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2.
Rev Esp Cir Ortop Traumatol ; 68(3): T223-T230, 2024.
Article in English, Spanish | MEDLINE | ID: mdl-38253236

ABSTRACT

INTRODUCTION: Developmental dysplasia of the hip is the cause of approximately one third of secondary coxarthrosis. Anatomy alterations make it difficult to place a total hip prosthesis in its anatomical position and for it to be stable in the long term; there are several techniques to achieve this goal. In the present work, we used autograft of the femoral head (shelf graft or reinforced roof), to improve the coverage of the acetabular component with favourable results. MATERIALS AND METHODS: Sixteen cases were included in 14 patients with a diagnosis of developmental dysplasia of the hip (13 women and one man), the mean age was 44.3 years (range 35-68 years), with a mean follow-up of 7 years (range 1-15 years). All the cases were evaluated clinically and radiographically, to demonstrate the osseointegration of the graft and the functional results in the medium term. RESULTS: All the acetabular components were placed in anatomical position (Ranawat technique), the mean percentage of host bone coverage was 54.53% (range 43.28-79.05%), obtaining additional coverage with the bone graft of 45.13%. Osseointegration of the graft of 100% at 12 weeks, resorption of the graft from the sixth month, stabilising in the third postoperative year. Only one case of dislocation is reported, no cases of infection, loosening, heterotopic ossification or revision. CONCLUSION: This procedure has shown good functional results in the medium term with 100% osseointegration, despite cases of severe bone resorption of the graft that does not compromise the stability of the prosthesis.

3.
J Inorg Biochem ; 252: 112471, 2024 03.
Article in English | MEDLINE | ID: mdl-38181612

ABSTRACT

We report on interactions of different types of DNA molecules including double-stranded and plasmid DNA as well as polynucleotides (poly[dGdC]2 and poly[dAdT]2) with fac-[ReI(CO)3(pterin)(H2O)] (or Reptr) complex. The interaction was characterized spectroscopically and changes in the plasmid structure were verified by both electrophoresis and AFM microscopy. For comparative reasons, two others related tricarbonyl rhenium(I) complexes, fac-[(4,4'-bpy)ReI(CO)3(dppz)]+ (or Redppz) and fac-[(CF3SO3)ReI(CO)3(2,2'-bpy)] (or Rebpy) were also studied to further explore the influence of the different co-ligands on the interaction and DNA (photo)damage. Data reported herein suggests that DNA molecules can be structurally modified either by direct interaction with Re(I) complexes in their ground states inducing DNA relaxation, and/or through photoinduced cross-linking processes. The chemical nature of the co-ligands modulates the extent of the damage observed.


Subject(s)
Pterins , Rhenium , Rhenium/chemistry , DNA/chemistry , Plasmids , Ligands
5.
Article in English, Spanish | MEDLINE | ID: mdl-37270055

ABSTRACT

Developmental dysplasia of the hip is the cause of approximately one third of secondary coxarthrosis. Anatomy alterations make it difficult to place a total hip prosthesis in its anatomical position and for it to be stable in the long term; there are several techniques to achieve this goal. In the present work, we used autograft of the femoral head (shelf graft or reinforced roof), to improve the coverage of the acetabular component with favorable results. MATERIALS AD METHODS: Sixteen cases were included in 14 patients with a diagnosis of developmental dysplasia of the hip (13 women and one man), the mean age was 44.3 years (range 35-68 years), with a mean follow-up of 7 years (range 1-15 years). All the cases were evaluated clinically and radiographically, to demonstrate the osseointegration of the graft and the functional results in the medium term. RESULTS: All the acetabular components were placed in anatomical position (Ranawat technique), the mean percentage of host bone coverage was 54.53% (range 43.28-79.05%), obtaining additional coverage with the bone graft of 45.13%. Osseointegration of the graft of 100% at 12 weeks, resorption of the graft from the sixth month, stabilizing in the third postoperative year. Only one case of dislocation is reported, no cases of infection, loosening, heterotopic ossification or revision. CONCLUSION: This procedure has shown good functional results in the medium term with 100% osseointegration, despite cases of severe bone resorption of the graft that does not compromise the stability of the prosthesis.

