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2.
J Microsc ; 285(3): 131-143, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34057229

RESUMO

Additive Manufacturing (AM) often produces complex engineered structures by precisely distributing materials in a layer-by-layer fashion. Multimaterial AM is a particularly flexible technique able to combine a range of hard and soft materials to produce designed composites. Critically, the design of AM multimaterial structures requires the development of precise three-dimensional (3D) computed aided design (CAD) files. While such digital design is heavily used, techniques able to validate the physically manufactured composite against the digital design from which it is generated are lacking for AM, especially as any evaluations must be able to distinguish material variation across the 3D space. Nowadays, there is a growing interest in volumetric tools that can provide topological information hidden by the surface of shaped materials. So far, technologies such as Optical microscopy (OM), Scanning Electron Microscopy (SEM), and Coordinate Measuring Machine (CMM) have paved the way into the metrology field to measure the external geometry of physical objects. Currently, alongside conventional metrology tools, X-ray computed tomography (XCT) is emerging to measure the subsurface of the objects but maintaining the integrity of the probed samples. Thereby, the volumetric nature of the XCT investigations and its associated imaging techniques, ensure 3D quantitative measurements comparable to the output data from 2D metrology tools, but above all, supply the missing subsurface description for an exhaustive metrology study. The reward associated with XCT applied to multimaterial AM is a map reflecting the fabricated distribution of materials following CAD, with the benefits of better understanding the mechanical interplay within phases, hence, describing the hidden processes as well as the changes in phases due to a range of mechanical or chemical phenomena. In this study, a nondestructive approach using X-ray computed tomography (XCT) is used to fully evaluate the 3D distribution of multimaterials from an AM process. Specifically, two diverse hard and soft materials are alternatively produced in the form of a fibre embedded in a matrix via ink-jet printing. XCT coupled with imaging evaluation were able to distinguish between the differing materials and, importantly, to demonstrate a reduction in the expected fabricated volumes when compared to the respective CAD designs. LAY DESCRIPTION: Additive Manufacturing (AM) has recently become important in producing complex engineered structures. Using 3D CAD files and/or reconstructed data sets from imaging, hard and soft materials are manufactured independently or in combination, according to geometrical features and shapes in the input data. However, the evaluation of the resultant manufactured parts in comparison with the original 3D drawing is currently lacking. In this sense, X-ray computed tomography (XCT) provides an important metrology tool for mono and multimaterial AM. In this work a volumetric metrology investigation is proposed using higher resolution XCT to provide 3D information comparable to that of the 3D CAD drawings. A commercial high-resolution multijetting material printer (ProJet 5500X, 3D Systems, USA) is used to manufacture single fibre composites, through a complementary deposition of photo sensible polymers. Hard and soft plastics are produced using a UV curable step, resulting in materials of similar attenuation under an X-ray probe. A critical aim of the evaluations is the potential for XCT to distinguish between different UV curable 3D printing materials.


Assuntos
Impressão Tridimensional , Tomografia Computadorizada por Raios X , Microscopia Eletrônica de Varredura , Polímeros , Tomografia Computadorizada por Raios X/métodos
3.
J Microsc ; 272(3): 213-228, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30047557

