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1.
Rev Neurol ; 78(6): 147-155, 2024 Mar 16.
Artigo em Espanhol | MEDLINE | ID: mdl-38482702

RESUMO

INTRODUCTION: The objective is to produce an average brain activation mapping template in healthy children using functional magnetic resonance imaging (fMRI), with specific paradigms for activating inhibitory attention and working memory functions. SUBJECTS AND METHODS: A nutritional and neuropsychological evaluation was performed on 87 right-handed children. The inclusion criteria were met by 30 children (15 boys and 15 girls) between 9 and 11 years old, who were studied with fMRI in two inhibitory attention tests (Go/No Go), with food cues, a working memory test (Continuous Performance Test Identical Pairs) and measurement of anatomical volumes. These data were subsequently processed with the FSL-v5 program, with a threshold of p < 0.05 (cluster-wise). The brain areas activated were located using a standard Montreal Neurological Institute brain template and the Harvard-Oxford structural cortical atlas. RESULTS: The inhibitory attention tests showed activation frontal areas predominantly on the right, and the cingulate, parietal and occipital areas, with preponderance in occipital areas in the food cues test. In the Continuous Performance Test-Identical Pairs test, activation was obtained predominantly in the occipital, frontal and parietal areas. CONCLUSIONS: Brain activity mapping templates are obtained in healthy children with tests for inhibitory attention, food cues and working memory. The activation areas are mostly those reported in the literature. This provides baseline brain activation patterns for studying pathologies related to inhibitory attention, impulsivity and working memory.


TITLE: Mapeo neuroanatómico de atención inhibitoria y memoria de trabajo con resonancia magnética funcional en niños sanos.Introducción. El objetivo es lograr una plantilla de mapeo de activación cerebral promedio en niños sanos usando la resonancia magnética funcional (RMf), con paradigmas específicos para activar funciones de atención inhibitoria y de memoria de trabajo. Sujetos y métodos. Se realizó una evaluación nutricional y neuropsicológica a 87 niños diestros. Cumplieron los criterios de inclusión 30 (15 niños y 15 niñas) entre 9 y 11 años, a quienes se estudió con RMf con realización de dos pruebas de atención inhibitoria (Go/No Go), con letras e imágenes de alimentos, un test de memoria de trabajo (Test de Atención Continua-Pares Idénticos) y obtención de volúmenes anatómicos. Los datos posteriormente se procesaron con el programa FSL-v5 con un umbral de p < 0,05 (cluster-wise). Las áreas cerebrales activadas se localizaron utilizando una plantilla cerebral estándar del Montreal Neurological Institute y el atlas cortical estructural de Harvard-Oxford. Resultados. En las pruebas de atención inhibitoria hay activación en áreas frontales de predominio derecho, cíngulo, parietales y occipitales, con preponderancia en áreas occipitales en la prueba con alimentos. En la prueba Test de Atención Continua-Pares Idénticos se obtuvo activación de predominio en áreas occipitales, frontales y parietales. Conclusiones. Se obtienen plantillas de mapeo de actividad cerebral en niños sanos con test de atención inhibitoria, de alimentos y de memoria de trabajo. Las áreas de activación corresponden mayoritariamente a las descritas en la bibliografía. Esto nos permite tener patrones basales de activación cerebral para estudiar patologías relacionadas con la atención inhibitoria, la impulsividad y la memoria de trabajo.


Assuntos
Encéfalo , Memória de Curto Prazo , Masculino , Feminino , Criança , Humanos , Memória de Curto Prazo/fisiologia , Encéfalo/fisiologia , Mapeamento Encefálico , Atenção/fisiologia , Imageamento por Ressonância Magnética/métodos , Testes Neuropsicológicos
2.
J Environ Manage ; 345: 118765, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37604103

