和谐教学的基本原理

本文作者密切联系构建和谐社会的理论与实践，科学地探讨了教学过程自身的和谐、教学过程与教学环境的和谐等实践问题。     

几种评价保湿产品无创性测试方法的相关性评价

目的:对测量皮肤角质层含水量和屏障功能的几种无创性皮肤测试方法进行相关性评价。方法:采用SKICON-200测定皮肤电导法、皮肤保水功能测定、TEWL测定、受试者主观评价的方法,比较某种保湿霜/精华素使用前、后皮肤角质层含水量和屏障功能的变化,并分析这些方法之间的相关性。结果:保湿霜的效果优于精华素,SKICON-200测定皮肤电导法、皮肤保水功能测定以及部分受试者临床症状和主观评价指标(如红斑、脱屑情况,皮肤滋润度的改善、皮肤细纹数量变化和皮肤弹性改善)有很好的平行关系。TEWL结果在本试验中变化不大,与上述指标没有平行关系。结论:SKICON-200测定皮肤电导法、皮肤保水功能测定适合用于保湿化妆品的功效评价。TEWL测定对于屏障功能受损的皮肤可能更敏感,对于健康皮肤使用前、后比较可作为参考指标。     

Does Fluid Flow Across the Intestinal Mucosa Affect Quantitative Oral Drug Absorption? Is It Time for a Reevaluation?

Purpose. Hydrophilic and charged solutes have a lower membrane permeability which is due to a lower partition into the lipid membrane (low solubility in the membrane phase) and/or a slower transcellular diffusion coefficient. They are therefore anticipated to be absorbed through the paracellular route, which is a consequence of diffusion and a convective volume flow through the water-filled intercellular space. Methods. Two approaches have been used to investigate the mechanisms underlying the paracellular drug transport across the intestinal mucosa: (a) including water transport by exposing the apical side of the epithelium with a hypotonic solution, and (b) stimulated paracellular transport by widening of tight junction and increased water absorption as a consequence of the sodium-coupled transport of nutrients. Results. Among the first studies that recognized this fluid flux dependent transmucosal transport of drugs, was one published by Oschenfahrt & Winne in 1973 and the one by Kitazawa et al. in 1975. During the last two decades the importance of this paracellular route for drug delivery have been explored in vitro and in situ. Conclusions. The limits concerning molecular weight, shape, ionization and the effect of physiological stimulants, such as luminal concentrations of nutrients, osmolality and motility, are currently under investigation. However, recently published in vivo human data by ourselves and others indicate that the promising results obtained in vitro and in situ for various hydrophilic compounds might not be valid in quantitative aspects in humans, especially not for drugs with a molecular weight over 200.     

不同饮水类型的若干癌症发病率研究

应用回顾前瞻性方法，在海宁市随机选择了８个乡（镇）作为研究区。１９７７至１９８８年间，研究区共有癌症病例１９８８人。研究结果示，饮用池塘水的肝、肺、胃、食道及结直肠的癌症平均发病率男女均为最高；而饮用井水的上述５种癌症的平均发病率最低。在各饮水类型问对各种癌症的平均发病率作了Ｐｏｉｓｓｏｎ检验，结果差异有统计学意义。将饮用井水作为非暴露，作相对危险度分析。表明饮用河水的ＲＲ值高达７．７９～１４．２５；饮用池塘水的ＲＲ则更高（２．５５～３６．９９）。本文揭示了不同饮水类型癌症发病率的差异及其联系。     

门诊部小黄家蚁防治的探讨

本文叙述了小黄家蚁危害以及对防治采取的措施,根据效果认为防治小黄家蚁危害首要是综合防制、以治理室内环境为主,辅以化学和物理方法能使小黄家蚁密度降至不足为害的水平。     

Monitoring of skin response to sodium lauryl sulphate: clinical scores versus bioengineering methods

