Implante endoscópico de mioblastos autólogos en el tratamiento de la incontinencia urinaria de esfuerzo y evaluación de su eficacia en conejos sometidos a esfinterotomía / Endoscopic implantation of autologous myoblasts for stress urinary incontinence and evaluation of its efficacy in sphincterotomized rabbits

Introducción La incontinencia urinaria de esfuerzo (IUE) constituye uno de los problemas de salud con mayor impacto en la vida de las personas. El objetivo del presente trabajo fue desarrollar una terapia para IUE dentro de la ingeniería de tejidos mediante aislamiento y cultivo de mioblastos autólogos (MAC), su implante endoscópico y el estudio de su eficacia en un modelo de incontinencia por esfinterotomía desarrollado en conejos. Materiales y métodos Se utilizaron conejos Nueva Zelanda, machos, sanos. Los animales fueron primero sangrados para obtención del plasma pobre en plaquetas (PPP) y biopsiados para el aislamiento de mioblastos. Posesfinterotomía, fueron divididos en dos grupos: grupo tratado (representado por aquellos animales que recibieron MAC resuspendidos en PPP) y grupo control (representado por aquellos animales que recibieron solo PPP). Se utilizó el punto de presión de pérdida (LPP) para medir la continencia de ambos grupos en diferentes instancias. Los resultados se evaluaron con modelos de regresión lineal jerárquica. Se efectuaron también estudios histológicos sobre los esfínteres de los conejos una vez finalizado el seguimiento. Resultados No se observaron diferencias estadísticamente significativas entre los valores basales de LPP de cada grupo. Los valores posesfinterotomía de ambos grupos estuvieron por debajo del 50% del valor basal, condición necesaria para considerarlos sujetos incontinentes. Los valores posimplante del grupo tratado fueron superiores al 50% del valor basal, permitiendo suponer una recuperación de la continencia. Se observó una diferencia estadísticamente significativa en los valores de LPP entre los dos grupos de tratamiento (p=0,003). El estudio histológico en el grupo tratado reveló islas interconectadas formadas por fibras musculares, mientras que en el grupo control se observó tejido conectivo periférico a la luz de la uretra e infiltrado inflamatorio. Discusión y conclusiones ... (AU)

Introduction Stress urinary incontinence (SUI) is one of the health problems with more impact on patients’ lives. The aim of the present work was to develop a therapy for SUI using tissue engineering by isolation and culture of autologous myoblasts (CAM) followed by endoscopic implantation. We also evaluated the efficacy of this therapy in a rabbit model of incontinence after sphincterotomy. Materials and methods We used healthy male New Zealand rabbits. The animals were first bled to obtain platelet-poor plasma (PPP) and biopsied for myoblast isolation. Post-sphincterotomy, they were divided into two groups: the treatment group (including animals that received CAM resuspended in PPP) and the control group (including animals receiving only PPP). The leak-point pressure (LPP) was used to measure continence in both groups at different time points. The results were evaluated with hierarchical linear regression models. Histological evaluation of the rabbits’ sphincters was also performed at the end of follow-up. Results No statistically significant differences were observed between the baseline LPP values of each group. The post-sphincterotomy values of both groups were below 50% of the baseline value, which was a mandatory condition for incontinence. The post-implantation values of the treatment group were higher than 50% of the baseline value, which led us to assume continence recovery. A statistically significant difference was observed in the LPP values between the two treatment groups (p=0.003). Histological study revealed interconnected islands formed by muscle fibers in the treatment group, and connective tissue surrounding the urethral lumen and inflammatory infiltrate in the control group. Discussion and conclusions The implantation of CAM significantly improved LPP values in the treatment group, and the improvement remained throughout the evaluation period. ... (AU)

Diseño y comparativa de biomateriales para el tratamiento de defectos óseos. Estudio de su comportamiento in vivo en modelo animal de conejo / Desing and comparison of bone substitutes. Study of in vivo behavior in a rabbit model

Objetivo: Comparar in vivo la capacidad de formación ósea de dos tipos de biomateriales diseñados como sustitutivos óseos respecto a autoinjerto de cresta iliaca, uno basado en carbonatohidroxiapatita y otro en vidrio mesoporoso bioactivo. Material y método: Estudio experimental compuesto por 14 conejos de Nueva Zelanda hembras adultas donde se realizó un defecto crítico en hueso radio. La muestra fue dividida en cuatro grupos: defecto sin material, con autoinjerto de cresta iliaca, con soporte de carbonatohidroxiapatita y con soporte de vidrio mesoporoso bioactivo. Se realizaron estudios seriados de radiología simple a las 2, 4, 6 y 12 semanas y estudio de micro-TC a eutanasia a las 6 y 12 semanas. Resultados: En el estudio de radiología simple, el grupo de autoinjerto mostró las mayores puntuaciones de formación ósea (7,5 puntos). Ambos grupos de biomateriales presentaron formación ósea similar (5,3 y 6 puntos, respectivamente) y mayor al defecto sin material (4 puntos), pero siempre menor que el grupo de autoinjerto. Los resultados del estudio de micro-TC mostraron el mayor volumen de hueso en el área de estudio en el grupo de autoinjerto. Los grupos con sustitutivos óseos presentaron mayor volumen de hueso que el grupo sin material, pero siempre menor que en el grupo de autoinjerto. Conclusiones: Ambos soportes parecen favorecer la formación ósea pero no son capaces de reproducir las características del autoinjerto. Por sus diferentes características macroscópicas cada uno podría ser adecuado para un tipo diferente de defecto.(AU)

Aim: Compare bone formation capacity in vivo of two types of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxyapatites and the other one on bioactive mesoporous glass. Materials and methods: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite support, and with bioactive mesoporous glass support. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. Results: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than in the autograft group. Conclusion: Both supports seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.(AU)

[Translated article] Design and comparison of bone substitutes. Study of in vivo behaviour in a rabbit model / Diseño y comparativa de biomateriales para el tratamiento de defectos óseos. Estudio de su comportamiento in vivo en modelo animal de conejo