9.
Acta Ortop Mex ; 37(5): 270-275, 2023.
Article in Spanish | MEDLINE | ID: mdl-38382451

ABSTRACT

INTRODUCTION: bisphosphonates are used for the management of postmenopausal osteoporosis with high risk of fracture, glucocorticoid-induced osteoporosis, Paget's disease and hypercalcemia; as well as an adjuvant for the management of hyperparathyroidism. Bisphosphonates have been associated with previously unknown adverse effects, including atypical femur fractures. OBJECTIVE: to analyze the relationship of the history of bisphosphonate (BF) use as a risk factor for presenting atypical femur fractures (AFF). MATERIAL AND METHODS: patients aged 40 years or older from two hospital centers seen from 2009 to 2018 for femur fracture were included. The radiographic studies of 441 records were reviewed, from which the fracture site was defined. Subtrochanteric (SF) and diaphyseal (DF) femur fractures were analyzed applying the criteria of the second report of the American Society for Bone and Mineral Research for case definition of AFF. Finally, the consumption of bisphosphonates in these groups was investigated to estimate a measure of association. RESULTS: of the 441 clinical records, 98 (22.2%) were male and 343 (77.7%) were female with a mean age of 77.8 (40-103) years. Fifty-nine FS/FD were identified, of which 53% (31 records) were categorized as AFF. BF use was determined in 80.6% of patients with AFF and 3.57% in FS/FD. BF use was significantly associated with the presence of AFF (OR: 112, p 0.000, CI 95%: 12.6-1001). CONCLUSIONS: BF use significantly increases the risk of presenting AFF. AFF in patients who used BF occurred after a minimum consumption of 24 months.


INTRODUCCIÓN: los bifosfonatos se usan para el manejo de osteoporosis postmenopáusica con riesgo elevado de fractura, osteoporosis inducida por glucocorticoides, enfermedad de Paget e hipercalcemia; así como coadyuvante para manejo del hiperparatiroidismo. Los bifosfonatos se han asociado a efectos adversos previamente desconocidos dentro de los que se encuentran fracturas de fémur de trazo atípico. OBJETIVO: analizar la relación del antecedente de uso de bifosfonatos (BF) como factor de riesgo para presentar fracturas atípicas de fémur (FAF). MATERIAL Y MÉTODOS: se incluyeron pacientes de 40 años o más de dos centros hospitalarios atendidos desde 2009 a 2018 por fractura de fémur. Se revisaron los estudios radiográficos de 441 registros, de los cuales se definió el sitio de fractura. Se analizaron las fracturas de fémur subtrocantéricas (FS) y diafisarias (FD) aplicando los criterios del segundo reporte de la American Society for Bone and Mineral Research para la definición de caso de FAF. Finalmente, se indagó el consumo de bifosfonatos en estos grupos para para estimar una medida de asociación. RESULTADOS: de los 441 registros clínicos, 98 (22.2%) fueron del sexo masculino y 343 (77.7%) del femenino, con edad promedio de 77.8 (40-103) años. Se identificaron 59 FS/FD, de las cuales 53% (31 registros) fueron catalogadas FAF. El consumo de BF se determinó en 80.6% de pacientes con FAF y en 3.57% con FS/FD. El uso de BF se asoció significativamente con la presencia de FAF (OR: 112, p 0.000, IC 95%: 12.6-1001). CONCLUSIONES: el uso de BF aumenta significativamente el riesgo de presentar FAF. Las FAF en pacientes que usaron BF se presentó tras un consumo mínimo de 24 meses.


