大鼠脑干缺血模型制备及早期超微结构观察

目的:制备脑干缺血动物模型并观察大鼠脑干缺血后早期组织学病理的超微结构。方法:应用两点电凝基底动脉的方法制作鼠脑干缺血动物模型。结果:病理学观察发现脑干缺血2小时即可出现超早期病理变化,并随时间的延长缺血性损害逐渐加重。结论:两点电凝基底动脉后可以造成稳定的脑干缺血,对急性脑干缺血的病理学研究有一定的价值。     

Deep brain stimulation for Parkinson''s disease: electropermeabilization and activation

Deep brain stimulation, DBS, is an accepted technique for the treatment of Parkinson's disease. DBS affects the electrical functions of neurons, but exactly how it alters those functions is not clearly explained. An electrical model is determined to simulate treatment with DBS of the sub thalamic nucleus. This model shows the difference in electrical fields between the inside and the outside the neurons. The generated electrical field near the electrodes is high enough to perform an electropermeabilization of the cell membranes, which most likely blockade normal nerve pulses or reduce the nerve impulse speed. Further away from the electrodes activation of large axons is performed.     

健身宝对衰老模型小鼠血清SOD和MDA的影响

目的　研究健身宝补脾益肾、延缓衰老的作用机制。方法　将 60只小鼠随机分为 6组 ,除正常对照组外均每日注射对D -半乳糖造成衰老模型 ,同时给予不同剂量的健身宝和金匮肾气丸。 6周后检测小鼠血清中SOD活性、MDA含量。结果　衰老模型组与正常对照组比较 ,小鼠血清中SOD活性显著降低 ,MDA含量显著升高 (P <0 .0 1 ) ;而健身宝大、中剂量组与正常对照组相比较 ,小鼠血清中SOD活性显著升高 ,MDA含量显著降低 ,与衰老模型组相比较有显著性差异 (P <0 .0 5 )。结论　健身宝明显提升D -半乳糖拟衰小鼠血清中SOD活性 ,降低MDA含量 ,可从调节自由基代谢和提高抗氧化能力方面发挥延缓衰老的作用。     

Unsupervised fuzzy clustering analysis supports behavioral cutoff criteria in an animal model of posttraumatic stress disorder.

BACKGROUND: Unsupervised fuzzy clustering (UFC) analysis is a mathematical technique that groups together objects in the multidimensional feature space according to a specified similarity measurement, thereby yielding clusters of similar data points that can be represented by a set of prototypes or centroids. METHODS: Since clinical studies of mental disorders distinguish between affected and unaffected individuals, we designed an inclusion/exclusion criteria (cutoff behavioral criteria [CBC]) approach for animal behavioral studies. The effect of classifying the study population into clearly affected versus clearly unaffected individuals according to behaviors on two behavioral paradigms was statistically significant. RESULTS: Here the raw data from previous studies were subjected to UFC algorithms as a means of objectively testing the validity of the concept of the CBC for our experimental model. The first UFC algorithm yielded two clearly discrete clusters, found to consist almost exclusively of the exposed animals in the one and unexposed animals in the other. The second algorithm yielded three clusters corresponding to animals designated as clearly affected, partially affected, and clearly unaffected. The algorithm for physiological data in addition to behavioral data failed to elicit discrete clusters. CONCLUSIONS: The UFC analysis yielded data that support the conceptual contention of the CBC and lends additional validity to our previous behavioral studies.     

Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis

The disaccharide trehalose is a key element involved in anhydrobiosis (the capability of surviving almost complete dehydration) in many organisms. Its presence also confers resistance to desiccation and high osmolarity in bacterial and human cells by protecting proteins and membranes from denaturation. The present study used a novel murine dry eye model induced by controlled low-humidity air velocity to determine whether topically applied trehalose could heal ocular surface epithelial disorders caused by ocular surface desiccation. In addition, the efficacy of 87.6 mM trehalose eyedrops was compared with that of 20% serum, the efficacy of which has been well documented. Mice ocular surface epithelial disorders were induced by exposure of murine eyes to continuous controlled low-humidity air velocity in an intelligently controlled environmental system (ICES) for 21 days, which accelerated the tear evaporation. The mice were then randomized into three groups: the control group received PBS (0.01M) treatment; a second group received 87.6 mM trehalose eyedrops treatment; and the third group received mice serum eyedrops treatment. Each treatment was administered as a 10 μl dose every 6 h for 14 days. The resultant changes in corneal barrier function and histopathologic examination of cornea and conjunctiva were analyzed and the level of apoptosis on the ocular surface was assessed using active caspase-3. After 14 days of treatment, the corneal fluorescein staining area, the ruffling and desquamating cells on the apical corneal epithelium, as well as the apoptotic cells on ocular surface epithelium had significantly reduced in eyes treated with trehalose compared with those treated with serum and PBS. In contrast, after 14 days of treatment, improvements in the thickness of the corneal epithelium, the squamous metaplasia in conjunctival epithelium and the number of goblet cells of the conjunctiva were less marked in eyes treated with trehalose compared with serum. These results demonstrated that trehalose could improve the appearance of ocular surface epithelial disorders due to desiccation through suppression of apoptosis. Trehalose produces some of the same responses as serum upon topical application and can maintain corneal health.     

