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Las Ciencias Médicas y Biológicas requieren, prioritariamente, que la investigación y la experimentación sean desarrolladas sobre organismos completos (los modelos animales). Su utilización ha permitido desarrollar innumerables ensayos preclínicos para evaluar los mecanismos patógenos y terapéuticos de diversas enfermedades, así como el estudio de las causas, naturaleza y cura de múltiples desórdenes de la salud humana. En este trabajo se muestra una panorámica general de los biomodelos de hipertensión arterial donde se describen: conceptos, características, origen, importancia, utilidad y procedimientos experimentales durante su fase de inducción. También se pondera la justificación de los biomodelos empleados en los estudios preclínicos de esta enfermedad. De igual forma, se describen los antecedentes para medir las alteraciones, las técnicas y los métodos directos e indirectos de medición de la presión arterial, la cual fue provocada experimentalmente en los animales de laboratorio para realizar los estudios de hipertensión humana.
Medical and biological sciences require, as a priority, that research and experimentation be carried out on complete organisms (animal models). Its use has allowed the development of innumerable preclinical tests to evaluate pathogenic and therapeutic mechanisms of various diseases, as well as to study the causes, nature and cure of multiple human health disorders. In this work, we show a general overview of arterial hypertension biomodels where concepts, characteristics, origin, importance, utility and experimental procedures during their induction phase are described. The justification of the biomodels used in preclinical studies of this disease is also considered. Antecedents are also described to measure alterations, techniques and direct and indirect methods of measurement of arterial pressure, which was provoked experimentally in the laboratory animals to carry out the studies of human hypertension.
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Rats , Models, Animal , Animal Experimentation , Hypertension , Animals, LaboratoryABSTRACT
Introducción: La diabetes es una enfermedad que afecta el embarazo provoca complicaciones fetales; dentro de ellas son frecuentes las malformaciones congénitas. Por la imposibilidad práctica y ética de estudiar este proceso en gestantes es imprescindible realizar estudios experimentales empleando procedimientos morfométricos para determinar si la diabetes afecta el neurodesarrollo. Objetivo: Caracterizar morfométricamente la sustancia gris de gazapos de ratas Wistar normales y con diabetes mellitus pregestacional. Métodos: Se realizó un estudio experimental básico de serie de casos a 20 gazapos de ratas Wistar de los cuales 10 eran descendientes de diabetes pregestacional. Se caracterizaron indicadores morfométricos del tejido nervioso como espesor de corteza e indicadores nucleares como el perímetro. Resultados: La media de la altura de la sustancia gris cortical mostró un valor de 1,224 ± 303,7 μm para el grupo control y 1,014 ± 376,0 para los casos, al aplicar el test de diferencias de medias se encontró diferencia significativa (p ≤ 0,05) a favor del grupo control. Los valores de la media del perímetro nuclear en el grupo control fue de 42,80 ± 7,23 μm y en el grupo experimental el promedio fue de 39,68 ± 6,52 μm, al aplicar el test de diferencias de medias se encontró diferencia significativa (p ≤ 0,05) a favor del grupo control al presentar mayor perímetro nuclear. Conclusiones: El mayor espesor cortical y perímetro nuclear correspondió al grupo control evidenciándose el efecto deletéreo de la diabetes mellitus en el neurodesarrollo.
Introduction: Diabetes is a disease that affects pregnancy causing fetal complications; within them congenital malformations are frequent. Due to the practical and ethical impossibility of studying this process in pregnant women, it is essential to carry out experimental studies using morphometric procedures to determine if diabetes affects neurodevelopment. Objective: To characterize morphometrically the gray matter of kits from normal Wistar rats and those with pregestational diabetes mellitus. Methods: A basic experimental study of a series of cases was carried out on 20 young Wistar rats, of which 10 were descendants of pregestational diabetes. Morphometric indicators of the nervous tissue were characterized as thickness of the cortex and nuclear indicators such as perimeter. Results: The average height of the cortical gray matter showed a value of 1.224 ± 303.7 μm for the control group and 1.014 ± 376.0 μm for the cases. When applying the mean difference test, a significant difference was found (p ≤ 0.05) in favor of the control group. The values of the measurement of the nuclear perimeter in the control group was 42.80 ± 7.23 μm and in the experimental group the average was 39.68 ± 6.52 μm. When applying the mean different test, a significant difference was found (p ≤ 0.05) at favor of control group presenting greater nuclear perimeter. Conclusions: The greatest cortical thickness and nuclear perimeter corresponded to the control group, evidencing the deleterious effect os diabetes mellitus on neurodevelopment.
