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1.
Brief Bioinform ; 25(2)2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38436559

RESUMEN

A wide range of approaches can be used to detect micro RNA (miRNA)-target gene pairs (mTPs) from expression data, differing in the ways the gene and miRNA expression profiles are calculated, combined and correlated. However, there is no clear consensus on which is the best approach across all datasets. Here, we have implemented multiple strategies and applied them to three distinct rare disease datasets that comprise smallRNA-Seq and RNA-Seq data obtained from the same samples, obtaining mTPs related to the disease pathology. All datasets were preprocessed using a standardized, freely available computational workflow, DEG_workflow. This workflow includes coRmiT, a method to compare multiple strategies for mTP detection. We used it to investigate the overlap of the detected mTPs with predicted and validated mTPs from 11 different databases. Results show that there is no clear best strategy for mTP detection applicable to all situations. We therefore propose the integration of the results of the different strategies by selecting the one with the highest odds ratio for each miRNA, as the optimal way to integrate the results. We applied this selection-integration method to the datasets and showed it to be robust to changes in the predicted and validated mTP databases. Our findings have important implications for miRNA analysis. coRmiT is implemented as part of the ExpHunterSuite Bioconductor package available from https://bioconductor.org/packages/ExpHunterSuite.


Asunto(s)
MicroARNs , Consenso , Bases de Datos Factuales , MicroARNs/genética , Oportunidad Relativa , RNA-Seq
2.
Artículo en Inglés | MEDLINE | ID: mdl-38832954

RESUMEN

BACKGROUND: The aim of this study is to evaluate long-term anatomical and functional outcomes of autologous internal limiting membrane (ILM) transplantation in refractory highly myopic macular holes (HMMHs). METHODS: Retrospective interventional analysis of 13 eyes with refractory HMMH undergoing autologous ILM transplantation with gas tamponade. Best-corrected visual acuity (BCVA, Snellen), optical coherence tomography and fundus photography were scheduled at baseline and every follow-up visit (1, 3, 6, 12, 18, 24 months and the most recent). Preoperatively, we collected minimum linear diameter (MLD) and basal diameter (BD). Post-operatively, rates of external limiting membrane (ELM)/ellipsoid zone (EZ) restoration, excessive gliosis and subfoveal retinal pigmented epithelium (RPE) atrophy were evaluated. RESULTS: Average AXL was 31.45 ± 2.07 mm and mean follow-up was 47.2 ± 31.4 months. Anatomical success was reached in 7/13 eyes (54%), while 2 cases showed persisting HMMH, 2 cases had early recurrence and 2 cases late recurrence. BCVA went from 0.19 ± 0.18 to 0.22 ± 0.20 at final follow-up (p = 0.64), improving in 5/13 eyes (38%). One eye showed continuous ELM and EZ lines, while another eye showed an irregular ELM but no EZ. Post-operatively, 5 eyes (71%) developed progressive atrophy of the subfoveal RPE, while excessive gliosis was reported in 3 eyes (43%). Furthermore, one patient developed post-operative chronic macular edema-like changes in the perifoveal area. CONCLUSION: Autologous ILM transplantation showed controversial anatomical outcomes and and poor visual results in refractory HMMH. Moreover, progressive subfoveal patchy atrophy and excessive gliosis are possible post-operative complications.

3.
Sensors (Basel) ; 24(7)2024 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-38610457

RESUMEN

This paper presents a visual compass method utilizing global features, specifically spherical moments. One of the primary challenges faced by photometric methods employing global features is the variation in the image caused by the appearance and disappearance of regions within the camera's field of view as it moves. Additionally, modeling the impact of translational motion on the values of global features poses a significant challenge, as it is dependent on scene depths, particularly for non-planar scenes. To address these issues, this paper combines the utilization of image masks to mitigate abrupt changes in global feature values and the application of neural networks to tackle the modeling challenge posed by translational motion. By employing masks at various locations within the image, multiple estimations of rotation corresponding to the motion of each selected region can be obtained. Our contribution lies in offering a rapid method for implementing numerous masks on the image with real-time inference speed, rendering it suitable for embedded robot applications. Extensive experiments have been conducted on both real-world and synthetic datasets generated using Blender. The results obtained validate the accuracy, robustness, and real-time performance of the proposed method compared to a state-of-the-art method.