RESUMO

A micromechanical characterization of biomaterials for bone tissue engineering is essential to understand the quality of the newly regenerated bone, enabling the improvement of tissue regeneration strategies. A combination of microcomputed tomography in conjunction with in situ mechanical testing and digital volume correlation (DVC) has become a powerful technique to investigate the internal deformation of bone structure at a range of dimensional scales. However, in order to obtain accurate three-dimensional strain measurement at tissue level, high-resolution images must be acquired, and displacement/strain measurement uncertainties evaluated. The aim of this study was to optimize imaging parameters, image postprocessing and DVC settings to enhance computation based on 'zero-strain' repeated high-resolution synchrotron microCT scans of trabecular bone and bone-biomaterial systems. Low exposures to SR X-ray radiation were required to minimize irradiation-induced tissue damage, resulting in the need of advanced three-dimensional filters on the reconstructed images to reduce DVC-measured strain errors. Furthermore, the computation of strain values only in the hard phase (i.e. bone, biomaterial) allowed the exclusion of large artefacts localized in the bone marrow. This study demonstrated the suitability of a local DVC approach based on synchrotron microCT images to investigate the micromechanics of trabecular bone and bone-biomaterial composites at tissue level with a standard deviation of the errors in the region of 100 microstrain after a thorough optimization of DVC computation. LAY DESCRIPTION: Understanding the quality of newly regenerated bone after implantation of novel biomaterials is essential to improve bone tissue engineering strategies and formulation of biomaterials. The relationship between microstructure and mechanics of bone has been previously addressed combining microcomputed tomography with in situ mechanical testing. The addition of an image-based experimental technique such as digital volume correlation (DVC) allows to characterize the deformation of materials in a three-dimensional manner. However, in order to obtain accurate information at the micro-scale, high-resolution images, obtained for example by using synchrotron radiation microcomputed tomography, as well as optimization of the DVC computation are needed. This study presents the effect of different imaging parameters, image postprocessing and DVC settings for as accurate investigation of trabecular bone structure and bone-biomaterial interfaces. The results showed that when appropriate image postprocessing and DVC settings are used DVC computation results in very low strain errors. This is of vital importance for a correct understanding of the deformation in bone-biomaterial systems and the ability of such biomaterials in producing new bone comparable with the native tissue they are meant to replace.


Assuntos
Materiais Biocompatíveis , Osso e Ossos/diagnóstico por imagem , Síncrotrons , Microtomografia por Raio-X/métodos , Humanos , Imageamento Tridimensional , Software
4.
J Microsc ; 272(3): 207-212, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29953620

RESUMO

Artificial teeth have several advantages in preclinical training. The aim of this study is to three-dimensionally (3D) print accurate artificial teeth using scans from X-ray microtomography (XMT). Extracted and artificial teeth were imaged at 90 kV and 40 kV, respectively, to create detailed high contrast scans. The dataset was visualised to produce internal and external meshes subsequently exported to 3D modelling software for modification before finally sending to a slicing program for printing. After appropriate parameter setting, the printer deposited material in specific locations layer by layer, to create a 3D physical model. Scans were manipulated to ensure a clean model was imported into the slicing software, where layer height replicated the high spatial resolution that was observed in the XMT scans. The model was then printed in two different materials (polylactic acid and thermoplastic elastomer). A multimaterial print was created to show the different physical characteristics between enamel and dentine. LAY DESCRIPTION: Objectives Trainee dentists practice procedures using artificial teeth that are far from real teeth. Using x-rays and 3D printing technology the project will recreate a real tooth, artificially. Methods X-rays produce a 3D image that can be printed out as a physical replica, after several conversions of files. Different settings can be used to allow the printed model, to be as accurate as possible. Data were collected on the forces from a dental drill on a tooth's surface, to measure hardness and resistance. Results Multiple teeth replicas were printed with a high accuracy. The materials printed did not mimic actual tooth properties, but using the data from real teeth, materials can be tested in future.


Assuntos
Imageamento Tridimensional , Impressão Tridimensional , Dente Artificial , Microtomografia por Raio-X , Humanos , Software
5.
Nature ; 485(7396): 99-103, 2012 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-22522934

RESUMO

Cell transplantation is a potential strategy for treating blindness caused by the loss of photoreceptors. Although transplanted rod-precursor cells are able to migrate into the adult retina and differentiate to acquire the specialized morphological features of mature photoreceptor cells, the fundamental question remains whether transplantation of photoreceptor cells can actually improve vision. Here we provide evidence of functional rod-mediated vision after photoreceptor transplantation in adult Gnat1−/− mice, which lack rod function and are a model of congenital stationary night blindness. We show that transplanted rod precursors form classic triad synaptic connections with second-order bipolar and horizontal cells in the recipient retina. The newly integrated photoreceptor cells are light-responsive with dim-flash kinetics similar to adult wild-type photoreceptors. By using intrinsic imaging under scotopic conditions we demonstrate that visual signals generated by transplanted rods are projected to higher visual areas, including V1. Moreover, these cells are capable of driving optokinetic head tracking and visually guided behaviour in the Gnat1−/− mouse under scotopic conditions. Together, these results demonstrate the feasibility of photoreceptor transplantation as a therapeutic strategy for restoring vision after retinal degeneration.