Objetivo: Comparar in vivo la capacidad de formación ósea de dos tipos de biomateriales diseñados como sustitutivos óseos respecto a autoinjerto de cresta iliaca, uno basado en carbonatohidroxiapatita y otro en vidrio mesoporoso bioactivo. Material y método: Estudio experimental compuesto por 14 conejos de Nueva Zelanda hembras adultas donde se realizó un defecto crítico en hueso radio. La muestra fue dividida en cuatro grupos: defecto sin material, con autoinjerto de cresta iliaca, con soporte de carbonatohidroxiapatita y con soporte de vidrio mesoporoso bioactivo. Se realizaron estudios seriados de radiología simple a las 2, 4, 6 y 12 semanas y estudio de micro-TC a eutanasia a las 6 y 12 semanas. Resultados: En el estudio de radiología simple, el grupo de autoinjerto mostró las mayores puntuaciones de formación ósea (7,5 puntos). Ambos grupos de biomateriales presentaron formación ósea similar (5,3 y 6 puntos, respectivamente) y mayor al defecto sin material (4 puntos), pero siempre menor que el grupo de autoinjerto. Los resultados del estudio de micro-TC mostraron el mayor volumen de hueso en el área de estudio en el grupo de autoinjerto. Los grupos con sustitutivos óseos presentaron mayor volumen de hueso que el grupo sin material, pero siempre menor que en el grupo de autoinjerto. Conclusiones: Ambos soportes parecen favorecer la formación ósea pero no son capaces de reproducir las características del autoinjerto. Por sus diferentes características macroscópicas cada uno podría ser adecuado para un tipo diferente de defecto.(AU)

Aim: Compare bone formation capacity in vivo of two types of biomaterials designed as bone substitutes with respect to iliac crest autograft, one based on carbonate hydroxyapatites and the other one on bioactive mesoporous glass. Materials and methods: Experimental study consisting on 14 adult female New Zeland rabbits where a critical defect was made in the rabbit radius bone. The sample was divided into four groups: defect without material, with iliac crest autograft, with carbonatehydroxyapatite support, and with bioactive mesoporous glass support. Serial X-ray studies were carried out at 2, 4, 6 and 12 weeks and a microCT study at euthanasia at 6 and 12 weeks. Results: In the X-ray study, autograft group showed the highest bone formation scores. Both groups of biomaterials presented bone formation similar and greater than the defect without material, but always less than in the autograft group. The results of the microCT study showed the largest bone volume in the study area in the autograft group. The groups with bone substitutes presented greater bone volume than the group without material but always less than in the autograft group. Conclusion: Both supports seem to promote bone formation but are not capable of reproducing the characteristics of autograft. Due to their different macroscopic characteristics, each one could be suitable for a different type of defect.(AU)

Modelo animal para la evaluación del sellado de colaterales venosas con dispositivos liberadores de energía en cirugía de revascularización / Animal model to assess collateral vein sealing with energy-based devices in revascularization surgery

Introducción: los dispositivos liberadores de energía permiten la hemostasia de los vasos mediante generación de calor y la coagulación de las proteínas de la pared. Sin embargo, se desconoce su comportamiento a medio plazo en la cirugía arterial con injertos venosos. Objetivos: desarrollar un modelo animal que permita evaluar la eficacia y seguridad del sellado a medio plazo tras el proceso de cicatrización. Comparar y evaluar qué modelo in vivo presenta menor morbilidad y mayor supervivencia a las 4 semanas. Material y métodos: estudio experimental animal de 16 conejos New Zealand a los que se interpuso un fragmento de vena safena humana (VS) con una colateral. Se desarrollaron dos modelos arteriales: bypass termino-terminal de VS en aorta infrarrenal (n = 5) y plastia de aorta con parche de VS (n = 11). La colateral venosa fue sellada, previa aleatorización, con electrocoagulación bipolar controlada por temperatura (EB) o bisturí armónico (BA). Todos los animales recibieron inmunosupresión y profilaxis antitrombótica. Se registró la tasa de paraplejia, de infección, de hemorragia y de supervivencia. Resultados: la supervivencia a los 7 días fue del 50 % (2/4) en el modelo de injerto de interposición. Sin embargo, ningún animal sobrevivió a las 4 semanas de seguimiento en este modelo. En el grupo de plastia de aorta, la supervivencia a los 7 días fue del 55,56 % (5/9) y del 44,44 % (4/9) a las 4 semanas (p = 0,5). La tasa de paraplejia en el grupo de interposición fue del 100 % e inferior en el modelo de plastia de aorta (25 %) (p = 0,03). El tiempo medio de isquemia en el modelo de plastia de aorta (37,11 ± 8,1 min) fue inferior al del grupo del bypass (42 ± 10,61 min) (p = 0,414). En ningún caso se objetivó hemorragia intraabdominal ni reacción adversa a la inmunosupresión. Conclusiones: el modelo arterial de plastia de aorta con parche de VS presentó menor tasa de paraplejia, así como menor mortalidad posoperatoria a los 7 días...(AU)

Introduction: energy sealing devices achieve hemostasis of the vessels through the heat generated and coagula-tion of the vascular wall proteins. However, the mid-term efficacy profile for venous graft sealing in arterial bypasssurgery remains unknown.Objectives: to create an animal model to compare the mid-term efficacy and safety profile at the sealing areaafter the healing process. To compare and assess which in vivo arterial models show lower morbidity and highersurvival rates after 4 weeks.Material and methods: this was an in vivo experimental study of 16 New Zealand rabbits. In each rabbit a humansaphenous vein (SV) with, at least, 1 venous collateral was implanted. Two arterial models were developed: infrarre-nal aorta bypass with SV (n = 5) and aortoplasty with SV patch (n = 11). In both models the collateral was randomizedand sealed with either 1 these 2 energy sealing devices: electrothermal bipolar vessel sealing (EBVS) or Harmonicscalpel (HS). Every animal was treated with antithrombotic prophylaxis and immunosuppressive medication. Therates of intraoperative mortality, paraplegia, infection, bleeding, and survival were all studied.Results: two animals (50 %) survive 7 days after surgery in the bypass model. However, no animal survived 4 daysafter surgery in this model. In the aortoplasty group, the 7-day survival rate was 55.56 % (5/9) while the 4-weeksurvival rate was 44.44 % (4/9) (p = 0.05). The rate of paraplegia was 100 % for the bypass model and much lowerfor the patch group (25 %) (p = 0.03). The mean ischemic time was lower for the aortoplasty model (37.11 ± 8.1 min)compared to the bypass group (42 ± 10.61 min) (p = 0.414). No animal showed intrabdominal hemorrhages oradverse drug reactions associated with the immunosuppressive medication.Conclusion: aortoplasty with the SV patch model showed lower rates of paraplegia and 7-day mortality in theanimal model...(AU)

Modelo animal de ectasia corneal en conejo mediante inyección intraestromal de colagenasa tipo ii / Animal model of corneal ectasia in rabbits by intrastromal injection of type II collagenase