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RESUMEN Introducción. El uso de Artemisia absinthium (ajenjo) en el trabajo de parto es ampliamente empleado en países de la región; sin embargo, no hay evidencia científica suficiente de su eficacia y seguridad, lo que representa un alto riesgo maternofetal. Objetivo. El propósito fue evaluar el efecto contractil de la Artemisia absinthium (ajenjo) en comparación a la oxitocina en útero aislado de ratas. Métodos. Se separaron 8 ratas Holtzman en i) Grupo experimental: Artemisia dosis 5, 10, 20, 30, 40 y 50 mg y ii) Grupo control: oxitocina 10-6 M. Se montaron los úteros en un baño de órganos aislados y se registraron contracciones por 5 minutos. Resultados. La frecuencia de contracciones con ajenjo 40 y 50 mg fueron comparables con oxitocina (p>0,05). Asimismo, dosis de 20 y 30 mg de Artemisia provocaron contracciones significativamente más duraderas que la oxitocina. La intensidad resultó ser comparable con oxitocina con dosis de 20, 40 y 50 mg de Artemisia. Conclusión. El extracto acuoso de Artemisia absinthium presentó efecto contráctil similar a la oxitocina y dependiente de la dosis en útero aislado de ratas.
ABSTRACT Introduction. The use of Artemisia absinthium (wormwood) in labour is widely used in countries in the region; however, there is no enough scientific evidence of its efficacy and safety, which represents a high maternalfetal risk. Objective. The purpose was to assess the contractile effect of Artemisia absinthium (wormwood) compared to oxytocin in utero isolated from rats. Methods. Eight Holtzman rats were separated into i) Experimental group: Artemisia dose 5, 10, 20, 30, 40, and 50 mg and ii) Control group: oxytocin 10-6 M. The uteruses were mounted in an isolated organ bath, and contractions were recorded for 5 minutes. Results. The frequency of contractions with wormwood 40 and 50 mg were comparable with oxytocin (p>0.05). Likewise, doses of 20 and 30 mg of Artemisia caused significantly longer-lasting contractions than oxytocin. The intensity was found to be comparable with oxytocin at doses of 20, 40, and 50 mg of Artemisia. Conclusion. The aqueous extract of Artemisia absinthium has a contractile effect similar to oxytocin and is dose dependent in utero isolated from rats.
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RESUMEN A raíz de la pandemia generada por el SARS-CoV-2, los sistemas de salud de los distintos países han experimentado un dramático aumento en la ocupación de las unidades de cuidado intensivo y, por ende, una alta demanda de ventiladores mecánicos. En este artículo se propone un protocolo de pruebas de ventiladores mecánicos de bajo costo en modelos porcinos, como parte del desarrollo de equipos biomédicos que pueden apoyar la crisis sanitaria suscitada por la pandemia. El protocolo aborda aspectos que incluyen la fase previa a la prueba, el manejo anestésico, de vía aérea, seguimiento de laboratorio, recuperación y seguimiento del animal. Como resultado, se presenta a la comunidad académica un protocolo de validación de prototipo de ventilador mecánico en espécimen porcino como un referente para su aplicación y revalidación por parte de grupos interesados en el desarrollo de tecnologías locales de bajo costo.
ABSTRACT As a result of the SARS-CoV-2 pandemic, health systems globally have seen a dramatic increase in the occupancy of intensive care units, with mechanical ventilators being a resource in high demand in the care of these patients. This article proposes a protocol for testing low-cost mechanical ventilators in pig models, as part of the development of locally manufactured biomedical equipment that can support the health crisis caused by the pandemic. The protocol addresses aspects that include the pre-test phase, anesthetic and airway management, laboratory monitoring, recovery and monitoring of the animal. This document presents to the academic community a validation protocol of a mechanical ventilator prototype in a pig specimen that can be a reference for its application and revalidation by other groups interested in the development of local and low-cost technologies.
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Animals , Swine , Ventilators, Mechanical , COVID-19 , Animals, Laboratory , Respiration, Artificial , Low Cost Technology , Clinical Trial ProtocolABSTRACT
RESUMEN A raíz de la pandemia generada por el SARS-CoV-2, los sistemas de salud de los distintos países han experimentado un dramático aumento en la ocupación de las unidades de cuidado intensivo y, por ende, una alta demanda de ventiladores mecánicos. En este artículo se propone un protocolo de pruebas de ventiladores mecánicos de bajo costo en modelos porcinos, como parte del desarrollo de equipos biomédicos que pueden apoyar la crisis sanitaria suscitada por la pandemia. El protocolo aborda aspectos que incluyen la fase previa a la prueba, el manejo anestésico, de vía aérea, seguimiento de laboratorio, recuperación y seguimiento del animal. Como resultado, se presenta a la comunidad académica un protocolo de validación de prototipo de ventilador mecánico en espécimen porcino como un referente para su aplicación y revalidación por parte de grupos interesados en el desarrollo de tecnologías locales de bajo costo.
ABSTRACT As a result of the SARS-CoV-2 pandemic, health systems globally have seen a dramatic increase in the occupancy of intensive care units, with mechanical ventilators being a resource in high demand in the care of these patients. This article proposes a protocol for testing low-cost mechanical ventilators in pig models, as part of the development of locally manufactured biomedical equipment that can support the health crisis caused by the pandemic. The protocol addresses aspects that include the pre-test phase, anesthetic and airway management, laboratory monitoring, recovery and monitoring of the animal. This document presents to the academic community a validation protocol of a mechanical ventilator prototype in a pig specimen that can be a reference for its application and revalidation by other groups interested in the development of local and low-cost technologies.
