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1.
J Endocrinol Invest ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733428

RESUMO

PURPOSE: Information on the general health of transgender and gender diverse (TGD) individuals continues to be lacking. To bridge this gap, the National Institute of Health in Italy together with the National Office against Racial Discriminations, clinical centres, and TGD organizations carried out a cross-sectional study to define the sociodemographic profile, health-related behaviours, and experiences of healthcare access in Italian TGD adult population. METHODS: A national survey was conducted by Computer-Assisted Web Interviewing (CAWI) technique. Collected data were compared within the TGD subgroups and between TGD people and the Italian general population (IGP). RESULTS: TGD respondents were 959: 65% assigned female at birth (AFAB) and 35% assigned male at birth (AMAB). 91.8% and 8.2% were binary and non-binary TGD respondents, respectively. More than 20% of the TGD population reported to be unemployed with the highest rate detectable in AMAB and non-binary people. Cigarette smoking and binge drinking were higher in the TGD population compared with IGP (p < 0.05), affecting TGD subgroups differently. A significant lower percentage of AFAB TGD people reported having had screening for cervical and breast cancer in comparison with AFAB IGP (p < 0.0001, in both cases). Over 40% was the percentage of AFAB and non-binary TGD people accessing healthcare who felt discriminated against because of their gender identity. CONCLUSIONS: Our results are a first step towards a better understanding of the health needs of TGD people in Italy in order to plan the best policy choices for a more inclusive public health.

2.
Phys Rev Lett ; 129(19): 195001, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36399760

RESUMO

Shock ignition enables high gain at low implosion velocity, reducing ablative Rayleigh-Taylor instability growth, which can degrade conventional direct drive. With this method, driving a strong shock requires high laser power and intensity, resulting in inefficiencies in the drive and the generation of hot electrons that can preheat the fuel. A new "shock-augmented ignition" pulse shape is described that, by preconditioning the ablation plasma before launching a strong shock, enables the shock ignition of thermonuclear fuel, but importantly, with substantially reduced laser power and intensity requirements. The reduced intensity requirement with respect to shock ignition limits laser-plasma instabilities, such as stimulated Raman and Brillouin scatter, reducing the risk of hot-electron preheat and restoring the laser coupling advantages of conventional direct drive. Simulations indicate that, due to the reduced power requirements, high gain (∼100) ignition of large-scale direct drive implosions (outer radius ∼1750 µm, deuterium-tritium ice thickness ∼165 µm) may be possible within the power and energy limits of existing facilities such as the National Ignition Facility. Moreover, this concept extends to indirect drive implosions, which exhibit substantial yield increases at reduced implosion velocity. Shock-augmented ignition expands the viable design space of laser inertial fusion.

3.
Psychol Med ; : 1-9, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33722320

RESUMO

BACKGROUND: Impulsivity is a central symptom of borderline personality disorder (BPD) and its neural basis may be instantiated in a frontoparietal network involved in response inhibition. However, research has yet to determine whether neural activation differences in BPD associated with response inhibition are attributed to attentional saliency, which is subserved by a partially overlapping network of brain regions. METHODS: Patients with BPD (n = 45) and 29 healthy controls (HCs; n = 29) underwent functional magnetic resonance imaging while completing a novel go/no-go task with infrequent odd-ball trials to control for attentional saliency. Contrasts reflecting a combination of response inhibition and attentional saliency (no-go > go), saliency processing alone (oddball > go), and response inhibition controlling for attentional saliency (no-go > oddball) were compared between BPD and HC. RESULTS: Compared to HC, BPD showed less activation in the combined no-go > go contrast in the right posterior inferior and middle-frontal gyri, and less activation for oddball > go in left-hemispheric inferior frontal junction, frontal pole, superior parietal lobe, and supramarginal gyri. Crucially, BPD and HC showed no activation differences for the no-go > oddball contrast. In BPD, higher vlPFC activation for no-go > go was correlated with greater self-rated BPD symptoms, whereas lower vlPFC activation for oddball > go was associated with greater self-rated attentional impulsivity. CONCLUSIONS: Patients with BPD show frontoparietal disruptions related to the combination of response inhibition and attentional saliency or saliency alone, but no specific response inhibition neural activation difference when attentional saliency is controlled. The findings suggest a neural dysfunction in BPD underlying attention to salient or infrequent stimuli, which is supported by a negative correlation with self-rated impulsiveness.

