RESUMEN
Cardiovascular disease(CVD) remains the major cause of mortality in the world, typically claiming a third of all deaths. The primary cause of CVD is atherosclerosis. Therefore, timely prevention and therapy of atherosclerosis are able to reduce the risk of the development of its clinical manifestations. Anti-atherosclerotic activity of medicinal plants mainly appears in their multiple effects.This study was carried out to evaluate the hypolipidemic activity of virgin olive oil in experimentally induced hyperlipemic Wistar. A total of 24 rats were randomly allocated to 4 equal groups and treated as follows for 50 days: (1) Normal control (NC); that were fed with a standart diet; (2) High Cholesterol Diet Control (HCD); which received high cholesterol diet for 50 days; (3) Animals receiving high cholesterol diet for 50 days, after this period the animals are fed for eight days by the standard foodand receiving by gavage virgin olive oil (HCD+VOO) and(4) Animals fed for eight days with the standard food and receiving by gavage olive oil (VOO). High Cholesterol Diet containing yolk egg and coconut oil. Results showed that olive oil caused a significant (p < 0.01) reduction in serum levels of Total Cholesterol (TC), Triglycerides (TG), LowDensity Lipoprotein Cholesterol (LDL) and Atherogenic Index Serum (AIS). The results also demonstrated a significant (p < 0.01) increase in HighDensity Lipoprotein Cholesterol (HDL). Moreover, virgin olive oil induced a significant reduction in liver lipid content. On the other hand, a High cholesterol diet induced oxidative stress was measured by estimating reduced glutathione level and amount of thiobarbituric acid reactive substances (TBARS) formed as an index of lipid peroxidation in a liver and a heart. Virgin olive oil supplementation attenuated all these variations. Our observations of the study indicate that the virgin olive oil has a significant antihyperlipidemic potential.
Asunto(s)
Animales , Ratas , Estrés Oxidativo/inmunología , Aterosclerosis/dietoterapia , Dieta Alta en Grasa/métodos , Aceite de Oliva/farmacología , Triglicéridos/farmacología , Peroxidación de Lípido/inmunología , Colesterol/farmacología , Ratas Wistar/inmunología , Dieta Aterogénica/métodos , Glutatión/farmacología , Hipercolesterolemia/inmunología , Lipoproteínas/inmunologíaRESUMEN
BACKGROUND: Ischemic stroke causes brain inflammation, which we postulate may result in lung damage. Several studies have focused on stroke-induced immunosuppression and lung infection; however, the possibility that strokes may trigger lung inflammation has been overlooked. We hypothesized that even focal ischemic stroke might induce acute systemic and pulmonary inflammation, thus altering respiratory parameters, lung tissue integrity, and alveolar macrophage behavior. METHODS: Forty-eight Wistar rats were randomly assigned to ischemic stroke (Stroke) or sham surgery (Sham). Lung function, histology, and inflammation in the lung, brain, bronchoalveolar lavage fluid (BALF), and circulating plasma were evaluated at 24 h. In vitro, alveolar macrophages from naïve rats (unstimulated) were exposed to serum or BALF from Sham or Stroke animals to elucidate possible mechanisms underlying alterations in alveolar macrophage phagocytic capability. Alveolar macrophages and epithelial and endothelial cells of Sham and Stroke animals were also isolated for evaluation of mRNA expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. RESULTS: Twenty-four hours following ischemic stroke, the tidal volume, expiratory time, and mean inspiratory flow were increased. Compared to Sham animals, the respiratory rate and duty cycle during spontaneous breathing were reduced, but this did not affect lung mechanics during mechanical ventilation. Lungs from Stroke animals showed clear evidence of increased diffuse alveolar damage, pulmonary edema, and inflammation markers. This was associated with an increase in ultrastructural damage, as evidenced by injury to type 2 pneumocytes and endothelial cells, cellular infiltration, and enlarged basement membrane thickness. Protein levels of proinflammatory mediators were documented in the lung, brain, and plasma (TNF-α and IL-6) and in BALF (TNF-α). The phagocytic ability of macrophages was significantly reduced. Unstimulated macrophages isolated from naïve rats only upregulated expression of TNF-α and IL-6 following exposure to serum from Stroke rats. Exposure to BALF from Stroke or Sham animals did not change alveolar macrophage behavior, or gene expression of TNF-α and IL-6. IL-6 expression was increased in macrophages and endothelial cells from Stroke animals. CONCLUSIONS: In rats, focal ischemic stroke is associated with brain-lung crosstalk, leading to increased pulmonary damage and inflammation, as well as reduced alveolar macrophage phagocytic capability, which seems to be promoted by systemic inflammation.