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Animals , Respiration, Artificial , Swine , Pandemics , COVID-19 , Health Systems , Animals, LaboratoryABSTRACT
RESUMEN El Laboratorio de Cirugía Experimental de la Universidad de Ciencia Médicas de Villa Clara cuenta con la tecnología necesaria para el montaje y desarrollo de técnicas y habilidades quirúrgicas y microquirúrgicas, las cuales son utilizadas por los profesionales y estudiantes en la docencia y la investigación biomédica. Se realizaron varias innovaciones con la recuperación de equipos, instrumentos y materiales en desuso; se creó el gimnasio quirúrgico conformado por modelos inanimados sintéticos, y se implementó el modelo «pollo¼, como técnica alternativa al uso de animales vivos en la experimentación animal. Se han desarrollado: importantes proyectos de investigación, entrenamientos de cirugía y microcirugía experimental, diversos programas docentes, y exitosos cursos internacionales con estudiantes y residentes. El laboratorio constituye un valioso aporte de alternativas éticas, económicas y sanitarias, que han favorecido la formación de recursos humanos y un servicio científico-técnico de calidad para la docencia y la investigación.
ABSTRACT The Laboratory of Experimental Surgery at the University of Medical Sciences of Villa Clara has the necessary technology for the assembly and development of skills, as well as, surgical and microsurgical techniques, which are used by professionals and students in teaching and biomedical research. Several innovations were made with the recovery of equipments, instruments and disused materials; the surgical gymnasium was made up of synthetic inanimate models, and the "chicken" model was implemented as an alternative technique to the use of live animals in animal experimentation. Important research projects, training in surgery and experimental microsurgery, diverse teaching programs, and successful international courses with students and residents have been developed. The laboratory constitutes a valuable contribution of ethical, economic and sanitary alternatives, which have favored the formation of human resources and a qualified scientific-technical service for teaching and research.
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Laboratory Equipment , Animals, LaboratoryABSTRACT
ABSTRACT Objective: Specific legislation regulating the use of animals in research in Brazil was introduced in 2008. However, the viewpoint of the Brazilian population regarding the use of animals in research and teaching activities remains largely unknown. Investigation of the public viewpoint on and understanding of the topic is required given the current shifts in the animal ethics scenario in Brazil. The objective of this study was to provide the first insight into the Brazilian population viewpoint on the use of animals in scientific research and teaching activities. Methods: Data collected in a survey involving 2,115 individuals aged 16 years or older and residing in 130 municipalities distributed across the five Brazilian macroregions (North, Northeast, South, Southeast, and Midwest) were analyzed. The margin of error for entire sample was set at 2%, with a 95% confidence interval. Results: This survey revealed that most Brazilian citizens are in favor of the use animals in research, particularly for medical purposes. Different views depending on the nature of research were identified. Approximately 80% of respondents were also in favor of frequent oversight of laboratories and animal facilities. Conclusion: Survey findings indicate that the opinion of the Brazilian population is divided when it comes to the use of animals in scientific research and teaching. Divided opinions expose a limited understanding of the importance of basic sciences and emphasizes the need for improved communication between the scientific community and the general population. Further strategies aimed to promote animal welfare are discussed.
RESUMO Objetivo: A legislação específica que regula o uso de animais em pesquisa no Brasil foi introduzida em 2008. No entanto, a opinião da população brasileira sobre o uso de animais em atividades de pesquisa e ensino ainda é desconhecida. No atual cenário brasileiro em mudança com relação à ética animal, é necessário avaliar as visões e o conhecimento da população sobre o assunto. O objetivo deste destudo foi realizar o primeiro levantamento da opinião da população brasileira sobre o uso de animais em atividades de ensino e pesquisa científica. Métodos: Analisamos os resultados de uma pesquisa com 2.115 indivíduos com 16 anos ou mais de 130 municípios das cinco macrorregiões brasileiras (Norte, Nordeste, Sul, Sudeste e Centro-Oeste). A margem de erro para toda a amostra foi de 2% dentro de um intervalo de confiança de 95%. Resultados: A pesquisa revelou que a maioria da população brasileira era favorável ao uso de animais em pesquisas, principalmente para fins médicos. Diferentes pontos de vista, dependendo da natureza da pesquisa, também foram identificados. Além disso, aproximadamente 80% dos entrevistados eram favoráveis ao monitoramento frequente de laboratórios e instalações de animais. Conclusão: A opinião da população brasileira está dividida com relação ao uso de animais em pesquisa e ensino científicos. Essa divisão expõe um entendimento limitado da importância das ciências básicas e destaca a necessidade de uma melhor comunicação entre a comunidade científica e a população em geral. Outras ações para alcançar as melhorias desejadas no bem-estar animal são discutidas.