4.
J Transl Med ; 21(1): 344, 2023 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-37221624

RESUMEN

BACKGROUND: As leading contributors to worldwide morbidity and mortality, sepsis and septic shock are considered a major global health concern. Proactive biomarker identification in patients with sepsis suspicion at any time remains a daunting challenge for hospitals. Despite great progress in the understanding of clinical and molecular aspects of sepsis, its definition, diagnosis, and treatment remain challenging, highlighting a need for new biomarkers with potential to improve critically ill patient management. In this study we validate a quantitative mass spectrometry method to measure circulating histone levels in plasma samples for the diagnosis and prognosis of sepsis and septic shock patients. METHODS: We used the mass spectrometry technique of multiple reaction monitoring to quantify circulating histones H2B and H3 in plasma from a monocenter cohort of critically ill patients admitted to an Intensive Care Unit (ICU) and evaluated its performance for the diagnosis and prognosis of sepsis and septic shock (SS). RESULTS: Our results highlight the potential of our test for early diagnosis of sepsis and SS. H2B levels above 121.40 ng/mL (IQR 446.70) were indicative of SS. The value of blood circulating histones to identify a subset of SS patients in a more severe stage with associated organ failure was also tested, revealing circulating levels of histones H2B above 435.61 ng/ml (IQR 2407.10) and H3 above 300.61 ng/ml (IQR 912.77) in septic shock patients with organ failure requiring invasive organ support therapies. Importantly, we found levels of H2B and H3 above 400.44 ng/mL (IQR 1335.54) and 258.25 (IQR 470.44), respectively in those patients who debut with disseminated intravascular coagulation (DIC). Finally, a receiver operating characteristic curve (ROC curve) demonstrated the prognostic value of circulating histone H3 to predict fatal outcomes and found for histone H3 an area under the curve (AUC) of 0.720 (CI 0.546-0.895) p < 0.016 on a positive test cut-off point at 486.84 ng/mL, showing a sensitivity of 66.7% and specificity of 73.9%. CONCLUSIONS: Circulating histones analyzed by MS can be used to diagnose SS and identify patients at high risk of suffering DIC and fatal outcome.


Asunto(s)
Sepsis , Choque Séptico , Humanos , Histonas , Enfermedad Crítica , Pronóstico , Diagnóstico Precoz , Espectrometría de Masas
5.
Int J Mol Sci ; 24(2)2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36674605

RESUMEN

Lafora disease is a rare, fatal form of progressive myoclonus epilepsy characterized by continuous neurodegeneration with epileptic seizures, characterized by the intracellular accumulation of aberrant polyglucosan granules called Lafora bodies. Several works have provided numerous evidence of molecular and cellular alterations in neural tissue from experimental mouse models deficient in either laforin or malin, two proteins related to the disease. Oxidative stress, alterations in proteostasis, and deregulation of inflammatory signals are some of the molecular alterations underlying this condition in both KO animal models. Lafora bodies appear early in the animal's life, but many of the aforementioned molecular aberrant processes and the consequent neurological symptoms ensue only as animals age. Here, using small RNA-seq and quantitative PCR on brain extracts from laforin and malin KO male mice of different ages, we show that two different microRNA species, miR-155 and miR-146a, are overexpressed in an age-dependent manner. We also observed altered expression of putative target genes for each of the microRNAs studied in brain extracts. These results open the path for a detailed dissection of the molecular consequences of laforin and malin deficiency in brain tissue, as well as the potential role of miR-155 and miR-146a as specific biomarkers of disease progression in LD.


Asunto(s)
Enfermedad de Lafora , MicroARNs , Ratones , Masculino , Animales , MicroARNs/genética , MicroARNs/metabolismo , Enfermedad de Lafora/genética , Enfermedad de Lafora/metabolismo , Enfermedades Neuroinflamatorias , Proteínas Tirosina Fosfatasas no Receptoras/genética , Proteínas Tirosina Fosfatasas no Receptoras/metabolismo , Estrés Oxidativo/genética , Ubiquitina-Proteína Ligasas/metabolismo
6.
Int J Mol Sci ; 22(18)2021 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-34576097

