The influence of bile salts on the distribution of simvastatin in the octanol/buffer system

Abstract

Introduction: Distribution coefficient (D) is useful parameter for evaluating drugs permeability properties across biological membranes, which are of importance for drugs bioavailability. Given that bile acids are intensively studied as drug permeation-modifying and -solubilizing agents, the aim of this study was to estimate the influence of sodium salts of cholic (CA), deoxycholic (DCA) and 12-monoketocholic acids (MKC) on distribution coefficient of simvastatin (SV) (lactone [SVL] and acid form [SVA]) which is a highly lipophilic compound with extremely low water solubility and bioavailability.

Methods: LogD values of SVA and SVL with or without bile salts were measured by liquid–liquid extraction in n-octanol/buffer systems at pH 5 and 7.4. SV concentrations in aqueous phase were determined by HPLC-DAD. Chem3D Ultra program was applied for computation of physico-chemical properties of analyzed compounds and their complexes.

Results: Statistically significant decrease in both SVA and SVL logD was observed for all three studied bile salts at both selected pH. MKC exerted the most pronounced effect in the case of SVA while there were no statistically significant differences between observed bile salts for SVL. The calculated physico-chemical properties of analyzed compounds and their complexes supported experimental results.

Conclusions: Our data indicate that the addition of bile salts into the n-octanol/buffer system decreases the values of SV distribution coefficient at both studied pH values. This may be the result of the formation of hydrophilic complexes increasing the solubility of SV that could consequently impact the pharmacokinetic parameters of SV and the final drug response in patients.     

功能需求与用户体验下的快递包装设计研究

目的针对目前快递包装在功能上发生的新变化,研究基于功能需求与用户体验的快递包装的设计策略,力求增加快递包装的适用性和附加价值,减少包装物废弃和资源浪费。方法秉承减量化和可循环的绿色包装设计理念,分析快递包装的功能变化与用户体验等层次的要求。结论基于功能需求与用户体验来进行的快递包装创新设计,需要外观设计独特,有趣味;信息传达智能化、突出品牌;结构设计注重保护性、针对性和便利性;通过趣味设计,交互体验,情感共鸣,来拓展快递包装的用途。     

On the Structure of Amorphous Mesoporous Silica Nanoparticles by Aberration‐Corrected STEM

Mesoporous silica materials have demonstrated a vast spectrum of applications, stimulating an intensive field of study due to their potential use as nanocarriers. Nonetheless, when produced at the nanoscale, their structural characterization is hindered due to the re‐arrangement of the pores. To address this issue, this work combines molecular dynamics simulations with electron microscopy computer simulations and experimental results to provide an insight into the structure of amorphous mesoporous silica nanoparticles. The amorphous silica model is prepared using a simple melt‐quench molecular dynamics method, while the reconstruction of the mesoporous nanoparticles is carried out using a methodology to avoid false symmetry in the final model. Simulated scanning transmission electron microscopy images are compared with experimental images, revealing the existence of structural domains, created by the misalignment of the pores to compensate the surface tension of these spherical nanoparticles.     

科技论文参考文献著录的规范表达

依据ＧＢ７７１４－８７《文后参考文献著录规则》,对３９０篇来稿所引用的参考文献进行统计,分析了几种不规范的著录方式,并给出正确的表达方法,可为科技论文写作者及科技期刊编缉提供参考。     

Veal colour assessment with three wavelengths

A method to derive reflectance spectra and colour coordinates of meat by measurement of reflectance at only three wavelengths, 480, 570 and 620 nm has been developed, by treating the spectra of a meat sample as a linear combination of the spectra of the three major myoglobin derivatives (reduced myoglobin, oxymyoglobin and metmyoglobin). Applied to 300 samples of Semitendinosus and Longissimus dorsi veal muscles at different times post mortem (24 h to 9 d), colour differences ΔE (?) between the derived spectra and the real ones were about 1.5 units. The total pigment content, with high correlation with the extraction method (P < 0.02), and the relative proportions of the derivatives can also be estimated.     