RESUMO

The aim of this work was to evaluate the feasibility of the use of different industrial and agricultural wastes as reactive materials in Permeable Reactive Barriers (PRB) for Acid Mine Drainage (AMD) remediation. Sugar foam (SF), paper mill sludge (PMS), drinking water sludge (DWS) and olive mill waste (OMW) were evaluated in terms of pH neutralization and metal removal from AMD. Laboratory batch tests and continuous pilot scale up-flow columns containing 82% of Volcanic Slag (VS), as porous fill material, and 18% w/w of one of the industrial and agricultural wastes previously indicated, were tested. From the batch tests it was observed that the reactive material presenting the best results were the SF and the PMS. The results obtained in all the PRB were accurately described by a pseudo-first order model, presenting coefficient of determination higher than 0.96 in all the cases. During the continuous operation of the PRB, the porosity and hydraulic retention time (HRT) of most of the up-flow columns strongly decreased due to chemical precipitation and biofilm growth. The SF presented a significant number of fine particles that were washed out by the liquid flow, generating an effluent with very high total suspended solid concentration. Despite SF was the material with the highest alkalinity potential, the reduction of the HRT limited its neutralization and metal removal capacity. PMS and DWS presented the best pollutant removal yields in the continuous operation of the PRB, ranging from 55 to 99% and 55-95% (except in the case of the Mn), respectively. These results allowed the metal removal from the AMD. Additionally, these wastes presented very good biological sulphate reduction. Based on these results, the use of PMS and DWS as reactive material in PRB would allow to simultaneously valorise the industrial waste, which is very interesting within the circular economy framework, and to remove metals from the AMD by means of a low-cost and environmentally sustainable procedure.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Esgotos , Metais , Mineração , Resíduos Industriais/análise , Ácidos , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio
3.
Comput Biol Med ; 164: 107249, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37473562

RESUMO

The increase in life expectancy combined with greater bone fragility over the years is causing a rise in the bone fracture cases. Femur fractures are the most important due to their high mortality rate. This multidisciplinary work is carried out in this context and focuses on the experimental reproduction of human femur fractures by compression. We describe a sequence of steps supervised by orthopaedic surgeons for the correct arrangement of specimens on the system set up to perform the experiment. The device applies force by compression until the human bone is fractured. All tests performed have been monitored and evaluated from different knowledge perspectives. The results obtained have demonstrated the repeatability of the fracture type in a controlled environment as well as identifying the main features involved in this process. In addition, the fractured bones have been digitized to analyze the fracture zone to recreate and evaluate future simulations.


Assuntos
Fraturas do Fêmur , Humanos , Fraturas do Fêmur/diagnóstico por imagem , Fêmur/diagnóstico por imagem , Estresse Mecânico , Fenômenos Biomecânicos
4.
Rev Esp Cir Ortop Traumatol ; 67(2): 125-133, 2023.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35985409

RESUMO

OBJECTIVE: The aim of our work is to check if the use of a pre-tensed bar connected to 2supra-acetabular Schanz pins is more stable in a pelvic with a tile C1 injury. MATERIAL AND METHODS: We used synthetic pelvis (N=5) with a unstable vertical injury, stabilized with both the standard and the pre-tensed system. They both were submitted to axial loading. We measured applied forces and the position of markers that were positioned in the sacroiliac and symphysis joints. We determined the relative movements between injured surfaces, rigidity, resistance and when each system failed. RESULTS: When using the pre-tensed fixator, the rigidity was much higher in the sacro-iliac joint (P=.043) being 3.45 times higher, being also 2.06 times higher in pubic symphysis (P=.043). The resistance against failure was 2 times higher too (P=.043). DISCUSSION: The increased axial stability with the pre-tensed external fixator accords with its ability to make active compression in both posterior and anterior elements of the pelvic ring, which was previously demonstrated. This result supports the preliminary clinic outcomes that were obtained. CONCLUSIONS: The pre-tensed external fixator increases the axial stability of the pelvic ring's posterior elements in a synthethic pelvis with a Tile C1 injury, without decreasing it's capacity to achieve an anterior stability.


Assuntos
Fraturas Ósseas , Ossos Pélvicos , Humanos , Fixação de Fratura , Ossos Pélvicos/lesões , Ossos Pélvicos/cirurgia , Fixadores Externos , Pelve/lesões , Pelve/cirurgia , Pinos Ortopédicos , Fenômenos Biomecânicos
5.
Rev Esp Cir Ortop Traumatol ; 67(2): T125-T133, 2023.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-36528300

RESUMO

OBJECTIVE: The aim of our work is to check if the use of a pre-tensed bar connected to 2 supra-acetabular Schanz pins is more stable in a pelvic with a tile C1 injury. MATERIAL AND METHODS: We used synthetic pelvis (N = 5) with a unstable vertical injury, stabilized with both the standard and the pre-tensed system. They both were submitted to axial loading. We measured applied forces and the position of markers that were positioned in the sacroiliac and symphysis joints. We determined the relative movements between injured surfaces, rigidity, resistance and when each system failed. RESULTS: When using the pre-tensed fixator, the rigidity was much higher in the sacro-iliac joint(P=.043) being 3.45 times higher, being also 2.06 times higher in pubic symphysis (P=.043). The resistance against failure was 2 times higher too (P=.043). DISCUSSION: The increased axial stability with the pre-tensed external fixator accords with its ability to make active compression in both posterior and anterior elements of the pelvic ring, which was previously demonstrated. This result supports the preliminary clinic outcomes that were obtained. CONCLUSIONS: The pre-tensed external fixator increases the axial stability of the pelvic ring's posterior elements in a synthethic pelvis with a Tile C1 injury, without decreasing it's capacity to achieve an anterior stability.