Subject(s)
Femoral Fractures , Osteoporosis , Humans , Male , Female , Aged , Diphosphonates/adverse effects , Femoral Fractures/chemically induced , Femoral Fractures/diagnostic imaging , Risk Factors , Diaphyses , Retrospective Studies
10.
Cient. dent. (Ed. impr.) ; 19(2): 129-134, may. - jun. - jul. - ago. 2022. ilus, tab, graf
Article in Spanish | IBECS | ID: ibc-208295

ABSTRACT

Introducción: En los comienzos de siglo, el asentamiento de cadenas dentales en el escenario de la odontología española produjo un aperturismo en el acceso al tratamiento implantológico, considerado hasta entonces como producto de lujo limitado por la capacidad económica del paciente. La financiación atrajo a cantidad de usuarios, creando una gran oferta que fomentó la aparición de publicidad dental invasiva que influye sobre las creencias y percepción de los pacientes para tomar decisiones. Se planteó como objetivo estudiar la influencia del nivel de ingresos, educación y salud bucodental en las creencias de la población en relación con los implantes dentales. Métodos: Sobre una encuesta de 48 preguntas a través de Google Formularios, abierta de marzo a junio de 2021, se tuvo acceso a un total de 535 usuarios no vinculados al sector odontoestomatológico. Los datos fueron secundariamente analizados mediante un análisis descriptivo. Resultados: El nivel de educación de los progenitores de los encuestados resultó ser más influyente en la salud bucodental de los encuestados que el nivel de ingresos o de educación de los propios encuestados. El nivel de ingresos no resultó influyente en relación con la elección del tipo de clínica dental, profesional o precio de los implantes, sino el nivel educativo intergeneracional. Conclusiones: El nivel educativo de los progenitores de los encuestados es el factor que más influyó en la muestra de este estudio, tanto en la salud bucodental, como en la toma de decisiones relacionadas con la implantología (AU)


Introduction: At the turn of the century, the establishment of dental chains on the Spanish dentistry scenario led to an opening up of access to implant treatments, which until then had been considered a luxury product limited by the patient’s financial capacity. Financing attracted a large number of users, creating a large supply that fostered the emergence of invasive dental advertising that influences patients’ beliefs and perceptions for decision making. The aim was to study the influence of income level, education and oral health on the beliefs of the population in relation to dental implants. Methods: A 48-question survey via Google Forms, opened from March to June 2021, provided access to a total of 535 users not linked to the dentistry sector. The data were secondarily analysed using an Excel spreadsheet. Results: The education level of the respondents’ parents was found to be more influential on the respondents’ oral health than the level of income or education of the respondents themselves. The level of income was not influential in relation to the choice of the type of dental clinic, professional or price of the implants, but rather the intergenerational educational level. Conclusions: The educational level of the respondents’ parents is the most influential factor in the sample of this study, both in terms of oral health and in decision-making related to implant dentistry (AU)


Subject(s)
Humans , Male , Female , Dental Implantation , Oral Health , Socioeconomic Factors , Surveys and Questionnaires
11.
An. sist. sanit. Navar ; 45(1): e0953, enero-abril 2022. ilus, tab
Article in English | IBECS | ID: ibc-202908

ABSTRACT

Fundamento. La precisión diagnóstica de la gammagrafía ósea (GO) aumenta con las imágenes SPECT/TAC haciendo conveniente reevaluar su utilidad diagnóstica en la sacroilitis de la espondiloartritis axial (EA). El objetivo fue comparar el rendimiento diagnóstico de la resonancia magnética (RM), la SPECT/TC y ambas pruebas combinadas, y evaluar la correlación entre los índices cuantitativos de ambas técnicas. Métodos. A 31 pacientes con EA activa y 22 con lumbalgia inflamatoria se les realizó una RM y una SPECT/TC de las articulaciones sacroilíacas y se calculó la precisión diagnóstica de ambas técnicas respecto al diagnóstico clínico. La correlación entre ambas pruebas se calculó comparando los índices de actividad del SPECT/TC con los sistemas de puntuación Berlín y SPARCC de RM. Resultados. Los valores de sensibilidad y especificidad de la SPECT/TC cuantitativa, tomando como punto de corte el cociente sacroilíaca/promontorio >1,36, fueron similares a los publicados para la RM. La combinación de ambas técnicas aumentó la sensibilidad manteniendo una alta especificidad. La correlación entre las escalas totales de RM y SPECT/TC fue moderada y mejoraba al utilizar únicamente las escalas de inflamación. Conclusiones. La SPECT/TC cuantitativa muestra una mejor precisión diagnóstica que la GO planar en la sacroilitis activa y una correlación moderada con las puntuaciones de RM. La combinación de ambas técnicas aumenta la precisión diagnóstica. Por tanto, la SPECT/TAC cuantitativa podría tener un papel relevante en el diagnóstico de sacroilitis en pacientes con alta sospecha de EA y RM negativa/no concluyente o en aquellos pacientes en los que no se pueda realizar una RM.(AU)