RESUMEN

Sepsis management remains one of the most important challenges in modern clinical practice. Rapid progression from sepsis to septic shock is practically unpredictable, hence the critical need for sepsis biomarkers that can help clinicians in the management of patients to reduce the probability of a fatal outcome. Circulating nucleoproteins released during the inflammatory response to infection, including neutrophil extracellular traps, nucleosomes, and histones, and nuclear proteins like HMGB1, have been proposed as markers of disease progression since they are related to inflammation, oxidative stress, endothelial damage, and impairment of the coagulation response, among other pathological features. The aim of this work was to evaluate the actual potential for decision making/outcome prediction of the most commonly proposed chromatin-related biomarkers (i.e., nucleosomes, citrullinated H3, and HMGB1). To do this, we compared different ELISA measuring methods for quantifying plasma nucleoproteins in a cohort of critically ill patients diagnosed with sepsis or septic shock compared to nonseptic patients admitted to the intensive care unit (ICU), as well as to healthy subjects. Our results show that all studied biomarkers can be used to monitor sepsis progression, although they vary in their effectiveness to separate sepsis and septic shock patients. Our data suggest that HMGB1/citrullinated H3 determination in plasma is potentially the most promising clinical tool for the monitoring and stratification of septic patients.


Asunto(s)
Biomarcadores/metabolismo , Cromatina/metabolismo , Choque Séptico/metabolismo , Animales , Anticuerpos Monoclonales/metabolismo , Citrulina/metabolismo , Estudios de Cohortes , Femenino , Proteína HMGB1/metabolismo , Histonas/metabolismo , Humanos , Inmunoensayo , Masculino , Ratones , Persona de Mediana Edad , Nucleoproteínas/sangre , Proyectos Piloto
7.
Graefes Arch Clin Exp Ophthalmol ; 257(11): 2547-2558, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31363832

RESUMEN

PURPOSE: To evaluate the effectiveness of temporary keratoprosthesis combined with vitreoretinal surgery and penetrating keratoplasty in patients with or without trauma. METHODS: This retrospective study included 49 eyes in 49 non-trauma patients and 51 eyes in 48 ocular trauma patients who underwent penetrating keratoplasty and vitreoretinal surgery with Eckardt temporary keratoprosthesis between 2009 and 2016, with a follow-up of at least 12 months. Study variables included previous corneal, glaucoma, or retinal surgeries; various intraoperative surgical maneuvers; lens status; vitreoretinal and corneal pathology; functional outcomes; anatomical retinal reattachment; graft clarity; and need for glaucoma surgery or treatment. RESULTS: The mean age was 56 years in the non-trauma group and 42 years in the ocular trauma group. A total of 45% of the non-trauma cases and 24% of the ocular trauma cases had a single functional eye. Pseudophakic and aphakic keratopathy was diagnosed in 41% of the non-trauma group and corneal laceration in 65% of the ocular trauma group. In the ocular trauma group, injuries were open globe injury in 78%, closed globe injury in 12%, and intraocular foreign body in 10%. Retinal detachment with proliferative vitreoretinopathy was present in 39% of patients in the non-trauma group and in 35% of the ocular trauma group. Improvement or stability of visual acuity was higher among ocular trauma patients (86%) than in non-trauma patients (78%). The rate of clear corneal grafts was 49% in both groups. Retinal attachment was achieved in 90% and 78% of patients in the non-trauma and ocular trauma groups, respectively. The use of retinotomy had a positive influence on the final attached retina (p = 0.016). The placement of a scleral buckle significantly increased the risk of glaucoma (p = 0.004). Poor functional outcome was related to persistent retinal detachment (10% versus 16% in the non-trauma and ocular trauma groups, respectively), phthisis (25% versus 12%), hypotony (33% versus 18%), corneal graft end failure (51% in both groups), and secondary glaucoma (18% versus 24%). CONCLUSION: In patients with both vitreoretinal and corneal pathology, the use of Eckardt temporary keratoprosthesis combined with vitreoretinal surgery and penetrating keratoplasty resulted in improvement of visual acuity, particularly in the groups of ocular trauma and monocular patients. The high rate of retinal reattachment and the low rate of graft rejection was probably related to the use of new vitreoretinal techniques, including retinotomy in selected patients.