Assuntos
Células Fotorreceptoras Retinianas Bastonetes/fisiologia , Células Fotorreceptoras Retinianas Bastonetes/transplante , Visão Ocular/fisiologia , Animais , Subunidades alfa de Proteínas de Ligação ao GTP/deficiência , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Luz , Aprendizagem em Labirinto , Camundongos , Células Bipolares da Retina/ultraestrutura , Células Horizontais da Retina/ultraestrutura , Células Fotorreceptoras Retinianas Bastonetes/citologia , Células Fotorreceptoras Retinianas Bastonetes/efeitos da radiação , Transducina/deficiência , Transducina/genética , Visão Ocular/efeitos da radiação , Córtex Visual/fisiologia , Córtex Visual/efeitos da radiação
6.
Hum Mol Genet ; 19(23): 4545-59, 2010 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-20858907

RESUMO

Retinal degenerative disease causing loss of photoreceptor cells is the leading cause of untreatable blindness in the developed world, with inherited degeneration affecting 1 in 3000 people. Visual acuity deteriorates rapidly once the cone photoreceptors die, as these cells provide daylight and colour vision. Here, in proof-of-principle experiments, we demonstrate the feasibility of cone photoreceptor transplantation into the wild-type and degenerating retina of two genetic models of Leber congenital amaurosis, the Crb1(rd8/rd8) and Gucy2e(-/-) mouse. Crx-expressing cells were flow-sorted from the developing retina of CrxGFP transgenic mice and transplanted into adult recipient retinae; CrxGFP is a marker of cone and rod photoreceptor commitment. Only the embryonic-stage Crx-positive donor cells integrated within the outer nuclear layer of the recipient and differentiated into new cones, whereas postnatal cells generated a 10-fold higher number of rods compared with embryonic-stage donors. New cone photoreceptors displayed unambiguous morphological cone features and expressed mature cone markers. Importantly, we found that the adult environment influences the number of integrating cones and favours rod integration. New cones and rods were observed in ratios similar to that of the host retina (1:35) even when the transplanted population consisted primarily of cone precursors. Cone integration efficiency was highest in the cone-deficient Gucy2e(-/-) retina suggesting that cone depletion creates a more optimal environment for cone transplantation. This is the first comprehensive study demonstrating the feasibility of cone transplantation into the adult retina. We conclude that flow-sorted embryonic-stage Crx-positive donor cells have the potential to replace lost cones, as well as rods, an important requirement for retinal disease therapy.


Assuntos
Transplante de Células/métodos , Amaurose Congênita de Leber/terapia , Células Fotorreceptoras Retinianas Cones/transplante , Células Fotorreceptoras Retinianas Bastonetes/transplante , Animais , Cegueira/terapia , Diferenciação Celular , Modelos Animais de Doenças , Embrião de Mamíferos , Camundongos , Camundongos Transgênicos , Retina/citologia
7.
Stem Cells ; 29(9): 1391-404, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21774040