Background. The diagnostic accuracy of bone scintigraphy (BS) increases with SPECT/CT imaging. It would therefore be appropriate to reassess the diagnostic utility of scintigraphy in sacroiliitis with axial spondyloarthritis (SpA). The aim of this study was to compare the diagnostic performance of MRI, SPECT/CT and a combination of both techniques in sacroiliitis, and to evaluate the correlation between quantitative SPECT/CT indices and quantitative MRI inflammatory lesion scores. Methods. Thirty-one patients with active SpA and 22 patients with inflammatory low back pain underwent MRI and SPECT/CT of the sacroiliac joints. The diagnostic accuracy of both techniques was calculated using clinical diagnosis as the gold standard. The correlation between MRI and SPECT/CT was calculated by comparing the SPECT/CT activity indices and the Berlin/SPARCC scoring systems for MRI. Results. The sensitivity and specificity values in quantitative SPECT/CT, taking the sacroiliac/promontory ratio of >1.36 as the cut-off value, were close to those from MRI published in the literature. The combination of both techniques increased sensitivity while maintaining high specificity. There was a moderate correlation between SPECT/CT and MRI total scores. This correlation was improved by using solely the MRI inflammation scores. Conclusion. Quantitative SPECT/CT showed better diagnostic accuracy than planar scintigraphy and showed a moderate correlation with MRI scores in active sacroiliitis. The combination of both tests increased the diagnostic accuracy. Quantitative SPECT/CT could play a relevant role in the diagnosis of active sacroiliitis in patients with high a suspicion of SpA and a negative/inconclusive MRI test or in patients with whom MRI studies cannot be carried out.(AU)


Subject(s)
Humans , Health Sciences , Radionuclide Imaging , Magnetic Resonance Spectroscopy , Low Back Pain , Arthritis
12.
An Sist Sanit Navar ; 45(1)2022 Apr 28.
Article in English | MEDLINE | ID: mdl-34142993

ABSTRACT

BACKGROUND: The diagnostic accuracy of bone scintigraphy (BS) increases with SPECT/CT imaging. It would therefore be appropriate to reassess the diagnostic utility of scintigraphy in sacroiliitis with axial spondyloarthritis (SpA). The aim of this study was to compare the diagnostic performance of MRI, SPECT/CT and a combination of both techniques in sacro-iliitis, and to evaluate the correlation between quantitative SPECT/CT indices and quantitative MRI inflammatory lesion scores. METHODS: Thirty-one patients with active SpA and 22 patients with inflammatory low back pain underwent MRI and SPECT/CT of the sacroiliac joints. The diagnostic accuracy of both techniques was calculated using clinical diagnosis as the gold standard. The correlation between MRI and SPECT/CT was calculated by comparing the SPECT/CT activity indices and the Berlin/SPARCC scoring systems for MRI. RESULTS: The sensitivity and specificity values in quantitative SPECT/CT, taking the sacroiliac/promontory ratio of >1.36 as the cut-off value, were close to those from MRI published in the literature. The combination of both techniques increased sensitivity while maintaining high specificity. There was a moderate correlation between SPECT/CT and MRI total scores. This correlation was improved by using solely the MRI inflammation scores. CONCLUSION: Quantitative SPECT/CT showed better diagnostic accuracy than planar scintigraphy and showed a moderate correlation with MRI scores in active sacroiliitis. The combination of both tests increased the diagnostic accuracy. Quanti-tative SPECT/CT could play a relevant role in the diagnosis of active sacroiliitis in patients with high a suspicion of SpA and a negative/inconclusive MRI test or in patients with whom MRI studies cannot be carried out.


