AIM:To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS:The Long-Evans cinnamon (LEC) rat model of Wilson's disease (WD) was used to study the im...AIM:To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS:The Long-Evans cinnamon (LEC) rat model of Wilson's disease (WD) was used to study the impact of high dietary copper (hCu) on the induction of fulminant hepatitis at early or late time points of life. High Cu diet was started in rat pups or in adults (month 5) for three months. Animals that received reduced dietary copper (rCu) throughout their lifetime served as a control. Hepatitis-associated serum markers (alanine aminotransferase, aspartate transaminase, bilirubin) were analyzed in animal groups receiving hCu or rCu. Liver copper content and liver histology were revealed at sacrifice. A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis (Vegfa), fat metabolism (Srebf1), ex-tracellular matrix (Timp1), oxidative stress (Hmox1), and the cell cycle (Cdkn1a) were analyzed by real-time polymerase chain reaction. RESULTS:Regardless of the time point when hCu was started, LEC rats (35/36) developed fulminant hepatitis and died. Animals receiving rCu (36/36) remained healthy, did not develop hepatitis, and survived long term without symptoms of overt disease, although liver copper accumulated in adult animals (477 ± 75 μg/g). With regard to start of hCu, onset of fulminant hepatitis was significantly (P < 0.001) earlier in adults (35 ± 9 d) that showed pre-accumulation of liver copper as compared to the pup group (77 ± 15 d). Hepatitis-associated serum markers, liver copper and liver histology, as well as gene expression, were affected in LEC rats receiving hCu. However, except for early and rapid onset of hepatitis, biochemical and molecular markers were similar at the early and late time points of disease. CONCLUSION:Rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper suggests that there is a critical threshold of liver copper which is important to trigger the course of WD.展开更多
An Otsuka Long-Evans Tokushima Fatty(OLETF)rat provides a useful model for studies to develop corneal wound healing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus.We investigated the eff...An Otsuka Long-Evans Tokushima Fatty(OLETF)rat provides a useful model for studies to develop corneal wound healing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus.We investigated the effects of sericin on corneal wound healing in OLETF rats.Corneal wounds were prepared by removal of the corneal epithelium and documented using a TRC-50X.Sericin was instilled into the eyes of rats five times a day following corneal abrasion.The plasma levels of glucose,triglycerides,cholesterol and insulin in 38 wk old OLETF rats were significantly higher than in normal control rats(LETO rats),and the rate of corneal wound healing in OLETF rats was slower than in normal rat,probably due to the suppression of cell migration and proliferation caused by high plasma glucose levels.The corneal wounds of OLETF rats instilled with saline showed almost complete healing 72h after corneal epithelial abrasion.On the other hand,the instillation of sericin has a potent effect in promoting wound healing and wound size reduction in OLETF rats and the wounds showed almost complete healing at 48 h after abrasion.The sericin may be an effective and safe drug to promote corneal wound healing in diabetic keratopathy.展开更多
The neural mechanisms underlying visual information transmission and coding are currently attracting the attention of neuroscience and brain-like computing scholars.The subcortical visual pathway is known to affect fe...The neural mechanisms underlying visual information transmission and coding are currently attracting the attention of neuroscience and brain-like computing scholars.The subcortical visual pathway is known to affect fear emotion regulation via the amygdala;however an experimental paradigm for visual fear cognition training remains undefined.In this study,Long-Evans(LE)rats were used to develop an experimental training paradigm for visual cognition-associated fear conditioning based on the Pavlovian conditioning reflex.Simple images were shown on a unilateral screen(conditioned stimulus)were combined with electric foot shocks(unconditioned stimulus).We designed training paradigms and set up an estimated index using the rate of successful active escape.The training results were analyzed using a two-way ANOVA,and curve fitting was used to analyze the influence of decision time between the conditioned stimulus(CS)and unconditioned stimulus(US)on choice behavior.While neither the CS nor US had a significant effect on visual fear association training in LE rats,the decision time duration(CS-US)did have an impact on training.The method described here is most effective in establishing visual fear associations in rats when the(CS-UC)=10 s.This study describes a new experimental training paradigm for fear conditioning using visual stimuli and a quantitative evaluation standard according to the training mode of visual stimulation graphics.Moreover,it is an efficient paradigm for future study on visual information-processing mechanisms in the subcortical visual pathway during fear conditioning.展开更多