Asunto(s)
Lesión Pulmonar/etiología , Macrófagos Alveolares/patología , Fagocitos/patología , Accidente Cerebrovascular/complicaciones , Animales , Isquemia Encefálica/complicaciones , Isquemia Encefálica/fisiopatología , Modelos Animales de Enfermedad , Terapia de Inmunosupresión/efectos adversos , Interleucina-6/análisis , Interleucina-6/sangre , Lesión Pulmonar/sangre , Lesión Pulmonar/patología , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/veterinaria , ARN Mensajero/análisis , ARN Mensajero/sangre , Ratas , Ratas Wistar/inmunología , Ratas Wistar/metabolismo , Estadísticas no Paramétricas , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/fisiopatología , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/sangreRESUMEN
O objetivo desta pesquisa foi avaliar qualitativa e quantitativamente, através de técnicas histológicas e histoquímicas, o córtex cerebral de ratos submetidos a uma subnutrição protéica e posterior recuperação precoce e tardia. Foram utilizados ratos Wistar submetidos às seguintes dietas nutricionais: dieta padrão - normoprotéica - /"AIN-93G/", contendo 20% de proteína (caseína) e dieta hipoprotéica - /"AIN-93G/", contendo 5% desta mesma proteína, durante os períodos experimentais de 42 e 60 dias. [...] Os grupos renutridos, independentemente se precoce (Rp42) ou tardio (Rt60) conseguem alguma recuperação em alguns parâmetros avaliados como peso encefálico, dimensões encefálicas e espessura cortical; porém outros como o peso corporal, e a área neuronal foram gravemente afetados. Todavia quando se observa a razão peso encefálico/peso corporal, os animais dos grupos subnutridos relativamente aos animais controles nutridos, apesar do peso corporal menor apresentam uma razão maior do que os respectivos controles, sugerindo ser o encéfalo menos afetado pela subnutrição do que o peso corporal. A subnutrição promoveu acentuada diminuição na área dos neurônios corticais e nitrérgicos, não recuperada com a renutrição, independentemente se precoce ou tardia. Portanto, conforme o proposto e com a metodologia utilizada no presente estudo pesquisa, os resultados permitem concluir que frente às condições de subnutrição, o organismo pode sofrer alterações irreparáveis dependendo do momento da vida em que ocorre, e que a renutrição pode promover recuperação ou mesmo adaptações em alguns parâmetros, preferencialmente se ocorrer em fases mais precoces
The objective of this study was to evaluate qualitative and quantitatively, through histological and histochemical techniques, the cerebral cortex of rats subjected to protein undernutrition subsequent to early and late recovery. Were used Wistar rats fed with standard (normal) diet-/"AIN-93G/" containing 20% of protein (casein), and hypoproteic diet- /"AIN-93G/" containing 5% of casein during experimental periods of 42 and 60 days. [...] Were observed that re-nourished groups either early (Rp42) or late (Rt60) have recovered in some parameters evaluated such as brain weight, brain measures and cortical thickness; however other parameters like body mass, and neuronal area was highly affected. Relatively to the proportion brain weight/body mass, animals from undernourished group although exhibit low body mass, shown higher proportion than respective control nourished, thus suggesting that brain is less affected by undernutrition than body mass. The undernutrition promoted great decreasing of cortical and nitrergic neurons area; the area was not recovered by early and/or late re-nourishment. In the view of the objectives and methodology used in the present study, we can be conclude that in under-nutrition conditions the body can go through irreversible changes depending on period of occurrence; additionally, re-nourishment can promote recovery or adaptations in some parameters preferentially if occur in early phases