Introducción La colagenasa ii ha sido utilizada para inducir queratocono experimental en modelos animales. Sin embargo, no ha sido estudiado su efecto cuando se administra por inyección intraestromal, por lo que el propósito de este estudio fue estudiar los efectos de la inyección intraestromal de colagenasa ii sobre la superficie corneal y la morfología de la córnea. Método Se trabajó con 6 conejos Nueva Zelanda, se administró colagenasa ii por inyección intraestromal (5μL de 2,5mg/mL) en los ojos derechos y solución salina balanceada en los ojos izquierdos. Se realizaron queratometrías para evaluar la alteración de la curvatura, también al séptimo día se obtuvieron las córneas y se realizó tinción hematoxilina-eosina para examinar los cambios morfológicos. Asimismo, se investigaron los cambios en la expresión de colágeno tipo i por tinción rojo sirio y PCR semicuantitativa. Resultados K1, K2 y Km presentaron diferencias en los promedios con cambios estadísticamente significativos. Los cambios morfológicos que se demostraron fueron degradación y disposición irregular del estroma corneal, incremento en la densidad celular de queratocitos y ligera infiltración celular. Finalmente se demostró que hay mayor expresión de fibras de colágeno tipo i en el grupo experimental a diferencia de los controles y el grosor de las fibras también aumentó por acción de la colagenasa ii; sin embargo, en cuestión génica no hubo cambios en la expresión de colágeno tipo i a nivel molecular entre el grupo control y experimental. Conclusiones La colagenasa ii administrada por inyección intraestromal es capaz de inducir cambios en la superficie corneal y el estroma, pudiendo simular un modelo de queratocono (AU)

Introduction Collagenase II has been used to induce experimental keratoconus in animal models. However, its effect when administered by intrastromal injection has not been studied, so the purpose of this study was to study the effects of intrastromal injection of collagenase II on corneal surface and corneal morphology. Method Six New Zealand rabbits were used, collagenase II was administered by intrastromal injection (5μL of 2.5mg/mL) in the right eyes and balanced salt solution in the left eyes. Keratometry was performed to evaluate curvature alteration, also at day 7 corneas were obtained and hematoxylin–eosin staining was performed to examine morphologic changes. Likewise, changes in type I collagen expression were investigated by Sirius Red staining and semi-quantitative PCR. Results K1, K2, and Km presented differences in the means with statistically significant changes. The morphological changes that were demonstrated were degradation and irregular arrangement of the corneal stroma, increase in the cellular density of keratocytes and slight cellular infiltration. Finally, it was demonstrated that there is greater expression of type I collagen fibers in the experimental group as opposed to the controls and the thickness of the fibers also increased due to the action of collagenase II, however, in terms of genetics there were no changes in the expression of type I collagen at molecular level between the control and experimental groups. Conclusions Collagenase II administered by intrastromal injection is able to induce changes in the corneal surface and stroma, being able to simulate a model of keratoconus (AU)

Thermal necrosis-aided dental implant removal: A rabbit model pilot study

Background: The significant advances in the materials and biological aspects of dental implants haven't completely eradicated the implant failures. The removal of osseointegrated but otherwise failed implants present several challenges including adjacent tissues damage and necessity of bone augmentation for reimplantation. Controlled thermal necrosis has emerged as an alternative technique to aid removal of osseointegrated dental implants with minimal to no defect to healthy bone or surrounding tissues. This study aimed to evaluate the thermal necrosis-aided implant removal method in a rabbit osseointegration model. Material and methods: A total of 8 male New Zealand rabbits were used in the study. Two dental implants were placed on each femur of the rabbits. Heating of the implants was performed after 7 weeks following the implantation. Heating was done by contacting the tip of an electrosurgey tool in monopolar mode at different power settings and contact durations (5W - 2 seconds, 5W - 10 seconds, and 10 W - 10 seconds). No heating was done on the control group. Implant stability right after implantation, before heat application and after heat application was determined using an Osstell™ Mentor Device. Following the removal of implants histological analyses were performed to determine the effects of heat application at cellular level. Results: ISQ values of the 10W-10s group was significantly lower compared to the other groups (p<0.001). No indication of progressive necrosis or irreversible damage was observed in any of the groups. However, the percent of empty-apoptotic lacunae were statistically higher in the 5W-10s and the 10W-10s groups compared the control and the 5W-2s groups. Conclusions: Within the conditions of this study, we conclude that heat application with an electrosurgery tool using monopolar mode at 10W power for 10 seconds is optimal for reversing osseointegration with no extensive or progressive damage to the bone. (AU)

De caballos y conejos: el primer intento de crear una escuela de veterinaria en Barcelona (1888-1890) / Of horses and rabbits: a first attempt to create a veterinary school in barcelona (1888-1890)

Las primeras escuelas de veterinaria en Europa se establecieron en el siglo XVIII. En España, este proceso se inició en 1793 con la apertura de la escuela de Madrid, seguida de otras instituciones similares fundadas en el siglo XIX. La creación de la primera Facultad de Veterinaria en Cataluña tuvo lugar en 1982. Hasta entonces, la organización en Barcelona de un centro que ofertara esos estudios se había convertido en un tema de interés recurrente. Esta investigación analiza, desde una perspectiva local, el proyecto que se gestó en 1888 para trasladar la escuela de Santiago de Compostela a la capital catalana. La propuesta, que recibió importantes apoyos entre la sociedad civil e instituciones públicas de la ciudad, se caracterizó por el énfasis que puso en una educación que no se focalizara únicamente en los animales grandes. Por primera vez en España, las demandas de la producción animal intensiva, como la avicultura o cunicultura que comenzaban a proliferar en Cataluña, se contemplaron como eje esencial de la formación del veterinario. Una modificación programática de envergadura para una escuela que, por las novedades que introducía, se asoció con el epíteto «modelo» en la documentación examinada.(AU)

The first veterinary schools in Europe were established in the eighteenth century. In Spain, this process began in 1793 with the opening of the Madrid veterinary school, followed by other similar institutions founded in the 19th century. The creation of the first Veterinary Faculty in Catalonia took place in 1982. Until then, the creation of a center that would offer these kind of studies had become a recurring topic of interest in Barcelona. This article analyzes, from a local perspective, the project that was conceived in 1888 to transfer the school from Santiago de Compostela to the Catalan capital. The proposal received strong support from civil society and public institutions in the city. It was characterized by the emphasis it placed on an education that did not focus solely on large animals. For the first time in Spain, the demands of intensive animal production, such as poultry or rabbit farming that were beginning to proliferate in Catalonia, were seen as an essential part of veterinary training. This represented a major programmatic modification for a school that, due to the new features it introduced, was labelled “model” in the documentation examined.(AU)

