Structure-acute toxicity relationship of aromatic hydrocarbons in mice

The structure-acute toxicity relationship of aromatic hydrocarbons was examined in mice. In all test compounds, the acute toxicity was determined under 2 conditions: control LD₅₀ (LD₅₀-cont) and carbon tetrachloride (CCl₄)-pretreated LD₅₀ (LD₅₀-CCl₄). The CCl₄-pretreatment was done in order to evaluate the toxic potency of compound itself without the influence of metabolism. Both log (1/LD₅₀-cont) and log (1/LD₅₀-CCl₄) were functions of the log P, n-octanol/water partition coefficient, i.e., log (1/LD₅₀-cont) = 0.080 log P − 1.532 and log (1/LD₅₀-CCl₄) = −0.040(log P)² + 0.157 log P − 1.373. Both equations were statistically significant (P < 0.01). The ratio of LD₅₀-cont/LD₅₀-CCl₄ indicated that metabolic activation is more evident in hydrophobic compounds than in hydrophilic compounds. The results suggest that hydrophobicity of the aromatic hydrocarbons plays an important role in determining their acute toxicity.     

The relationship between receptor-effector unit heterogeneity and the shape of the concentration-effect profile: Pharmacodynamic implications

The apparent concentration-effect relationship is the ensemble of many effector units (such as individual cells or channels) that do not always exhibit a uniform stimulus-effect relationship. This concept is substantiated by many observations of heterogeneity in receptor-effector populations including hormone secreting cells, response to hormonal stimuli, activity pattern of second messengers, stimulus-evoked synaptic currents, and single ion channels. The relationship between drug concentration and magnitude of pharmacologic response is commonly described by the sigmoidalE _max model which was derived from the Hill equation. The sigmoidicity factor (N) in this model is assumed to be a pure mathematical parameter without physiological connotations. This work demonstrates that the numerical value ofN (measured empirically) is the product of two factors: (i) the degree of heterogeneity of the effector subunits, i.e., the elemental component that upon drug stimulus contributes its pharmacological effect independently and does not interact with other subunits (it could range from a single receptor up to a whole tissue), and (ii) value ofN ^*—the shape factor of the subunits' concentration-effect relationship. A special case of this approach occurs whenN ^*>5, which is an on-off case. HereN is determined by the distribution (density equation) of the subunit values. In case of heterogeneity of the microparameters of the effector subunits the apparentN will always have a lower value thanN ^*. According to this theory it can be concluded that without knowledge of the distribution of the microparameters no mechanistic interpretation can be deduced from the apparentN value. If in the futureN ^* can be determined by theoretical or experimental methods, the distribution function relatingN ^* toN can be calculated. The relevance of this theory is increased in view of the progress being made in advanced research techniques which may enable us to determine the concentration-effect relationship at the level of the individual effector unit.     

Reversible and irreversible effects of chemical fixation on the NMR properties of single cells.

The effects of chemical fixation are known to alter MR parameters, such as relaxation times and the apparent diffusion coefficient (ADC) of water. It is often assumed that such changes are reversible after samples have been reimmersed in a buffer solution for a sufficient period of time. In this study we characterize the changes associated with fixation of single Xenopus laevis oocytes and their subsequent reimmersion in buffer. Substantial reductions in both T(1) and T(2) values were measured for all compartments of the cell after fixation, with the cytoplasm showing larger changes than the nucleus. After reimmersion in buffer, there were small but statistically significant differences in MR parameters between fresh and reimmersed cells. Experiments with a gadolinium (Gd) contrast agent showed evidence of irreversible changes in the permeability of cellular membranes to small molecules.     

曲肘式机构的优化设计

以功效系数为目标函数,相应地确定了设计变量和约束函数,对塑料注塑机合模机构的参数进行优化计算,提高了机构的综合性能。     

磁共振扩散加权成像在肝癌介入治疗前后应用的初步研究

目的探讨肝癌经导管动脉化疗栓塞术(TACE)前后不同b值下瘤区组织的平均表观扩散系数(ADC)的变化及其意义。方法对17例临床及影像学诊断为肝癌并行介入治疗的患者,术前及术后7天行常规平扫和磁共振扩散加权成像,比较不同b值下瘤区组织的平均ADC值的变化。结果在b值为50和100s/mm2时术前术后比较无统计学意义。在b值为300、500和700s/mm2时,术前术后的平均ADC值变化有显著性差异。当b值大于300s/mm2时,随着b值的升高平均ADC值逐渐升高,术后瘤区组织的平均ADC值较术前升高,在b值为1000和1300s/mm2时图像质量太差无法测量。结论对肝癌TACE术后疗效进行评价时,b值最好选择300～700s/mm2之间。DWI通过瘤区DWI图像、eADC图像、ADC图像信号的变化和平均ADC值可以反映TACE术后瘤组织内的微观及超微结构的变化,平均ADC值可以为其早期疗效的判断提供量化标准。     

Comparing diffusion-weighted and T2-weighted MR imaging for the quantification of infarct size in a neonatal rat hypoxic–ischemic model at 24 h post-injury