Asunto(s)
Animales , Ratas , Corteza Cerebral/fisiopatología , Desnutrición/veterinaria , Fenómenos Fisiológicos Nutricionales de los Animales/fisiología , Ratas Wistar/inmunología , Neuronas NitrérgicasRESUMEN
O fipronil, um inseticida e acaricida de amplo espectro de ação, atua como bloqueador dos canais de cloreto acoplados aos receptores GABA (GABA-Cls) e aos receptores glutamatérgicos (GluCls), estes últimos são alvo inseto-específico não presente nos vertebrados. O fipronil é utilizado na agricultura, medicina veterinária e saúde publica no combate a vetores de doenças. Comercialmente conhecido pelas marcas Frontline® (uso veterinário) e Regent 800 WG® (uso agrícola), esse inseticida, além de atuar sobre sistema nervoso central, atua, ainda, em organismos não-alvo como desregulador endócrino, podendo causar prejuízos nos sistemas reprodutor, nervoso e imunológico, por gerações. Assim, o presente estudo buscou investigar os efeitos da exposição pré-natal ao fipronil na geração F1 de ratas Wistar. Quarenta ratas virgens, Wistar, adultas (a partir de 90 dias de vida), foram acasaladas e separadas em quatro grupos: três experimentais, que receberam: 0,1, 1,0 e 10,0 mg/Kg de peso de fipronil; e o grupo controle, que recebeu água (1 mL/Kg de peso), via gavagem, do 6º ao 20º dia de gestação (n = 10 animais por grupo). O estudo foi então dividido em três partes: 1) estudos sobre a toxicidade materna e o comportamento maternal dessas ratas no 5º dia pós-nascimento (DPN5); 2) avaliação do desenvolvimento físico e reflexológico da geração F1, desde o dia de seu nascimento (DPN0) até o DPN35; e 3) avaliações comportamentais e de necropsia dos filhotes na idade adulta. O tratamento pré-natal com fipronil causou leve toxicidade materna na maior dose, apenas na segunda semana de gestação, caracterizada pela redução do consumo de ração (p<0,01), porém, essa redução não causou prejuízos no desempenho reprodutivo dessas ratas quando comparadas ao grupo controle. Além disso, o tratamento do fipronil mostrou leve melhoria do comportamento maternal, onde as ratas que receberam as doses de 1,0 e 10,0 mg/Kg apresentaram aumento do tempo de lambedura em seus filhotes (p<0,05), enquanto a maior dose agrupou toda a ninhada mais rapidamente (p<0,05) quando comparadas ao grupo controle. Na infância, não foram observadas alterações significantes nos parâmetros do desenvolvimento físicos da prole, porém os filhotes que estiveram expostos à menor dose durante o período gestacional, apresentaram retardo para o desenvolvimento do reflexo de geotaxia negativa, tanto machos (p<0,01), quanto fêmeas (p<0,05). A análise do desenvolvimento motor desses filhotes, constatou alterações nos perfis da atividade geral em campo aberto, observados por sete dias consecutivos, nos grupos de 0,1 e 1,0 mg/Kg, tanto na prole feminina, quanto na prole masculina. Na idade adulta, as proles de ratas tratadas com fipronil, tanto masculina, quanto feminina, apresentaram alterações comportamentais, indicando aumento de ansiedade e alterações no tempo de interação social.