4.
Phys Rev Lett ; 125(6): 067202, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32845695

RESUMO

A set of electron-correlation energies as large as 10 eV have been measured for a magnetic 2 ML Fe film deposited on Ag(001). By exploiting the spin selectivity in angle-resolved Auger-photoelectron coincidence spectroscopy and the Cini-Sawatzky theory, the core-valence-valence Auger spectrum of a spin-polarized system have been resolved: correlation energies have been determined for each individual combination of the two holes created in the four subbands involved in the decay: majority and minority spin, as well as e_{g} and t_{2g}. The energy difference between final states with parallel and antiparallel spin of the two emitted electrons is ascribed to the spin-flip energy for the final ion state, thus disentangling the contributions of Coulomb and exchange interactions.

5.
Opt Express ; 24(9): 9465-72, 2016 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-27137560

RESUMO

A compact (1.2 mm2) fully integrated mid-IR spectrometer operating in the 3 µm wavelength range is presented. To our knowledge this is the longest wavelength integrated spectrometer operating in the important wavelength window for spectroscopy of organic compounds. The spectrometer is based on a silicon-on-insulator arrayed waveguide grating filter. An array of InAs0.91Sb0.09 p-i-n photodiodes is heterogeneously integrated on the spectrometers output grating couplers using adhesive bonding. The spectrometer insertion loss is less than 3 dB and the waveguide-referred responsivity of the integrated photodiodes at room temperature is 0.3 A/W.

6.
Opt Express ; 22(22): 27300-8, 2014 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-25401880

RESUMO

This paper demonstrates a very compact wavelength meter for on-chip laser monitoring in the shortwave infrared wavelength range based on an optimized arrayed waveguide grating (AWG) filter with an integrated photodiode array. The AWG response is designed to obtain large nearest neighbor crosstalk (i.e. large overlap) between output channels, which allows accurately measuring the wavelength of a laser under test using the centroid detection technique. The passive AWG is fabricated on a 220 nm silicon-on-insulator (SOI) platform and is combined with GaInAsSb-based photodiodes. The photodiodes are heterogeneously integrated on the output grating couplers of the AWG using DVS-BCB adhesive bonding. The complete device with AWG and detectors has a footprint of only 2 mm(2) while the measured accuracy and resolution of the detected wavelength is better than 20pm.

7.
Adv Mater ; : e2400703, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824387

RESUMO

The integration of optoelectronic devices, such as transistors and photodetectors (PDs), into wearables and textiles is of great interest for applications such as healthcare and physiological monitoring. These require flexible/wearable systems adaptable to body motions, thus materials conformable to non-planar surfaces, and able to maintain performance under mechanical distortions. Here, fibre PDs are prepared by combining rolled graphene layers and photoactive perovskites. Conductive fibres (~500 Ωcm-1) are made by rolling single-layer graphene (SLG) around silica fibres, followed by deposition of a dielectric layer (Al2O3 and parylene C), another rolled SLG as a channel, and perovskite as photoactive component. The resulting gate-tunable PD has a response time~9ms, with an external responsivity~22kAW-1 at 488nm for a 1V bias. The external responsivity is two orders of magnitude higher, and the response time one order of magnitude faster, than state-of-the-art wearable fibre-based PDs. Under bending at 4mm radius, up to~80% photocurrent is maintained. Washability tests show~72% of initial photocurrent after 30 cycles, promising for wearable applications.

