注射硬化剂法制作家兔椎动脉型颈椎病动物模型

采用家兔 5 8只 ,于颈椎左侧注射组织硬化剂 775注射液 ,制成慢性椎动脉型颈椎病动物模型。分别以经颅多谱勒 (TCD)测定双侧椎动脉 (VA)、基底动脉 (BA)血流状况 ,以脑干听觉诱发电位 (BAEP)测定脑干听觉通路功能 ,以组织病理学了解左侧颈椎软组织及小脑浦肯野氏细胞病理变化 ,并观察胃肠灌注丹参注射液后的恢复过程。结果显示 :①造模后BA、双侧VA血流动力学异常 (P <0 .0 1) ,双侧BAEPⅢ、V波峰潜伏期 (PL)和Ⅰ Ⅲ、Ⅰ Ⅴ波峰间潜伏期 (IPL)显著延长 (P <0 .0 1或 0 .0 5 )。病理检查提示颈部软组织早期水肿、变性、坏死显著 ,后期瘢痕化显著 ,小脑浦肯野氏细胞缺血缺氧改变明显。②使用丹参后 ,BA血流恢复显著 (P >0 .0 5 ) ,VA血流未见显著恢复 (P <0 .0 1) ,BAEP恢复至造模前水平 (P >0 .0 5 ) ,小脑浦肯野氏细胞未见缺血缺氧改变。提示本法制作的动物模型 ,方法简便、可靠 ,符合椎动脉型颈椎病发病机理 。

Anti-Helicobacter pylori therapy significantly reduces Helicobacter py/ori-Induced gastric mucosal damage in Mongolian gerbils

AIM: To investigate the effectiveness of 4 d' anti-Helicobacter pylori therapy on the H pylori-infected Mongolian gerbils based on physiological and pathological changes. METHODS: We used 6-wk-old male gerbils orally inoculated with H pylori (ATCC43504, 2×108 CFU/mL). Seven weeks after H pylori inoculation, the animals of study group received 4 d' anti-H pylori triple therapy (H pylori-eradicated group). Seven days later, all animals of the H pylori-eradicated and control groups (H pylori-infected & H pylori-uninfected groups) were sacrificed. We examined gastric mucosal lesions macroscopically, studied gastritis microscopically and determined the stomach weight ratio, myeloperoxidase (MPO) activity and prostaglandin (PG) E2 level. RESULTS: The results showed that both macroscopic and histological gastric damages were significantly less in H pylori-eradicated group than H pylori-infected group. Stomach weight ratio, MPO activity and PGE2 levels were significantly higher in H pylori-infected group than those in the other two groups. CONCLUSION: Four days' anti-H pylori therapy was effective in the improvement of H pylori-induced gastric lesions in Mongolian gerbils.

Modifications of reduced-size hepatic transplantation in rats

Objective: To establish a stable reduced-size hepatic transplantation model in rats. Methods: Liver transplantation was performed in accordance with Kamada techniques. Many modifications were made including: Surgical manipulative innovation, adjustment of pre-operative drug administration and removed liver volume. Results: Forty-two rats underwent reduced-size hepatic transplantation; of them 33(84.6%) survived more than 1 week. The causes of postoperative death were peritonitis, inferior vena cava thrombus and unknown complications. Conclusion: Manipulative innovation and proper drug administration can improve the survival rate of rats apparently. Grafts regeneration can be triggered by the removal of left lateral segment and caudate lobe.

Methods for the development and assessment of atrial fibrillation and heart failure dog models

Objective To report Medtronic experiences with the development of animal models for atrial fibrillation （AF） and chronic heart failure （CHF） using high-rate pacing for AF and microemboli for CHF. Methods For the AF model, an atrial lead was attached to a Medtronic SynergyTM neurostimulator, which was programmed to stimulate at 50 Hz in an on-off duty cycle. Atrial natfiuretic peptide （ANP）, brain natriuretic peptide （BNP） and N-terminal pro brain nalriuretic peptide （NT-proBNP） were assayed at select time points. For CHF model, a serial injection of 90 μm polystyrene microspheres at 62,400 beads/mL （Polybead, Polysciences, Inc.） was performed to induce global ischemia, either with weekly monitoring and embolization schedule （group 1, n = 25） or with biweekly monitoring and emboliation schedule （group 2, n = 36 ）. Echocardiograms were used along with ventriculograms and magnetic resonance imaging scans weekly to assess cardiac function and ANP, BNP and NT-proBNP were monitored. Results For the AF model, the days to sustained AF for four animals following surgery were 7, 25, 21 and 19, respectively; For the CHF model, the days to meet CHF endpoints were 116 in group 1 and 89 in group 2. For both AF and CHF models, NT-proBNP correlated well with the development of disease states. Conclusion Our experience for the development and assessment of AF and CHF dog models may help researchers who are in search for animal model for assessing the safety and efficacy of a device-based therapy.