RESUMO

Retinal degenerative diseases are a major cause of untreatable blindness. Stem cell therapy to replace lost photoreceptors represents a feasible future treatment. We previously demonstrated that postmitotic photoreceptor precursors expressing an NrlGFP transgene integrate into the diseased retina and restore some light sensitivity. As genetic modification of precursor cells derived from stem cell cultures is not desirable for therapy, we have tested cell selection strategies using fluorochrome-conjugated antibodies recognizing cell surface antigens to sort photoreceptor precursors. Microarray analysis of postnatal NrlGFP-expressing precursors identified four candidate genes encoding cell surface antigens (Nt5e, Prom1, Podxl, and Cd24a). To test the feasibility of using donor cells isolated using cell surface markers for retinal therapy, cells selected from developing retinae by fluorescence-activated cell sorting based on Cd24a expression (using CD24 antibody) and/or Nt5e expression (using CD73 antibody) were transplanted into the wild-type or Crb1(rd8/rd8) or Prph2(rd2/rd2) mouse eye. The CD73/CD24-sorted cells migrated into the outer nuclear layer, acquired the morphology of mature photoreceptors and expressed outer segment markers. They showed an 18-fold higher integration efficiency than that of unsorted cells and 2.3-fold higher than cells sorted based on a single genetic marker, NrlGFP, expression. These proof-of-principle studies show that transplantation competent photoreceptor precursor cells can be efficiently isolated from a heterogeneous mix of cells using cell surface antigens without loss of viability for the purpose of retinal stem cell therapy. Refinement of the selection of donorphotoreceptor precursor cells can increase the number of integrated photoreceptor cells,which is a prerequisite for the restoration of sight.


Assuntos
Antígenos de Superfície/biossíntese , Células Fotorreceptoras Retinianas Bastonetes/transplante , Células-Tronco/citologia , Animais , Diferenciação Celular , Perfilação da Expressão Gênica , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , Retina/citologia , Células Fotorreceptoras Retinianas Bastonetes/citologia , Células Fotorreceptoras Retinianas Bastonetes/imunologia , Células-Tronco/imunologia
8.
Sci Rep ; 12(1): 7830, 2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35550557

RESUMO

Human teeth are mechanically robust through a complex structural composite organisation of materials and morphology. Efforts to replicate mechanical function in artificial teeth (typodont teeth), such as in dental training applications, attempt to replicate the structure and morphology of real teeth but lack tactile similarities during mechanical cutting of the teeth. In this study, biomimetic typodont teeth, with morphology derived from X-ray microtomography scans of extracted teeth, were 3D printed using an approach to develop novel composites. These composites with a range of glass, hydroxyapatite and porcelain reinforcements within a methacrylate-based photopolymer resin were compared to six commercial artificial typodont teeth. Mechanical performance of the extracted human teeth and 3D printed typodont teeth were evaluated using a haptic approach of measuring applied cutting forces. Results indicate 3D printed typodont teeth replicating enamel and dentine can be mechanically comparable to extracted human teeth despite the material compositions differing from the materials found in human teeth. A multiple parameter variable of material elastic modulus and hardness is shown to describe the haptic response when cutting through both human and biomimetic, highlighting a critical dependence between the ratio of material mechanical properties and not absolute material properties in determining tooth mechanical performance under the action of cutting forces.


Assuntos
Biomimética , Dente , Resinas Compostas/química , Durapatita , Humanos , Teste de Materiais , Impressão Tridimensional , Dente/diagnóstico por imagem , Microtomografia por Raio-X
9.
Front Robot AI ; 9: 997415, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466736

RESUMO

Despite recent advances in robotic technology, sewer pipe inspection is still limited to conventional approaches that use cable-tethered robots. Such commercially available tethered robots lack autonomy, and their operation must be manually controlled via their tethered cables. Consequently, they can only travel to a certain distance in pipe, cannot access small-diameter pipes, and their deployment incurs high costs for highly skilled operators. In this paper, we introduce a miniaturised mobile robot for pipe inspection. We present an autonomous control strategy for this robot that is effective, stable, and requires only low-computational resources. The robots used here can access pipes as small as 75 mm in diameter. Due to their small size, low carrying capacity, and limited battery supply, our robots can only carry simple sensors, a small processor, and miniature wheel-legs for locomotion. Yet, our control method is able to compensate for these limitations. We demonstrate fully autonomous robot mobility in a sewer pipe network, without any visual aid or power-hungry image processing. The control algorithm allows the robot to correctly recognise each local network configuration, and to make appropriate decisions accordingly. The control strategy was tested using the physical micro robot in a laboratory pipe network. In both simulation and experiment, the robot autonomously and exhaustively explored an unknown pipe network without missing any pipe section while avoiding obstacles. This is a significant advance towards fully autonomous inspection robot systems for sewer pipe networks.