8.
Psychol Med ; 43(9): 1953-63, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23149223

RESUMO

BACKGROUND: Emotion dysregulation represents a core symptom of borderline personality disorder (BPD). Deficits in emotion perception are thought to underlie this clinical feature, although studies examining emotion recognition abilities in BPD have yielded inconsistent findings. Method The results of 10 studies contrasting facial emotion recognition in patients with BPD (n = 266) and non-psychiatric controls (n = 255) were quantitatively synthesized using meta-analytic techniques. RESULTS: Patients with BPD were less accurate than controls in recognizing facial displays of anger and disgust, although their most pronounced deficit was in correctly identifying neutral (no emotion) facial expressions. These results could not be accounted for by speed/accuracy in the test-taking approach of BPD patients. CONCLUSIONS: Patients with BPD have difficulties recognizing specific negative emotions in faces and may misattribute emotions to faces depicting neutral expressions. The contribution of state-related emotion perception biases to these findings requires further clarification.


Assuntos
Transtorno da Personalidade Borderline/fisiopatologia , Expressão Facial , Reconhecimento Visual de Modelos , Transtornos da Percepção/fisiopatologia , Percepção Social , Adulto , Transtorno da Personalidade Borderline/complicações , Feminino , Humanos , Masculino , Transtornos da Percepção/etiologia , Adulto Jovem
9.
Phys Rev Lett ; 109(12): 126401, 2012 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-23005963

RESUMO

Spin selectivity in angle-resolved Auger photoelectron coincidence spectroscopy (AR-APECS) is used to probe electron correlation in ferromagnetic thin films. In particular, exploiting the AR-APECS capability to discriminate Auger electron emission events characterized by valence hole pairs created either in the high or in the low total spin state, a strong correlation effect in the Fe M(2,3)VV Auger line shape (measured in coincidence with the Fe 3p photoelectrons) of Fe/Cu(001) thin films is detected and ascribed to interactions within the majority spin subband. Such an assignment follows from a close comparison of the experimental AR-APECS line shapes with the predictions of a model based on spin polarized density functional theory and the Cini-Sawatzky approach.

10.
Skeletal Radiol ; 41(9): 1141-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22318350

RESUMO

BACKGROUND: Preoperative diffusion-weighted MRI (DW-MRI) has been described as an efficient method to differentiate good and poor responders to chemotherapy in osteosarcoma patients. A DW-MRI performed earlier during treatment could be helpful in monitoring chemotherapy. OBJECTIVE: To assess the accuracy of DW-MRI in evaluating response to chemotherapy in the treatment of osteosarcoma, more specifically at mid-course of treatment. MATERIALS AND METHODS: This study was carried out on a prospective series of adolescents treated for long-bone osteosarcoma. MR examinations were performed at diagnosis (MRI-1), at mid-course of chemotherapy (MRI-2), and immediately before surgery (MRI-3). A DW sequence was performed using diffusion gradients of b0 and b900. The apparent diffusion coefficients (ADC1, ADC2, ADC3, respectively), their differentials (ADC2 - ADC1 and ADC3 - ADC1), and their variation (ADC2 - ADC1/ADC1 and ADC3 - ADC1/ADC1) were calculated for each of these three time points. RESULTS: Fifteen patients were included. Patients with no increase in ADC showed a poor response to chemotherapy on their histology results. At mid-course, the three calculated values were significantly different between good and poor responders. ADC2 - ADC1 enabled us to detect, with 100% specificity, four out of seven of the poor responders. There was no significant difference in the values at MRI-3 between the two groups. CONCLUSION: DW-MRI performed both at baseline and mid-course of neoadjuvant chemotherapy is an efficient method to predict further histological response of osteosarcoma. This method could be used as an early prognostic factor to monitor preoperative chemotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Adolescente , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Projetos Piloto , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
11.
Phys Rev Lett ; 107(21): 217602, 2011 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-22181926