PURPOSE: In a neonatal rat model of hypoxic-ischemic (HI) brain injury, using T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI), we aim to determine the best MRI method of lesion quantification that reflects infarct size. MATERIALS AND METHODS: Twenty 7-day-old rats underwent MRI 24h after HI brain injury was induced. Lesion size relative to whole brain was measured using T2WI and apparent diffusion coefficient (ADC) maps, applying thresholds of 60%, 70% and 80% contralateral control hemisphere mean ADC, and at day 10 post-HI on pathology with TTC staining. Multiple linear regression analysis was used to study the relationships between lesion size at MRI and pathology. RESULTS: Lesion size measurement using all MRI methods significantly correlated with infarct size at pathology; using T2WI, r=0.808 (p<0.001), using 80% ADC, 70% ADC and 60% ADC thresholds, r=0.888 (p<0.001), 0.761, (p<0.001) and 0.569 (p=0.014), respectively. Eighty percent ADC threshold was found to be the only significant independent predictor of final infarct volume (adjusted R(2)=0.775). CONCLUSION: At 24h post-HI, lesion size on DWI, using 80% ADC threshold is the best predictor of final infarct volume. Although T2WI performed less well, it has the advantage of superior spatial resolution and is technically less demanding. These are important considerations for experiments which utilize MRI as a surrogate method for lesion quantification in the neonatal rat HI model.     

Structure and Behavior in Hydrophilic Matrix Sustained Release Dosage Forms: 4. Studies of Water Mobility and Diffusion Coefficients in the Gel Layer of HPMC Tablets Using NMR Imaging

Purpose. The purpose of this study was to characterise the water mobility in the gel layer of hydrating HPMC tablets. Water mobility in the gel layer of different HPMCs was studied. Methods. NMR imaging, a non-invasive technique, has been used to measure the spatial distribution of self-diffusion coefficient (SDC) and T₂ relaxation times across the gel layer. Results. It has been shown that there is a water mobility gradient across the gel layer of HPMC tablets. Although SDC and T₂ relaxation times in the outer parts of the gel layer approached that of free water, in the inner parts they decreased progressively. Water mobility and SDC in the gel layer of different HPMCs appeared to vary with degree of substitution of the polymer and the lowest values were obtained across the gel layer of K4M tablets. Conclusions. Water mobility varies across the gel layer of hydrating HPMC tablets and it is dependent on the degree of substitution of the polymer.     

环隙气升式反应器在非牛顿流体体系中的应用──反应器特性研究和体积氧传递系数的关联

以羧甲基纤维素钠（ＣＭＣ）水溶液模拟非牛顿型发酵介质，在内径为０．１５ｍ，高为０．９７５ｍ的环隙气升式反应器内，考察了液体流变性质和导流筒结构对气液传质的影响，提出了体积氧传递系数（ＫＬａ）的经验关联式。实验表明：对于较高粘度的假塑性流体，反应器内部采用整体式导流筒结构，将有利于传质和混合，其性能优于采用开窗式导流筒或无导流筒的反应器。     

云南省卫生资源配置标准的弹性系数研究

目的　在进行云南省区域分类基础上制定云南省区域卫生资源配置标准标志值后 ,根据云南省各个地区的特点增加不同弹性系数。方法　采用流行病学研究方法 ,收集和分析云南省不同地州市 1990～ 1999年有关人口、社会经济状况及卫生经费的投入、居民健康状况、居民文化、生活水平、少数民族状况、旅游地区、边境线长短及贫困状况等资料。结果　研究结果表明曲靖地区、玉溪市、保山地区增加弹性系数最少 ,分别为 0 67%、 1 5 8%和1 68% ,怒江州、迪庆州和西双版纳州增加弹性系数最多 ,分别为 11 15 %、 10 2 5 %和 9 84 %。其它地区的弹性系数分别为昆明市 5 88% ,昭通地区 2 3 1% ,楚雄州 2 3 0 % ,红河州 7 0 3 % ,文山州 5 5 3 % ,思茅地区 7 4 3 % ,大理州4 94 % ,德宏州 6 78% ,丽江地区 4 3 5 % ,临沧地区 6 13 %。结论　云南省区域卫生配置标准的弹性系数研究为云南省卫生资源区域分类配置标准提供了科学依据 ,不同弹性系数体现了云南省不同地区的卫生资源区域分类配置标准的公平性、合理性及实用性     

用神经网络法预测药物在体透过人皮肤的渗透性

目的：预测药物在体透过人皮肤的渗透性。方法：以正辛醇／水分配系数(logP)、分子体积(V)、氢键酸度(∑β2^H)和氢键碱度(∑β2^H)等理化参数作为输入层神经元，以药物在一定时间内在体透过人皮肤的透过比的对数值(R，透过量／未透过量)作为输出层神经元，建立起合适的BP(Back—propagation)神经网络。结果：17个药物在一定时间内在体透过人皮肤的透过比的神经网络计算值和实测值均相当符合。结论：用BP神经网络法可以较好地预测药物在体透过人皮肤的渗透性。