大鼠C6脑胶质细胞移植瘤肿瘤模型动态生长核磁共振表现

目的: 建立大鼠C6脑胶质瘤模型。在不同时段以磁共振平扫、增强扫描、DWI和MRS多种技术对大鼠脑组织进行扫描成像分析, 动态观察接种后大鼠脑组织内胶质瘤的生长情况, 测量肿瘤体积变化, 细胞的凋亡情况以及肿瘤细胞密集区域, 无创性检测活体组织器官能量代谢、生化改变和特定化合物定量分析。建立大鼠C6脑胶质瘤模型MRI肿瘤动态生长数据库。方法: 建立大鼠C6脑胶质瘤模型。大鼠接种C6脑胶质瘤细胞的不同时段(接种前、接种后第7天、第14天、第21天)在活体无创状态下, 在不同时段分别运用MRI常规、增强扫描, DWI和MRS多种技术对大鼠脑组织进行扫描成像分析, 建立大鼠C6脑胶质瘤模型MRI肿瘤动态生长数据库, 最后将大鼠处死取脑组织进行肉眼、病理和电镜验证。结果: 肿瘤体积生长第14天与第7天均值比是5.010 0±0.450 0倍, 第21天与7天均值比是17.990 0±0.910 0倍, 解剖肉眼、病理、电镜均可见肿瘤及肿瘤细胞。正常脑组织DWI弥散成像ADC值测定, 平均值(B＝1 000)420.183 3±75.598 0)明显低于各时间肿瘤组, 接种肿瘤后7、14、21天ADC均值为738.598 0±219.568 0、660.645 0±105.322 0、551.366 7±103.578 0均高于正常脑组织, ADC均值T检验正常脑组织与7天及14天肿瘤组比, P值＜0.05, 有显著差异。 肿瘤生长的第14、21天ADC值不断的降低。大鼠C6脑胶质瘤移植瘤模型接种不同时间MRS测定cho/NAA均值, 正常脑在第1、7、14、21天在0.5左右, 而接种后的大鼠C6脑胶质瘤7、14、21天测定cho/NAA均值为5.532 0±4.066 4、6.560 0±3.440 0、8.938 0±4.079 4, 随着肿瘤的长大比值均值在不断加大。结论: 磁共振平扫、增强扫描、DWI和MRS多种技术对大鼠脑组织进行扫描成像分析, 能在无创情况下动态观察接种后大鼠脑组织内胶质瘤的生长情况, 测量肿瘤体积变化, 细胞的凋亡情况以及肿瘤细胞密集区域, 无创性检测活体组织器官能量代谢、生化改变和特定化合物定量分析。     

Investigation of the mechanisms of improved oral bioavailability of bergenin using bergenin–phospholipid complex

Aim: The purpose of this study was to investigate the detailed mechanisms of oral absorption enhancement of bergenin (BN) using BN–phospholipid complex (BPC).

Methods: Multiple models such as ex vivo everted rat gut sac model and in vitro Caco-2 cell model were used. Meanwhile, the effect of chitosan on the enhancement of the permeability of BPC was evaluated.

Results: The limited absorption of BN was significantly improved in both ex vivo everted rat gut sac model and in vitro Caco-2 cell model when combined with phospholipid. The transport of BPC was uppermost 5.19-fold higher than that of BN. The results of ex vivo everted rat gut sac model showed that small intestine was a more suitable site for the absorption of BN and BPC than colon. Passive diffusion was the only way employed in the transport of BN, while BPC could transport across enterocytes by both passive diffusion and active transport which was found to be the clathrine-dependent receptor-mediated endocytosis. The absorption of BN was barely improved by the physical mixture of BN and phospholipid due to lack of stable intermolecular interactions. Moreover, the addition of chitosan could open the tight junctions of intestinal epithelial cells, thus significantly increasing the transport of BPC via paracellular route.

Conclusions: Totally different mechanisms, which led to the enhanced oral bioavailability, were utilized in the uptake and transport process of BPC compared with BN. These results would be of significance for the future development of oral delivery systems of BN.     

Hypolipidemic Effect of Bamboo Shoot Oil (P. pubescens) in Sprague–Dawley Rats

Abstract: Atherosclerosis and its related complications are the leading causes of death in the West and in many developed countries. This study aims to investigate the hypolipidemic effect of bamboo shoot oil (BSO) in Sprague–Dawley rats. A group of rats had induced hyperlipidemia, hypercholesterolemia, and fatty liver by being fed with a high-fat, high-cholesterol diet for 4 wk. The control group was administered 10 mL distilled water per kg body weight, while the other groups were, respectively, administered 250 mg beta-sitosterol, 250 mg BSO, 500 mg BSO, and 1000 mg BSO per kg body weight by oral gavage. The results demonstrated that BSO could significantly decrease the levels of total cholesterol, triacylglycerol, low-density lipoprotein-cholesterol, phytosterol, lipoprotein lipase, hepatic lipase, and atherogenic index in serum, and increase the levels of cholesterol in feces. It could also significantly decrease the level of relative liver weight and liver lipids. The pronounced hypolipidemic effects of BSO might be attributed to its ability to inhibit cholesterol absorption and increase cholesterol excretion. These results suggest that consuming BSO may provide benefits in managing hypercholesterolemia. Therefore, BSO may be a good candidate for development as a functional food and nutraceutical.     

Increased liking for a solution is not necessary for the attenuation of neophobia in rats.