Subject(s)
Axial Spondyloarthritis , Low Back Pain , Sacroiliitis , Spondylarthritis , Humans , Low Back Pain/diagnostic imaging , Low Back Pain/etiology , Sacroiliitis/complications , Sacroiliitis/diagnostic imaging , Spondylarthritis/complications , Spondylarthritis/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed
13.
Int Ophthalmol ; 42(3): 747-756, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34622374

ABSTRACT

KEY MESSAGES: Visual acuity is the most used method to assess visual function in children. Contrast sensitivity complements the information provided for visual acuity, but it is not commonly used in clinical practice. Digital devices are increasingly used as a method to evaluate visual function, due to multiple advantages. Testing with these devices can improve the evaluation of visual development in children from a few months of age. Visual acuity and contrast sensitivity tests, using eye tracking technology, are able to measure visual function in children across a wide range of ages, objectively, quickly and without need of an experienced examiner. PURPOSE: To report age-normative values for grating visual acuity and contrast sensitivity in healthy children using a digital device with eye tracking technology and to validate the grating acuity test. METHODS: In the first project of the study, we examined healthy children aged between 6 months and 7 years with normal ophthalmological assessment. Grating visual acuity (VA) and contrast sensitivity (CS) were assessed using a preferential gaze paradigm with a DIVE (Device for an Integral Visual Examination) assisted with eye tracking technology to provide age norms. For the validation project, we compared LEA grating test (LGT) with DIVE VA in a group of children aged between 6 months and 4 years with normal and abnormal visual development. RESULTS: Fifty-seven children (2.86 ± 1.55 years) were examined with DIVE VA test and 44 successfully completed DIVE CS test (3.06 ± 1.41 years). Both, VA and CS values increased with age, mainly along the first two years of life. Sixty-nine patients (1.34 ± 0.61 years) were included in the DIVE VA test validation. The mean difference between LGT and DIVE VA was - 1.05 ± 4.54 cpd with 95% limits of agreement (LoA) of - 9.95-7.84 cpd. Agreement between the two tests was higher in children younger than 1 year with a mean difference of - 0.19 ± 4.02 cpd. CONCLUSIONS: DIVE is an automatic, objective and reliable tool to assess several visual function parameters in children, and it has good agreement with classical VA tests, especially for the first stage of life.


Subject(s)
Contrast Sensitivity , Ophthalmology , Child , Eye-Tracking Technology , Humans , Infant , Vision Tests/methods , Visual Acuity
14.
O.F.I.L ; 32(4): 395-396, 2022. tab
Article in Portuguese | IBECS | ID: ibc-212273

ABSTRACT

En situaciones de riesgo vital asociadas a una intoxicación digitálica están indicados los fragmentos de unión al antígeno (Fab) antidigoxina cuya eliminación es mayoritariamente renal. Las alteraciones cardiacas asociadas a esta intoxicación pueden traducirse en oligoanuria. Dado que ni la digoxina, ni los complejos Fab-digoxina pueden eliminarse por hemofiltración o hemodiálisis, la presencia de insuficiencia renal es una limitación importante para el tratamiento de pacientes con intoxicación digitálica con Fab antidigoxina. Se describe el caso de una paciente con insuficiencia renal e intoxicación digitálica a la que se le administran en 2 ocasiones Fab antidigoxina. A las 61 horas de la primera administración se observó un rebote en los niveles de digoxina. Esta misma situación se repitió a las 38 horas de la segunda administración del antídoto. Encontramos una correlación entre el estado clínico de la paciente y las determinaciones analíticas, lo que sugiere que, tras las dos administraciones del antídoto, se produjo un efecto rebote. (AU)