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Humans , Animals , Public Opinion , Animal Experimentation , Brazil , Surveys and Questionnaires , CitiesABSTRACT
Resumo O uso de animais para fins didáticos e de pesquisa requer cuidados específicos. Atualmente, vigora no Brasil a Lei 11.794/2008, que rege parâmetros legais de manejo e conduta neste caso. Esta lei foi acompanhada da instalação ou adequação de comissões de ética em instituições que utilizam animais para ensino e investigação, bem como da criação do Conselho Nacional de Controle de Experimentação Animal. No entanto, apesar dos avanços, especialmente na legislação, ainda não foi consolidada nenhuma grande mudança de comportamento de pesquisadores e alunos de graduação que manuseiam animais em laboratório. A divulgação de informações deixa a desejar, e a prática acaba por repercutir a carência de reflexão ética. Este artigo busca averiguar o atual conhecimento bioético de alunos de graduação e professores com o objetivo de estimular mudanças de conduta. Aprovado CEP-Unioeste CAAE 8563417.8.0000.0107
Abstract Used for education and research, laboratory animals require special care on their handling. Brazilian Law 11,794/2008 establishes the legal parameters for animal manipulation and welfare. It was accompanied by the obligatory installation of the Institutional Ethics Committees on the Use of Animals and the creation of the National Council for Animal Experimentation Control. There have been advances in the field of animal bioethics legislation. However, considering the behavior of those who handle the animals in laboratory environment, especially undergraduate students, these advances are insufficient: the information does not reach them and their attitudes remain in need of ethical reflection. This article seeks to investigate the current bioethical knowledge of undergraduate students and teachers in order to stimulate changes in conduct. Aprovado CEP-Unioeste CAAE: 78563417.8.0000.0107
Resumen El uso de animales con fines didácticos y de investigación requiere cuidados específicos. Actualmente, rige en Brasil la Ley 11.794/2008 que regula los parámetros legales de manejo y conducta en estos casos. Esta ley estuvo acompañada de la instalación o adecuación de comisiones de ética en instituciones que utilizan animales para enseñanza e investigación, así como de la creación del Consejo Nacional de Control de Experimentación Animal. No obstante, a pesar de los avances, especialmente en la legislación, aún no se ha consolidado ninguna gran transformación en el comportamiento de los investigadores y alumnos que manipulan animales en el laboratorio. La divulgación de informaciones es insuficiente, y la práctica acaba reflejando la falta de reflexión ética. Este artículo procura identificar el conocimiento bioético actual de los alumnos de grado y de los profesores, con el objetivo de estimular cambios en la conducta. Aprovado CEP-Unioeste CAAE: 78563417.8.0000.0107
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Bioethics , Animal Experimentation , Ethics , Animal Use Alternatives , Animal Care Committees , Animals, LaboratoryABSTRACT
Objective To discuss the application value of diatom examination in lung tissue for the forensic diagnosis of drowning. Methods The experimental animals were divided randomly into drowning, postmortem submergence and dying on land group. Diatoms in lung tissue and drowning fluid were analyzed quantitatively by microwave digestion-vacuum filtration-automated scanning electron microscopy diatom examination method. The ratios of content of diatoms in lung tissue and drowning fluid （CL/CD ratio） were recorded. Results The CL/CD ratios of experimental rabbits in the drowning group （5.82±3.50） were much higher than that of postmortem submergence group （0.47±0.35）; the CL/CD ratios of different parts of the lung lobes of experimental pigs in the drowning group were higher than that of postmortem submergence group （P<0.05）; in seawater, brackish water, river fresh water and lake fresh water, the CL/CD ratios of experimental pigs in the drowning group were higher than that of postmortem submergence group （P<0.05）. In animal experiments, all the cases with CL/CD ratio >1.6 were from drowning group. Conclusion CL/CD ratio is an indicator with good application prospects in the diagnosis of drowning.