Time-dependent viscoelastic properties along rat small intestine

AIM： To measure the time-dependent （viscoelastic） behavior in the change of the small intestinal opening angle and to test how well the behavior could be described by the Kelvin model for a standard linear solid. METHODS： Segments from the duodenum, jejunum, and ileum were harvested from 10 female Wistar rats and the luminal diameter, wall thickness, and opening angle over time （θ（t）） were measured from rings cut from these segments. RESULTS： Morphometric variations were found along the small intestine with an increase in luminal area and a decrease in wall thickness from the duodenum to the ileum. The opening angle obtained after 60 rain was highest in the duodenum （220.8±12.9°）and decreased along the length of the intestine to 143.9±8.9° in the jejunum and 151.4±9.4° in the ileum. The change of opening angle as a function of time, fitted well to the Kelvin model using the equation θ（t）/θo = [1-ηexp （-λt）] after the ring was cut. The computed creep rate λ. did not differ between the segments. Compared to constant calculated from pig aorta and coronary artery, it showed that α agreed well （within 5%）, η was three times larger than that for vascular tissue, and λ ranged ±40% from the value of the pig coronary artery and was a third of the value of pig aorta. CONCLUSION： The change of opening angle over time for all the small intestine segments fits well to the standard linear spring-dashpot model. This viscoelastic constant of the rat small intestine is fairly homogenous along its length. The data obtained from this study add to a base set of biomechanical data on the small intestine and provide a reference state for comparison to other tissues,diseased intestinal tissue or intestinal tissue exposed to drugs or chemicals.

Gastric cancer:Animal studies on the risk of hypoacidity and hypergastrinemia

Gastric hypoacidity and hypergastrinaemia are seen in several conditions associated with an increased risk of gastric malignancy.Hypoacidity and hypergastrinaemia are closely related and their long-term effects are difficult to study separately in patients.Studies using animal models can provide valuable information about risk factors and mechanisms in gastric cancer development as the models allow a high degree of intervention when introducing or eliminating factors possibly affecting carcinogenesis.In this report,we briefly review findings from relevant animal studies on this topic.Animal models of gastric hypoacidity and hypergastrinaemia provide evidence hypergastrinaemia is a common causative factor in many otherwise diverse settings.In all species where sufficient hypoacidity and hypergastrinaemia have been induced,a proportion of the animals develop malignant lesions in the gastric oxyntic mucosa.

Induction of ischemic tolerance in rat liver via reduced nicotinamide adenine dinucleotide phosphate oxidase in Kupffer cells

AIM: To elucidate the mechanisms of hepatocyte preconditioning by H2O2 to better understand the pathophysiology of ischemic preconditioning. METHODS: The in vitro effect of H2O2 pretreatment was investigated in rat isolated hepatocytes subjected to anoxia/reoxygenation. Cell viability was assessed with propidium iodide fluorometry. In other experiments, rat livers were excised and subjected to warm ischemia/ reperfusion in an isolated perfused liver system to determine leakage of liver enzymes. Preconditioning was performed by H2O2 perfusion, or by stopping the perfusion for 10 min followed by 10 min of reperfusion. To inhibit Kupffer cell function or reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, gadolinium chloride was injected prior to liver excision, or diphenyleneiodonium, an inhibitor of NADPH oxidase, was added to the perfusate, respectively. Histological detection of oxygen radical formation in Kupffer cells was performed by perfusion with nitro blue tetrazolium. RESULTS: Anoxia/reoxygenation decreased hepatocyte viability compared to the controls. Pretreatment with H2O2 did not improve such hepatocyte injury. In liver perfusion experiments, however, H2O2 preconditioning reduced warm ischemia/reperfusion injury, which wasreversed by inhibition of Kupffer cell function or NADPH oxidase. Histological examination revealed that H2O2 preconditioning induced oxygen radical formation in Kupffer cells. NADPH oxidase inhibition also reversed hepatoprotection by ischemic preconditioning. CONCLUSION: H2O2 preconditioning protects hepato- cytes against warm ischemia/reperfusion injury via NADPH oxidase in Kupffer cells, and not directly. NADPH oxidase also mediates hepatoprotection by ischemic preconditioning.