Assuntos
Fraturas Ósseas , Ossos Pélvicos , Humanos , Fixação de Fratura , Ossos Pélvicos/lesões , Ossos Pélvicos/cirurgia , Fixadores Externos , Pelve/lesões , Pelve/cirurgia , Pinos Ortopédicos , Fenômenos Biomecânicos
6.
Artigo em Inglês | MEDLINE | ID: mdl-32908559

RESUMO

Damage to intramuscular tendons is very common in sports injuries, specifically in soleus muscle injuries. This study sought to compare the effects of applying ultrasound- (US-) guided percutaneous needle electrolysis (PNE) in combination with an eccentric exercise program on pain and functionality in dancers with chronic soleus injury, located in the central tendon. Thirty dancers with injured central tendon of the soleus muscle were randomly allocated to a PNE group (n = 10), an eccentric exercise group (n = 10), or a combined group (n = 10). Pain, ankle dorsiflexion range of motion (DROM), endurance, the heel raise test, the DFOS questionnaire, and the minimal clinically important difference (MCID) were analyzed at baseline and after treatment (four weeks). Over half (52%) of the dancers had a chronic soleus muscle injury. Variables for pain, DROM, the heel rise test, ADL, technique, DFOS total, and DFOS-subjective variables showed significant differences (P < 0.05) in pretreatment and posttreatment in all groups, whereas no significant differences were observed between intervention groups. However, the combined group showed a higher percentage of changes compared to the other groups, and these dancers had greater perceived changes (MCID = 4.70 ± 1.42). The conclusion of the study was that dancers with chronic soleus injury, located in the central tendon, treated with a combination of US-guided PNE and an eccentric exercise program displayed improved outcomes compared to the application of PNE therapy or eccentric exercise alone. The US-guided PNE, combined with an eccentric exercise program, is a useful therapeutic tool for the treatment of chronic soleus injury, located in the central tendon. The trial is registered with NCT04042012.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32565858

RESUMO

An increase in the spontaneous release of acetylcholine (ACh) at the motor endplate is directly related to the generation of myofascial trigger points (MTrPs). In this study, percutaneous electric fields were applied to an animal model of MTrPs with high levels of spontaneous ACh release. All experiments were performed on Swiss mice and Sprague Dawley rats. For evaluating the spontaneous neurotransmission, intracellular recordings were performed, and the frequency of miniature endplate potentials was evaluated. Electromyographic recordings were also conducted to evaluate the endplate noise. Finally, the number and strength of local twitch responses (LTR) were evaluated using ultrasound recordings. The protocols used for the electric currents were 0.4 mA for five seconds and four repetitions (protocol 1), 1.5 mA for five seconds and three repetitions (protocol 2), and 3 mA for three seconds and three repetitions (protocol 3). After a subcutaneous injection of neostigmine (NTG), a great increase was observed in the frequency of mEPPs, together with an elevated endplate noise. Protocols 2 and 3 were the most effective. Protocol 3 could completely reverse the action of NTG at both three hours and 24 hours, respectively. The application of percutaneous currents produced both an increase in the number (144%) and in the speed (230% faster) of LTR compared with dry needling. In conclusion, higher doses of electrical current are more effective for decreasing MTrPs findings in an animal model.