Important interaction between urethral taste bud-like structures and Onuf's nucleus following spinal subarachnoid hemorrhage: A hypothesis for the mechanism of dysorgasmia / Interacción importante entre las estructras de tipo papila gustativa de la uretra y el núcleo de Onuf tras hemorragia subaracnoidea espinal: una hipótesis para el mecanismo de la disorgasmia

Background: We previously postulated that orgasmic sensation may occur through recently discovered genital taste bud-like structures. The interaction between the pudendal nerve and Onuf's nucleus may be important for developing orgasmic information. The study aims to investigate whether ischemic damage to Onuf's nucleus-pudendal network following spinal subarachnoid hemorrhage (SAH) causes taste bud degeneration or not.Methods: The study was conducted on 22 fertile male rabbits who were divided into three groups: control (GI; n=5), SHAM (GII; n=5) and study (GIII; n=12). Isotonic solution, .7cm3, for the SHAM, and .7cm3 homologous blood was injected into spinal subarachnoid spaces at S2 level of the study group. Two weeks later, Onuf's nucleus, pudendal ganglia and the taste bud-like structures of the penile urethra were examined histopathologically. Degenerated neuron densities of Onuf's nucleus, pudendal ganglia and atrophic taste bud-like structures were estimated per mm3 and the results analyzed statistically.Results: The mean degenerated neuron densities of taste bud-like structures, Onuf's nucleus and pudendal ganglia were estimated as 2±1/mm3, 5±1/mm3, 6±2/mm3 in GI; 12±4/mm3, 35±9/mm3, 188±31/mm3, in GII and 41±8/mm3, 215±37/mm3, 1321±78/mm3, in GIII. Spinal SAH induced neurodegeneration in Onuf's nucleus, pudendal ganglia and taste bud atrophy was significantly different between GI/GII (p<.005); GII/GIII (p<.0005) and GI/GIII (p<.0001). (AU)

Antecedentes: Hemos postulado previamente que la sensación orgásmica puede producirse a través de las recientemente descubiertas estructuras de tipo papila gustativa de los genitales. La interacción entre el nervio pudendo y el núcleo de Onuf puede ser importante para desarrollar información orgásmica. El objetivo del estudio fue estudiar si el daño isquémico a la red núcleo-ganglios pudendos de Onuf tras una hemorragia subaracnoidea espinal (HSA) puede causar o no una degeneración de las estructuras de tipo papila gustativa.Métodos: El estudio fue realizado en 22 conejos fértiles que se dividieron en 3 grupos: control (GI; n=5), placebo (GII; n=5) y de etudio (GIII; n=12). Se inyectaron 0,7cc de solución isotónica a los miembros del grupo placebo, y 0,7cc de sangre homóloga en los espacios subaracnoideos espinales a nivel de S2, al grupo de estudio. Al cabo de 2 semanas se examinaron histopatológicamente el núcleo de Onuf, los ganglios pudendos y las estructuras de tipo papila gustativa de la uretra. Se calcularon por mm3 las densidades de las neuronas degeneradas del núcleo de Onuf, los ganglios pudendos y las estructuras atróficas de tipo papila gustativa, analizándose estadísticamente los resultados.Resultados: Las densidades medias de las neuronas degeneradas de las estructuras de tipo papila gustativa, el núcleo de Onuf y los ganglios pudendos se calcularon como 2±1, 5±1, 6±2/mm3 en GI; 12±4, 35±9, 188±31 en GII y 41±8, 215±37, 1321±78/mm3, en GIII. La neurodegeneración inducida de HSA en el núcleo de Onuf, los ganglios pudendos y la atrofia de las papilas gustativas fue significativamente diferente entre los grupos GI/GII (p<0,005); GII/GIII (p<0,0005) y GI/GIII (p<0,0001). (AU)

Hemodynamic resuscitation with fluids bolus and norepinephrine increases severity of lung damage in an experimental model of septic shock / La resucitación hemodinámica con bolos de fluidos y noradrenalina incrementa la severidad del daño pulmonar en un modelo experimental de shock séptico

Objective Hemodynamic resuscitation is considered a cornerstone of the initial treatment of septic shock. However, there is growing concern about its side effects. Our objective was to assess the relationship between fluid administration and norepinephrine infusion and the development of lung injury. Design Randomized in vivo study in rabbits. Setting University animal research laboratory. Patients Eighteen New Zealand rabbits. Control group (SHAM, n=6), Sepsis group with or without hemodynamic resuscitation (ETX-R, n=6; ETX-NR, n=6). Interventions Sepsis was induced by intravenous lipopolysaccharide administration and animals were followed-up for 4h. Hemodynamic resuscitation with Ringer lactate (20mL·kg−1) was administered and later norepinephrine was initiated 3h after sepsis induction. At the end, the left lung was excised. Main variables of interestAn indwelling arterial catheter and an esophageal Doppler were placed. Lung mechanics were monitored with side stream spirometry. Lung damage was analyzed by histopathological examination. Results The SHAM group did not show hemodynamic or respiratory changes. Lipopolysaccharide administration aimed an increase in cardiac output and arterial hypotension. In the ETX-NR group, animals remained hypotensive until the end of the experiment. Resuscitation with fluids and norepinephrine reversed arterial hypotension. Compared to the ETX-NR group, the remaining lung of the ETX-R group showed greater accumulation of neutrophils and reactive type-II pneumocytes, thicker alveolar wall, alveolar hemorrhage and non-aerated pulmonary areas. Lung injury score was larger in the ETX-R group. Conclusions In our experimental study, following a strategy with bolus fluids and late norepinephrine used in the early phase of endotoxic septic shock has a negative influence on the development of lung injury. (AU)

Objetivo La resucitación hemodinámica es considerada piedra angular en el tratamiento inicial del shock séptico. Sin embargo, existe creciente preocupación sobre sus efectos indeseables. Nuestro objetivo fue evaluar la relación entre la administración de fluidos e infusión de noradrenalina y el desarrollo de lesión pulmonar. Diseño Estudio aleatorizado en animales vivos. Ámbito Laboratorio universitario de investigación. Participantes Dieciocho conejos de raza New Zealand White. Grupo control (SHAM, n=6), grupo séptico con o sin resucitación hemodinámica (ETX-R, n=6; ETX-NR, n=6). Intervención La sepsis fue inducida tras administración intravenosa de lipopolisacárido, y los animales fueron seguidos durante 4h. La resucitación hemodinámica mediante suero Ringer lactato (20ml·kg-1) y posterior noradrenalina fue iniciada a las 3h de ser inducida la sepsis. Al final del estudio, el pulmón izquierdo fue extraído. Principales variables de interés Fueron empleados catéter arterial y doppler esofágico. La mecánica pulmonar fue monitorizada con sensor de flujo. El daño pulmonar fue analizado mediante examen histopatológico. Resultados El grupo control no mostró cambios hemodinámicos ni respiratorios. La administración del lipopolisacárido produjo un incremento del gasto cardíaco e hipotensión arterial. En el grupo ETX-NR, los animales permanecieron hipotensos hasta el final del estudio. La resucitación con fluidos y noradrenalina revirtió la hipotensión arterial. Comparados con el grupo ETX-NR, en el grupo ETX-R el estudio histopatológico mostró mayor acumulación de neutrófilos, así como mayor presencia de neumocitos activados tipo II, engrosamiento de la pared alveolar, hemorragia alveolar y zonas pulmonares no aireadas. La escala final de daño pulmonar fue mayor en el grupo ETX-R. Conclusiones En nuestro estudio experimental ... (AU)