RESUMO

The absence of sharp structures in the Auger line shapes of partially filled bands has severely limited the use of electron spectroscopy in magnetic crystals and other correlated materials. By a novel interplay of experimental and theoretical techniques we achieve a combined understanding of the photoelectron, Auger, and Auger-photoelectron coincidence spectra (APECS) of the antiferromagnetic CoO. A recently discovered dichroic effect in angle resolved (DEAR) APECS reveals a complex pattern in the Auger line shape, which is here explained in detail, labeling the final states by their total spin. Since the dichroic effect exists in the antiferromagnetic state but vanishes at the Néel temperature, the DEAR-APECS technique detects the phase transition from its local effects, thus providing a unique tool to observe and understand magnetic correlations where the usual methods are not applicable.

12.
Nat Commun ; 12(1): 3733, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145226

RESUMO

Graphene integrated photonics provides several advantages over conventional Si photonics. Single layer graphene (SLG) enables fast, broadband, and energy-efficient electro-optic modulators, optical switches and photodetectors (GPDs), and is compatible with any optical waveguide. The last major barrier to SLG-based optical receivers lies in the current GPDs' low responsivity when compared to conventional PDs. Here we overcome this by integrating a photo-thermoelectric GPD with a Si microring resonator. Under critical coupling, we achieve >90% light absorption in a ~6 µm SLG channel along a Si waveguide. Cavity-enhanced light-matter interactions cause carriers in SLG to reach ~400 K for an input power ~0.6 mW, resulting in a voltage responsivity ~90 V/W, with a receiver sensitivity enabling our GPDs to operate at a 10-9 bit-error rate, on par with mature semiconductor technology, but with a natural generation of a voltage, rather than a current, thus removing the need for transimpedance amplification, with a reduction of energy-per-bit, cost, and foot-print.

13.
J Chem Phys ; 131(17): 174710, 2009 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-19895038

RESUMO

The electronic properties of Cu-phthalocyanine (CuPc) molecules flat lying along the channels of the Au(110) reconstructed surface have been investigated by means of ultraviolet and x-ray photoelectron spectroscopy. The ordered chains give rise to a highly ordered single-layer structure with a (5x3) symmetry. Although from the core-level analysis not any significant charge transfer between the molecules and the underlying Au surface is observed, the valence band photoemission data bring to light CuPc-induced features localized at the interface. In particular, energy versus momentum dispersion of an interface state reveals a bandwidth of about 90 meV along the enlarged Au channels, where the CuPc chains are formed, with a defined fivefold symmetry well fitting the CuPc intermolecular distance.

14.
Braz J Biol ; 79(4): 722-734, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30088529

RESUMO

Small hydroelectric power plants (SHP) have been considered as an alternative for the generation of electricity with reduced environmental impacts. Nevertheless, no studies have addressed changes in a particular kind of river macrohabitat commonly affected by SHPs, the knickzones. This study aimed to assess the impact of a SHP construction on the aquatic macroinvertebrate fauna associated with two basaltic knickzones located in Sapucaí-Mirim River, Southeast Brazil. The first, considered as a functional knickzone, follows the natural dynamics of the river flow and preserves the original rock substrate. The second, considered as non-functional knickzone, was permanently flooded after the SHP construction and the consolidated rock substrate was changed by fine sediment. Sampling was carried out in two seasonal periods and the data were analysed through multivariate analysis. It was observed differences in composition and structure of the macroinvertebrates community between the knickzones and periods. The functional knickzone exhibited a much higher richness, 72 taxa compared to 44 in the non-functional, as well as a large number of exclusive taxa (38, being only nine exclusive to the non-functional). Diversity, equitability and density mean values were also higher in the functional knickzone. The limnological parameters varied significantly between dry and rainy seasons but not between the distinct knickzones. This kind of macrohabitats and its potential role for the rivers biodiversity is practically unknown. In the scenery of fast SHP expansion, further studies and protection measures are necessary.