8.
Phys Rev Lett ; 124(16): 164101, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32383906

RESUMO

Out of equilibrium systems under the influence of enough energy injection exhibit complex spatiotemporal behaviors. Based on a liquid crystal light valve experiment with translational optical feedback, we observe propagation, spatiotemporal intermittency, and defect turbulence of striped waves. A prototype model of pattern formation with translational coupling shows the same phenomenology. Close to the spatial instability, a local amplitude equation is derived. This amplitude equation allows us to reveal the origin and bifurcation diagram of the observed complex spatiotemporal dynamics. Experimental observations have a qualitative agreement with theoretical findings.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33424988

RESUMO

Nerve entrapments such as carpal tunnel syndrome are the most common mononeuropathies. The lesional mechanism includes a scarring reaction that causes a vascular compromise. The most effective treatment is surgery, which consists of removing the scarred area, thus reverting the vascular impairment. In the present study, a more conservative therapeutic approach has been undertaken to release the nerve by means of galvanic current (GC) applied with a needle: percutaneous needle electrolysis (PNE). For this purpose, a mouse model of sciatic nerve entrapment has been created using albumin coagulated by glutaraldehyde (albumin 35% and glutaraldehyde 2% volume applied, 10 µl). After two weeks, a fibrous reaction was obtained which entrapped the nerve to the extent of causing atrophy of the leg musculature (14.7%, P < 0.05 compared to the control leg). Ultrasound imaging confirmed that the model's image was compatible with that of nerve entrapment in patients. To quantify the degree of entrapment, nerve conduction recordings were made. The amplitude (peak-to-peak) of the compound muscle action potential (CMAPs) decreased by 32.2% (P < 0.05), and the proximal latency increases by 17.7% (P < 0.05, in both cases). In order to release the sciatic nerve, PNE was applied (1.5 mA for 3 seconds and 3 repetitions; 1.5/3/3) by means of a solid needle in the immediacy of perineural fibrosis before and 5 minutes after the application of GC, and the proximal latency shows a decrease of 16% (P < 0.05). The recovery of CMAPs amplitude was about 48.7% (P < 0.05). Three weeks later, the CMAPs amplitude was almost completely recovered (94.64%). Therefore, with the application of GC by means of a solid needle, the sciatic nerve was definitively released from its fibrous entrapment.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31015854

RESUMO

AIMS: To evaluate the presence of perforating cutaneous vessels (PCV) in different lower limb acupuncture points (AP) using thermography. MATERIAL AND METHODS: An analytical cross-sectional study was performed on the two lower limbs (n=6) of volunteer subjects. In total, 144 AP and 144 control points (CP) were analysed, one for each AP. First, the AP and CP were located on each individual. Subsequently, both the real and thermographic images were created. In the real images, the location of the AP and the established CP were highlighted with boxes. FLIR Tools Plus and Physio Thermal Imaging software were used to merge the real image with the AP and the CP and to merge the thermographic image with the PCV. By superimposing both images, we were able to verify the presence of PCV among the AP and CP. RESULTS: PCV were identified in 87.5% of the 144 AP examined and in 18.1% of the respective CP. All the AP had a higher percentage of PCV compared to their respective CP, with statistically significant differences in all points, except for ST33 and ST34. The probability of finding PCV in AP was 11 times higher than the probability of not finding it. DISCUSSION: Thermography may serve as a useful tool in the assessment and treatment of patients using acupuncture. The presence of PCV in the area of the acupuncture needle insertion could partially influence the effects generated by the acupuncture technique from the vascular autonomic point of view. CONCLUSIONS: There is a high proportion of PCV in the AP area located in the lower limb.

12.
Cont Lens Anterior Eye ; 42(2): 200-205, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30448180

RESUMO

PURPOSE: To evaluate the perception of light disturbances (LD) in children wearing Dual Focus (DF) MiSight® contact lenses (CLs) for myopia control compared with children wearing single vision spectacles (SV). METHODS: This was a randomized, controlled clinical trial involving subjects aged 8-12 with myopia of -0.75 to -4.00D and astigmatism <1.00D allocated to MiSight® study CLs group or control group wearing SV. LD was determined at baseline, 12 and 24 months visit with a validated device, Light Disturbance Analyzer (LDA) to determine the shape, size and regularity of the LD phenomena with parameters of Light Disturbance Index (LDI) Best Fit Circle (BFC) and Standard Deviation between LD and BFC (BFCIrreg.SD). RESULTS: 74 children completed the study, 41 in the CL group and 33 in the SV group. SV group didn´t show any significant differences between monocular and binocular LD measurements throughout the study. Binocular BFCRadius was smaller at 24 months visit compared with 12 month visit (p < 0.05) and for BFCIrreg.SD was significantly smaller at 24 month visit compared with baseline (p < 0.05). In MiSight® group, binocular and monocular LDI, BFCRadius and BFCIrreg.SD measurements didn't show any significant change between 12 and 24 month visits (p > 0.05). However, monocular BFCIrreg. as well as monocular and binocular BFCIrreg.SD showed a significant decrease at 24 month visit compared with 12 month visit. CONCLUSIONS: DF lenses increase the monocular light disturbance perception compared with a single vision spectacle correction. However, this effect decreased over the follow-up time and presented a significant binocular attenuation effect.