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Animals , Rabbits , Autopsy , Diatoms/cytology , Drowning/diagnosis , Lung , Microscopy, Electron, Scanning , Random Allocation , SwineABSTRACT
Objectvie@#To investigate the effects of secreting cytokines interferon-gamma (IFN-γ) and interleukin-17 (IL-17) of T helper 1 cells (Th1) and T helper 17 cells (Th17) on the peripheral blood and alveolar bone destruction, so as to provide a new explanation for cellular immunity-mediated alveolar bone destruction.@*Methods@#Eighteen eight-week-old male Sprague-Dawley rats were divided, randomly and equally, into 3 groups: lipopolysaccharide (LPS) group, ligation group and normal control group. In the LPS group, Escherichia coli LPS was injected into the alveolar mucosa on the buccalmedian site of the left upper first molar, while the right upper first molar was injected with equal volume of physiological saline as self-controls. The injections were performed every other day for four times totally. In the ligation group, the left upper first molars were ligatured with 0.2 mm orthodontic cords, while the right upper first molars were left untreated as self-controls, and supplemented with high-sugar diet to promote the periodontitis status. The rats in normal control group were fed normally. The concentrations of IFN-γ and IL-17 in peripheral blood were measured using enzyme linked immunosorbent assay (ELISA) method at the fourth week after the start of injection and at the eighth week after ligation. The histological of periodontal tissues were observed after hematoxylin-eosin (HE) staining and osteoclast count was performed under light microscope. The histological of osteoclasts were observed after tartrate-resistant acid phosphatase (TRAP) staining. Expression of IFN-γ and IL-17 were detected by immunohistochemical assay.@*Results@#The concentrations of IFN-γ in peripheral blood of LPS group [(185.0±50.7) ng/L] and ligation group [(202.9±60.4) ng/L] were significantly higher than that of normal control group [(106.3±17.2) ng/L](P<0.05). Meanwhile, histological examination showed inflammatory cells infiltration in the gingival epithelium, the height reduction of alveolar bone accompanied with absorption lacuna. There were significantly higher HE and TRAP stained osteoclasts in LPS group (9.50±1.05) and ligation group (10.83±1.17) than that in controlgroup (0.33±0.52)(P<0.05). Moreover, the expressions of IL-17 in alveolar bone absorption area of LPS group and ligation group were significantly stronger than that in control group (P<0.05).@*Conclusions@#The rat models of experimental periodontitis and alveolar bone resorption could be successfully established by means of ligationand LPS injection, respectively. The periodontal inflammatory responses were related to secreting cytokines IFN-γ and IL-17 of Th1 and Th17 cells, while Th17 cells might exert a positive effect on alveolar bone destruction.
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BACKGROUND:The nervous reconstruction and repair after spinal cord injury have become a research hotspot. OBJECTIVE:To investigate the change rule of neurogliocyte reactive hyperplasia after spinal cord injury. METHODS:Forty-two adult male Sprague-Dawley rats were selected and equivalently randomized into seven groups:normal control group (no intervention), sham operation group (lamina decompression) and operation groups (postoperative 1, 7, 14, 21 and 28 days). After the establishment of spinal cord injury models, the rats were sacrificed at each corresponding time point. The functional recovery of the rat hind limbs was evaluated by Basso, Beattie and Bresnahan scores, and complete spinal cord tissue was removed to undergo hematoxylin-eosin staining, immunohistochemistry staining and immunofluorescence staining. RESULTS AND CONCLUSION:(1) Basso, Beattie and Bresnahan scores showed that rats in the normal control and sham operation groups had normal neurologic function. Rats at 1 day after spinal cord injury paralyzed completely, the neurologic function of hind limbs began to recover gradual y at the 7th day, and the recovery became most obvious at the 14th day, which had no significant differences compared with the 21st and 28th days. (2) Hematoxylin-eosin staining found that the diffuse hemorrhage and neuronal necrosis were observed in the injured area at 1 day after operation;inflammatory cel infiltration and some vacuoles appeared at the 7th day, and the hemorrhage was absorbed gradual y;the hemorrhage disappeared completely and capsule cavity formed at the 14th day;up to the 28th day, spinal cord structure was completely destroyed and that was replaced by cicatricial tissue accompanying with a large cavity. (3) Immunohistochemistry staining showed that the astrocyte in damaged area proliferated with the cel synapse increasing, which was most overt at the14th day;the axon clearance widened and the structure was in disorder at the 7th day, and the myelin sheath in the damaged area was destroyed at the 21st day. (4) Immunofluorescence staining showed that there were numerous visible glial fibril ary acidic protein+/nestin+cel s in the injured area at 14 days after operation. (5) These results suggest that glial cel hyperplasia and hypertrophy, the up-regulated expressions of glial fibril ary acidic protein and nest protein are advantageous to the early repair of spinal cord injury.
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OBJECTIVE To explore cell death type of lateral line hair cellsinduced by cisplatin in zebrafish. METHODS Zebrafish larva were incubated in 1mM cisplatin solution for 6 hrs to induce about 90%lateral line hair cells loss. Time lapse imaging was used to detect the morphology of cisplatin-incubated hair cells in wildtypezebrafish pre-labelled by live dyes Bodipy TR C5-ceramide and Sytogreen 24. TUNEL assay and In situ anti-active Caspase-3 antibody staining were performed to detect nuclei fragmentation and Caspase-3 activity respectively. RESULTS Compared to control group, hair cells condensationand nuclei fragmentation (P<0.05) were detected in cisplatin-incubated group, and active Caspase-3 activity was also observed after cisplatin addition. CONCLUSION Cisplatinmay induced zebrafish lateral line hair cells loss by Caspase-3-dependent apoptotic pathway.