Design and Characterization of Combinational Domperidone-Famotidine Floating Drug Delivery System - In vitro and In vivo studies / Diseño y caracterización del sistema de administración flotante de fármacos de domperidona-famotidina combinatoria. Estudios in vitro e in vivo

INTRODUCTION: The drawbacks assosiated with oral administration of drugscan be controlled or minimized by gastro retentive formulations that remain buoyant within the stomach for an extended time by providing prolonged gastric retention and release the drug in an exceedingly extended manner thereby improving bioavailability. The current research was to develop and optimize Domperidone and Famotidine floating tablets with extended release by Quality by Design approach. METHOD: Based on QTPP (Quality Target Product Profile), CQAs (Critical Quality Attributes) were identified. Risk analysis by the evaluation of formulation and process parameters showed that optimizing the levels of polymers could reduce high risk to achieve the target profile. A 23 factor experimental design with midpoints was selected for statistical analysis and optimization. RESULTS: HPMC K100 and Carbopol 934P had a positive effect while ethyl cellulose demonstrated a negative effect on the selected responses. Drug release kinetics followed the first-order release with Higuchi diffusion and Fickian diffusion. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values. Abdominal X-ray imaging after oral administration of the tablets on a healthy rabbit's stomach confirmed the extended floating behavior with shorter lag time. In vivo, pharmacokinetic studies in rabbits revealed that the optimized formulation exhibited prolonged drug release with enhanced Cmax, tmax, AUCo-t, and t1/2 of an optimized product when compared to the marketed product. CONCLUSIONS: It has been concluded that the application of Quality by Design in the formulation and optimization reduced the number of trials to produce a cost-effective formula

INTRODUCCIÓN: Los inconvenientes de la administración oral pueden controlarse o minimizarse mediante formulaciones gastro-retentivas que permanecen flotantes dentro del estómago durante un tiempo prolongado al proporcionar una retención gástrica prolongada y liberan el fármaco de una manera excesivamente prolongada mejorando así la biodisponibilidad. La investigación actual fue desarrollar y optimizar las tabletas flotantes de domperidona y famotidina con liberación prolongada mediante el enfoque Calidad por diseño. MÉTODO: Basado en QTPP (Perfil de producto objetivo de calidad), se identificaron CQA (Atributos críticos de calidad). El análisis de riesgos mediante la evaluación de los parámetros de formulación y proceso mostró que la optimización de los niveles de polímeros podría reducir el alto riesgo para lograr el perfil objetivo. Se seleccionó un diseño experimental de 2 factores de nivel 3 con puntos medios para el análisis estadístico y la optimización. RESULTADOS: HPMC K100, Carbopol 934P tuvo un efecto positivo y la etilcelulosa tuvo un efecto negativo sobre las respuestas seleccionadas. La cinética de liberación del fármaco siguió a la liberación de primer orden con difusión de Higuchi y difusión de Fickian. Se seleccionó y evaluó una fórmula optimizada que satisfacía todos los parámetros requeridos. Los valores de respuesta previstos estaban en estrecha concordancia con los valores de respuesta experimental. Las imágenes de rayos X abdominales después de la administración oral de las tabletas en el estómago sano del conejo confirmaron el comportamiento de flotación prolongado con un tiempo de retraso más corto. Losin vivo estudios farmacocinético sen conejos revelaron que la formulación optimizada exhibía una liberación prolongada del fármaco con una mayor Cmax, tmax, AUCo-t y t1 / 2 del producto. CONCLUSIONES: Se concluyó que la aplicación de Quality by Design en la formulación y optimización redujo el número de ensayos para producir una fórmula rentable

Effectiveness of turmeric (Curcuma Longa Linn) Gel Extract (GE) on wound healing: Pre-clinical test

Objective: This research was basic research to identify the effect of turmeric extract tested by the in vivo method. The purpose of this study was to identify differences in the length of the wound at each concentration of gel preparations on days 3, 7, and 14, as well as differences in wound healing time at each concentration of gel preparations and, identify the most effective gel preparations for wound healing. Method: This study is an experimental laboratory study with experimental animals using post-test only with control groups, the type of research used is a pre-clinical test (pre-clinical trial) on female rabbits. The sample size in this study was 12 rabbits grouped randomly. The length of each group's wounds was measured and observed on days 3, 7, and 14. Gel application was carried out twice a day in the morning and evening for 14 days. In this study, the experimental data were tested using Kruskal Wallis. Results: There were differences in wound length in each group treated with turmeric extract gel and base gel. Based on the mean wound length of each group, they experienced a reduction in wound length on days 3, 7, and 14. There were also differences in wound healing time in each group. In each group, wherein this case, the treatment group that was given 5% turmeric extract gel experienced a faster healing time <14 days than the other groups. Conclusion: In general, turmeric extract gel at each concentration is effective against wound healing. Turmeric extract gel concentration is the most effective gel with a concentration of 5%, then followed by concentrations of 10% and 15%. (AU)

Stent traqueal biodegradable de polidioxanona. Estudio de la reactividad en conejo / Reactivity study of a biodegradable polydioxanone tracheal stent in a rabbit model

