). Our results suggest that RAGE is directly responsible for beta A((1-42)) actions on CECs, such as its toxic effect on cell survival, viability and angiogenic capability. We observed that a 6-h incubation period exposing CECs to beta A((1-42)) increased the extracellular levels of nitrite. Furthermore, the presence of a nitric oxide synthase inhibitor, L-NAME, was able to enhance CEC survival and viability. Immunocytochemical analyses demonstrated that the peptide induced expression of the inducible form of NOS, iNOS, typically synthesized in response to immune/inflammatory stimuli. Upon blocking the interaction of beta A((1-42)) and RAGE, we observed significantly decreased levels of NO and suppression of iNOS immunoreactivity. In conclusion, our data suggest the involvement of RAGE, at least partly, in mediating the effects of beta A((1-42)) on CECs. In particular, the decrease of in vitro cell viability and functionality and nitrosative stress activation was inhibited by blocking beta A((1-42))-RAGE interaction
The impact of risk factors of Alzheimer's disease in the Down syndrome
No full textDown syndrome (DS) patients, after the fourth decade of life, display some neurophatological features of the Alzheimer's disease (AD). Several hypotheses suggested that apoE4 protein, an AD risk factor, might promote amyloid formation by stabilizing an aggregated conformation of the beta amyloid protein (Abeta). This peptide is the major proteinaceous component of the senile plaques either in AD or DS, and it is a proteolytic product of the amyloid precursor protein (APP). Both brain and platelets express three APP transcripts of the apparent molecular weight of 106, 110 and 130 kDa. In DS the Abeta deposits may ensue, at least in part, from the overexpression of the Abeta precursor gene located on chromosome 21. Aims of the present study were to evaluate the frequency of apoE4 isoform in DS population, and to ascertain whether the ratio between the 130 and the 106-110 kDa platelet APP isoforms is lower in DS, as seems to occur in AD patients. ApoE4 frequency was significantly lower in DS when compared to AD patients. E4 allele frequency of older DS patients was about half that of younger ones. The 130 to 106-110 kDa APP isoform ratio was similar in young DS and control subjects, and markedly lower in AD patients. Our results indicate that: i) in DS patients the early, selective accumulation of Abeta peptides is independent of the ApoE genotype, but the allele epsilon4 predisposes to various causes of premature death; and ii) platelet APP isoform abnormalities, which can be observed in AD patients, do not occur in young DS patients, suggesting a different processing of APP platelets in DS with respect to AD
Psychological well-being outcomes in disease-free survivors of mid-low rectal cancer following curative surgery
No full textOBJECTIVE:
The aim of this cross-sectional study was to evaluate psychological well-being outcomes in disease-free survivors who previously underwent radical surgery for rectal adenocarcinoma.
METHODS:
All patients with rectal adenocarcinoma who underwent primary surgery at a single institution from 1990 to 2002 were considered for inclusion in the study. We identified and sent questionnaires to 145 patients after excluding those who had died or had recurrent disease. One hundred and seventeen patients (men/women: 74/43; median age: 65 years) returned the questionnaires. Patients' well being was evaluated using the Psychological General Well-Being Index (PGWBI) questionnaire. The mean PGWBI score was compared with normative data of the general population. The impact of patient-, tumor- and treatment-related factors on patients' long-term psychological well-being status was also evaluated.
RESULTS:
Compared with the general population, study patients had significantly better anxiety, depressed mood, positive well being, general health, vitality scales and global index scores. On multivariate analysis, positive well being was independently affected by time from diagnosis (36 months; p=0.025) and occurrence of early major complications (p=0.024). Variables that were independently associated with worse self-control included primary education (p=0.04) and the presence of fecal urgency (p=0.049). General health was negatively affected by time from diagnosis (36 months; p=0.047) and fecal urgency (p=0.009).
CONCLUSIONS:
Patients who have survived cancer are likely to re-evaluate the importance of everyday events and this may explain why they had better PGWBI scores. This study also identified that a short time from diagnosis, early adverse events and bowel dysfunction had a negative impact on patients' well being
Tailored PVA/ECM Scaffolds for Cartilage Regeneration
Full text linkArticular cartilage lesions are a particular challenge for regenerative medicine due to cartilage low self-ability repair in case of
damage. Hence, a significant goal of musculoskeletal tissue engineering is the development of suitable structures in virtue of
their matrix composition and biomechanical properties. The objective of our study was to design in vitro a supporting structure
for autologous chondrocyte growth. We realized a biohybrid composite scaffold combining a novel and nonspecific extracellular
matrix (ECM), which is decellularizedWharton’s jelly ECM, with the biomechanical properties of the synthetic hydrogel polyvinyl
alcohol (PVA).Wharton’s jelly ECMwas tested for its ability in promoting scaffold colonization by chondrocytes and compared with
polyvinyl alcohol itself and the more specific decellularized cartilage matrix. Our preliminary evidences highlighted the chance of
usingWharton’s jelly ECMin combinationwith PVAhydrogels as an innovative and easily available scaffold for cartilage restoration
Apolipoprotein-E modulates the cytotoxic effect of beta-amyloid on rat brain endothelium in an isoform-dependent specific manner
No full textSeveral studies support the hypothesis that apolipoprotein-E (ApoE) acts as a pathological chaperone protein that promotes the beta-plated sheet conformation of beta-amyloid (Abeta) peptides into amyloid fibers. In vitro evidence is also available that ApoE inhibits the neurotoxic effect of Abeta in an allele-specific manner (E2 >/= E3 > E4). We have recently shown that Abeta peptides exert a time- and concentration-dependent toxic effect on rat neuromicrovascular endothelial cells (NECs), and this study aimed to ascertain whether ApoE isoforms are able to modulate this effect. ApoE2 and ApoE4 decreased and increased, respectively, the cytotoxic effect of Abeta(1-40) and Abeta(1-42) on NECs, as evaluated by their survival and viability rates. The toxic effect of both Abeta peptides and ApoE4 was associated with the rise in the necrosis rate of NECs within a 24-h incubation period. Moreover, ApoE2 prevented and ApoE4 magnified the inhibitory effect of Abeta on the capability of NECs cultured on Matrigel to form a capillary-like network. The opposite effects of ApoE isoforms could be due to their different interactions with the C-terminal domain of Abeta. ApoE2, at variance with ApoE4, is thought to form sodium dodecyl sulphate-stable complexes with Abeta and, as a consequence, it could block the interactions of the non-fibrillar Abeta peptide with the plasma membrane, Abeta peptide aggregation and the ensuing cytotoxicity. Collectively, our findings confirm the view that ApoE plays a relevant role in the pathogenesis of Alzheimer's disease
A cross-sectional study of homocysteine-, NO-levels, and CT-findings in Alzheimer dementia, vascular dementia and controls
No full textRepetitive measurement with neuroimaging techniques could be useful instruments permitting to differentiate between Alzheimer disease (AD) and vascular dementia (VD). The major genetic risk factor for the development of late-onset AD is the allele ε4 of the apolipoprotein E (ApoE). Moreover nitric oxide (NO) and homocysteine (Hcy) seems to be correlated with the degree of cognitive impairment in demented subjects. The aim of this study was to investigate the association between serum NO and Hcy levels, global brain atrophy and brain vascular lesion in AD and VD patients. We report that high plasma levels of homocysteine resulted associated with AD and VD, suggesting that in AD elevated plasma Hcy might be a consequence of concomitant vascular dementia. Otherwise, plasma NO levels were not significantly different in any of the groups. Moreover, neuroimaging measures of vascular lesion level could be of usefulness to differentiate between AD and VD
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