Recent evidence suggests that liking and wanting of food rewards can be experimentally dissociated (e.g., Berridge, 1996); this dissociation extends to attenuated neophobia in the present study. Rats tend to eat less of a novel food than a familiar food, a phenomenon called neophobia. The present experiments evaluated whether attenuation of neophobia by prior exposure reflects enhanced liking of the flavor using the Taste Reactivity (TR) test. In Experiment 1, rats given five 10-s TR trials with water or various concentrations of saccharin solution (0.1%, 0.2%, 0.5%) did not show a change in the number of hedonic reactions displayed across trials. However, in a subsequent consumption test from a bottle containing 0.25% saccharin solution, rats with no prior saccharin exposure (group water) consumed less than rats with prior saccharin exposure; that is they displayed neophobia. In Experiment 2, whether rats received five 10-s TR trials with water or 0.5% saccharin solution, they did not display a difference in hedonic reactions to 0.25% saccharin solution in two 5-min TR test trials. These results suggest that the attenuation of neophobia is evidenced as an increase in the tendency to approach a bottle containing the flavored solution (wanting), but not as an enhanced liking of that solution. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rats (Rattus norvegicus) in a water maze learn both an egocentric trajectory and landmarks.

In two experiments we investigated the extent to which rats (Rattus norvegicus) use an egocentric trajectory and landmarks to locate a goal. In Experiment 1 we trained groups to locate the hidden platform in a water maze with either 1 of 3 or 3 of 3 predictive landmarks, and with either a random or fixed egocentric trajectory. A choice test revealed that regardless of the landmark configuration, rats relied on a directional, egocentric trajectory, when it was available, to locate the platform. In Experiment 2 we found that adding four predictive landmarks following training with a constant egocentric trajectory did not alter rats' initial attention to the trajectory. We conclude that the presence of nonpredictive landmarks in a predictive array did not affect the use of landmarks. With a blocking design, rats used initially an egocentric path, then landmarks. These results add to the notion that animals use available spatial cues sequentially. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers

Context: The nonpsychoactive cannabinoid, cannabidiol (CBD), has great potential for the treatment of chronic and ‘breakthrough’ pain that may occur in certain conditions like cancer. To fulfill this goal, suitable noninvasive drug delivery systems need to be developed for CBD. Chronic pain relief can be best achieved through the transdermal route, whereas ‘breakthrough’ pain can be best alleviated with intranasal (IN) delivery. Combining IN and transdermal delivery for CBD may serve to provide patient needs-driven treatment in the form of a nonaddictive nonopioid therapy. Objective: Herein we have evaluated the IN and transdermal delivery of CBD with and without permeation enhancers. Materials and Methods: In vivo studies in rats and guinea pigs were carried out to assess nasal and transdermal permeation, respectively. Results: CBD was absorbed intranasally within 10 minutes with a bioavailability of 34–46%, except with 100% polyethylene glycol formulation in rats. Bioavailability did not improve with enhancers. The steady-state plasma concentration of CBD in guinea pigs after transdermal gel application was 6.3 ± 2.1 ng/mL, which was attained at 15.5 ± 11.7 hours. The achievement of a significant steady-state plasma concentration indicates that CBD is useful for chronic pain treatment through this route of administration. The steady-state concentration increased by 3.7-fold in the presence of enhancer. A good in vitro and in vivo correlation existed for transdermal studies. Conclusion: The results of this study indicated that CBD could be successfully delivered through the IN and transdermal routes.     

Differential effects on effort discounting induced by inactivations of the nucleus accumbens core or shell.

The authors investigated the contribution of the nucleus accumbens (NAc) core and shell to effort-based decision making using a discounting procedure. Selection of 1 lever delivered a smaller, 2-pellet reward immediately, whereas the other lever delivered a 4-pellet reward after a fixed ratio of presses (2, 5, 10, or 20) that increased over 4 blocks of 10 discrete choice trials. Subsequent testing employed an equivalent delays procedure, whereby the relative delay to reward delivery after selection of either option was equalized. In well-trained rats, inactivation of the core, but not the shell, via infusion of GABA A/B agonists muscimol/baclofen reduced preference for the high-effort option under standard conditions and also when rats were tested using an equivalent delays procedure. However, inactivation of the core did not alter preference for 4-pellet versus 2-pellet rewards when the relative costs of each option were the same (1 press). Thus, the NAc core, but not the shell, appears to be part of a neural circuit that biases choice toward larger rewards associated with a greater effort cost. Furthermore, the contributions by the NAc core to this form of decision making can be dissociated from its role in delay discounting. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Metabolic Fate of the Environmental Mutagen 3-Nitrofluoranthene in the Rat

3-Nitrofluoranthene, a potent environmental mutagen, was administered to rats intraperitoneally at 10 mg/kg, labelled with ¹⁴C. Urine contained 15 to 20% of the dose, eliminated mainly within the first 24 hours after dosing. Over 95% of the radioactivity in unhydrolysed urine chromatographed with the solvent front in a reverse-phase HPLC system, indicating extensive conjugation. After hydrolysis with β-glucuronidase (containing sulfatase) and concentration on C18-Sep-Pak, urine was fractionated by HPLC for further characterization. NMR analysis of the metabolite fractions indicated that positions 4, 8 and 9 were major sites of oxidation. Both acetamide and amine derivatives were formed. The finding of multiple oxidation and incomplete acetylation is in contrast to the fate of 1-nitropyrene, where 1-acetamidopyren-6-ol, itself a potent mutagen, represents the major metabolic product. This difference in metabolism pathways may have implications for the genotoxicity of 3-nitrofluoranthene.