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41.
42.
D.-S. Yang D.H. Small U. Seydel J.D. Smith J. Hallmayer S.E. Gandy R.N. Martins 《Neuroscience》1999,90(4):403-1226
The 4 allele of apolipoprotein E gene is a major risk factor for Alzheimer's disease. However, the mechanism by which the E4 isoform of apolipoprotein E increases the risk of Alzheimer's disease is poorly understood. To determine whether the isoform-specific effects of apolipoprotein E may be mediated via clearance of bound β-amyloid, we examined the uptake of β-amyloid 1–40 into Chinese hamster ovary cells in the presence or absence of the apolipoprotein E isoforms E2, E3 and E4. Apolipoprotein E2 and E3 treatments were associated with higher association of β-amyloid with cells as compared to treatment with E4. Heparin blocked the association of β-amyloid with cells, as did an antibody to one of the apolipoprotein E receptors (the low-density lipoprotein receptor-related protein).
Thus, the apolipoproteins E2 and E3, but not E4, may play important roles in the clearance of β-amyloid from the extracellular space via the low-density lipoprotein receptor-related protein. 相似文献
43.
de Almeida CE Pereira AJ Marechal MH Pereira G Cruz JC Ferraz JC Giordani AJ Khalil CM Martins RH Menegussi G Moreira D Rocha JR Pinto MA 《Physics in medicine and biology》1999,44(3):N31-N38
The lack of well established dosimetry protocols for HDR sources is a point of great concern regarding the uniformity of procedures within a particular country and worldwide. The main objective of this paper is to report the results from ten institutions of an intercomparison of calibration procedures for 192Ir HDR sources currently in use in Brazil. The treatment irradiator of one institution was calibrated by a reference system and used by all participants with their own measuring electrometers and ionization chambers under the same experimental conditions. Two methods were used: the calibration jig and the well-type ionization chamber. Each participant was allowed to use their own method and formalism. The results of this exercise were very positive since this was the first time in Brazil that a group of users gathered to share their experience and openly discuss the physical concepts behind the calibration procedures. The results were all within +/-3.0%, except one case where -4.6% was observed and later identified as a problem with the Nk value for x-rays. Though the magnitude of the deviations found was generally acceptable considering the diversity of formalisms currently in use, a proposal is now being prepared to be adopted as a national protocol. The identification of the institutions was left out for the sake of confidentiality. 相似文献
44.
J Miklossy K Taddei R Martins G Escher R Kraftsik O Pillevuit D Lepori M Campiche 《Journal of neuropathology and experimental neurology》1999,58(8):803-814
The filamentous brain lesions that define Alzheimer disease (AD) consist of senile plaques and neurofibrillary tangles. Undulated pathological filaments--curly fibers or neuropil threads--also occur in the neuropil. Beta-amyloid precursor proteins are synthesized by many cells outside the central nervous system and recently, deposition of beta-amyloid-protein was reported to occur in non-neuronal tissues. In addition, increasing data claim the importance of chronic inflammation in the pathogenesis of AD. These observations suggest that AD may be a widespread systemic disorder. Here we report that pathological argyrophilic filaments with histochemical properties of amyloid showing striking morphological similarity to curly fibers and/or tangles accumulate not only in ependymal layer and in epithelial cells of choroid plexus, but also in several other organs (e.g. liver, pancreas, ovary, testis, thyroid) in AD. The ependyma, choroid plexus, and various organs of 39 autopsy cases were analyzed. In search of curly fiber and tangle-like changes in organs other than brain, 395 blocks from 21 different tissues of 24 AD cases, 5 cases with discrete or moderate AD-type changes, and 10 control cases were investigated. We found in non-neuronal cells "curly fibers" or "tangles" immunoreactive with antibodies to P component, Tau-protein, ubiquitin, fibronectin, and Apolipoprotein-E, but lacking immunoreactivity with antibodies to neurofilament proteins. Ultrastructurally they consist of densely packed straight and paired helical filaments and closely resemble neurofibrillary tangles and neuropil threads. These observations indicate that the formation of "curly fibers" and "tangles" is not unique to the central nervous system. The results suggest that AD might be a systemic disorder or that similar fibrillary changes to tangles and curly fibers may also be associated with other amyloidosis than beta-amyloidosis. Further investigations are necessary to understand the pathogenetic interest of these fibrillary changes outside the CNS. 相似文献
45.
