Animal models in the investigation of anorexia

Anorexia nervosa (AN) is an eating disorder of unknown origin that most commonly occurs in women and usually has its onset in adolescence. Patients with AN invariably have a disturbed body image and an intense fear of weight gain. There is currently no definitive treatment for this disease, which carries a 20% mortality over 20 years. Development of an appropriate animal model of AN has been difficult, as the etiology of this eating disorder likely involves a complex interaction between genetic, environmental, social, and cultural factors. In this review, we focus on several possible rodent models of AN. In our laboratory, we have developed and studied three different mouse models of AN based on clinical profiles of the disease; separation stress, activity, and diet restriction (DR). In addition, we discuss the spontaneous mouse mutation anx/anx and several mouse gene knockout models, which have resulted in an anorexic phenotype. We highlight what has been learned from each of these models and possibilities for future models. It is hoped that a combination of the study of such models, together with genetic and clinical studies in patients, will lead to more rational and successful prevention/treatment of this tragic, and often fatal, disease.     

采用高脂饲料加空气干燥术建立颈动脉粥样硬化动物模型

目的:利用高脂饮食加空气干燥术建立一种稳定、重复性好、有较典型动脉粥样硬化病理改变的动物模型。方法:32只日本大耳白兔随机分为模型组(n=24)、对照组(n=8)。模型组给予高脂饲料喂养加空气干燥术,术中结扎左侧颈动脉分支血管,对照组正常饲料喂养,分别于术后第2、4、8、12周处死动物。取颈动脉组织切片HE染色,光镜下观察。结果:(1)75%兔颈总动脉存在细小血管分支,暂时结扎侧支血管后干燥效果更好。(2)对双侧颈动脉实施手术,结扎左侧分支,成模率更高。部分斑块显示出不稳定性。结论:采用改进后高脂饮食加空气干燥术可成功建立兔颈动脉粥样硬化模型,其病理特点适合于目前临床研究。     

Flat crossed-coil detector for blood flow measurement using nuclear magnetic resonance

A new flat crossed-coil nuclear magnetic resonance (n.m.r.) detector can be used to measure flood flow at many regions of the body, is introduced. It is compared, bothin vitro andin vivo, with the already proven cylindrical crossed-coil n.m.r. detector. Both detectors use a single high-field homogenous magnet. A single-sideband receiver reduces the effect of transmitter leakage into the receiver coil to allow the use of a high-level transmitter field. Preliminary application of the flat crossed-coil detector to the detection of cerebral blood flow is presented.     

Comparative analysis of seizures induced by intracerebroventricular administration of NMDA,kainate and quisqualate in mice

Summary The dose-related time course and occurrence of different seizure subtypes was examined in mice after i.c.v. administration of N-methyl-D-aspartate (NMDA), kainate (KA) or quisqualate (QA). At doses of 0.2 to 1 nmol, NMDA dose-dependently induced a single clonic-tonic seizure. Low doses (0.1 to 0.3 nmol) of KA induced only mild myoclonus and whole body clonus, which were dose-dependently replaced by short-delay clonic-tonic seizures at higher doses (0.4 to 1.2 nmol). In contrast, mice treated with 13 to 32 nmol of QA exhibited either mild myoclonus or whole body clonus as well as clonic-tonic seizures. Clonic-tonic seizures induced by NMDA or KA appeared at shorter latencies than those induced by QA, whereas whole body clonus induced by KA or QA appeared with long onset latencies. These results clearly show that i.c.v. administration of NMDA, KA and QA produces different patterns of seizures in mice. This study confirms that NMDA, KA and QA induce convulsions through different underlying mechanisms and suggests that different anatomical pathways are involved in these models.     