A new fuzzy regression algorithm

A new fuzzy regression algorithm is described and compared with conventional ordinary and weighted least-squares and robust regression methods. The application of these different methods to relevant data sets proves that the performance of the procedure described in this paper exceeds that of the ordinary least-squares method and equals and often exceeds that of weighted or robust methods, including the two fuzzy methods proposed previously (Otto, M.; Bandemer, H., Chemom. Intell. Lab. Syst. 1986, 1, 71. Hu, Y.; Smeyers-Verbeke, J.; Massart, D. L. Chemom. Intell. Lab. Syst. 1990, 8, 143). Moreover, we emphasize the effectiveness and the generality of the two new criteria proposed in this paper for diagnosing the linearity of calibration lines in analytical chemistry.     

The behavior of the fibrinolytic system during long-term orthopedic immobilization]

Our previous experimental studies on rats motionless for 7 to 60 days in special devices limiting their movements revealed a significantly increased activity of the fibrinolytic system (Groza, Artino) due to the "detention stress" rather then to the immobilization. Starting from these studies we have tried to observe the behaviour of the fibrinolytic system during long-term orthopedic immobilization (7-28 days) on patients having different injuries of the lower limb and submitted to orthopedic therapy (with or without osteosynthesis) to which an anticoagulant preventive treatment was added (heparin or low-molecular-weight substitutes such as Clivarine, Fraxiparine). We studied on 23 patients (11 male and 12 female) motionless for 14, 21, 28 days the plasma fibrinolytic activity (PFA) through euglobulin lysis time (ELT). Clinical investigation revealed that PFA did not change significantly during long-term orthopedic immobilization regardless of the duration of immobilization (14,21,28 days). Rosenfeld et al. (1994) described in healthy volunteers on bedrest for 36 hours an increase of PFA beginning at 24 hours of immobilization, this variation being capable of preventing stasis effects. Our results suggest that preventive anticoagulant therapy properly given during immobilization prevents thromboembolic events.     

Multiple spatial sounds in hierarchical menu navigation for visually impaired computer users

This paper describes a user study on the benefits and drawbacks of simultaneous spatial sounds in auditory interfaces for visually impaired and blind computer users. Two different auditory interfaces in spatial and non-spatial condition were proposed to represent the hierarchical menu structure of a simple word processing application. In the horizontal interface, the sound sources or the menu items were located in the horizontal plane on a virtual ring surrounding the user’s head, while the sound sources in the vertical interface were aligned one above the other in front of the user. In the vertical interface, the central pitch of the sound sources at different elevations was changed in order to improve the otherwise relatively low localization performance in the vertical dimension. The interaction with the interfaces was based on a standard computer keyboard for input and a pair of studio headphones for output. Twelve blind or visually impaired test subjects were asked to perform ten different word processing tasks within four experiment conditions. Task completion times, navigation performance, overall satisfaction and cognitive workload were evaluated. The initial hypothesis, i.e. that the spatial auditory interfaces with multiple simultaneous sounds should prove to be faster and more efficient than non-spatial ones, was not confirmed. On the contrary—spatial auditory interfaces proved to be significantly slower due to the high cognitive workload and temporal demand. The majority of users did in fact finish tasks with less navigation and key pressing; however, they required much more time. They reported the spatial auditory interfaces to be hard to use for a longer period of time due to the high temporal and mental demand, especially with regards to the comprehension of multiple simultaneous sounds. The comparison between the horizontal and vertical interface showed no significant differences between the two. It is important to point out that all participants were novice users of the system; therefore it is possible that the overall performance could change with a more extensive use of the interfaces and an increased number of trials or experiments sets. Our interviews with visually impaired and blind computer users showed that they are used to sharing their auditory channel in order to perform multiple simultaneous tasks such as listening to the radio, talking to somebody, using the computer, etc. As the perception of multiple simultaneous sounds requires the entire capacity of the auditory channel and total concentration of the listener, it does therefore not enable such multitasking.     

Scenario-based testing from UML/OCL behavioral models

We present in this article a way to produce test suites applied to the POSIX mini-challenge based on a behavioral model of a file system manager written in UML/OCL. We illustrate the limitations of a fully automated test generation approach, which justifies the use of test scenarios as a complement to a functional testing approach. Scenarios are expressed through regular expressions describing sequences of operations, possibly punctuated by intermediate states that have to be reached by the execution of the model. Scenarios are unfolded into extended sequences of operations that are played on the model using symbolic animation techniques. We experimented our approach by testing the conformance of two different file systems w.r.t. the POSIX standard: a recent Linux distribution and a customized Java implementation of POSIX used to evaluate the relevance of our approach and its complementarity with a structural test generation approach.