Fátima Martel M. João Martins Isabel Azevedo 《Naunyn-Schmiedeberg's archives of pharmacology》1996,354(3):305-311
1-Methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is efficiently taken up and accumulated by rat hepatocytes. However, the nature of the mechanism(s) involved in the hepatic uptake of MPP+ remains partially unknown. The aim of the present study was to further characterize the hepatic uptake of 3H-MPP+, namely by investigating the interactions of catecholamines (which are also efficiently taken up by rat hepatocytes) with MPP1 transport.The accumulation of 3H-MPP+ in isolated rat hepatocytes occurred through saturable and non-saturable mechanisms. The kinetics of the saturable component of 3H-MPP+ uptake was as follows: Vmax = 181.3 ± 11.1 pmol mg protein–1 min–1 and Km = 47.1 M (27.9, 66.3) (n = 5). The diffusion constant (in ml mg protein–1 min–1) for the non-saturable uptake of 3H-MPP+ was 0.00068 (0.00052, 0.00083) (n = 5). From the analysis of the time course of 3H-MPP+ accumulation at a substrate concentration of 100 nM 3H-MPP+, it was found that the rate constant of inward transport of 3H-MPP+ into hepatocytes (kin) was 15.7 ± 3.8 l mg protein–1 min–1, the rate constant of outward transport of 3H-MPP+ from hepatocytes (kout) was 0.077 ± 0.023 min–1 and the equilibrium accumulation (Amax) of 3H-MPP+ was 20.2 ± 2.0 pmol mg protein–1 (n = 36). Decynium22 (1,1-diethyl-2,2-cyanide; 1 M) significantly reduced kin to 6.1 ± 1.8 l mg protein–1 min–1 (P < 0.05) and the equilibrium accumulation (Amax) of 3H-MPP+ to 9.6 ± 1.3 pmol mg protein–1 (P < 0.005) (n = 36). 3H-MPP+ accumulation (in cells incubated with 200 nM 3H-MPP+) was sensitive to (–)-adrenaline, (–)-isoprenaline, (–)-dopamine, (±)-adrenaline and (–)-noradrenaline. The most potent catecholamine in inhibiting 3H-MPP+ uptake was (–)-adrenaline, with an IC50 of 99 (22, 449) M (n = 6). (–)-Adrenaline competitively inhibited 3H-MPP+ uptake, as it significantly increased the Km value of 3H-MPP+ uptake (to 125.4 M (63.6; 187.1); P < 0.02; n = 3) but did not change the Vmax value. The cyanide-derivatives decynium22 and cyanine863 (1-ethyl-2-([1,4-dimethyl-2-phenyl-6-pyrimidinylidene]methyl)quinolinium), which inhibit uptake2 as well as the apical type of the renal transporter for organic cations, potently inhibited 3H-MPP+ uptake with IC50's of 1.4 (0.4–5.3) (n = 6) and 6.5 (2.6–16) (n = 4) M, respectively. Under conditions of monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) inhibition with either pargyline (500 M + Ro01-2812) (3,5-dinitropyrocatechol; 2 M) or pargyline (500 M) + U-0521(3,4-dihidroxy-2-methyl-propiophenone; l2 M)), (–)-adrenaline (up to 1 mM) had no inhibitory effect on the uptake of 3H-MPP+. Moreover, the uptake of 3H-MPP+ in the presence of pargyline + Ro 01-2812 was significantly lower (66.9 ± 30.4%; P < 0.05; n = 4) than in the absence of these compounds. Therefore, the effect of these MAO and COMT inhibitors on 3H-MPP+ uptake was examined. Interestingly enough, pargyline, Ro 01-2812 and U-0521 were found to inhibit the uptake of 3H-MPP+ (in cells incubated with 200 nM 3H-MPP+): 500 M pargyline, 2 M Ro 012812 and 100 M U-0521 decreased the accumulation of 3H-MPP+ to 38.1 ± 6.8 (n = 5), 60.5 ± 10.1(n = 7) and 71.3 ± 14.5 (n = 7) % of control, respectively.It is concluded that 3H-MPP+ is efficiently taken up by rat hepatocytes by a carrier-mediated mechanism sensitive to catecholamines, decynium22 and cy anine863, and to the enzyme inhibitors pargyline, Ro 01-2812 and U-0521. 相似文献
46.
