A Novel In Vitro and In Silico System for Analyzing Complex Mechanobiological Behavior of Chondrocytes in Three-Dimensional Hydrogel Constructs.

Physiological loading is essential for the maintenance of articular cartilage through the regulation of tissue remodeling. To correctly understand the behavior of chondrocytes in their native environment, cell stimulating devices and bioreactors have been developed to examine the effect of mechanical stimuli on chondrocytes. This study describes the design and validation of a novel system for analyzing chondrocyte deformation patterns. This involves an in vitro mechanical device for a controlled application of multi-axial-loading regimes to chondrocyte-seeded agarose constructs and in silico models for analyzing chondrocyte deformation patterns. The computer-controlled device precisely applies compressive, tensile, and shear strains to hydrogel constructs using a customizable macro-based program. The synchronization of the displacements is shown to be accurate with a 1.2% error and is highly reproducible. The device design allows housing for up to eight novel designed free-swelling three-dimensional hydrogel constructs. Constructs include mesh ends and are optimized to withstand the application of up to 7% mechanical tensile and 15% shear strains. Constructs were characterized through mapping the strain within as mechanical load was applied and was validated using light microscopy methods, chondrocyte viability using live/dead imaging, and cell deformation strains. Images were then analyzed to determine the complex deformation strain patterns of chondrocytes under a range of dynamic mechanical stimulations. This is one of the first systems that have characterized construct strains to cellular strains. The features in this device make the system ideally suited for a systematic approach for the investigation of the response of chondrocytes to a complex physiologically relevant deformation profile.

The effects of intravenous anesthetics on mouse embryonic fibroblast viability and proliferation.

PURPOSE: The aim of this study is to evaluate the cytotoxic and antiproliferating effects of intravenous anesthetics on an mouse fibroblast in vitro cell culture system. METHODS: The cells were exposed to the usual clinical plasma concentration of intravenous anesthetics, i.e., midazolam (0.15 µg/ml), propofol (2 µg/ml), remifentanil (2 µg/ml), thiopental (10 µg/ml), for 4, 8, or 24 h. Cell proliferation (n = 6 for each) under intravenous anesthetics was analyzed using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Cytotoxicity (n = 6 for each) of intravenous anesthetics was investigated using a LIVE/DEAD viability assay kit. RESULTS: Intravenous anesthetic exposure time did not affect the proliferation rate of mouse fibroblasts. The cytotoxicity of intravenous anesthetics did not differ in accordance with exposure time. CONCLUSION: Our results showed that intravenous anesthetics may not affect mouse fibroblast proliferation and viability.

Effect of conical configuration of fixture on the maintenance of marginal bone level: preliminary results at 1 year of function.

OBJECTIVES: To evaluate and to compare the effect of the conical neck design on marginal bone loss around the fixtures, when both implants were provided with micro-threads to the top of the fixture. MATERIALS AND METHODS: Two types of implant, one with a straight shape (S) and the other with a conical neck design (C) provided with a retentive element to the top of the fixture, were placed adjacent to each other in the partially edentulous areas of 12 patients. Bone loss around each implant was analyzed after 1 year of functional loading. The bone losses after loading were compared using Wilcoxon's signed-rank test. RESULTS: The mean marginal bone losses (S, 0.05 + or - 0.09 mm; C, 0.07 + or - 0.14 mm) were not statistically significant between the two groups (P=0.578). CONCLUSIONS: There was no significant difference between conical and straight neck implants in terms of marginal bone loss after 1 year of loading.

Design of new potent and selective secretory phospholipase A2 inhibitors. Part 5: synthesis and biological activity of 1-alkyl-4-[4,5-dihydro-1,2,4-[4H]-oxadiazol-5-one-3-ylmethylbenz-4'-yl(oyl)] piperazines.

Among the different PLA(2)s identified to date, the group IIA secretory PLA(2) (sPLA(2) GIIA) is implied in diverse pathological conditions. In this work we describe the synthesis, inhibitory activities, and structure-activity relationships (SAR) of a new class of substituted piperazine derivatives. The in vitro fluorimetric assay using two groups of enzymes, GIB and GIIA, revealed several compounds as highly potent inhibitors (IC(50)=0.1 microM). The in vivo activity assessed by ip or per os administration in a carrageenan-induced edema test in rats showed that two compounds proved to be as potent as indomethacin (10 mg/kg).

Understanding Mind-Body Interaction from the Perspective of East Asian Medicine.

OBJECTIVE: Attempts to understand the emotion have evolved from the perspective of an independent cognitive system of the mind to that of an interactive response involving the body. This study aimed to quantify and visualize relationships between different emotions and bodily organ systems from the perspective of East Asian medicine. METHODS: Term frequency-inverse document frequency (tf-idf) method was used to quantify the significance of Five Viscera and the gallbladder relative to seven different emotions through the classical medical text of DongUiBoGam. Bodily organs that corresponded to different emotions were visualized using a body template. RESULTS: The emotions had superior tf-idf values with the following bodily organs: anger with the liver, happiness with the heart, thoughtfulness with the heart and spleen, sadness with the heart and lungs, fear with the kidneys and the heart, surprise with the heart and the gallbladder, and anxiety with the heart and the lungs. Specific patterns between the emotions and corresponding bodily organ systems were identified. CONCLUSION: The present findings will further the current understanding of the relationship between the mind and body from the perspective of East Asian medicine. Western medicine characterizes emotional disorders using "neural" language while East Asian medicine uses "somatic" language.

Regioselectivity and the nature of the reaction mechanism in nucleophilic substitution reactions of 2,4-dinitrophenyl X-substituted benzenesulfonates with primary amines.

Second-order rate constants have been measured for the reaction of 2,4-dinitrophenyl X-substituted benzenesulfonates with a series of primary amines. The nucleophilic substitution reaction proceeds through competitive S-O and C-O bond fission pathways. The S-O bond fission occurs dominantly for reactions with highly basic amines or with substrates having a strong electron-withdrawing group in the sulfonyl moiety. On the other hand, the C-O bond fission occurs considerably for the reactions with low basic amines or with substrates having a strong electron-donating group in the sulfonyl moiety, emphasizing that the regioselectivity is governed by both the amine basicity and the electronic effect of the sulfonyl substituent X. The apparent second-order rate constants for the S-O bond fission have resulted in a nonlinear Brønsted-type plot for the reaction of 2,4-dinitrophenyl benzenesulfonate with 10 different primary amines, suggesting that a change in the rate-determining step occurs upon changing the amine basicity. The microscopic rate constants (k(1) and k(2)/k(-)(1) ratio) associated with the S-O bond fission pathway support the proposed mechanism. The second-order rate constants for the S-O bond fission result in good linear Yukawa-Tsuno plots for the aminolyses of 2,4-dinitrophenyl X-substituted benzenesulfonates. However, the second-order rate constants for the C-O bond fission show no correlation with the electronic nature of the sulfonyl substituent X, indicating that the C-O bond fission proceeds through an S(N)Ar mechanism in which the leaving group departure occurs rapidly after the rate-determining step.