10.
Gene Ther ; 18(5): 509-16, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21209626

RESUMO

Multiple myeloma causes approximately 10% of all hematologic malignancies. We have previously shown that human T cells expressing chimeric NKG2D receptors (chNKG2D) consisting of NKG2D fused to the CD3ζ cytoplasmic domain secrete proinflammatory cytokines and kill human myeloma cells. In this study, we show chNKG2D T cells are effective in a murine model of multiple myeloma. Mice with established 5T33MM-green fluorescent protein tumors were treated with one or two infusions of chNKG2D T cells. Compared with mice treated with T cells expressing wild type (wt)NKG2D receptors, a single dose of chNKG2D T cells increased survival, with half of the chNKG2D T-cell-treated mice surviving long term. Two infusions of chNKG2D T cells led to tumor-free survival in all mice. ChNKG2D T cells were located at sites of tumor growth, including the bone marrow and spleen after intravenous injection. There was an increase in activated host T cells and NK cells at tumor sites and in serum interferon-γ after chNKG2D T-cell injection. Surviving mice were able to resist a rechallenge with 5T33MM cells but not RMA lymphoma cells, indicating that the mice developed a protective, specific memory response. These data demonstrate that chNKG2D T cells may be an effective adoptive cellular therapy for multiple myeloma.


Assuntos
Complexo CD3/genética , Imunoterapia Adotiva , Mieloma Múltiplo/terapia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Linfócitos T/imunologia , Transgenes , Animais , Medula Óssea/imunologia , Modelos Animais de Doenças , Memória Imunológica , Interferon gama/metabolismo , Camundongos , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/mortalidade
11.
Pharmacogenomics J ; 10(5): 385-95, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19997081

RESUMO

Biomarkers that can be measured in preclinical models in a high-throughput, reproducible manner offer the potential to increase the speed and efficacy of drug development. Development of therapeutic agents for many conditions is hampered by the limited number of validated preclinical biomarkers available to gauge pharmacoefficacy and disease progression, but the validation process for preclinical biomarkers has received limited attention. This report defines a five-step preclinical biomarker validation process and applies the process to a case study of diabetic retinopathy. By showing that a gene expression panel is highly reproducible, coincides with disease manifestation, accurately classifies individual animals and identifies animals treated with a known therapeutic agent, a biomarker panel can be considered validated. This particular biomarker panel consisting of 14 genes (C1inh, C1s, Carhsp1, Chi3l1, Gat3, Gbp2, Hspb1, Icam1, Jak3, Kcne2, Lama5, Lgals3, Nppa, Timp1) can be used in diabetic retinopathy pharmacotherapeutic research, and the biomarker development process outlined here is applicable to drug development efforts for other diseases.


Assuntos
Biomarcadores Farmacológicos/análise , Descoberta de Drogas/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Animais , Bases de Dados Genéticas , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/genética , Determinação de Ponto Final , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Marcadores Genéticos/genética , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Insulina/administração & dosagem , Insulina/uso terapêutico , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
12.
Science ; 217(4564): 1048-50, 1982 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-7051285

RESUMO

Gametocytes of two strains of the human malaria parasite Plasmodium falciparum have been produced in high density by means of a continuous-flow cultivation system. The gametocytes of these two strains infected a mean of 36 percent and 71 percent, respectively, of Anopheles freeborni mosquitoes that fed on a suspension of red blood cells containing the culture gametocytes. Sporozoites harvested from the infected mosquito salivary glands were infective to the chimpanzee (Pan troglodytes) and the owl monkey (Aotus trivirgatus).