Câmara Vd Filhote MI Lima MI Alheira FV Martins MS Dantas TO Luiz RR 《Cadernos de saúde pública / Ministério da Saúde, Funda??o Oswaldo Cruz, Escola Nacional de Saúde Pública》1996,12(2):149-158
The main objective of this study was to promote the evaluation of an educational method to identify health risks among adolescents exposed to mercury by their work in gold mining production.The project was carried out with adolescents from a public school from the District of Monsenhor Horta, Municipality of Mariana, state of Minas Gerais. Statistical evaluation of the results revealed a significant increase in the amount of correct answers between the first and fifth stage concerning the definition of work accidents and its importance in relation to work-related diseases, accidents on route to and from the work place and violence at work site itself. 相似文献
47.
J. D. Martins J. P. Monteiro M. C. Antunes-Madeira A. S. Jurado V. M. C. Madeira 《Toxicology in vitro》2003,17(5-6):595-601
Microorganisms are very powerful tools for the supply of information about the toxic effects of lipophilic compounds, since an impairment of cell growth usually occurs as a result of perturbations related, in most cases, with the partition of toxicants in membranes. The thermophilic eubacterium Bacillus stearothermophilus has been used as a model system to identify - and β-endosulfan interactions with the membrane possibly related with the insecticide toxicity. Two approaches have been pursued: (a) bacterial growth is followed and the effects of endosulfan isomers determined; (b) biophysical studies with the fluorescent fluidity probe 1,6-diphenyl-1,3,5-hexatriene (DPH) were performed to assess the effects of - and β-endosulfan on the organization of the membrane lipid bilayer. The effects on growth were quantitatively evaluated by determination of growth parameters, namely the lag phase, the specific growth rate and the cell density reached by cultures in the stationary phase. Growth inhibition by and β-endosulfan dependent on the concentration is diminished or removed by the addition of 2.5 m
Ca2+ to bacterial cultures. Fluorescence DPH polarization consistently showed opposite effects of Ca2+ and - and β-endosulfan on the physical state of bacterial polar lipid dispersions. 相似文献
48.
49.
Martins K Ahrenholz P Matic GB Hofmann D Tiess M Winkler RE Ramlow W 《Artificial organs》2000,24(7):526-532
Release of microparticles into the blood during extracorporeal circulation must be kept low because of possibly serious acute and chronic adverse effects. Concentration and size distribution of microparticles were measured during simulated treatments (n = 7) on original equipment for 2 standard low-density lipoprotein (LDL) elimination procedures (DALI 750, Fresenius AG, St. Wendel, Germany and Liposorber, Kaneka Corporation, Osaka, Japan) and compared to hemofiltration solutions. For both systems as well as in hemofiltration solutions, the mean particle concentrations in 500 ml portions gathered from the efferent blood line stayed below 10% of pharmacopoeia standards for infusion solutions (United States Pharmacopoeia, European Pharmacopoeia) in all measured size classes. Although particle concentrations were comparable in all systems, the mean total number of particles > or =2 microm released per session was lowest in the DALI (167,000) compared to the Liposorber (465,000) and hemofiltration solutions (2,240,000). This was mainly due to different total processed blood volumes necessary to achieve the required LDL reduction. 相似文献
50.