The present trial was designed to evaluate clinical scores (single observer) of sodium lauryl sulphate (SLS)-induced skin irritation in a group of subjects (n = 10) over a 10-day period along with various skin function parameters. In order to avoid significant variations due to secondary phenomena, the following parameters were recorded with non-invasive instruments in this order: skin capacitance (C1; arbitrary units; CM420 Corneometer), transepidermal water loss (TEWL; g/m2.h; Evaporimeter) and laser Doppler flowmetry (CBFV: cutaneous blood flow values; Periflux). All examinations were performed during winter on reclined relaxed subjects present for at least 10 min in a test room with controlled temperature and relative humidity (t degrees: 19.5-20.7 degrees C and RH: 47.3-60.3%). The analysis of differential data (delta = value at tx-value before test; 2-way ANOVA) was made on single parameters as a function of site (volar forearm versus neck) and time (from 24 h after 48-h occlusion with 5% SLS up to 10 days later). The profile of erythema scores over time differed between neck and forearm, but the delta CBFV readings with the laser Doppler instrument did not detect significant site-time interactions. Roughness (blind evaluation with palpating finger) and capacitance readings (delta C1) showed significant differences between sites, but the profile over time was similar in both locations. delta TEWL did not differ according to anatomical location. The reason for different erythema scores on neck and forearm might be related to inherent regional variation of optical properties of the skin or to a substantial contribution of SLS-induced roughness to the readings of erythema.(ABSTRACT TRUNCATED AT 250 WORDS)     

Water imbibition in the rat prostate during castration-induced regression

The present study was conducted to examine changes in water concentration in the ventral prostate of adult rats at different intervals following castration. The prostatic dry weight was obtained by drying the fresh prostate at 70 degrees C for at least 110 hr and the prostatic water content was calculated from its wet and dry weight. Under normal conditions, the prostatic water concentration ranges from 81.9 to 82.7% in uncastrated rats. The prostatic water concentration started to increase at 8 hr postcastration (83.1%) but this increase was not statistically significant. By 16 hr postcastration, the prostatic water concentration (83.8%) became significantly higher than that of the uncastrated animals. In rats of day 1 to day 10 postcastration, the prostate contained significantly more water (84.4%-84.7%) than those in uncastrated animals. By day 21 postcastration, the prostatic water concentration (81.5%) was not significantly different from that of uncastrated rats. Unlike the prostate, the skeletal muscle did not significantly change the water concentration following castration. The 51Cr-EDTA space in the prostate was not significantly different in rats before and after castration. These results indicate that water imbibition in the rat prostate is associated with an active period of prostatic regression and that the change in the 51Cr-EDTA space during prostatic regression is not the major cause of water imbibition in the tissue. Therefore, the present findings suggest that castration-induced water imbibition in the rat prostate is caused by an increase in the intracellular water space.     

Regulation of fluid intake in dogs following water deprivation

Whereas water loss in land living animals occurs continuously, water intake takes place discontinuously. At the normal operating set point of plasma osmolality, urine is more concentrated than plasma due to secretion of vasopressin. Thus animals operate around a state of mild dehydration. As water loss occurs, the severity of dehydration and thirst increase in intensity and at some point water intake occurs. Sufficient water is consumed to return plasma osmolality to the normal operating set point. Food intake and water balance are interdependent as food provides the osmoles which determine obligatory renal solute excretion. When dry food with the same osmotic content was substituted for canned food (water content 74%), dogs increased water intake from 24.2 +/- 4.3 to 62.2 +/- 8.8 ml/kg. Urine output and urine osmolality were unchanged, as under conditions of normal hydration, near maximal urine concentration is achieved. Changing water intake is the only available variable to maintain water balance. During water deprivation, the major renal mechanism appears to be natriuresis. In rehydration, satiety mechanisms ensure appropriate water intake and renal sodium conservation restores sodium balance.     

When poor solubility becomes an issue: From early stage to proof of concept

Drug absorption, sufficient and reproducible bioavailability and/or pharmacokinetic profile in humans are recognized today as one of the major challenges in oral delivery of new drug substances. The issue arose especially when drug discovery and medicinal chemistry moved from wet chemistry to combinatorial chemistry and high throughput screening in the mid-1990s. Taking into account the drug product development times of 8–12 years, the apparent R&D productivity gap as determined by the number of products in late stage clinical development today, is the result of the drug discovery and formulation development in the late 1990s, which were the early and enthusiastic times of the combinatorial chemistry and high throughput screening. In parallel to implementation of these new technologies, tremendous knowledge has been accumulated on biological factors like transporters, metabolizing enzymes and efflux systems as well as on the physicochemical characteristics of the drug substances like crystal structures and salt formation impacting oral bioavailability. Research tools and technologies have been, are and will be developed to assess the impact of these factors on drug absorption for the new chemical entities.

The conference focused specifically on the impact of compounds with poor solubility on analytical evaluation, prediction of oral absorption, substance selection, material and formulation strategies and development. The existing tools and technologies, their potential utilization throughout the drug development process and the directions for further research to overcome existing gaps and influence these drug characteristics were discussed in detail.