Assuntos
Plasmodium falciparum/crescimento & desenvolvimento , Animais , Anopheles/parasitologia , Aotus trivirgatus/parasitologia , Sangue/parasitologia , Células Cultivadas , Meios de Cultura , Humanos , Pan troglodytes/parasitologia , Glândulas Salivares/parasitologia
13.
J Physiol Biochem ; 65(1): 43-50, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19588730

RESUMO

Several studies have suggested that oxidative stress might cause and aggravate the inflammatory state associated with obesity and could be the link between excessive weight gain and its related disorders such as insulin resistance and cardiovascular diseases. Thus, antioxidant treatment has been proposed as a therapy to prevent and manage obesity and associated complications. Therefore, the aim of the present study was to investigate the effects of supplementation of a standard or high fat diet with the antioxidant lipoic acid (LA) during 56 days, on body weight gain, adiposity, feed efficiency and intestinal sugar absorption, in male Wistar rats. LA supplementation induced a lower body weight gain and adipose tissue size in both control or high fat fed rats accompanied by a reduction in food intake. The group fed on a high fat diet and treated with LA (OLIP group) showed a lower body weight gain than its corresponding Pair-Fed (PF) group (P < 0.05), which received the same amount of food than LA-treated animals but with no LA. In fact, LA induced a reduction on feed efficiency and also significantly decreased intestinal alpha-methylglucoside (alpha-MG) absorption both in lean and obese rats. These results suggest that the beneficial effects of dietary supplementation with LA on body weight gain are mediated, at least in part, by the reduction observed in food intake and feed efficiency. Furthemore, the inhibitory action of LA on intestinal sugar transport could explain in part the lower feed efficiency observed in LA-treated animals and therefore, highlighting the beneficial effects of LA on obesity.


Assuntos
Metabolismo dos Carboidratos/efeitos dos fármacos , Gorduras na Dieta/farmacologia , Absorção Intestinal/efeitos dos fármacos , Ácido Tióctico/farmacologia , Aumento de Peso/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Ingestão de Alimentos , Masculino , Tamanho do Órgão , Ratos , Ratos Wistar
14.
Cytotherapy ; 10(1): 30-7, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18202972

RESUMO

BACKGROUND: We have previously demonstrated a laboratory model for expanding autologous mononuclear cells into populations of effector killer cells. The goal of the current experiments was to develop a good manufacturing practice (GMP) method for expanding clinical-grade activated effector cells that mediate tumor cell killing through various mechanisms that could be infused into patients following high-dose chemotherapy and autologous stem cell transplant. METHODS: Mobilized mononuclear cells (MNC) from myeloma patients were placed in culture with serum-free AIM V media, interleukin-2 (1000 IU/mL) and OKT-3 (500 ng/mL) at 37 degrees C and 5% CO2. After 7 days of expansion, the cells were analyzed for cell concentration, viability, phenotype and cytotoxicity directed against human myeloma cell lines. Expansion was compared using culture bags and flasks. Cryopreserved expanded cells were also analyzed. RESULTS: This clinical model of ex vivo expansion yielded polyclonal populations of cytotoxic lymphocytes, including CD3+ CD4+ T cells, CD3+ CD8+ T cells, CD8+ CD56+ T cells and CD56+ natural killer cells. Compared with flasks, culture bags provided a 2-3-fold effector cell expansion with minimal risk of contamination. The optimal cell concentration at the time of expansion was 2.5-3.5 x 10(6) peripheral blood MNC/mL. Viability and cytotoxicity were maintained if the expanded cells were cryopreserved and then thawed for use. DISCUSSION: The results demonstrate a reproducible and reliable GMP procedure that is currently being employed in a clinical trial. These expanded cells, and their various pathways of tumor cell killing, may circumvent tumor escape mechanisms and improve outcomes.