Asunto(s)
Córnea/cirugía , Enfermedades de la Córnea/cirugía , Lesiones Oculares/complicaciones , Queratoplastia Penetrante/métodos , Prótesis e Implantes , Enfermedades de la Retina/cirugía , Cirugía Vitreorretiniana/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Córnea/patología , Enfermedades de la Córnea/complicaciones , Lesiones Oculares/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Enfermedades de la Retina/complicaciones , Estudios Retrospectivos , Agudeza Visual , Adulto Joven
8.
Sci Technol Adv Mater ; 20(1): 673-687, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31275459

RESUMEN

First magnetic characterization of a recently developed generation of carbide free bainitic steels, known as Nanobain, has been performed. Stability of its retained austenite at cryogenic temperatures has been studied by means of X-ray diffraction, microscopy, dilatometry and magnetic measurements. Two morphologies for this phase (blocky-type and film-type) appear in a different proportion depending on the chemical composition and the applied thermal treatment. Inhibition of the martensitic transformation, when decreasing the temperature down to -271°C, has been observed in those microstructures with higher proportion of film-type austenite. The paramagnetic state of austenite at room temperature seems to lead to different magnetic behaviors (ferromagnetic, antiferromagnetic) at cryogenic temperatures (TC or TN being around -23°C in all the studied samples), depending on the proportion of such morphological features. Furthermore, irreversibility with temperature on the evolution of such magnetic behaviors has been observed for all the studied bainitic structures and is proposed to be due to a magnetic proximity effect.

9.
Graefes Arch Clin Exp Ophthalmol ; 256(5): 863-877, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29589106

RESUMEN

PURPOSE: The aim of this study is to review anatomical and functional outcomes following macular buckling (MB) in high myopia and to compare such results with those obtained by pars plana vitrectomy (PPV). METHODS: PubMed articles on MB in high myopia (2000-2016) were reviewed. Main outcomes included retinal reattachment and macular hole (MH) closure rates, resolution of myopic foveoschisis (MFS), and postoperative visual acuity. RESULTS: Thirty-one articles included 16 in patients with retinal detachment due to MH (MHRD group), 11 in MFS with or without foveal detachment (MFS group), and 4 in MH patients with MFS (MH-MFS group). Surgical techniques mainly differed in the type of buckle, rectus muscles involvement, and concurrent PPV. In eyes with persistent MH, prognosis in the MHRD and MH-MFS groups differed between eyes receiving MB compared to PPV: functional outcome was markedly poorer and there was a higher risk of retinal redetachment associated with PPV. In the MSF group, secondary MHs were more likely to develop in eyes treated with PPV and internal limiting membrane peeling than those undergoing MB alone or combined with PPV. Retinal pigment epithelium changes, malpositioning, perforation, and choroidal detachment were the main complications. CONCLUSIONS: Although different approaches are used, complete resolution of foveoschisis, retinal reattachment, and MH closure seem to be achieved more frequently with MB than PPV.


Asunto(s)
Miopía Degenerativa/complicaciones , Desprendimiento de Retina/cirugía , Curvatura de la Esclerótica/métodos , Vitrectomía , Humanos , Miopía Degenerativa/fisiopatología , Retina/fisiopatología , Desprendimiento de Retina/etiología , Desprendimiento de Retina/fisiopatología , Perforaciones de la Retina/complicaciones , Perforaciones de la Retina/fisiopatología , Retinosquisis/complicaciones , Retinosquisis/fisiopatología , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología
10.
Crit Rev Clin Lab Sci ; 54(7-8): 529-550, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29226748

RESUMEN

Epigenetic modifications and regulators represent potential molecular elements which control relevant physiological and pathological features, thereby contributing to the natural history of human disease. These epigenetic modulators can be employed as disease biomarkers, since they show several advantages and provide information about gene function, thus explaining differences among patient endophenotypes. In addition, epigenetic biomarkers can incorporate information regarding the effects of the environment and lifestyle on health and disease, and monitor the effect of applied therapies. Technologies used to analyze these epigenetic biomarkers are constantly improving, becoming much easier to use. Laboratory professionals can easily acquire experience and techniques are becoming more affordable. A high number of epigenetic biomarker candidates are being continuously proposed, making now the moment to adopt epigenetics in the clinical laboratory and convert epigenetic marks into reliable biomarkers. In this review, we describe some current promising epigenetic biomarkers and technologies being applied in clinical practice. Furthermore, we will discuss some laboratory strategies and kits to accelerate the adoption of epigenetic biomarkers into clinical routine. The likelihood is that over time, better markers will be identified and will likely be incorporated into future multi-target assays that might help to optimize its application in a clinical laboratory. This will improve cost-effectiveness, and consequently encourage the development of theragnosis and the application of precision medicine.