Assuntos
Biota/fisiologia , Centrais Elétricas , Animais , Brasil/epidemiologia , Monitorização de Parâmetros Ecológicos/métodos , Monitoramento Ambiental/métodos , Inundações , Invertebrados/classificação , Invertebrados/fisiologia , Limnologia/métodos , Chuva , Rios , Estações do Ano
15.
Braz J Biol ; 78(2): 375-385, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28793033

RESUMO

The knickzones are defined as locally steep riverbed segments, such as a convex reach in a concave-up longitudinal profile. They are worldwide distributed and geologically well studied, but despite their distinctiveness as a particular kind of macrohabitat there is a notorious lack of ecological knowledge. In this context, this research proposal aims to provide a physical description, in terms of kind of habitats, and a limnological characterization of a basaltic knickzone. Information is based on a case study carried out in the Sapucaí-Mirim River, Southeast Brazil. Samplings were performed in three different habitats well represented in the knickzone (runs, riffles and pools) during rainy and dry conditions. A clear discrimination in terms of habitat type and seasonality was demonstrated through a principal component analysis. Pools exhibited higher amplitude of variation for most limnological parameters when compared to runs and riffles, probably due to a great influence of the internal metabolism (photosynthetic production and community respiration). Despite of their geological ancient formation and the little understanding of their ecological role, the knickzones are in imminent threat in several regions of the world by hydropower dams implementation. The lack of ecological information on knickzones is probably due to inherent access difficulties and how to compare the distinct kinds of habitats. Thereby, further studies should be encouraged.


Assuntos
Ecossistema , Limnologia , Rios , Animais , Brasil
16.
Cancer Res ; 37(6): 1915-7, 1977 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-322862

RESUMO

In a systematic study of the mutagenic effect of chemical compounds used as pesticides, we found that D. D. soil fumigant and Telone are mutagenic. The test was performed using the bacterial tester strains following the procedure developed by Ames. The active principle of D. D. soil fumigant and Telone is a mixture of the cis and trans isomers of 1,3-dichloropropene. Both isomers are mutagenic in Salmonella strains TA 1535 and TA 100. 2,3-Dichloro-1-propene, a minor component (5%) of the commercial preparation Telone, was also found to be mutagenic in strains TA 1535 and TA 100. Mutagenesis of these tester strains is an indication of a base-pair substitution event causing a missense mutation. 1,3-Dichloropropene is widely used in agriculture all over the world. In Italy 2,187,100 kg were produced in 1972. In California over 1,000,000 kg of 1,3-dichloropropene-containing pesticides were used in 1971.


Assuntos
Compostos Alílicos/farmacologia , Hidrocarbonetos Clorados/farmacologia , Mutagênicos , Praguicidas/farmacologia , Compostos Alílicos/metabolismo , Animais , Hidrocarbonetos Clorados/metabolismo , Técnicas In Vitro , Microssomos Hepáticos/metabolismo , Mutação/efeitos dos fármacos , Praguicidas/metabolismo , Salmonella typhimurium/efeitos dos fármacos
18.
J Cereb Blood Flow Metab ; 19(12): 1345-53, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10598939