A corneal model for slit-scanning elevation topography

Computerised videokeratography is increasing in sophistication and accuracy. The Orbscan II Videokeratographer combines the advantages of Placido derived and slit-scanning derived topography, to acquire shape information on the posterior surface of the cornea. The purpose of this paper is to construct a model of slit-scanning elevation topography and highlight potential sources of variation in this methodology. Ray tracing calculations were performed on a defined, theoretical, spherical model to obtain a pachymetric measurement. These calculations were tested by comparing the pachymetry measurement derived from the model, over a refractive index shift from 1.376 to 1.400 with the pachymetry measurement obtained by Orbscan II, of a human eye, with an identical alteration in refractive index. The two methods of measurement differed by only 0.157 microm, suggesting that the model is a good representation of slit-scanning elevation topography, and that refractive index variations have only a minimal effect on Orbscan II pachymetry measurement.     

Performance in population models for count data,part II: A new SAEM algorithm

Analysis of count data from clinical trials using mixed effect analysis has recently become widely used. However, algorithms available for the parameter estimation, including LAPLACE and Gaussian quadrature (GQ), are associated with certain limitations, including bias in parameter estimates and the long analysis runtime. The stochastic approximation expectation maximization (SAEM) algorithm has proven to be a very efficient and powerful tool in the analysis of continuous data. The aim of this study was to implement and investigate the performance of a new SAEM algorithm for application to count data. A new SAEM algorithm was implemented in MATLAB for estimation of both, parameters and the Fisher information matrix. Stochastic Monte Carlo simulations followed by re-estimation were performed according to scenarios used in previous studies (part I) to investigate properties of alternative algorithms (Plan et al., 2008, Abstr 1372 []). A single scenario was used to explore six probability distribution models. For parameter estimation, the relative bias was less than 0.92% and 4.13% for fixed and random effects, for all models studied including ones accounting for over- or under-dispersion. Empirical and estimated relative standard errors were similar, with distance between them being <1.7% for all explored scenarios. The longest CPU time was 95 s for parameter estimation and 56 s for SE estimation. The SAEM algorithm was extended for analysis of count data. It provides accurate estimates of both, parameters and standard errors. The estimation is significantly faster compared to LAPLACE and GQ. The algorithm is implemented in Monolix 3.1, (beta-version available in July 2009).     

柯萨奇病毒诱发实验性多发性肌炎的初步研究

分别用不同量的柯萨奇病毒Ｂ１、２、３感染和兔肌匀浆加完全弗氏佐剂免疫正常豚鼠；拟建立多发性肌炎模型。结果发现：０．１ｍｌ毒力为１０－５ＴＣＩＤ５０柯萨奇病毒Ｂ１感染豚鼠组，３周后出现多发性肌炎症状。肌酶谱异常与其它组有明显差异，病理检查证实为多发性肌炎改变。单纯兔肌匀浆免疫对照组未发病。提示柯萨奇病毒Ｂ１感染及感染的病毒量与多发性肌炎的发病相关     

The influence of support conditions in the loading fixture on failure mechanisms in the push-out test: a finite element study

The usefulness of the push-out test as an indicator of interface strength was evaluated using finite element models of intact and partially failed cylindrical push-out specimens loaded against a rigid annular support. The irregular stress distributions that were found in intact specimens depended more on interface conditions at the loading fixture than on a 35% increase in interface area. The maximum stress at the interface was a tensile stress. Critical energy release rates for interface failure were calculated for flawed specimens in which flaw size was either 10 or 100 microns, and for boundary conditions at the loading fixture that were either fixed or slipping in the radial direction. The critical energy release rates depended heavily on the support boundary conditions. Thus, the results of parametric push-out tests can be reasonably compared only for specimens that are very similar in geometry and that are loaded in very carefully controlled fixtures.     

Lower level of serum potassium and higher level of C-reactive protein as an independent risk factor for giant aneurysms in Kawasaki disease

Giant aneurysms are the most serious issue of patients with Kawasaki disease (KD). To clarify risk factors for these giant aneurysms, we conducted a matched case-control study. Among the patients reported in nationwide surveys, 117 patients with giant aneurysms had an unequivocal new diagnosis and presented at the treatment center within 9 d of illness. We obtained clinical information on admission of about 69 patients (case) from the treatment centers. One control was selected for each case, an age- and sex-matched patient without coronary involvement, reported from the same treatment center at about the same time as the case, and we obtained the same clinical information about controls. Fourteen variables were analysed with a conditional logistic regression model: body temperature, hematocrit, hemoglobin, numbers of leukocyte and platelets, concentrations of serum albumin, globulin, total cholesterol, sodium, potassium and chloride, erythrocyte sedimentation rate, C-reactive protein and alanine aminotransferase activity. After adjustment for age, duration of illness before admission and use of intravenous gamma globulin therapy, C-reactive protein [odds ratio (OR) = 1.142, 95% confidence interval (CI) 1.054-1.237], alanine aminotransferase activity (OR = 1.008, 95% CI 1.002-1.014), serum sodium concentration (OR = 0.877, 95% CI 0.770-0.999) and serum potassium concentration (OR = 0.319, 95% CI 0.124-0.822) were significantly related to the risk for giant aneurysms. Further analyses with these four explanatory variables revealed that C-reactive protein (OR = 1.159, 95% CI 1.022-1.315) and serum potassium concentration (OR = 0.222, 95% CI 0.052-0.948) met the significant level. Thus, the values for serum C-reactive protein and potassium are independent risk factors for the development of the giant aneurysms of Kawasaki disease.