Assuntos
Imunoterapia Adotiva/métodos , Células Matadoras Naturais/citologia , Leucócitos Mononucleares/citologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Células Cultivadas , Criopreservação , Citotoxicidade Imunológica/imunologia , Citometria de Fluxo , Granulócitos/citologia , Granulócitos/imunologia , Humanos , Imunofenotipagem , Células K562 , Células Matadoras Naturais/imunologia , Leucaférese , Leucócitos Mononucleares/imunologia , Receptores de Lipopolissacarídeos/imunologia , Monócitos/citologia , Monócitos/imunologia , Mieloma Múltiplo/sangue , Mieloma Múltiplo/imunologia , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/imunologia
15.
An Med Interna ; 25(2): 81-4, 2008 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-18432365

RESUMO

Hemoperitoneum due to spontaneous rupture of hepatocellular carcinoma (HCC) constitutes a life-threatening situation if no appropriate therapy is provided. This complication is a well-known form of HCC presentation in countries with high incidence of liver tumours, but is an unusual event in Western countries, where it has been described in 5% or less of cases with HCC. We report three patients admitted to our centre with acute hemoperitoneum secondary to non-traumatic rupture as a first manifestation of not previously diagnosed HCC. A review of the related literature is also performed.


Assuntos
Carcinoma Hepatocelular/complicações , Hemoperitônio/etiologia , Neoplasias Hepáticas/complicações , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Ruptura Espontânea
16.
Sci Rep ; 8(1): 1248, 2018 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-29352193

RESUMO

Molar incisor hypomineralization is a developmental defect of dental enamel associated with rapid caries progression. In order to discover whether molar incisor hypomineralization predisposes to dental caries, a cross-sectional cohort study was conducted in a sample of 414 children aged between eight and nine years. It was found that 24.2% of the children presented molar incisor hypomineralization. Of these, 72% had a mild form and 28% a severe form. Caries prevalence was greater among the children with severe form (60.7%) than in those with mild form (43.1%) or no molar incisor hypomineralization (45.5%). The caries indices were higher in out molar incisor hypomineralization (1.18) or with mild form (1.08). The tooth-surface caries ratio was significantly higher in surfaces with severe hypomineralization than in those with no hypomineralization or mild hypomineralization. A linear regression model showed that cariogenic food intake and the presence of severe molar incisor hypomineralization were significantly associated with DMFS. Consequently, an association was found to exist between dental caries and the presence of surfaces affected by severe molar incisor hypomineralization, which should be considered a risk factor within the multifactorial etiology of caries.


Assuntos
Cárie Dentária/epidemiologia , Hipoplasia do Esmalte Dentário/epidemiologia , Criança , Cárie Dentária/patologia , Hipoplasia do Esmalte Dentário/patologia , Feminino , Humanos , Masculino
17.
J Clin Invest ; 102(4): 783-91, 1998 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-9710447

RESUMO

This study determined whether retinal degeneration during diabetes includes retinal neural cell apoptosis. Image analysis of retinal sections from streptozotocin (STZ) diabetic rats after 7.5 months of STZ diabetes identified 22% and 14% reductions in the thickness of the inner plexiform and inner nuclear layers, respectively (P < 0. 001). The number of surviving ganglion cells was also reduced by 10% compared to controls (P < 0.001). In situ end labeling of DNA terminal dUTP nick end labeling (TUNEL) identified a 10-fold increase in the frequency of retinal apoptosis in whole-mounted rat retinas after 1, 3, 6, and 12 months of diabetes (P < 0.001, P < 0. 001, P < 0.01, and P < 0.01, respectively). Most TUNEL-positive cells were not associated with blood vessels and did not colocalize with the endothelial cell-specific antigen, von Willebrand factor. Insulin implants significantly reduced the number of TUNEL-positive cells (P < 0.05). The number of TUNEL-positive cells was also increased in retinas from humans with diabetes. These data indicate that retinal neural cell death occurs early in diabetes. This is the first quantitative report of an increase in neural cell apoptosis in the retina during diabetes, and indicates that neurodegeneration is an important component of diabetic retinopathy.