INTRODUCCIÓN: El objetivo de este estudio es evaluar la reactividad traqueal inducida por un stent traqueal biodegradable de polidioxanona. MATERIAL Y MÉTODOS: Veintidós conejos se dividieron en 3 grupos con diferentes tiempos de supervivencia (30, 60 y 90 días postimplantación). Se implantó un stent biodegradable en cada animal, excepto en uno de cada grupo (control negativo). La implantación se realizó a través de una pequeña traqueotomía y bajo control fluoroscópico. Al finalizar los tiempos de supervivencia programados se realizaron estudios de TC y anatomopatológicos. RESULTADOS: Ningún animal murió durante el procedimiento ni en el seguimiento. El stent había desaparecido en el 100% de los casos a los 90 días, en el 50% a los 60 días y en ninguno a los 30 días. En los estudios de TC se observó un grosor de la pared traqueal mayor a los 30 que a los 60 y 90 días (1,60 ± 0,41 mm en la parte central del stent frente a 1,11 ± 0,18 y 0,94 ± 0,11; p = 0,007). En el estudio anatomopatológico no se encontraron granulomas. A los 30 días se observaba cierto grado de alteración histológica, la cual se reduce a los 60 y 90 días. También se encuentran las diferencias, tanto en las TC como en la histología, entre animales con el stent presente y animales con el stent degradado. CONCLUSIONES: Los stents de polidioxanona producen una leve reacción traqueal que revierte con la degradación. El uso de estos stents biodegradables en la patología traqueal benigna es prometedor

INTRODUCTION: The objective of this study was to evaluate tracheal reactivity induced by a biodegradable polydioxanone tracheal stent. MATERIALS AND METHODS: Twenty-two rabbits were divided into 3 groups assigned to different survival times (30, 60 and 90 days post-implantation). A biodegradable stent was implanted in each animal, except for 1 of each group (negative control). Implantation was performed through a small tracheotomy under fluoroscopic control. CT and histopathological studies were scheduled at the end of survival times. RESULTS: No animal died during the procedure or follow-up. The stent had disappeared in 100% of the cases at 90 days, in 50% at 60 days, and in none at 30 days. CT studies revealed a greater tracheal wall thickness at 30 days than at 60 and 90 days (1.60 ± 0.41 mm in the central part of the stent versus 1.11 ± 0.18 and 0.94 ± 0.11; P = .007, respectively). No granulomas were observed on histopathology. Some degree of histological changes were noted at 30 days, which had reduced at 60 and 90 days. Differences were also found in both CT and histology between animals in which the stent was present and animals in which it had degraded. CONCLUSIONS: Polydioxanone stents produce a mild reaction that reverts with tracheal degradation. The use of these biodegradable stents in benign tracheal disease is promising

Immunohistochemical and morphological characteristics of tissues response to polylactic acid membranes with silver nanoparticles

BACKGROUND: The aim of this research was to study anti-microbial and anti-inflammatory characteristics of silver nanoparticles helping bone structures to recover during late stage of parodontitis, which afterwards will increase the effect of bone regeneration operations. MATERIAL AND METHODS: We assessed colloid solution-derived silver nanoparticles coating of polylactic acid membrane regarding tissue foreign body response. Thirty eight polylactic acid membranes were implanted intracranially in rabbits ten unmodified (control group) and twenty eight with silver nanoparticles coating (experimental group). In controls, penicillin was used for infection prophylaxis. Tissue response was assessed by light microscopy and immunohistochemistry (CD3, CD15, CD30) 2 weeks after implantation. RESULTS: inflammation markers in experimental group were significantly lower than in control group, there were no signs of forming a fibrosis capsule nor infectious signs. CONCLUSIONS: colloid silver solution can be used as a source of nanoparticles for anti-microbial and antiinflammatory biodegradable membranes' coating

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Effects of locally applied Insulin-like Growth Factor-I on osseointegration

Background: The aim of this study was to assess the effect of local application of IGF-I on osseointegration of dental implants placed in osteoporotic bones. Material and Methods: 16 rabbits were randomly distributed into two groups: eight animals were ovariectomized and fed a low-calcium diet for six weeks, in order to induce experimental osteoporosis, and the others were sham-operated and fed a standard diet. A titanium implant was inserted into the tibiae in both groups. In half of the rabbits, 4 μg of IGF-I was applied into the ostectomy, prior to the implant insertion. A total of 32 implants were placed. Animals were sacrificed two weeks after surgery and decalcified samples were processed for Bone-To-Implant Contact (BIC) and Bone Area Density (BAD) measurements. Analysis of variance (ANOVA) was used for statistical evaluation. P < 0.05 was considered to be significant. Results: Ovariectomy induced statistically significant lower BAD values (p = 0.008) and a tendency towards lower BIC values when compared osteoporotic and healthy groups. The administration of 4 μg of IGF-I did not produce statistically significant differences neither on BIC nor on BAD values, neither in the osteoporotic animals nor in healthy. Conclusions: Within the limitations of this experimental study, local administration of 4 μg of IGF-I was not able to induce any changes in the osseointegration process two weeks after surgery, neither in healthy rabbits nor in the osteoporotic group

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Effect on osseointegration of two implant macro-designs: A histomorphometric analysis of bicortically installed implants in different topographic sites of rabbit's tibiae

Background: To evaluate the effect of two different implant macro-designs on the sequential osseointegration at bicortically installed implants in the rabbit tibia. A further aim is to compare the osseointegration at different topographic zones. Material and Methods: 27 New Zealand rabbits were implemented. Two implants, one for each macro-design (Ticare Inhex(R) or Ticare Quattro(R), Mozo-Grau, Valladolid, Spain), were randomly implanted in the diaphysis or metaphysis of each tibia. The flaps were sutured to allow a submerged healing. The animals were sacrificed after 2, 4 or 8 weeks. Ground sections were prepared and analyzed. Results: No statistically significant differences were found between the two groups for newly formed bone in contact with the implant surface, being about 16%, 19% and 33% in both groups, after 2, 4, and 8 weeks of healing. Bone apposition was slightly higher in the diaphysis, reaching values of 36.4% in the diaphysis, and 29.3% in the metaphysis at 8 weeks of healing. It was observed that the implant position showed a statistical significance regarding BIC values at 4 and 8 weeks (p < 0.05). Multivariate analysis fails to detect statistical significant differences for the interaction between implant designs and topographic site. Ticare Quattro(R) design had a slight better BIC values at diaphysis sites across healing stages, but without reaching a statistical significance. Conclusions: The both implant macro-designs provided similar degrees of osseointegration. Bone morphometry and density may affect bone apposition onto the implant surface. The apposition rates were slightly better in diaphysis compared to metaphysis

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Validación experimental de un modelo de análisis de elementos finitos en fractura de cadera y su aplicabilidad clínica / Experimental validation of finite elements model in hip fracture and its clinical applicability

