RESUMEN
Allergic asthma is characterized by intermittent airway obstruction, inflammation, airway hyperreactivity, and increased production of IgE. The pathophysiology of asthma is well understood but little is known about its influences on brain activity and behavior. We recently described the neural correlates of food allergy and its associated modulation of behavior using an experimental model that also generates a T helper type 2 (Th2)-skewed response, with high levels of IgE. Here we show that mice allergic to ovalbumin (OVA) have an increase in the activity of the paraventricular nucleus of the hypothalamus (PVN) and in the central nucleus of the amygdala (CeA) following a single nasal OVA challenge. Moreover, we adapted a classical passive avoidance test using an OVA aerosol as the aversive stimulus. We found that allergic mice avoid entering the dark compartment of the apparatus that had been previously associated with nebulization of the allergen, while their non-immunized controls still move into the dark side of the test box. Thus, allergic mice have increased activity in areas of the CNS commonly associated with emotionality-related behavioral responses, such as the avoidance of a context previously associated with an unpleasant or harmful situation. Moreover, our findings on the avoidance test illustrate that previous experience with an airborne allergen can modify behavior.
Asunto(s)
Amígdala del Cerebelo/fisiología , Aprendizaje por Asociación/fisiología , Asma/fisiopatología , Reacción de Prevención/fisiología , Núcleo Hipotalámico Paraventricular/fisiología , Administración por Inhalación , Alérgenos/administración & dosificación , Alérgenos/inmunología , Animales , Asma/inmunología , Condicionamiento Clásico/fisiología , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/administración & dosificación , Ovalbúmina/inmunologíaRESUMEN
High doses of diazepam (10-20 mg/kg) were shown to reduce the volume of acute carrageenan-induced inflammatory paw edema in rats. This effect was not observed after adrenalectomy or long-term use of similar doses of diazepam. The present experiment was undertaken to analyze the effects of long-term (21 daily injections) treatment with diazepam (10 mg/kg) on both carrageenan-induced paw edema (CIPE) and corticosterone serum levels. For comparison, the effects of a single and acute 10 mg/kg dose of diazepam were also analyzed. Results showed that: 1- long-term diazepam treatment induced no changes in CIPE values and corticosterone serum levels; 2- acute diazepam treatment reduced CIPE values and increased corticosterone serum levels; 3- the plasmatic levels of diazepam measured 1 hour after the single treatment or 1 hour after the last dose of long-term diazepam administration were not different. These results indicate the development of tolerance to diazepam effects on both CIPE and corticosterone serum levels and suggest a relevant role for corticosterone on diazepam-induced inhibition of acute inflammation. Data were discussed in the light of peripheral benzodiazepine receptor site (PBR) activation within adrenal gland cells by diazepam, thereby increasing the serum levels of corticosterone and thus reducing CIPE. Possible actions of diazepam on HPA axis activity and/or on cytokine network were also discussed.
Asunto(s)
Antiinflamatorios/uso terapéutico , Diazepam/uso terapéutico , Tolerancia a Medicamentos/fisiología , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/sangre , Carragenina/farmacología , Corticosterona/sangre , Diazepam/administración & dosificación , Diazepam/sangre , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Edema/sangre , Edema/tratamiento farmacológico , Edema/patología , Miembro Posterior/efectos de los fármacos , Inyecciones Intraperitoneales , Masculino , Ratas , Organismos Libres de Patógenos EspecíficosRESUMEN
Angiogenesis is a key mechanism that influences several physiological and pathological processes, including wound healing. During the past decades, many groups have shown that controlling angiogenesis might be an answer to overcome pathological situations when this process is out of control. Many altered metabolic states exert considerable influence on the development of angiogenesis. We have chosen diabetes as a model of a progressive metabolic disease with many associated conditions, including an alteration of wound healing dynamics described elsewhere. To evaluate the growth of newly formed blood vessels during diabetes, we induced corneal angiogenesis through silver nitrate cauterization in streptozotocin-induced diabetic rats, always comparing to control non-diabetic or insulin-treated diabetic rats. Computer-aided analysis showed that both the percentage of area taken by vessels on the cornea and their average length were decreased in diabetic animals; furthermore, this diminishment was prevented by insulin treatment in previously diabetic rats. Immunohistochemical staining of neutrophils and macrophages (EDI clone) did not show any differences on number of migrating cells in the cornea. Immunolocalization of vascular endothelial growth factor and basic fibroblast growth factor did not differ considerably among groups either. These results support previous findings that angiogenesis is decreased due to the development of diabetes mellitus but contrasts to descriptions from other investigators in regard to the inflammatory infiltrate and production of growth factors. In our experimental conditions, the cause of the decreased angiogenesis in diabetic rats remains for further elucidation.
Asunto(s)
Córnea/irrigación sanguínea , Diabetes Mellitus Experimental/metabolismo , Factores de Crecimiento Endotelial/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Linfocinas/metabolismo , Neovascularización Patológica/metabolismo , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/farmacología , Inmunohistoquímica , Inflamación/metabolismo , Insulina/farmacología , Masculino , Ratas , Ratas Sprague-Dawley , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
A angiogênese participa de inúmeros processos fisiológicos e patológicos. Vários modelos experimentais säo encontrados na literatura mostrando a importância de seu estudo. Estabelecemos um modelo de angiogênese utilizando duas membranas biológicas -pericárdio e membrana amniótica eqüinas conservadas em glicerina, implantadas em microbolsa em córnea de 63 ratos. Implantou-se pericárdio na córnea direita e membrana amniótica na córnea esquerda, de tal forma que pudemos analisar os resultados em um mesmo animal. As córneas dos animais foram submetidos à análise histológica aos 1, 3, 7, 15, 30 e 60 dias de pós-operatório. A angiogênese induzida pelo pericárdio xenólogo foi mais intensa e mais duradoura que a membrana amniótica xenóloga. Concluímos que ambas as membranas biológicas induziram angiogênese corneana após terem sido implantadas no interior do estroma em ratos, podendo ser utilizadas como modelo de angiogênese
Asunto(s)
Animales , Femenino , Adulto , Ratas , Córnea , Neovascularización de la CórneaRESUMEN
Dentre as alteraçöes hepáticas encontradas na rotina de necrópsias em medicina veterinária, as lesöes nodulares säo as menos caracterizadas. Estas incluem processos reacionais ou hiperplásicos, neoplásicos e hamartomas. Este estudo foi realizado com a finalidade de diferenciar os adenomas hepatocelulares (AH) das hiperplasias nodulares focais (HNF) do fígado em cäes. Dez casos de lesöes nodulares hepáticas em cäes foram levantados dos arquivos do Departamento de Patologia da Faculdade de Medicina Veterinária e Zootecnia da Universidade de Säo Paulo. Métodos histoquímicos e imunohistoquímicos foram aplicados a cada caso, com a finalidade de caracterizar as lesöes, de acordo com critérios histológicos definidos para as mesmas lesöes no homem. Dos resultados descritos foi possível diagnosticar oito casos de HNF e dois casos de AH. Conclui-se que estas técnicas podem ser facilmente utilizadas e que säo adequadas para os objetivos propostos