Asunto(s)
Epigénesis Genética , Marcadores Genéticos , Genómica , Metilación de ADN , Humanos , Técnicas de Diagnóstico Molecular
11.
Opt Express ; 25(4): 3694-3708, 2017 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-28241582

RESUMEN

This article proposes an optimized version of a canonical piece-wise-linear (CPWL) digital predistorter in order to enhance the linearity of a radio-over-fiber (RoF) LTE mobile fronthaul. In this work, we propose a threshold allocation optimization process carried out by a genetic algorithm (GA) in order to optimize the CPWL model (GA-CPWL). Firstly, experiments show how the CPWL model outperforms the classical memory polynomial DPD in an intensity modulation/direct detection (IM/DD) RoF link. Then, the GA-CPWL predistorter is compared with the CPWL model in several scenarios, in order to verify that the proposed DPD offers better performance in different optical transmission conditions. Experimental results reveal that with a proper threshold allocation, the GA-CPWL predistorter offers very promising outcomes.

12.
Retina ; 37(3): 477-486, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27557083

RESUMEN

PURPOSE: Pigmentary alterations along the presumed edge of staphyloma in wide-field fundus images have been reported to be highly correlated with the eye shape in three-dimensional magnetic resonance images. The purpose of this study was to analyze Optos images in a large series of highly myopic patients to determine the prevalence, types, and features of staphylomas. METHODS: One thousand and sixty eyes of 541 patients with high myopia (axial length ≥ 26.5 mm) in at least one eye were retrospectively analyzed in Japan and Spain. To determine the presence and types of staphyloma, the authors focused on pigmentary abnormalities along the presumed edge of staphylomas with at least one positive finding in fundus images, autofluorescent images, and infrared images by Optos. RESULTS: Posterior staphyloma was detected in 552 of 1,060 eyes (55%) in Optos images. Wide macular type was the most common (79%), followed by narrow macular (15%), then peripapillary (3%), inferior, and finally nasal. In the 60 non-highly myopic eyes of patients with unilateral high myopia, staphyloma was detected in 40%, suggesting that unilateral high myopia might be a bilateral disorder with marked differences in the degree of staphyloma between the two eyes. Combined staphylomas such as the peripapillary type within the wide macular type were also found. CONCLUSION: Posterior staphyloma was found in 55% of 1,060 eyes with bilateral or unilateral pathologic myopia. Wide macular was the most common type, although there were much more variations in the shape of staphylomas than that had been previously believed.


Asunto(s)
Miopía Degenerativa/diagnóstico , Segmento Posterior del Ojo/diagnóstico por imagen , Segmento Posterior del Ojo/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Dilatación Patológica , Femenino , Fondo de Ojo , Humanos , Imagenología Tridimensional , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Miopía Degenerativa/epidemiología , Oftalmoscopía/métodos , Prevalencia , Estudios Retrospectivos , Agudeza Visual
13.
Retina ; 36(9): 1688-93, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26966865

RESUMEN

PURPOSE: To evaluate the closure rate of macular holes in highly myopic eyes treated with the inverted internal limiting membrane flap technique. METHODS: Retrospective study in 33 consecutive patients (33 eyes) with a myopic macular hole (axial length ≥30 mm) and no associated macular retinoschisis, undergoing 23-gauge pars plana vitrectomy combined with the inverted internal limiting membrane flap technique. RESULTS: Mean initial logarithm of the minimum angle of resolution best-corrected visual acuity was 0.59 (range, 0.22-1.8) (Snellen fraction, 20/80). At the 1-month postoperative control visit, the macular hole was closed in all patients. Reopening of the hole occurred in 2 patients. Visual acuity improved in 13 patients (39.4%): final mean ETDRS (Early Treatment Diabetic Retinopathy Study) improvement was +80 letters, and logarithm of the minimum angle of resolution was 0.4 (20/50). Staphyloma with macular involvement was present in all patients. Dissociated optic nerve fiber layer was observed in 25 patients (75.7%) and was absent in 2 (6.1%); in the remaining 6 patients, the layer could not be assessed. Gliosis was found in 14 patients (42.4%). CONCLUSION: Vitrectomy plus the inverted internal limiting membrane flap technique was effective for treating macular holes in eyes with axial length ≥30 mm and no associated retinoschisis.