Anti-digoxin antigen-binding fragments (Fab) are indicated in life-threatening situations associated with digitalis toxicity. The elimination of anti-digoxin Fab occurs through the renal route. The cardiac alterations associated with this toxicity translate into oligoanuria. Since neither digoxin nor Fab-digoxin complexes can be removed by hemofiltration or hemodialysis, the presence of renal failure is an important limitation for the treatment with anti-digoxin Fab of patients with digitalis toxicity. The case of a patient with renal insufficiency and digitalis toxicity is described, who were administered Fab antidigoxin on 2 occasions. At 61 hours after the first administration, a rebound effect in digoxin levels was observed. This same situation was repeated 38 hours after the second administration of the antidote. We found a correlation between the patient’s clinical status and the analytical determinations, which suggests that, after the two administrations of the antidote, there was a rebound effect.(AU)


Subject(s)
Humans , Female , Aged , Antibodies , Digoxin , Toxicity , Renal Insufficiency
15.
Biomed Mater ; 16(3): 035004, 2021 02 26.
Article in English | MEDLINE | ID: mdl-33634797

ABSTRACT

Despite advances in cancer treatment, breast cancer remains the second foremost cause of cancer mortality among women, with a high rate of relapse after initial treatment success. A subpopulation of highly malignant cancer cells, known as cancer stem cells (CSCs), is suspected to be linked to metastasis and relapse. Targeting of CSCs may therefore provide a means of addressing cancer-related mortality. However, due to their low population in vivo and a lack of proper culture platform for their propagation, much of the CSC biology remains unknown. Since maintenance of CSCs is heavily influenced by the tumor microenvironment, this study developed a 3D culture platform that mimics the metastatic tumor extracellular matrix (ECM) to effectively increase CSC population in vitro and allow CSC analysis. Through electrospinning, nanofibers that were aligned, porous, and collagen-coated were fabricated from polycaprolactone to recreate the metastatic tumor ECM assemblage. Breast cancer cells seeded onto the nanofiber scaffolds exhibited gross morphology and cytoskeletal phenotype similar to invasive cancer cells. Moreover, the population of breast cancer stem cells increased in nanofiber scaffolds. Analysis of breast cancer cells grown on the nanofiber scaffolds demonstrated an upregulation of mesenchymal markers and an increase in cell invasiveness suggesting the cells have undergone epithelial-mesenchymal transition. These results indicate that the fabricated nanofiber scaffolds effectively mimicked the tumor microenvironment that maintains the cancer stem cell population, offering a platform to enrich and analyze CSCs in vitro.


Subject(s)
Breast Neoplasms/physiopathology , Neoplastic Stem Cells/cytology , Tissue Scaffolds , Cell Line, Tumor , Collagen/chemistry , Cytoskeleton/metabolism , Electrochemistry , Epithelial-Mesenchymal Transition , Extracellular Matrix/metabolism , Female , Humans , In Vitro Techniques , Nanofibers , Neoplasm Metastasis , Phenotype , Polyesters , Polymerase Chain Reaction , Tumor Microenvironment
16.
Infect Dis (Lond) ; 53(4): 291-302, 2021 04.
Article in English | MEDLINE | ID: mdl-33620019

ABSTRACT

BACKGROUND: There is an urgent need to reduce mortality of COVID-19. We examined if corticosteroids and tocilizumab reduce risk for death in patients with severe pneumonia caused by SARS-CoV-2. METHODS: A retrospective cohort study was performed in a single university hospital. All adult patients admitted with confirmed severe COVID-19 pneumonia from 9 March to 9 April 2020 were included. Severe pneumonia was defined as multi-lobar or bilateral pneumonia and a ratio of oxygen saturation by pulse oximetry to the fraction of inspired oxygen (SpFi)<315. All patients received antiviral and antibiotic treatment. From March 26, patients also received immunomodulatory treatment with corticosteroids (methylprednisolone 250 mg/day for 3 days), or tocilizumab or both. In-hospital mortality in the entire cohort and in a 1:1 matched cohort sub-analysis was evaluated. RESULTS: 255 patients were included, 118 received only antiviral and antibiotic treatment while 137, admitted after March 26, also received immunomodulators. In-hospital mortality of patients on immunomodulatory treatment was significantly lower than in those without [47/137(34.3%) vs. 69/118(58.5%), (p < .001)]. The risk of death was 0.44 (CI, 0.26-0.76) in patients receiving corticosteroids alone and 0.292 (CI, 0.18-0.47) in those treated with corticosteroids and tocilizumab. In the sub-analysis with 202 matched patients, the risk of death was 0.356 (CI 0.179-0.707) in patients receiving corticosteroids alone and 0.233 (0.124-0.436) in those treated with the combination. CONCLUSIONS: Combined treatment with corticosteroids and tocilizumab reduced mortality with about 25% in patients with severe COVID-19 pneumonia. Corticosteroids alone also resulted in lower in-hospital mortality rate compared to patients receiving only antiviral and antibiotic treatment. Corticosteroids alone or combined with tocilizumab may be considered in patients with severe COVID-19 pneumonia.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 Drug Treatment , Hospital Mortality , Methylprednisolone/therapeutic use , Aged , COVID-19/mortality , Female , Hospitals , Humans , Male , Middle Aged , Retrospective Studies , Spain
19.
Exp Eye Res ; 198: 108151, 2020 09.
Article in English | MEDLINE | ID: mdl-32721426