RESUMO

Various studies describe increased concentrations of transforming growth factor-beta (TGF-beta) in brain tissue after acute brain injury. However, the role of endogenously produced TGF-beta after brain damage to the CNS remains to be clearly established. Here, the authors examine the influence of TGF-beta produced after an episode of cerebral ischemia by injecting a soluble TGF-beta type II receptor fused with the Fc region of a human immunoglobulin (TbetaRIIs-Fc). First, this molecular construct was characterized as a selective antagonist of TGF-beta. Then, the authors tested its ability to reverse the effect of TGF-beta1 on excitotoxic cell death in murine cortical cell cultures. The addition of 1 microg/mL of TbetaRIIs-Fc to the exposure medium antagonized the neuroprotective activity of TGF-beta1 in N-methyl-D-aspartate (NMDA)-induced excitotoxic cell death. These results are consistent with the hypothesis that TGF-beta1 exerts a negative modulatory action on NMDA receptor-mediated excitotoxicity. To determine the role of TGF-beta1 produced in response to brain damage, the authors used a model of an excitotoxic lesion induced by the intrastriatal injection of 75 nmol of NMDA in the presence of 1.5 microg of TbetaRIIs-Fc. The intrastriatal injection of NMDA was demonstrated to induce an early upregulation of the expression of TGF-beta1 mRNA. Furthermore, when added to the excitotoxin, TbetaRIIs-Fc increased (by 2.2-fold, P < 0.05) the lesion size. These observations were strengthened by the fact that an intracortical injection of TbetaRIIs-Fc in rats subjected to a 30-minute reversible cerebral focal ischemia aggravated the volume of infarction. In the group injected with the TGF-beta1 antagonist, a 3.5-fold increase was measured in the infarction size (43.3 +/- 9.5 versus 152.8 +/- 46.3 mm3; P < 0.05). In conclusion, by antagonizing the influence of TGF-beta in brain tissue subjected to excitotoxic or ischemic lesion, the authors markedly exacerbated the resulting extent of necrosis. These results suggest that, in response to such insults, brain tissue responds by the synthesis of a neuroprotective cytokine, TGF-beta1, which is involved in the limitation of the extent of the injury. The pharmacologic potentiation of this endogenous defensive mechanism might represent an alternative and novel strategy for the therapy of hypoxic-ischemic cerebral injury.


Assuntos
Ataque Isquêmico Transitório/fisiopatologia , Neurônios/citologia , Fármacos Neuroprotetores , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/fisiologia , Animais , Morte Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Infarto Cerebral/patologia , Infarto Cerebral/fisiopatologia , Infarto Cerebral/prevenção & controle , Feto , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fragmentos Fc das Imunoglobulinas , Ataque Isquêmico Transitório/patologia , Ataque Isquêmico Transitório/prevenção & controle , Masculino , Camundongos , Artéria Cerebral Média , N-Metilaspartato/toxicidade , Neurônios/efeitos dos fármacos , Proteínas Serina-Treonina Quinases , Ratos , Ratos Sprague-Dawley , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/fisiologia , Proteínas Recombinantes de Fusão/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta/genética
19.
Neurobiol Aging ; 17(3): 325-30, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8725892

RESUMO

Werner's Syndrome is a rare genetic disease, characterized by premature aging of many tissues and organs. We studied the brain morphology and function in two patients with Werner's syndrome to assess the possible involvement of the central nervous system in this premature aging process. The two patients (brother and sister, respectively) were studied by magnetic resonance imaging (MRI) and angiography (MRA), single photon emission computed tomography (SPECT) with (99mTc)-d,l-hexamethyl propilene amine oxime (HMPAO), positron emission tomography (PET) with 2(18F)-Fluoro-2-deoxyglucose (FDG), electroencephalography (EEG), and electromyography (EMG). Some of these investigations were also repeated after 1 year. The results of all these studies were normal. The premature aging process in patients with Werner's syndrome, while affecting most tissues, seems to spare the central nervous system.