Asunto(s)
Longitud Axial del Ojo/patología , Membrana Basal/cirugía , Miopía Degenerativa/complicaciones , Perforaciones de la Retina/cirugía , Colgajos Quirúrgicos , Vitrectomía , Anciano , Endotaponamiento , Femenino , Humanos , Masculino , Persona de Mediana Edad , Perforaciones de la Retina/etiología , Perforaciones de la Retina/fisiopatología , Estudios Retrospectivos , Hexafluoruro de Azufre/administración & dosificación , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología
14.
Sensors (Basel) ; 16(5)2016 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-27164102

RESUMEN

Sensing techniques are important for solving problems of uncertainty inherent to intelligent grasping tasks. The main goal here is to present a visual sensing system based on range imaging technology for robot manipulation of non-rigid objects. Our proposal provides a suitable visual perception system of complex grasping tasks to support a robot controller when other sensor systems, such as tactile and force, are not able to obtain useful data relevant to the grasping manipulation task. In particular, a new visual approach based on RGBD data was implemented to help a robot controller carry out intelligent manipulation tasks with flexible objects. The proposed method supervises the interaction between the grasped object and the robot hand in order to avoid poor contact between the fingertips and an object when there is neither force nor pressure data. This new approach is also used to measure changes to the shape of an object's surfaces and so allows us to find deformations caused by inappropriate pressure being applied by the hand's fingers. Test was carried out for grasping tasks involving several flexible household objects with a multi-fingered robot hand working in real time. Our approach generates pulses from the deformation detection method and sends an event message to the robot controller when surface deformation is detected. In comparison with other methods, the obtained results reveal that our visual pipeline does not use deformations models of objects and materials, as well as the approach works well both planar and 3D household objects in real time. In addition, our method does not depend on the pose of the robot hand because the location of the reference system is computed from a recognition process of a pattern located place at the robot forearm. The presented experiments demonstrate that the proposed method accomplishes a good monitoring of grasping task with several objects and different grasping configurations in indoor environments.

15.
Mol Pharm ; 12(6): 2158-66, 2015 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-25923048

RESUMEN

The abundance and function of transporter proteins at the plasma membrane are likely to be crucial in drug responsiveness. Functional detection of human concentrative nucleoside transporters (hCNTs) is of interest for predicting drug sensitivity because of their ability to transport most nucleoside-derived drugs. In the present study, two fluorescent nucleoside analogues, uridine-furan and etheno-cytidine, were evaluated as tools to study in vivo nucleoside transporter-related functions. These two molecules showed high affinity interactions with hCNT1 and hCNT3 and were shown to be substrates of both transporters. Both fluorescence microscopy and flow cytometry experiments showed that uridine-furan uptake was better suited for distinguishing cells that express hCNT1 or hCNT3. These data highlight the usefulness of fluorescent nucleoside derivatives, as long as they fulfill the requirements of confocal microscopy and flow cytometry, for in vivo analysis of hCNT-related function.


Asunto(s)
Citometría de Flujo/métodos , Microscopía Confocal/métodos , Proteínas de Transporte de Nucleósidos/metabolismo , Nucleósidos/química , Humanos
16.
Ophthalmic Res ; 54(3): 143-9, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26394206

RESUMEN

BACKGROUND: To evaluate the effect of Ozurdex® on intraocular pressure in patients with macular edema alone (group 1) or associated with glaucoma or ocular hypertension (group 2). METHODS: A clinical, retrospective, observational, comparative study included 92 eyes with macular edema treated with a single injection of Ozurdex®; 27 eyes were previously diagnosed with glaucoma or ocular hypertension. RESULTS: The mean intraocular pressure (group 1 vs. group 2) after injection was 12.1 versus 19.9 mm Hg, (p < 0.05; day 1); 17.5 versus 19.7 mm Hg (p < 0.05; month 1); 18.4 versus 20.9 mm Hg (p < 0.05; month 2); 15 versus 17.4 mm Hg (p < 0.05; month 3); 13.9 versus 16.7 mm Hg (p > 0.05; month 6); 13.8 versus 15.1 mm Hg (p > 0.05; month 9) and 13.1 versus 16.4 mm Hg (p > 0.05; month 12). Thirty eyes (32.6%) showed ocular hypertension (intraocular pressure >21 mm Hg) after the injection: 21.5% of group 1 and 59.3% of group 2. In group 2, 27 eyes (100%) needed medical treatment to reduce intraocular pressure in comparison to 8 patients (12.3%) in group 1 (p < 0.001). CONCLUSIONS: Intravitreal injection of Ozurdex® was associated with ocular hypertension in 32.6% of the eyes. Previous glaucoma or ocular hypertension are risk factors for this increase.