Assuntos
Lentes de Contato Hidrofílicas , Óculos , Miopia/terapia , Transtornos da Visão/fisiopatologia , Criança , Feminino , Humanos , Masculino , Procedimentos Ortoceratológicos , Visão Binocular/fisiologia
13.
Arch Soc Esp Oftalmol (Engl Ed) ; 93(4): 186-192, 2018 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29422223

RESUMO

OBJECTIVE: In 2015 the picture of a dress went viral on social media. A significant proportion of the population saw it as golden and white (G&W), while another significant proportion saw it as blue and black (B&B). The aim of this article is to review the related literature. MATERIAL AND METHODS: Bibliographic search conducted in Pubmed and Google. The algorithm used was: (color OR colour) AND (dress OR #thedress). The search was limited to the years 2015-2017. No language restrictions were used. The references of the located articles were used to widen the search. RESULTS: The search algorithm retrieved 23 articles related to the topic. Most of the works have been published in journals in the field of perception. Most works address the topic from the point of view of chromatic constancy. Genetic factors seem to have a low weight in the way the dress is perceived. There are few studies on the potential influence of ocular factors. CONCLUSION: This illusion has gained little attention in ophthalmology journals. Although colour constancy is certainly involved, there is still no theory available to explain the dichotomous character of this optical illusion.


Assuntos
Percepção de Cores , Cor , Ilusões Ópticas , Humanos
15.
Int Orthop ; 42(1): 33-38, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29075808

RESUMO

PURPOSE: This work seeks to verify the utility of the KLIC score as a predictor of treatment success or failure in patients with knee and hip acute prosthetic joint infections (APJI). These patients were treated in our centre, which is not a prosthetic joint infection reference centre. The KLIC score assesses factors such as chronic kidney failure (2 points) (Kidney), liver disease (1.5 points) (Liver), revision surgery or femoral neck fracture (1.5 points)and cemented prosthesis (2 points) (Index surgery) and a C-reactive protein level (CRP) greater than 11.5 mg/dL (2.5 points), as a predictor of treatment success or failure in patients with knee and hip acute prosthetic joint infections (APJI). METHODS: We retrospectively reviewed 30 patients with APJI who were treated using debridement, antibiotics, irrigation and retention (DAIR) treatment between January 2007 and December 2016. Patients' KLIC scores were calculated. The main outcome was success or failure of DAIR treatment of APJI. RESULTS: DAIR treatment succeeded in 21 cases and failed in nine cases. Differences in outcome were found according to the KLIC score. For KLIC scores >2 and ≤4, there were three successes and zero failures; for scores 4-5, there were nine successes and two failures; for scores >5 and ≤7,there were nine successes and four failures; and for scores >7, there were zero successes and three failures (p = 0.025). We found a positive predictive value and negative predictive value of 33% and 100% for scores ≤4 (score for calculations: 3.5), 43% and 84% for scores 4-5 (4.5), 50% and 68% for scores >5 and ≤7 (5.5), and 100% and 76% for scores >7 (7.5), respectively. The area under the ROC curve was 0.762 (95% confidence interval, 0.569-0.955). CONCLUSIONS: The KLIC score was useful in predicting success or failure of DAIR treatment of APJI. This supports the conclusion that with a score < 3.5, treatment is likely to succeed and with a score of >6, it is likely to fail.


Assuntos
Antibacterianos/uso terapêutico , Desbridamento/métodos , Infecções Relacionadas à Prótese/terapia , Irrigação Terapêutica/métodos , Idoso , Idoso de 80 Anos ou mais , Artroplastia/efeitos adversos , Proteína C-Reativa/análise , Feminino , Articulação do Quadril/cirurgia , Humanos , Prótese Articular/efeitos adversos , Rim/patologia , Articulação do Joelho/cirurgia , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento , Resultado do Tratamento
16.
Int Orthop ; 42(1): 39, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29164288

RESUMO

There is an error in the name of one of the author in the original publication. The correct name is I Rodríguez-Delourme and not Delourne.