Fipronil, a broad spectrum action insecticide and acaricide, acts blocking GABA-regulated chloride channels and Glutamate-gated chloride channels, which is a specific insect target not present on vertebrates. It is used in crops, veterinarian medicine and public health against disease vectors. Commercially known as Frontline® (vet) and Regent 800 WG® (crops), it acts on the central nervous system and on non-target organisms as an endocrine disruptor causing impairment on reproductive, nervous and immunological system, through generations. Thus, this study investigated effects of prenatal exposition to fipronil in Wistar rats offspring. Forty adult Wistar rats (90 days old) were matted and separated into four groups: three experimental, that received 0.1, 1.0, and 10.0 mg/Kg (bw) of fipronil; and the control group, that received water (1 mL/Kg bw), through gavage from the 6th to 20th pregnancy day (n=10 animals per group). The study was divided into three sections: 1) maternal toxicity and maternal behavior evaluations; 2) physical end reflexological development of F1 generation, since day of birth until the 35th day of life; and 3) behavior and necropsy evaluation of the adult offspring. The fipronil prenatal treatment caused slight maternal toxicity in the highest dose on the second pregnancy week, by the reduction of food intake (p<0,01), although, these reduction did not caused reproductive performance impairment, compared to the control group. Furthermore, the fipronil treatment showed slight increase of maternal behavior in rats treated with 1.0 and 10.0 mg/Kg. Both groups showed increased pup-grooming time (p<0,05), and the highest dose, grouped theirs pups earlier than the control group (p<0,05). No alterations were observed in the offspring physical development, however, the lowest dose exposed offspring showed delay on geotaxis reflex development, in both male (p<0,01) and female offspring (p<0,05). The motor development assessment, of the 0.1 and 1.0 mg/Kg dose offspring, showed variation on motor activity profile on the open field arena, observed for seven consecutive days. In the adulthood, the treated offspring, male and female, showed behavior changes denoting anxiety increase and social behavior alterations. Furthermore, in the lower dose, male offspring showed decrease on sexual motivation without interfering on copulatory efficiency and the female offspring showed estrus cycle deregulation without interfering on lordosis performance. Despite behavior alterations, there were no anatomic alterations in these animals/' organs. Therefore, these results suggest that the prenatal exposition to fipronil caused alterations on F1 generation, being proposed involvement of the endocrine system controlled by GABAeregciystem
Asunto(s)
Femenino , Animales , Embarazo , Cobayas , Insecticidas/efectos adversos , Insecticidas/toxicidad , Ratas Wistar/inmunologíaRESUMEN
This study evaluated antibody production against sheep red blood cells (SRBC) in hyperthyroid rats during treatment with triiodothyronine (T(3)). The immune response was evaluated by measuring plaque forming cells (PFC) in the spleen and by enzyme-linked immunosorbent assay (ELISA) in serum of male Wistar rats (180+/-10 g) treated with 25 mug/day of triiodotironine (T(3)) during 7-12 days and immunized with SRBC at the 8th day of treatment. The results showed that anti-SRBC antibody production was significantly decreased in animals treated for 12 days when compared to normal rats immunized with the same antigen, as evaluated by the two assays. These results show that in this experimental model hyperthyroidism decreases antibody response. We previously observed the opposite effect, that is, an increase in this response in hypothyroid rats resulting from the treatment with propylthyouracil, a blocker of thyroid hormone biosynthesis. It is suggested that antibody production is affected by thyroid hormone levels.
Asunto(s)
Formación de Anticuerpos/inmunología , Hipertiroidismo/inmunología , Animales , Células Productoras de Anticuerpos/inmunología , Antitiroideos/farmacología , Regulación hacia Abajo/inmunología , Ensayo de Inmunoadsorción Enzimática , Eritrocitos/inmunología , Técnica de Placa Hemolítica , Hipertiroidismo/inducido químicamente , Inmunoglobulina M/biosíntesis , Inmunoglobulina M/sangre , Inyecciones Intraperitoneales , Masculino , Propiltiouracilo/farmacología , Ratas , Ratas Wistar/inmunología , Oveja Doméstica/sangre , Tirotropina/sangre , TriyodotironinaRESUMEN