Assuntos
Envelhecimento/patologia , Encéfalo/patologia , Síndrome de Werner/patologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada de Emissão de Fóton Único
20.
Atherosclerosis ; 118(2): 259-73, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8770320

RESUMO

Patients with homozygous familial hypercholesterolemia (FH), as a result of the increased levels and prolonged residence time of low density lipoprotein (LDL) in plasma, have a strong tendency toward accumulation of LDL-cholesterol in the arterial wall, causing premature atherosclerosis. This phenomenon may enhance per se the physiological degradation of both protein and lipid component of LDL, which be more susceptible to oxidative damage induced by oxygen radicals. It is well known that LDL may undergo oxidative modification before being taken up by macrophages which are then transformed into foam cells. It has been suggested that platelet-activating factor (PAF) may play an important role in atherogenesis and PAF catabolism is known to be mediated by serum acetylhydrolase, an enzyme that is normally associated with LDL. Thus, the present study was designed to investigate the structural properties of LDL, including acetylhydrolase activity, in homozygous FH as compared to normolipidemic subjects before and after xanthine/xanthine oxidase-mediated oxidation. We studied 8 homozygous FH patients matched with 8 normolipidemic volunteers. Lipids of LDL fraction were extracted and verified by thin layer chromatography (TLC) analysis. Fatty acids were methylated and injected into a gas chromatograph/mass spectrometer. Vitamin E in LDL was determined by high performance liquid chromatography (HPLC). As an index of susceptibility of LDL to oxidative modifications, the formation of lipid-conjugated dienes was continuously monitored at 234 nm. Lipid peroxidation was also evaluated from the amount of both lipid peroxides (LPO) and malonyldialdehyde (MDA) content. Apolipoprotein (apo) B-100 on LDL was carried on polyacrylamide and agarose gel electrophoresis. In the homozygous FH patients, the relative content of cholesteryl ester was slightly increased. Interestingly, the relative amount of arachidonic acid (20:4) was constantly increased in each lipid fraction in homozygous FH patients. The amount of vitamin E was not significantly different in the patient group from that in the control group. However, LDL from patients carried lower levels of vitamin E (nmol/mg LDL) than controls (2.7 +/- 0.4 vs. 2.9 +/- 0.3 P = NS). The results shows that lag time (min) was decreased (82 +/- 19 vs. 111 +/- 21; P < 0.05) and the maximal rate of diene production and total diene production was increased in homozygous FH patients. Mean levels of MDA were similar in both groups before oxidation, but levels after initiation of oxidation were significantly higher in the patient group. In contrast, mean levels of LPO were already higher in patients before oxidation (58 vs. 27 nmol/mg of protein; P < 0.05), and after initiation of oxidation were also significantly higher at each time points. When oxidized LDL was run on a polyacrylamide gel, an extensive apo B-100 fragmentation replaced by lower molecular mass fragments ranging from 45,000 to 205,000 m.wt., was observed only in LDL from homozygotes. Relative LDL agarose gel mobility shows that LDL from patients migrated higher than LDL of controls. Finally acetylhydrolase activity associated with LDL in patients was significantly reduced as compared to controls. Thus, in homozygous FH patients, LDL appeared more susceptible to oxidation in vitro; the indices for LDL oxidizability were all significantly different from those of controls. This phenomenon might be due to prolonged residence time of LDL in these patients, as suggested from high basal LPO levels and lower vitamin E levels carried by LDL. This hypothesis may explain together with the high content of arachidonic acid, the enhanced susceptibility of LDL from homozygous FH patients to oxidative damage.


Assuntos
Hiperlipoproteinemia Tipo II/sangue , Lipoproteínas LDL/química , Proteínas de Membrana , Receptores de Lipoproteínas , Apolipoproteína B-100 , Apolipoproteínas B/sangue , Ésteres do Colesterol/sangue , Cromatografia em Camada Fina , Ácidos Graxos/sangue , Cromatografia Gasosa-Espectrometria de Massas , Homozigoto , Humanos , Hiperlipoproteinemia Tipo II/genética , Peroxidação de Lipídeos , Lipoproteínas LDL/sangue , Malondialdeído/sangue , Oxirredução , Espécies Reativas de Oxigênio , Receptores Imunológicos/metabolismo , Receptores Depuradores , Receptores Depuradores Classe B , Vitamina E/sangue , Xantina Oxidase/metabolismo
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