Asunto(s)
Dexametasona/efectos adversos , Glucocorticoides/efectos adversos , Presión Intraocular/efectos de los fármacos , Edema Macular/tratamiento farmacológico , Hipertensión Ocular/inducido químicamente , Adulto , Anciano , Anciano de 80 o más Años , Dexametasona/administración & dosificación , Implantes de Medicamentos , Femenino , Glaucoma/complicaciones , Glucocorticoides/administración & dosificación , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tonometría Ocular , Cuerpo Vítreo , Adulto Joven
17.
Hum Mol Genet ; 21(7): 1521-33, 2012 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-22186026

RESUMEN

Lafora disease (LD), a fatal neurodegenerative disorder characterized by the presence of intracellular inclusions called Lafora bodies (LBs), is caused by loss-of-function mutations in laforin or malin. Previous studies suggested a role of these proteins in the regulation of glycogen biosynthesis, in glycogen dephosphorylation and in the modulation of the intracellular proteolytic systems. However, the contribution of each of these processes to LD pathogenesis is unclear. We have generated a malin-deficient (Epm2b-/-) mouse with a phenotype similar to that of LD patients. By 3-6 months of age, Epm2b-/- mice present neurological and behavioral abnormalities that correlate with a massive presence of LBs in the cortex, hippocampus and cerebellum. Sixteen-day-old Epm2b-/- mice, without detectable LBs, show an impairment of macroautophagy (hereafter called autophagy), which remains compromised in adult animals. These data demonstrate similarities between the Epm2a-/- and Epm2b-/- mice that provide further insights into LD pathogenesis. They illustrate that the dysfunction of autophagy is a consequence of the lack of laforin-malin complexes and a common feature of both mouse models of LD. Because this dysfunction precedes other pathological manifestations, we propose that decreased autophagy plays a primary role in the formation of LBs and it is critical in LD pathogenesis.


Asunto(s)
Autofagia , Enfermedad de Lafora/patología , Ubiquitina-Proteína Ligasas/genética , Animales , Conducta Animal , Encéfalo/metabolismo , Encéfalo/patología , Fosfatasas de Especificidad Dual/análisis , Fosfatasas de Especificidad Dual/metabolismo , Glucanos/química , Enfermedad de Lafora/genética , Enfermedad de Lafora/fisiopatología , Ratones , Ratones Noqueados , Trastornos de la Destreza Motora/genética , Miocardio/ultraestructura , Proteínas Tirosina Fosfatasas no Receptoras , Ubiquitina/análisis , Ubiquitina-Proteína Ligasas/deficiencia
19.
Graefes Arch Clin Exp Ophthalmol ; 252(4): 571-81, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24158373

RESUMEN

PURPOSE: To evaluate postoperative outcomes after macular buckling together with pars plana vitrectomy (PPV) in previously untreated and recurrent retinal detachment secondary to macular hole (MH) in highly myopic eyes. METHODS: In a retrospective cohort study, 42 eyes of 42 high myopic patients with retinal detachment due to MH were evaluated. Patients were divided into previously untreated retinal detachment (group 1, 21 eyes) and recurrent retinal detachment (group 2, 21 eyes). Macular buckling and PPV were performed in all patients. Main outcomes included retinal reattachment rate, macular hole closure rate and best-corrected visual acuity (BCVA) at 3, 6, and 12 months. Optical coherence tomography (OCT) was performed both pre- and postoperatively in all patients to assess the anatomical status of the macula. RESULTS: Primary retinal reattachment rate in group 1 was 95% (20/21), which increased to 100% (21/21) after a second surgery. MH closure was achieved in 81% of patients (17/21) after one surgery. The mean preoperative BCVA (logarithm of the minimum angle of resolution, LogMAR) improved from 1.32 (95% CI 1.19;1.44) to 0.76 (95% CI 0.56;0.96) 12 months postoperatively. In all except one case, gas tamponade was preferred. Primary reattachment and MH closure rate in group 2 were 90.5% (19/21) and 57% (12/21) respectively, and did not improve after a second surgery. Preoperative BCVA (LogMAR) was 1.39 (95% CI 1.29;1.49) and improved to 0.95 (95% CI 0.75;1.15) at 12 months. Silicone oil tamponade was used in seven of 21 patients, and finally was removed in five of them. CONCLUSIONS: Macular buckling combined with PPV should be considered a preferred surgical approach both in primary and recurrent retinal detachment secondary to MH in high myopic eyes. Nevertheless, visual outcomes seem to be better when macular buckling is chosen as first-line treatment.