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Fundamento: estudios epidemiológicos y experimentales sugieren que el desarrollo de las enfermedades cardiovasculares en la adultez está influenciado por eventos de la vida prenatal o posnatal temprana, independientemente de los factores de riesgo relacionados con el estilo de vida. Objetivo: caracterizar la morfometría cardiaca en ratas de la línea Wistar portadoras de crecimiento intrauterino retardado, así como determinar las diferencias existentes entre adolescentes y adultos, en ambos sexos y la asociación con algunas variables morfométricas en el momento del nacimiento. Métodos: se estudiaron 80 crías del grupo control y 80 de un grupo experimental y se analizaron las siguientes variables morfométricas del recién nacido: peso, talla, circunferencia abdominal, diámetro biparental del cráneo, diámetro antero posterior del cráneo, todas en milímetros. Resultados: el bajo peso al nacer como resultado de crecimiento intrauterino retardado provocó cambios en la morfometría cardiaca, especialmente en el peso del corazón y en el grosor del ventrículo izquierdo. Estos cambios se observan en ambos sexos en la adolescencia y muestran un ligero predominio en el sexo masculino en la adultez. Conclusiones: los resultados obtenidos permitieron profundizar en el conocimiento de los eventos que participan en el desarrollo cardiaco en respuesta a la restricción de nutrientes durante la vida intrauterina, lo que podría contribuir al planteamiento de estrategias de salud encaminadas a disminuir la morbilidad y mortalidad perinatal de estas enfermedades.
Background: epidemiological and experimental studies suggest that cardiovascular disease in adulthood is influenced by prenatal or early postnatal events, regardless of lifestyle-related risk factors. Objective: to characterize the heart morphometry in Wistar rats with intrauterine growth restriction and to determine the differences between adolescents and adults of both sexes as well as the association with some morphometric variables at birth. Methods: a total of 80 rats in the control group and 80 in the experimental group were studied. The following morphometric variables were analyzed in the newborns: weight, height in addition to size, weight and volume of the heart, all in millimeters. Results: low birth weight resulting from intrauterine growth restriction caused changes in heart morphometry, especially in heart weight and thickness of the left ventricle. These changes were observed in both sexes during adolescence and showed a slight predominance in adult males. Conclusions: these results led to an increased knowledge of the events involved in heart development in response to nutrient restriction in utero, which could contribute to the design of health strategies to reduce morbidity and perinatal mortality from heart diseases.
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Objective To observe the effect of renal denervation (RDN) on the cardiac oxidative stress and sympathetic nerve remodeling after myocardial infarction (MI) in canine. Methods Canine (n=18) were randomly divided into three groups: Sham operation group (SHAM group, n=6), MI group (n=6), MI+RDN group (n=6). Anterior myocardial infarction was gained by gelatin sponge embolization of the left anterior descending artery. At four weeks post-MI, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were examined using echocardiography. Immunohistochemical assay was used to analyze the distribution and density of tyrosine hydroxylase (TH) stained nerve fibers at peri-infarct zone. Myocardial superoxide dismutase (SOD) activity and malondialde?hyde (MDA) were also assessed. Results Compared with dogs in SHAM group, LVEF and SOD expression were decreased in MI group and MI+RDN group (P<0.05), but Left ventricular end diastolic pressure (LVEDP), LVEDV, LVESV, MDA and rate of TH positive staining nerve fibers were increased (P<0.05). There was a negative correlation between the rate of TH positive staining nerve fibers and SOD level (rs=-0.818,P<0.05) and a positive correlation between rate of TH positive stain?ing nerve fibers with MDA level (rs=0.900,P<0.05). By contract, compared with MI group, LVEF and SOD in MI +RDN group were increased (P<0.05), while LVEDV, LVESV, MDA and rate of TH positive staining nerve fibers were significant?ly lowered (P<0.05). Conclusion RDN is effective to decrease the level of cardiac oxidative stress and improve cardiac sympathetic nerve remodeling and heart function after myocardial infarction in canine.
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Objective To determine whether polarized arrest using adenosine and lidocaine cold crystalloid cardioplegia would give satisfactory myocardial protection in the cardiac surgery of experimental animals.Methods Twelve pigs were randomized divided into 2 groups (n =6) to receive adenosine-lidocaine cardioplegia or St.Thomas cardioplegia.Left ventricular systolic and diastolic function,cardiac output,cardiac troponin 1 were monitored at before operation (T1),1 hour after crossclamp was removed (T2) and 2 hours after cross-clamp was removed (T3).After T3 the left ventricular ultrastructure was observed,mitochondrial ultrastructure was analyzed by CMIAS image system.Results There were no statistical differences between the two groups in T1.The left ventricular systolic pressure,± dp/dt and cardiac output in adenosine-lidocaine group wasmuch higher than St.Thomas group in T2 and T3,meanwhile the left ventricular diastolic pressure,capillary wedge pressureand cardiac troponin Ⅰ value was lower than St.Thomas group.The hemodynamic values was more stable in adenosine-lidocaine group.St.Thomas group got more myocardial injury alterations in intracellular structure than adenosine-lidocaine group.The image analysis of mitochondrial ultrastructure shows St.Thomas group got lower shape factor,higher area density and perimeter density compared with baseline and adenosine-lidocaine group values.Conclusion Adenosine-lidocaine cold crystalloid car-dioplegia gave satisfactory cardiac arrest,got better myocardial protection than St.Thomas cardioplegia.