基金Supported by Deutsche Forschungsgemeinschaft, SCHM 964/10-1Innovative Medizinische Forschung, Münster
文摘AIM:To investigate the impact of dietary copper given at different time points on the onset of fulminant hepatitis. METHODS:The Long-Evans cinnamon (LEC) rat model of Wilson's disease (WD) was used to study the impact of high dietary copper (hCu) on the induction of fulminant hepatitis at early or late time points of life. High Cu diet was started in rat pups or in adults (month 5) for three months. Animals that received reduced dietary copper (rCu) throughout their lifetime served as a control. Hepatitis-associated serum markers (alanine aminotransferase, aspartate transaminase, bilirubin) were analyzed in animal groups receiving hCu or rCu. Liver copper content and liver histology were revealed at sacrifice. A set of 5 marker genes previously found to be affected in injured liver and which are related to angiogenesis (Vegfa), fat metabolism (Srebf1), ex-tracellular matrix (Timp1), oxidative stress (Hmox1), and the cell cycle (Cdkn1a) were analyzed by real-time polymerase chain reaction. RESULTS:Regardless of the time point when hCu was started, LEC rats (35/36) developed fulminant hepatitis and died. Animals receiving rCu (36/36) remained healthy, did not develop hepatitis, and survived long term without symptoms of overt disease, although liver copper accumulated in adult animals (477 ± 75 μg/g). With regard to start of hCu, onset of fulminant hepatitis was significantly (P < 0.001) earlier in adults (35 ± 9 d) that showed pre-accumulation of liver copper as compared to the pup group (77 ± 15 d). Hepatitis-associated serum markers, liver copper and liver histology, as well as gene expression, were affected in LEC rats receiving hCu. However, except for early and rapid onset of hepatitis, biochemical and molecular markers were similar at the early and late time points of disease. CONCLUSION:Rapid onset of fulminant hepatitis in asymptomatic LEC rats with elevated liver copper suggests that there is a critical threshold of liver copper which is important to trigger the course of WD.
文摘An Otsuka Long-Evans Tokushima Fatty(OLETF)rat provides a useful model for studies to develop corneal wound healing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus.We investigated the effects of sericin on corneal wound healing in OLETF rats.Corneal wounds were prepared by removal of the corneal epithelium and documented using a TRC-50X.Sericin was instilled into the eyes of rats five times a day following corneal abrasion.The plasma levels of glucose,triglycerides,cholesterol and insulin in 38 wk old OLETF rats were significantly higher than in normal control rats(LETO rats),and the rate of corneal wound healing in OLETF rats was slower than in normal rat,probably due to the suppression of cell migration and proliferation caused by high plasma glucose levels.The corneal wounds of OLETF rats instilled with saline showed almost complete healing 72h after corneal epithelial abrasion.On the other hand,the instillation of sericin has a potent effect in promoting wound healing and wound size reduction in OLETF rats and the wounds showed almost complete healing at 48 h after abrasion.The sericin may be an effective and safe drug to promote corneal wound healing in diabetic keratopathy.
基金Science and Technology Research Project of Henan Province(162102310167)A Key Science and Technology Program(17A120004)from the Education Department of Henan Province+1 种基金Open Foundation of Henan Key Laboratory of Brain Science and Brain-Computer Interface Technology(No.HNBBL17006)National Natural Science Foundation of China(61673353)
文摘The neural mechanisms underlying visual information transmission and coding are currently attracting the attention of neuroscience and brain-like computing scholars.The subcortical visual pathway is known to affect fear emotion regulation via the amygdala;however an experimental paradigm for visual fear cognition training remains undefined.In this study,Long-Evans(LE)rats were used to develop an experimental training paradigm for visual cognition-associated fear conditioning based on the Pavlovian conditioning reflex.Simple images were shown on a unilateral screen(conditioned stimulus)were combined with electric foot shocks(unconditioned stimulus).We designed training paradigms and set up an estimated index using the rate of successful active escape.The training results were analyzed using a two-way ANOVA,and curve fitting was used to analyze the influence of decision time between the conditioned stimulus(CS)and unconditioned stimulus(US)on choice behavior.While neither the CS nor US had a significant effect on visual fear association training in LE rats,the decision time duration(CS-US)did have an impact on training.The method described here is most effective in establishing visual fear associations in rats when the(CS-UC)=10 s.This study describes a new experimental training paradigm for fear conditioning using visual stimuli and a quantitative evaluation standard according to the training mode of visual stimulation graphics.Moreover,it is an efficient paradigm for future study on visual information-processing mechanisms in the subcortical visual pathway during fear conditioning.