La fractura de la extremidad proximal de fémur es objeto de interés en investigación. La complejidad del entramado óseo y la ineficiencia estructural asociada al envejecimiento hacen que existan muchas variables todavía por comprender desde el punto de vista experimental, pero no existe un modelo de investigación estructural y biomecánico de la fractura de cadera claramente definido. La hipótesis de este trabajo es que es posible desarrollar un modelo de experimentación computacional que caracterice el hueso de la extremidad proximal del fémur como un material heterogéneo a partir de la traslación directa de los parámetros mecánicos obtenidos de piezas anatómicas de experimentación. Material y método: Trabajo experimental que compara la experimentación real en cadáver y un modelo numérico basado en análisis de elementos finitos (AEF). Las variables que se han empleado son: punto de inicio de la fractura, su propagación, carga progresiva y la carga máxima hasta fractura. Al modelo computacional se trasladaron los parámetros mecánicos reales obtenidos de las piezas anatómicas basándose en la relación entre las unidades Hounsfield de la TAC de alta resolución y la densidad mineral ósea de cada elemento virtual, mientras que la propagación de la fractura se modeló mediante desarrollo computacional propio del equipo investigador, con disminución de las propiedades mecánicas de los elementos dañados conforme avanza la línea fractuaria. Resultados: El modelo computacional fue capaz de determinar el punto de inicio de la fractura, con una discreta tendencia a la medialización anatómica de dicho punto respecto a lo ocurrido de manera experimental. El grado de correlación fue muy alto al comparar el valor real de deformación progresiva de las muestras frente al obtenido por el modelo computacional. Sobre 32 puntos analizados, se obtuvo una pendiente de 1,03 en regresión lineal, con un error relativo entre las deformaciones del 6% y un coeficiente de Pearson de R2=0,99. El modelo computacional infraestimó discretamente la carga máxima de fractura, con un error relativo aproximado al 10%. Conclusión: El modelo computacional de AEF desarrollado por este equipo investigador multidisciplinar se puede considerar, en conjunto, un modelo completo de AEF de la extremidad proximal del fémur con aplicabilidad clínica futura al ser capaz de simular e imitar el comportamiento biomecánico de fémures humanos contrastado con un modelo experimental clásico realizado en piezas anatómicas. Sobre esta base podrán evaluarse interacciones cualitativas y cuantitativas que lo consoliden como un potente banco de ensayos de experimentación computacional sobre el fémur proximal humano

Fracture of the proximal extremity of the femur is the subject of research interest. The complexity of the bone framework and the structural inefficiency associated with ageing leave many variables yet to be understood from an experimental perspective. However, there is no clearly defined structural and biomechanical research model for hip fracture. The hypothesis of this paper is that it is possible to create a computational experimentation model that characterises the bone of the proximal extremity of the femur as a heterogeneous material from directly translating the mechanical parameters obtained from anatomical experimentation specimens. Material and method: An experimental paper comparing real experimentation on cadavers and a numerical model based on finite element analysis (FEA). The variables uses were: the start point of the fracture, propagation of the fracture, progressive load and maximum load until fracture. The real mechanical parameters obtained from the anatomical specimens were translated to the computational model based on the relationship between the Hounsfield units of the high resolution CAT scan and the bone mineral density of each virtual element, whereas the propagation of the fracture was modelled by the research team's own computational design, reducing the mechanical properties of the damaged elements as the fracture line advanced. Results: The computational model was able to determine the start point of the fracture, with a slight tendency towards anatomical medialisation of this point compared to what happened experimentally. The degree of correlation was very high on comparing the real value of progressive deformation of the samples compared to that obtained by the computational model. Over 32 points analysed, a slope of 1.03 in lineal regression was obtained, with a relative error between the deformations of 16% and a Pearson's coefficient of R2=.99. The computational model slightly underestimated the maximum fracture load, with a relative error of approximately 10%. Conclusion: The FEA computational model developed by this multi-disciplinary research team could be considered, as a whole, a complete FEA model of the proximal extremity of the femur with future clinical applicability since it was able to simulate and imitate the biomechanical behaviour of human femurs contrasted with a traditional experimental model made from anatomical specimens. On this basis, qualitative and quantitative interactions can be assessed which consolidate it as a powerful computational experimentation test bench for the human proximal femur

D-Ribose-L-Cysteine prevents intervertebral disc degeneration in annular puncture-induced rabbit model

Degeneration of the intervertebral discs is strongly implicated as the main cause of low back pain. To determine the preventive potential of D-Ribose-L-Cysteine in annular punctured intervertebral disc degeneration in rabbit model. Twenty New Zealand white rabbits (1.5 to 3.0 kg each) underwent annular puncture of the L2-L3, L3-L4, and L4-L5 discs. Group 1 (non-punctured control) were given phosphate-buffered saline; group 2 (model control) were given phosphate-buffered saline immediately after puncture for 4 weeks ; group 3 (punctured treated) were given 150 mg/kg/bw of D-Ribose-L-Cysteine solution immediately after puncture for 4 weeks; group 4 (punctured treated) were given 300 mg/kg/bw of D-Ribose-L-Cysteine solution immediately after puncture for 4 weeks. Rabbits were sacrificed at 4 weeks after puncture. The animals were housed individually in a meshed wire bottom cages with access to water and standard chow ad libitum. The serial X-rays were performed at 0 and 4 weeks for the rabbits and whole spinal column and discs were extracted and analyzed for various histological staining techniques (H&E and HVG), biochemical and immunohistochemical analysis. The X-rays showed a progressive decrease in disc height over timewhich was significantly prevented by the D-Ribose-L-Cysteine administration. The histological grade, collagen type 1 and 2, aggrecan, and matrix metalloprotease-13 mRNA expression and histological analysis were consistently indicative of degeneration, supporting the results of the X-ray data. This study has now documented that D-Ribose-L-Cysteine halts the progression of intervertebral disc degeneration and can be useful as prophylactic agents especially in people prone to disc degeneration

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Comparación de la reacción inflamatoria inducida por implantes faciales de silicona y politetrafluoroetileno. Estudio en conejos / Comparison of the inflammatory reaction induced by facial implants os silicone and polytetrafluoroethylene. Study in rabbits

Introducción y Objetivo: Existen diferentes tipos de injertos autólogos y materiales aloplásticos para el tratamiento de las diversas deformidades faciales. El politetrafluoroetileno (PTFE) tiene varias ventajas debido a su propiedad hidrofóbica, que induce menor reacción inflamatoria. Presentamos un estudio que evalúa y compara la reacción inflamatoria inducida por los implantes faciales de silicona y de PTFE. Material y Método: Colocamos fragmentos de implantes de silicona y de PTFE en orejas de conejos mediante incisión y disección de un bolsillo subcutáneo. Realizamos análisis histológico a las 8 semanas: tinción de las muestras con hematoxilina / eosina y calificación del grado de reacción inflamatoria crónica, presencia de neutrófilos, linfocitos, eosinófilos, neoangiogénesis, fibroblastos y edema, presencia o no de hemorragia y valoración de la cicatriz. Hicimos la recolección de muestras para análisis microbiológico y evaluación de la presencia de hematoma y absceso en el momento del sacrificio. Resultados: La prevalencia de abscesos en el sacrificio, el hematoma y el edema durante las primeras semanas, fueron significativamente menores (p <0.05) en el grupo de PTFE. Conclusiones: El PTFE indujo reacción inflamatoria crónica al igual que la silicona, pero con menos absceso, edema y formación de hematomas