Animal models for the study of hepatitis C virus infection and replication

Hepatitis C virus (HCV) hepatitis, initially termed non-A, non-B hepatitis, has become one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide. With the help of animal models, our understanding of the virus has grown substantially from the time of initial discovery. There is a paucity of available animal models for the study of HCV, mainly because of the selective susceptibility limited to humans and primates. Recent work has focused modification of animals to permit HCV entry, replication and transmission. In this review, we highlight the currently available models for the study of HCV including chimpanzees, tupaia, mouse and rat models. Discussion will include methods of model design as well as the advantages and disadvantages of each model. Particular focus is dedicated to knowledge of pathophysiologic mechanisms of HCV infection that have been elucidated through animal studies. Research within animal models is critically important to establish a complete understanding of HCV infection, which will ultimately form the basis for future treatments and prevention of disease.

Lagrangian model of zooplankton dispersion:numerical schemes comparisons and parameter sensitivity tests

This paper presents two comparisons or tests for a Lagrangian model of zooplankton dispersion:numerical schemes and time steps.Firstly,we compared three numerical schemes using idealized circulations.Results show that the precisions of the advanced Adams-Bashfold-Moulton(ABM) method and the Runge-Kutta(RK) method were in the same order and both were much higher than that of the Euler method.Furthermore,the advanced ABM method is more efficient than the RK method in computational memory requirements and time consumption.We therefore chose the advanced ABM method as the Lagrangian particle-tracking algorithm.Secondly,we performed a sensitivity test for time steps,using outputs of the hydrodynamic model,Symphonie.Results show that the time step choices depend on the fluid response time that is related to the spatial resolution of velocity fields.The method introduced by Oliveira et al.in 2002 is suitable for choosing time steps of Lagrangian particle-tracking models,at least when only considering advection.

Comparative systems biology between human and animal models based on next-generation sequencing methods

Animal models provide myriad benefits to both experimental and clinical research. Unfortunately, in many situations, they fall short of expected results or provide contradictory results. In part, this can be the result of traditional molecular biological approaches that are relatively inefficient in elucidating underlying molecular mechanism. To improve the efficacy of animal models, a technological breakthrough is required. The growing availability and application of the high-throughput methods make systematic comparisons between human and animal models easier to perform. In the present study, we introduce the concept of the comparative systems biology, which we define as "comparisons of biological systems in different states or species used to achieve an integrated understanding of life forms with all their characteristic complexity of interactions at multiple levels". Furthermore, we discuss the applications of RNA-seq and ChIP-seq technologies to comparative systems biology between human and animal models and assess the potential applications for this approach in the future studies.

Evaluation of Biological Assets： Problems and Solutions

The chief production elements of an agricultural enterprise are its biological assets and the choice and practical application of the evaluation methods, as the assets directly affect many aspects： decision making of economic character by the financial statement user, indicators of financial operation analysis, inter-comparison of sector enterprises, assessment of the company value and taxes on its economic activity, and statistical data of the agricultural sector. The authors have used the discounted cash flow （DCF） as an alternative method and a model of system dynamics. Such a system dynamics method has not been used for assessment of biological assets so far. In the operating process, the company acquires or loses possession of the resources. It is vital to analyze the resources to see whether they comply with the concept of the assets and the terms of recognition. It is necessary for the same company as well as for external users of financial statements to get true information about the business and the value of money. Biological assets may be recognized in the company＇s accounting only when it is predictable that future benefits associated with these assets will flow into the enterprise. It is also important that the fair value or the cost can be measured reliably.