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Objective To investigate the inhibitory effect of Qingpeng ointment,a topical Tibetan medicine,on induced irritant contact dermatitis (ICD) in mice and its possible mechanisms.Methods An ICD model was developed in 180 seven-week-old BALB/c mice by applying sodium dodecyl sulfate (SDS,10％ in distilled water) on shaved backs,and the mice were then equally divided into 5 groups to remain untreated (model control),be treated with 100％,75％,50％ Qingpeng ointment and vehicle of the ointment (vehicle control),respectively,for 11 days.Thirty-six mice receiving no irritation or treatment served as the blank control.At day 8 and 12 after the beginning of treatment,drill biopsy specimens were gained from induced lesions of these mice and subjected to the measurement of skin thickness and weight,observation of histopathological changes with hematoxylin and eosin staining,and calculation of inflammatory cells infiltrating the dermis; blood samples were also obtained,and enzyme linked immunosorbent assay (ELISA) was performed to quantify the expression level of interleukin (IL)-2,tumor necrosis factor (TNF)-α and interferon (IFN)-γ in sera and homogenates of skin lesions.Results Compared with the model control and vehicle control mice,those treated with 100％ Qingpeng ointment showed an attenuated inflammation and swelling,together with a decreased neutrophil skin infiltration.At day 12,the levels of IL-2,TNF-α and IFN-γ were significantly lower in the sera ( (5.55 ± 0.33) vs.(6.41 ± 0.96) and (6.25 ± 0.92) pg/ml,(70.88 ± 1.55 )vs.(76.67 ± 1.14) and (76.95 ± 1.08) pg/ml,(76.99 ± 1.85) vs.(82.20 ± 2.36) and (81.76 ± 3.19) pg/ml,respectively,all P ＜ 0.05) and homogenates of skin lesions ((17.75 ± 0.97) vs.(23.92 ± 0.82) and (23.11 ± 0.82) pg/ml,(66.95 ± 3.58) vs.(70.66 ± 2.68) and (71.17 ± 3.30) pg/ml,(46.85 ± 2.43) vs.(55.14 ± 2.68) and (53.55 ± 3.24) pg/ml.all P ＜ 0.05) in mice treated with 100％ Qingpeng ointment than those in the model control and vehicle control groups.Conclusion The 100％ Qingpeng ointment can suppress the inflammatory response in experimental ICD in mice,with a decrease in the level of IL-2,TNF-α and IFN-γ in sera and skin lesions.
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ObjectiveTo observe the healing effect of deep partial thickness burns by the injecting of breviscapine and discuss the possible mechanisms. Methods A rat model of deep partial thickness burns was designed,and was injected with breviscapine.The control group was injected with normal saline.The healing time of burn wound of the two groups was recorded,respectively.Seven days later,the tissues of bum wound of each group were extracted and the contents of hydroxyproline,collagenase-1,nitrogen monoxidum,erythrocuprein,and malonaldehyde that were contained in each extracts were measured.The results of each group were statistically analyzed.ResultsThe healing time of burn wound of the experimental group was [ ( 12 ± 1.428 ) days ],which was significantly shorter than the control group [ ( 14.75 ±1.291 )days] ( P ＜0.05).The contents of hydroxyproline[ (3.17 ± 1.136) mg/g],collagenase-1 [ ( 1.28± 0.651 ) mg/g ],nitrogen monoxidum [ ( 2.62 ± 0.30 ) μmol/gprot ],and erythrocuprein [ ( 221.25 ±25.94) U/mgprot ] in the experimental group were all higher than the control group [ (7.32 ± 2.173 )mg/g,(5.38 ±0.363) mg/g,(7.28 ± 0.40) μmol/gprot,(296.36 ± 29.29) U/mgprot ] ( P ＜ 0.05 or P ＜0.01 ).However,the content of malonaldehyde [ (6.36 ± 0.93 ) nmol/mgprot ] was lower than the control group [ ( 1.25 ± 0.59) nmoL/mgprot ] ( P ＜ 0.05 ).ConclusionsThe breviscapine injection can decurtate the healing time of deep partial thickness bums and it may be related to the extension of blood vessel,improvement of microcirculation,elimination of oxygen free radical,and degradation of lipid peroxidation.
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Objective To investigate the influence of m4-1BBL on the anti-tumor effects induced by truncated human prostate specific membrane antigen (tPSMA) gene in mice. Methods A eukaryotic expression plasmid encoding tPSMA and m4-1BBL (pDC316-tPSMA-IRES-m4-1BBL), pDC316-tPSMA and pDC316 were constructed. C57BL/6 mice were vaccinated in the quadriceps femoris, respectively. The CTL activity of spleen cells from the immunized mice against prostate cancer RM-1-tPSMA was detected by CCK-8 kit in vitro. The tumor growth was then observed. Results The target cell specific cytotoxicity rate induced by pDC316-tPSMA-IRES-m4-1BBL was 42.6%, compared to 24.8% in the pDC316-tPSMA group and 10.8% in the pDC316 group. The difference was significant (P<0.05). The volume of tumor in the pDC316 group was 2657.4mm3 7 d after vaccination, compared to 1334.5 mm3 in the pDC316-tPSMA group, 9 d after vaccination. In the pDC316-tPSMA-IRES-m4-1BBL group, the tumor volume was 445.8 mm3, 12d after vaccination. The difference was significant (P<0.05). Conclusion Gene vaccines co-expressing tPSMA gene and m4-1BBL gene could significantly enhance anti-prostate cancer effects in mice.