PURPOSE: To evaluate and compare neutrophils sequestration in the renal cortex of rats, result of total hepatic ischemia and reperfusion after controlled hemorrhagic shock, with use of different electrolytic solutions. METHODS: Used 18 rats Wistar, males, adult, divided into three groups as the solution used to reanimation: Group PSS: physiologic saline solution; Group HSS: hypertonic saline hypertonic (7,5%) followed by lactated ringer's solution; Group LRS: lactated ringer's solution. All the animals were submitted to the bleeding controlled until mean arterial pressure (MAP) 40 mmHg, for 20 minutes. Performed volemic replacement until PAM=80 mmHg with the solution according the studied group, followed by laparotomy and Pringle's Maneuver for 15 minutes. The animals were accompanied until for two hours. To statistical comparisons between mean of neutrophils sequestration, in interstitium of the renal cortex, were made the tests One-way ANOVA and covariance analysis, adjusting itself for time of supervened. The hemodynamic parameters evaluated were: MAP, heat rate, cardiac index, vascular resistance system index. The analyzed metabolic variables were: pH, bicarbonate, base deficit and lactato, besides electrolytes. RESULTS: The mean values of supervened, in minutes, for group were: Group PSS 79,0+ or -12,0; Group LRS 97,0+ or -11,0; Group HSS 67,0+ or -10. The mean values of neutrophils/field in the renal cortex were: Group PSS 0,55+ or -0,68; Group LRS 1,68+ or -0,53; Group HSS 1,33+ or -0,43. When adjusted for time of supervened: Group PSS 0,55; Group LRS 1,62; Group HSS 1,39. There was statistically significant difference in neutrophils sequestration, between Group PSS regarding the others groups, using itself or not the adjustment by time of supervened (p=0,016 and p=0,0128). CONCLUSION: Both critical situations in this model, controlled hemorrhagic shock followed by Pringle's maneuver, promoted neutrophils sequestration in the interstitium renal of rat...(AU)
OBJETIVO: Avaliar e comparar o seqüestro de neutrófilos no rim de rato, como efeito da isquemia e reperfusão hepática total após estado de choque hemorrágico controlado, com uso de diferentes soluções eletrolíticas. MÉTODOS: Utilizou-se 18 ratos Wistar, machos, adultos, divididos em três grupos conforme a solução utilizada para reanimação: Grupo SF: solução fisiológica; Grupo SH: solução hipertônica de NaCl a 7,5% seguido pela solução de ringer com lactato; Grupo RL: solução de ringer com lactato. Todos os animais foram submetidos à sangria controlada até pressão arterial média (PAM) atingir 40 mmHg, permanecendo por 20 minutos. Realizou-se reanimação volêmica até PAM=80 mmHg com a solução conforme o grupo estudado. Em seguida realizou-se uma laparotomia e a manobra de Pringle por 15 minutos. Os animais foram acompanhados até duas horas. Para comparações estatísticas entre as contagens de neutrófilos, no interstício do córtex renal, foram efetuados os testes ANOVA e a análise de covariância, ajustando-se para o tempo de sobrevida. Os parâmetros hemodinâmicos avaliados foram: PAM, freqüência cardíaca, índice cardíaco, índice de resistência vascular sistêmica. As variáveis metabólicas analisadas foram: pH, bicarbonato, reserva de base e lactato, além de eletrólitos. RESULTADOS: Os valores médios de tempo de sobrevida, em minutos, por grupo foram: Grupo SF 79,0+ ou -12,0; Grupo RL 97,0+ ou -11,0; Grupo SH 67,0+ ou -10. Os valores médios da contagem de neutrófilos/campo no córtex renal foram: Grupo SF 0,55+ ou -0,68; Grupo RL 1,68+ ou -0,53; Grupo SH 1,33+ ou -0,43. E quando são ajustados para o tempo de sobrevida encontram-se: Grupo SF 0,55; Grupo RL 1,62; Grupo SH 1,39. Houve diferença estatisticamente significativa, na contagem de neutrófilo entre o Grupo SF com os demais, usando-se ou não o ajuste pelo tempo de sobrevida (p=0,016 e p=0,0128).CONCLUSÃO: As duas situações críticas, choque hemorrágico controlado e manobra de Pringle, promoveram seqüestro de...(AU)
Asunto(s)
Animales , Masculino , Ratas , Isquemia , Reperfusión , Choque Hemorrágico/complicaciones , Choque Hemorrágico/fisiopatología , Neutrófilos , Riñón/irrigación sanguínea , Riñón/patología , Hígado/patología , Corteza Renal/inmunología , Corteza Renal/fisiopatología , Hipovolemia , Ratas Wistar/inmunologíaRESUMEN
An overall 44% transplacental transmission rate was observed in 221 rats fed cysts of 12 Toxoplasma strains at 15 days of pregnancy, with a range of 0-90% transmission. Considerable variability in the transmission rate was seen among different groups of rats that received similar Toxoplasma inocula; this is attributed to genetically based susceptibility to Toxoplasma among individuals of the outbred Wistar strain of rats. Transplacental transmission was more frequent in Long Evans than in Wistar rats. Significant differences in the rate of transmission were not found between rats that were fed similar Toxoplasma inocula 6-8 days or 15 days after conception. The frequency of transmission was not affected by the strain or dose of Toxoplasma used.