Background and Objective: The treatment for many facial deformities uses many kinds of autologous grafts or alloplastic materials. Polytetrafluoroethylene (PTFE) has several advantages due to its hydrophobic properties, inducing less inflammatory reaction. Our study evaluates and compares the inflammatory reaction induced by silicone and PTFE stripes. Methods: Fragments of silicone and PTFE implants were placed in rabbits ears using an incision and a subcutaneous gap. The histological analysis was made 8 weeks later. The samples were stained with hematoxylin/eosin and classified as chronic inflammatory reaction graduation, the presence of neutrophils, lymphocytes, eosinophils, neoangiogenesis, fibroblasts, edema and presence of bleeding and scar. Samples to microbiological analysis and evaluation of bruise and abs- cess were collected at the moment of sacrifice. Results: Prevalence of abscess at sacrifice and hematoma during the first weeks were significantly higher (p>0.05) in the silicon group. Conclusions: PTFE induced as much inflammatory reaction as the silicon but with less abscess and hematoma formation

Hepatic subcellular distribution of squalene changes according to the experimental setting

Squalene is the main unsaponifiable component of virgin olive oil, the main source of dietary fat in Mediterranean diet, traditionally associated with a less frequency of cardiovascular diseases. In this study, two experimental approaches were used. In the first, New Zealand rabbits fed for 4 weeks with a chow diet enriched in 1% sunflower oil for the control group, and in 1% of sunflower oil and 0.5% squalene for the squalene group. In the second, APOE KO mice received either Western diet or Western diet enriched in 0.5% squalene for 11 weeks. In both studies, liver samples were obtained and analyzed for their squalene content by gas chromatography-mass spectrometry. Hepatic distribution of squalene was also characterized in isolated subcellular organelles. Our results show that dietary squalene accumulates in the liver and a differential distribution according to studied model. In this regard, rabbits accumulated in cytoplasm within small size vesicles, whose size was not big enough to be considered lipid droplets, rough endoplasmic reticulum, and nuclear and plasma membranes. On the contrary, mice accumulated in large lipid droplets, and smooth reticulum fractions in addition to nuclear and plasma membranes. These results show that the squalene cellular localization may change according to experimental setting and be a starting point to characterize the mechanisms involved in the protective action of dietary squalene in several pathologies

Efecto del resveratrol sobre las concentraciones séricas del factor de crecimiento endotelial vascular durante la aterosclerosis / Effect of resveratrol on seric vascular endothelial growth factor concentrations during atherosclerosis

Introducción: El resveratrol tiene propiedades antiinflamatorias y antiaterogénicas; sin embargo, se desconoce su efecto sobre el factor de crecimiento endotelial vascular (VEGF) en la aterosclerosis. Objetivo: Evaluar el efecto del resveratrol sobre las concentraciones séricas del VEGF durante la progresión y evolución de la aterosclerosis y su evolución en el tiempo en conejos alimentados con dieta enriquecida con colesterol. Materiales y métodos: Cuarenta y ocho conejos machos divididos en cuatro grupos de 12 conejos recibieron: grupo 1 (control): conejarina; grupo 2: conejarina suplementada con 0,5% colesterol; grupo 3 (control resveratrol): conejarina y resveratrol (2 mg/kg); grupo 4: conejarina suplementada con 0,5% colesterol y resveratrol, durante 12 semanas. Se realizaron determinaciones séricas de triglicéridos, colesterol y sus fracciones, VEGF y proteína C reactiva (PCR) al inicio, a la 6.a y a la 12.a semana de experimentación. La mitad de los conejos fueron sacrificados a la 6.a y a la 12.a semana y se realizó estudio histológico de su aorta. Resultados: El VEGF y la PCR aumentaron en los grupos2 y 4 desde la 6.a semana de experimentación con respecto a los grupos 1 y 3, respectivamente (p < 0,001). En la duodécima semana se observó una disminución de los niveles de VEGF y PCR en el grupo 4 con respecto al grupo 2 (p < 0,004). El tratamiento con resveratrol disminuyó la formación de ateromas. Conclusiones: El VEGF y la PCR séricos constituyen marcadores tempranos no invasivos de inflamación y aterosclerosis. La suplementación oral de resveratrol ejerce efectos antiinflamatorios y antiateroscleróticos, disminuyendo las concentraciones séricas de VEGF y PCR, y la formación y evolución de las lesiones ateroscleróticas

Introduction: Although it is known that resveratrol has anti-inflammatory and anti-atherogenic actions, its effect on vascular endothelial growth factor (VEGF) in atherosclerosis is unknown. Objective: To evaluate the effect of resveratrol on serum concentrations of VEGF during the progression and evolution of atherosclerosis, as well as and its evolution over time in rabbits fed with a cholesterol diet. Materials and methods: A total of 48 New Zealand white male rabbits were randomly divided into four groups of 12 rabbits: group 1 (control): standard diet (commercial rabbit food); group 2: cholesterol diet (0.5% cholesterol); group 3 (control resveratrol): standard diet (commercial rabbit food) and resveratrol (2 mg/Kg); group 4: cholesterol diet (0.5% cholesterol) and resveratrol (2 mg/Kg), for 12 weeks. Blood samples of overnight-fasted rabbits were collected at baseline and the sixth and twelfth weeks, and the lipid profile, VEGF, and C-reactive protein (CRP) levels were determined. Half of the animals were sacrificed on the sixth or twelfth week, and the aorta was dissected for histological studies. Results: VEGF and CRP levels were significantly higher in groups 2 and 4 than in groups1 and 3, respectively, from the 6th week (p < 0.001). VEGF and CRP were significantly lower in group 4 than in group 2 on 12 th week (p < 0.004). Supplementation of resveratrol reduced the formation of atherosclerotic lesions. Conclusions: Serum VEGF and CRP levels are early markers of atherosclerosis. Oral supplementation of resveratrol exerts anti-inflammatory and anti-atherosclerotic effects, decreasing serum concentrations of VEGF and CRP and the formation and evolution of atherosclerotic lesions