ABSTRACT

Due to the unique anatomical structure of the eye, ocular drug delivery is a promising delivery route for the treatment of several ocular diseases, such as the ocular neovascularization that contributes to diabetic retinopathy. This disease is triggered by inflammation, retinal ischemia, and/or deposits of advanced-glycation end-products (AGEs), as well as increased levels of vascular endothelial growth factor (VEGF), interleukins, or reactive oxygen species (ROS). Gold has unique antioxidant and antiangiogenic properties and can inhibit angiogenic molecules. Furthermore, gold nanoparticles (GNPs) are not only biocompatible, they are easy to synthesize, they absorb and scatter visible light, and they can be made with precise control over size and shape. GNPs are an excellent candidate for ocular drug delivery because they can be conjugated to an extraordinarily diverse array of different biomolecules, and surface functionalization can improve the mobility of GNPs across the physiological barriers of the eye, such as the vitreous humour or the inner limiting membrane. For this purpose, we employed low molecular weight hyaluronan (HA) to increase the mobility of the nanoparticles as well as target them to HA receptors that are expressed in different cells of the eye. In this study, the combination of gold and HA enhanced the stability of the whole carrier and promoted their distribution across ocular tissues and barriers to reach the retina. Moreover, analysis in vitro, ex vivo, and in ovo revealed the protective and antiangiogenic effect of GNPs as inhibitors of AGEs-mediated- retinal pigment epithelial cell death and neovascularization. We demonstrated that conjugation with HA enhances GNP stability and distribution due to a specific CD44 receptor interaction. The capacity of HA-GNPs to distribute through the vitreous humour and their avidity for the deeper retinal layers ex vivo, suggest that HA-GNPs are a promising delivery system for the treatment of ocular neovascularization and related disorders.


Subject(s)
Gold/administration & dosage , Hyaluronic Acid/pharmacology , Metal Nanoparticles , Retina/metabolism , Retinal Diseases/drug therapy , Vitreous Body/metabolism , Animals , Cells, Cultured , Disease Models, Animal , Drug Delivery Systems , Intravitreal Injections , Microscopy, Electron, Transmission , Retina/ultrastructure , Retinal Diseases/diagnosis , Retinal Diseases/metabolism , Surface Properties , Swine , Vitreous Body/ultrastructure
20.
MethodsX ; 7: 100909, 2020.
Article in English | MEDLINE | ID: mdl-32461922

ABSTRACT

We carry out experiments on the fragmentation of nitromethane by multiphoton absorption at the wavelength 266 nm. This was conducted in a reflectron (Jordan), modified in the laboratory. Due to the large number of fragments, special care has been taken into the calibration of the system, in the simultaneity between the laser pulse and the sample, and the associated electronics to ensure that produced fragment spectra arise from the interaction laser-sample. We emphasize the next aspects of the method:•Simple design for introducing a gas sample at laser interaction region to facilitate the cluster formation•Astonishing number of fragments produced by multiphoton absorption.

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