内皮素性大鼠门静脉高压模型的建立

目的： 建立内皮素-1(ET-1)引起门静脉压力升高的动物模型。方法: 正常雄性SD大鼠48只，随机分为生理盐水组、ET-1低剂量组(0.3 μg/kg)，ET-1中剂量组(1.0 μg/kg)和ET-1高剂量组(3.0 μg/kg)。生理盐水组大鼠经股静脉注入生理盐水，其余各组大鼠按相应剂量经股静脉注入ET-1溶液，观察门静脉压力和颈动脉压力的变化情况,并筛选出能使门静脉压力升高最适宜的剂量；另取15只大鼠随机分为对照组、ETAR阻断剂(BQ-123)组和ETBR阻断剂(BQ-788)组，实验开始前30 min经各组大鼠股静脉分别注入生理盐水、ETR阻断剂BQ-123(给药剂量为12.5 μg/kg)和BQ-788(给药剂量为15 μg/kg)，然后以选定的适宜剂量匀速注入ET-1溶液，观察各组大鼠门静脉压力变化。结果: 不同剂量的ET-1均能使门静脉压力升高，尤以高剂量组最为明显；而提前注入ETR阻断剂之后，再注入ET-1溶液门静脉压力虽然升高，但升高的幅度较小。结论: 成功创建了内皮素性大鼠门静脉高压模型，此模型可用于研究ET-1在PHT发病机制中的作用和药物对PHT时血中ET-1的影响。     

Conditioned taste aversion using four different means to deliver sucrose to rats

A solution of sucrose either to be drunk from a drinking tube-self-drinking procedure (SD)-or perfused intraorally as a consequence of nose-pokes-self-administration procedure (SA)-or perfused as a consequence of licking an empty tube (LA)-was paired with an LiCl-induced malaise in rats. The effects were compared to those of a procedure consisting of intraoral administration (IO) of sucrose not contingent to any specific action of the rat. Similar levels of conditioned taste aversion (CTA) were obtained but extinction in the IO procedure was quicker than in the SA procedure, which was itself quicker than in the SD procedure. Extinctions in the IO and LA procedures resembled one another and were quicker than in the SD procedure. A step towards deciding between several explanatory hypotheses of these differences was made by conducting two more experiments. The third experiment was based on reinstatement, or not, of the conditioning procedure for the test after standard IO extinction. CTA was produced only when SD was used both at conditioning and test. A fourth experiment was based on latent inhibition where the procedure was changed, or not, between preexposure and conditioning. Latent inhibition was absent only when the rats had been preexposed to sucrose with the SA procedure and conditioned with the SD procedure.     

Investigation and comparison of some models for removing ocular artefacts from EEG signals

An investigation of ocular artefacts (OAs) in the human electroencephalogram (EEG) to quantify the effectiveness of OA removal and to find the most effective model for removing OAs online is described. In Part 1, the models used in the investigation are described and the data analysed. The analysis showed that the ‘true’ EEG exhibited a high degree of serial correlation and so the ordinary least-squares (OLS) method employed to remove OA was inefficient. Efficient alternative methods based on autoregressive models of the ‘true’ EEG are discussed. It is also shown that the EOGs are linearly dependent making some of them redundant. In Part 2, the models are compared.     

Computer analysis system of blood oxygen saturation in an animal hypoxia model

An experimental animal hypoxia model has been developed. It consists of two sensors (an in vitro and in vivo model), an experimental device and a computer signal processing system. This method can easily be applied to determine and analyse blood oxygen saturation at various hypoxia levels. It can also be used to evaluate the accuracy of pulse oximetry over a wide range of oxyhemoglobin desaturation levels. The DC and AC components of recorded red and infra-red signals, the dual-wavelength ratio R₁₂ and the reading of a pulse oximeter (SpO₂) can be automatically calculated and displayed on a computer screen. Preliminary results of the animal hypoxia test indicate that the measurements made by the instrument correlate well with the oxygen saturation readings of the automatic blood gas analyser AVL945. The computer analysis system is suitable for repeated estimations in the animal model.     

Orientation of the peptidoglycan chains in the sacculus of Escherichia coli

The organization of chains of oligopeptidoglycan in the saccular wall is of critical importance in the study of the mechanism and physiology of prokaryotic wall growth. The electron microphotographs of De Pedro et al, present new findings and can be used to negate or at least raise questions about the previously accepted conclusion that the glycan chains are oriented transversely to the axis of rod-shaped Escherichia coli. This suggests caution in assuming that the glycan chains in the murein structure are parallel to each other and are perpendicular to the axis of the cell.These results should reopen the question of not only the orientation of the peptidoglycan chains, but the possibility of variability in orientation. Three classes of hypotheses about wall growth are reconsidered and problems with them are presented. The new results from De Pedro's laboratory and the experimental glycan chain length distribution argue against proposed systematic models. These include models that postulate belts or hoops stretched around the circumference of the cell and mechanisms that insert new chains of the length of presumptive “docking” strands in the stress-bearing wall. They are consistent, however, with the surface stress theory that proposes that random enzyme action together with physical forces are involved in the elongation of the rod-shaped Gram-negative wall.