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Objective To evaluate pharmacodynamics of prepared long-circulating superparamagnetic iron oxide (SPIO) liposomes. Methods Control and experimental groups were established after adding SPIO or long-circulating SPIO liposomes as agents. (1)Macrophages experiment in vitro: the RAW 264.7 macrophage cell strains were recovered, cultured and seeded in the culture plate at a density of 2.5×105 cells/well until they reached 80%-90% confluence. The intracellular Fe uptake of control and experimental group cells were quantified by Ferrozine assay after incubation with different concentrations of drugs. Factorial design analysis of variance was used as statistics method. Prussian blue staining method was used to detect staining of experimental cells.(2)Drug biodistribution in mice: C57BL/6J(n=6) were classified into blank control group (n=2), control group(n=2) and experimental group(n=2).Saline, SPIO and long circulating SPIO were injected via the tail vein in the blank control group, control group and experimental group respectively. Then distribution of drugs in the body was observed by pathological examination.(3) MR imaging of tumor-bearing nude mice: 20 BALB/c nude mice bearing lung cancer models were established and classified into control group and experimental group. After administration of drugs, all animals underwent MR scanning. Signal intensities of livers and tumors were measured, SNR-time dynamic curves were drew. Covariance analysis was used to compare post-enhanced SNR at the 12th hour. (4)Cytotoxicity studies (MTT): cytotoxicity of both drugs on human liver cell line HL-7702 was studied, and statistically analyzed using factorial design analysis of variance. Results (1) Macrophages experiment in vitro: The nanoparticle uptake by macrophage cells evaluated by ferrozine assay showed the uptake of blank SPIO was higher than long-circulating SPIO liposomes. Compared with the blank control group, there was strong blue staining in the macrophages with Prussian staining in the control group and little blue staining in the experimental group. (2) Drug biodistribution in mice: for blue stained cells composed of iron particles, the amounts in the liver, spleen, lung, kidney of the control group were more than those in the experimental group. (3) MR imaging of tumor-bearing nude mice: the non-enhanced SNR of livers and tumors in the control group and experimental group were 31.47 ± 0.56, 30.89 ± 1.41, 58.41 ± 0.61, 58.44 ± 1.08, respectively. After injecting of contrast agents, SNR of livers and tumors in the control group and experimental group were 17.00 ± 0.96, 22.29 ± 0.73, 58.50 ± 0.63, 52.47 ± 1.18, respectively. The covariance analysis showed that SNR of the livers in the control group after 12 hours was significantly lower than the experimental group (F=167.022, P=0.000); while the SNR of the tumors in the experimental group was significantly lower than the control group (F=266.106, P=0.000).(4) Cytotoxicity of nanoparticles by MTT method: the viability of HL-7702 cells tend to decrease with the increase of Fe concentration. Cytotoxicity in the long-circulating SPIO liposomes was lower than the SPIO(F=2256.204,P=0.000). Conclusions Long-circulating SPIO liposomes we prepared reveal suitable sizes, even distribution, and good anti-macrophage ability in vitro and in vivo. They have long circulation characteristic and T2 negative enhancement effect in the transplanted lung cancers, while they still maintain low cytotoxicity.
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Objective To study the inhibitory effects of radiotherapy and 125I seed brachytherapy on the growth of transplanted human lung cancer cell line A549 in nude mice and the impact of HIF-1αexpression after therapy.Methods Forty nude mice bearing human lung cancer cell line A549 were randomly divided into control group,radiotherapy group,125I seed brachytherapy group and radiotherapy + 125I seed group when tumor volume achieved (300±50) mm3.The tumor growth was observed and the alteration of tumor size was calculated at different time.On 15th day,the expression of HIF-1α was detected by immunohistochemistry and western blot.Results When eighth day after treatment,compared with the control group,the tumor volume of the combined treatment group was significantly smaller (t = 46.4,P ＜0.05).After fifteenth day after treatment,compared with control group,the group of radiotherapy,125I seed brachytherapy and radiotherapy + 125I seed gained the tumor control rate of 45.9 %,44.4 %,69.4 % respectively.Compared with other groups,the change of expression of HIF-1α in the combined treatment group was not significant (P ＞0.05).Conclusion Radiotherapy combined with 125I seed brachytherapy can inhibit the growth of transplanted human lung cancer cell line A549 in nude mice,and the tumor regression can be observed in early stage.But in our study,the expression of HIF-1α in tumors cannot be inhibited by 125I seed.