Asunto(s)
Enfermedades de los Roedores/congénito , Enfermedades de los Roedores/transmisión , Toxoplasma/fisiología , Toxoplasmosis Animal/congénito , Toxoplasmosis Animal/transmisión , Animales , Animales no Consanguíneos , Anticuerpos Antiprotozoarios/análisis , Modelos Animales de Enfermedad , Femenino , Edad Gestacional , Transmisión Vertical de Enfermedad Infecciosa , Embarazo , Ratas , Ratas Long-Evans/inmunología , Ratas Long-Evans/parasitología , Ratas Wistar/inmunología , Ratas Wistar/parasitología , Enfermedades de los Roedores/inmunología , Especificidad de la Especie , Toxoplasma/clasificación , Toxoplasma/inmunología , Toxoplasmosis Animal/inmunologíaRESUMEN
Se utilizaron un total de 22 ratas (cepa Wistar) de las cuales 2 animales fueron testigo y 20 ratas fueron inoculadas con 1 ml del paramixovirus del ojo azul (POA) con un título de 10 5.55 DICC/ml, por vía intramuscular. El día 0 se tomaron muestras sangúineas por vía intracardiaca de 2 animales testigos, los cuales se sacrificaron posteriormente. Los días 1, 3, 5, 7, 10, 15, 20, 25, 30, 35 posinoculación (PI) se tomaron muestras de sangre para la detección serológica de anticuerpos contra POA, utilizando la técnica de inhibición de la hemaglutinación (IHA), seroneutralización (SN), para realizar biometrías hemáticas (BH) y la obtención de la capa flogística para aislamiento viral. Además se obtuvieron muestras de órganos (encéfalo, pulmón y tonsila) para intentar el aislamiento en tres líneas celulares (MDBK, PK-15, BT) e inmunofluorescencia en cultivo celular (IFCC); de estas mismas muestras se hicieron estudios histopatológicos (HP). Se recolectaron heces y orina durante los 35 días, para el aislamiento e IFCC. En los resultados de las pruebas serológicas se detectaron anticuerpos a partir del décimo día PI, con títulos de 1:4 hasta 1:256 para SN y de 1:8 hasta 1:64 para IHA. En el aislamiento viral de órganos, capas flogísticas, heces y orina se pudo aislar el virus durante todo el periodo de experimentación en las tres líneas celulares, coincidiendo estos resultados con las IFCC; las BH mostraron variación en los valores de neutrófilos, linfocitos y monocitos. No hubo presencia de lesiones significativas tanto macro como microscópicas
Asunto(s)
Ratas , Animales , Masculino , Infecciones por Respirovirus/inducido químicamente , Infecciones por Respirovirus/veterinaria , Células Cultivadas/citología , Ratas Wistar/inmunología , Respirovirus/patogenicidad , Técnica del Anticuerpo Fluorescente/veterinaria , Pruebas de Inhibición de Hemaglutinación/veterinariaRESUMEN
Los glucocorticoides tópicos se usan en diversas enfermedades inflamatorias dermatológicas, respiratorias, etc. Al igual que los glucocorticoides sistémicos pueden suprimir el eje hipotálamo-hipófisis-suprarrenal y producir efectos locales adversos. Por su uso en afecciones crónicas interesa conocer si los glucocorticoides tópicos tienen influencia sobre el número de linfocitos periféricos, lo que repercutiría en el sistema inmune. Se estudió el efecto de dos formas de corticoide de acción porlongada, dipropionato de betametasona, sobre los linfocitos circulantes y algunos órgano como la glándula suprarrenal y piel, en 46 ratas Wistar, aplicándose corticoide tópico en el 25 por ciento de la superficie corporal 2 veces al día a un grupo y sistémico por vía intramuscular por una sola vez en distintas dosis a otros 3 grupos. Después de realizar recuento de linfocitos los días 0,3 y 21, se observaron diferencias estadísticamente significativas en el número de linfocitos al día 3, alteración que revirtió en el análisis del recuento del día 21. En relación al uso de glucocorticoides sistémicos se observaron variaciones características de linfopenia y neutrofilia, que fueron más intensas a mayor dosis empleada. En análisis histopatológico se ralizó en el grupo de ratas con glucocorticoide tópico y sistémico a dosis baja y en las controles. Hubo cambios histopatológicos sólo a nivel de la corteza suprarrenal de las ratas tratadas con glucocorticoide sistémico a dosis baja y a nivel de piel para las ratas sometidasa tratamiento tópico