18.
Sci Total Environ ; 536: 268-278, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26218566

RESUMO

Thallium (Tl) and its compounds are toxic to biota even at low concentrations but little is known about Tl concentration and speciation in soils. An understanding of the source, mobility, and dispersion of Tl is necessary to evaluate the environmental impact of Tl pollution cases. In this paper, we examine the Tl source and dispersion in two areas affected by abandoned mine facilities whose residues remain dumped on-site affecting to soils and sediments of natural water courses near Madrid city (Spain). Total Tl contents and partitioning in soil solid phases as determined by means of a sequential extraction procedure were also examined in soils along the riverbeds of an ephemeral and a permanent streams collecting water runoff and drainage from the mines wastes. Lastly, electronic microscopy and cathodoluminescence probe are used as a suitable technique for Tl elemental detection on thallium-bearing phases. Tl was found mainly bound to quartz and alumino-phyllosilicates in both rocks and examined soils. Besides, Tl was also frequently found associated to organic particles and diatom frustules in all samples from both mine scenarios. These biogenic silicates may regulate the transfer of Tl into the soil-water system.


Assuntos
Monitoramento Ambiental , Mineração , Poluentes do Solo/análise , Solo/química , Tálio/análise , Espanha
19.
Sci Total Environ ; 500-501: 23-33, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25217741

RESUMO

The formation of scorodite is an important mechanism for the natural attenuation of arsenic in a wide range of environments. It is dumped on site by metallurgical industries to minimize arsenic release. However, the long-term stability of these deposits is unclear. Sequential As extractions and synchrotron-based X-ray absorption near-edge structure (XANES) spectroscopy were used to determine both As and Fe speciation in a small catchment area affected by a scorodite-rich waste pile at an abandoned smelting factory. Our results indicate that this deposit behaves as an acute point source of As and metal pollution and confirms the strong association of As(V) with Fe(III) oxide phases, highlighting the important role of ferrihydrite as an As scavenger in natural systems. In this seasonally variable system, other trapping forms such as jarosite-like minerals also play a role in the attenuation of As. Overall, our results demonstrate that scorodite should not be considered an environmental stable repository for As attenuation when dumped outside because natural rainfall and the resulting runoff drive As dispersion in the environment and indicate the need to monitor and reclamate As-rich mine deposits.


Assuntos
Arsênio/análise , Monitoramento Ambiental , Mineração , Poluentes do Solo/análise , Solo/química , Espanha
20.
Cancer Gene Ther ; 21(8): 317-32, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24971583

RESUMO

Optimal tumor cell surface expression of human leukocyte antigen (HLA) class I molecules is essential for the presentation of tumor-associated peptides to T-lymphocytes. However, a hallmark of many types of tumor is the loss or downregulation of HLA class I expression associated with ineffective tumor antigen presentation to T cells. Frequently, HLA loss can be caused by structural alterations in genes coding for HLA class I complex, including the light chain of the complex, ß2-microglobulin (ß2m). Its best-characterized function is to interact with HLA heavy chain and stabilize the complex leading to a formation of antigen-binding cleft recognized by T-cell receptor on CD8+ T cells. Our previous study demonstrated that alterations in the ß2m gene are frequently associated with cancer immune escape leading to metastatic progression and resistance to immunotherapy. These types of defects require genetic transfer strategies to recover normal expression of HLA genes. Here we characterize a replication-deficient adenoviral vector carrying human ß2m gene, which is efficient in recovering proper tumor cell surface HLA class I expression in ß2m-negative tumor cells without compromising the antigen presentation machinery. Tumor cells transduced with ß2m induced strong activation of T cells in a peptide-specific HLA-restricted manner. Gene therapy using recombinant adenoviral vectors encoding HLA genes increases tumor antigen presentation and represents a powerful tool for modulation of tumor cell immunogenicity by restoration of missing or altered HLA genes. It should be considered as part of cancer treatment in combination with immunotherapy.


Assuntos
Adenoviridae/genética , Expressão Gênica , Vetores Genéticos/genética , Antígenos de Histocompatibilidade Classe I/genética , Neoplasias/genética , Neoplasias/imunologia , Subpopulações de Linfócitos T/imunologia , Microglobulina beta-2/genética , Apresentação de Antígeno/imunologia , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células , Loci Gênicos , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Imuno-Histoquímica , Imunofenotipagem , Melanoma/genética , Melanoma/metabolismo , Subpopulações de Linfócitos T/metabolismo , Transcrição Gênica , Transdução Genética , Transgenes , Microglobulina beta-2/metabolismo
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