Asunto(s)
Miopía Degenerativa/complicaciones , Desprendimiento de Retina/cirugía , Perforaciones de la Retina/complicaciones , Curvatura de la Esclerótica , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Endotaponamiento , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Reoperación , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/etiología , Estudios Retrospectivos , Curvatura de la Esclerótica/métodos , Resultado del Tratamiento , Agudeza Visual/fisiología , Vitrectomía
20.
Graefes Arch Clin Exp Ophthalmol ; 252(2): 191-9, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24384802

RESUMEN

PURPOSE: To review postoperative anatomical and functional outcomes in high myopic macular hole (HM-MH) without retinal detachment. METHODS: In the PubMed database, published articles on myopic macular hole surgery from 2000 to 2013 (present days) were reviewed. Inclusion criteria were high myopia and macular hole (MH). Series with posterior retinal detachment secondary to MH and myopic foveoschisis (MFS) without MH were excluded. Main outcomes included MH closure rate, resolution of the foveoschisis, if present, and postoperative visual acuity. Optical coherence tomography (OCT) features and postoperative evolution were also evaluated when reported. RESULTS: A total of 131 articles were initially found. After having applied the exclusion criteria, 15 articles were reviewed. Four were focused on HM-MH with concomitant foveoschisis (Schisis Group), and ten included only HM-MH without FS case series (Flat Group). Only one comparative study between these two groups was found. Surgical techniques were observed to be similar for both groups in most series, including vitrectomy with or without internal limiting membrane (ILM) removal, and gas or silicone oil tamponade. However, in one retrospective study, macular buckling was applied together with pars plana vitrectomy in cases of HM-MH with foveoschisis. When available, preoperative and postoperative OCT provided a useful evaluation of the status of the macula. Different prognosis were observed in the two groups in cases of vitreous surgery: anatomical success rate and functional outcomes for HM-MH with foveoschisis were markedly poorer than that for cases of HM-MH without foveoschisis, and multiple procedures might be required. By the contrast, better results seemed to be achieved using the posterior buckle technique for patients with HM-MH and concomitant foveoschisis. Moreover, when compared, final anatomical and functional outcomes seem to be less satisfactory than in emmetropic eyes. Postoperative non-closure or reopening of the macular hole is more common in eyes with HM-MH and concomitant foveoschisis, and possible retinal detachment may occur in these patients. CONCLUSIONS: Despite similar surgical procedures, anatomical and functional results after vitreous surgery in cases of HM-MH may be very different from series to series. The prognosis is generally better in cases involving only HM-MH without foveoschisis than in cases with MH and associated foveoschisis. Persistent MHs are more frequent in eyes with concomitant retinoschisis, and this seems to represent a possible risk factor for late retinal detachment in the case of unsuccessful vitreous surgery. However, although vitrectomy can lead to anatomical and visual improvements, an higher axial length > 30 mm and the presence of a posterior staphyloma seem to remain the two most important risk factors for poor visual outcomes. For these reasons, a different surgical approach, including macular buckling, might be considered in casse of HM-MH and concomitant myopic foveoschisis, in order to counteract the traction exerted by the posterior staphyloma.


Asunto(s)
Miopía Degenerativa/complicaciones , Retina/fisiopatología , Desprendimiento de Retina/etiología , Perforaciones de la Retina/etiología , Agudeza Visual/fisiología , Membrana Basal/cirugía , Endotaponamiento , Humanos , Miopía Degenerativa/fisiopatología , Desprendimiento de Retina/fisiopatología , Desprendimiento de Retina/cirugía , Perforaciones de la Retina/fisiopatología , Perforaciones de la Retina/cirugía , Retinosquisis/etiología , Retinosquisis/fisiopatología , Retinosquisis/cirugía , Factores de Riesgo , Tomografía de Coherencia Óptica , Vitrectomía
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