Assuntos
Apoptose , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/patologia , Retinopatia Diabética/patologia , Degeneração Retiniana/patologia , Adulto , Animais , Glicemia/análise , Peso Corporal , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Retinopatia Diabética/complicações , Feminino , Hemoglobinas Glicadas/análise , Humanos , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neuroglia/patologia , Neurônios/patologia , Ratos , Ratos Sprague-Dawley , Degeneração Retiniana/complicações , Células Ganglionares da Retina/patologia , Estreptozocina
18.
ACS Biomater Sci Eng ; 3(11): 2761-2767, 2017 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33418700

RESUMO

Cortical bone is an example of a mineralized tissue containing a compositional distribution of hard and soft phases in 3-dimensional space for mechanical function. X-ray computed tomography (XCT) is able to describe this compositional and morphological complexity but methods to provide a physical output with comparable mechanical function is lacking. A workflow is presented here to establish a method of using high contrast XCT to establish a virtual model of cortical bone that is manufactured using a multiple material capable 3D printer. Resultant 3D printed structures were produced based on more and less remodelled bone designs exhibiting a range of secondary osteon density. Variation in resultant mechanical properties of the 3D printed composite structures for each bone design was achieved using a combination of material components and reasonable prediction of elastic modulus provided using a Hashin-Shtrikman approach. The ability to 3D print composite structures using high contrast XCT to distinguish between compositional phases in a biological structure promises improved anatomical models as well as next-generation mechano-mimetic implants.

19.
Science ; 358(6365): 911-914, 2017 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-29146808

RESUMO

The unexpectedly high flux of cosmic-ray positrons detected at Earth may originate from nearby astrophysical sources, dark matter, or unknown processes of cosmic-ray secondary production. We report the detection, using the High-Altitude Water Cherenkov Observatory (HAWC), of extended tera-electron volt gamma-ray emission coincident with the locations of two nearby middle-aged pulsars (Geminga and PSR B0656+14). The HAWC observations demonstrate that these pulsars are indeed local sources of accelerated leptons, but the measured tera-electron volt emission profile constrains the diffusion of particles away from these sources to be much slower than previously assumed. We demonstrate that the leptons emitted by these objects are therefore unlikely to be the origin of the excess positrons, which may have a more exotic origin.

20.
Artigo em Inglês | MEDLINE | ID: mdl-16314134

RESUMO

Due to exoskeleton, the absorption of nutrients in adult insects takes place across the gastrointestinal tract epithelium. In most physiological studies, sugar intestinal absorption has been described as a diffusional process and to date no sugar transporter has been cloned from the digestive tract of insects. In the present work, the existence of a saturable transport system for galactose in the gastric caeca of Locusta migratoria is clearly demonstrated. This transport shows a relatively high affinity for galactose (apparent K0.5=2-3 mM) and is inhibited by glucose, 2-deoxyglucose and with less potency by fructose and alpha-methyl-d-glucoside. The absence of sodium or the presence of phloridzin hardly affects galactose absorption, indicating that it is not mediated by a SGLT1-like transporter. The absence of K+, Cl-, Mg2+ and Ca2+ or changes in the pH do not modify galactose absorption either. Nevertheless, phloretin, cytochalasin B and theophylline (inhibitors of facilitative transporters) decrease sugar uptake around 50%. Xenopus laevis oocytes microinjected with poly A+ RNA isolated from gastric caeca show sodium-independent galactose uptake that is three times higher than in non-injected oocytes, further supporting the existence of a mRNA coding for at least one equilibrative sugar transporter in L. migratoria gastric caeca.


Assuntos
Galactose/metabolismo , Trato Gastrointestinal/metabolismo , Locusta migratoria/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Desoxiglucose/farmacologia , Feminino , Glucose/farmacologia , Masculino , Proteínas de Transporte de Monossacarídeos/metabolismo , Oócitos/metabolismo , Xenopus laevis
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