Estimation of Intragastric Solubility of Drugs: In What Medium?

Purpose To measure the solubility of four drugs in human gastric aspirates, canine gastric aspirates (CGF) and simulated gastric fluids in order to propose a medium for estimating intragastric drug solubility relevant to a bioavailability study in the fasted state. Materials and Methods Intragastric environment after administration of water to healthy fasted adults and to healthy fasted dogs (this study) was initially characterized. Solubilities were then measured with the shake-flask method in gastric fluid aspirated after the administration of water to healthy fasted adults and to healthy fasted dogs, in various simulated gastric fluids, i.e. SGF_SLS, SGF_Triton, FaSSGF, FaSSGF_NaCl, and in various HCl solutions with pH values ranging from 1.2 to 2.9. Results In all cases, FaSSGF performed better than canine aspirates, SGF_SLS, SGF_Triton, or FaSSGF_NaCl in predicting solubility in HGF. However, its superiority over HCl pH 1.6 was not clear. For ketoconazole, dipyridamole, miconazole, and felodipine deviations of solubility data in FaSSGF from solubility data in HGF were non-significant, 34, −39 and 252%, respectively, whereas the corresponding deviations of data in HCl pH 1.6 from data in HGF were non-significant, 24, 70, and 130%, respectively. Conclusions Combining data in FaSSGF and HCl pH 1.6 is comparatively the most efficient way to get an estimate of drug solubility in the fasting gastric contents during a bioavailability study. However, accurate estimation of intragastric solubility is limited by the changing environment during intragastric residence of solid particles and the degree of simulation of intragastric composition.     

模拟失重对肺微血管内皮细胞凋亡的影响

目的：观察回转模拟失重对肺微血管内皮细胞凋亡的影响。方法：组织块贴壁法原代培养肺微血管内皮细胞（pulmonary microvascular endothelial cells,PMVEC）,采用回转器模拟失重效应。PMVEC回转培养48h,同时设1g对照静置培养。采用Hoechst33258染色,荧光显微镜观细胞凋亡的形态学改变;采用Annexin V—FITC试剂盒对细胞染色,以流式细胞仪进行细胞凋亡检测。结果：回转模拟失重48h后,Hoeehst33258染色结果发现细胞凋亡明显增加;流式细胞仪定量结果表明回转48hPMVEC的凋亡率为19．85％,显著高于同步对照组PMVEC的凋亡率13．72％（19．85％±1．29％vs13．72％±1．15％,P〈0．01）。结论：48h回转模拟失重可明显诱导PMVEC发生凋亡。     

基于Alopex的进化优化算法

提出了一种基于Alopex的进化优化算法。该算法在进化过程中从种群中随机选择2个个体,通过计算2个个体和目标函数值的变化情况,确定算法进一步搜索方向的概率,逐步迭代最终收敛到全局最优。该算法具备基本进化算法的特点,同时具备Alopex算法的优点,即在一定程度上具有梯度下降法和模拟退火算法的优点。对典型函数的测试表明：新算法的全局搜索能力有了显著提高,特别是对多峰函数能够有效地避免早熟收敛问题。     

五味子复方对模拟航渡及高强度运动大鼠下丘脑-垂体-肾上腺轴功能和代谢的影响

目的:探讨五味子复方对模拟航渡及大强度运动大鼠下丘脑-垂体-肾上腺轴功能和代谢的影响。方法:选取31只大鼠,随机分成安静组(A组),应激组(B组)和五味子复方组(C组),大鼠给予五味子复方煎液10 mL.kg-1,2次/d ig,剂量为20 g·kg-1,共1周,B组和C组给予模拟渡航及高强度运动,比较3组大鼠血糖(blood glucose)、甘油三酯(triglyceride,TG)、胆固醇(cholesterol,CHO)及皮质醇(corticosterone,CORT)水平,并观察3组大鼠垂体促肾上腺皮质激素(adrenocorticotropichormone,ACTH)、神经肽Y(neuropeptide Y,NPY)阳性细胞数量和肾上腺皮质的超微结构。结果:①与A组相比,B组血糖水平显著增高(9.41±2.56)mmol.L-1,P<0.01,TG和CHO水平显著降低,TG(0.42±0.16)mmol.L-1,P<0.01;CHO(1.69±0.23)mmol.L-1,P<0.05;C组与B组相比,其血糖水平降低(6.45±2.25)mmol.L-1,P<0.05,TG水平升高(0.63±0.22)mmol.L-1,P<0.05,CHO无明显差异(1.83±0.19)mmol.L-1。②垂体ACTH和NPY阳性细胞免疫组化结果:C组ACTH阳性细胞和NPY阳性细胞数量较应激组增加,但两组都少于A组。③肾上腺电镜结果:与A组相比,B组肾上腺皮质细胞中分泌颗粒数目明显减少;C组肾上腺皮质细胞内分泌颗粒数目较B组明显增多。结论:五味子复方能降低应激大鼠血糖水平,维持物质代谢平衡,提高大鼠抗应激能力,保护垂体和肾上腺组织的结构功能。     

物理仿真实验教学心得

在物理实验教学过程中,仿真实验发挥了一定的作用,但同时也存在有一定的弊端。通过实际教学的切身体会,分析了仿真实验在实验教学中的积极作用和消极影响,并提出了一些需要注意的问题。     

An in vitro investigation into retention strength and fatigue resistance of various designs of tooth/implant supported overdentures

Previously,the choice of prosthetic implant-retained overdentures has depended on data from previous studies about the retention-fatigue strength of the attachment system selected.Little or no data have been available on the correlation between the attachment system selected and the overdenture support configuration.The purpose of the present study was to evaluate the retention force and fatigue resistance of three attachment systems and four support designs of overdenture prosthesis.Four lower edentulous acrylic models were prepared and eight combinations of attachments groups were investi-gated in the study.These included:O-Rings with mini-dental implants (MDIs),Dalbo elliptic with Dalbo Rotex and fabricated flexible acrylic attachments with both MDI and Dalbo Rotex.The study was divided into four test groups:groups A and B,controls,and groups C and D,experimental groups.Con-trol group A contained three overdenture supports:two free standing MDIs in the canine region and at the midline,and one simulated tooth root with Dalbo Rotex screwed in.Control group B contained four overdenture support foundations:two free standing MDIs in the right canine region and the first premo-lar region,and two simulated tooth roots with Dalbo Rotex screwed in at the same MDI position,but on the left side of the model.Experimental group C contained three overdenture support foundations:two free standing MDIs in the canine region and at the midline,and one simulated tooth root with MDI screwed in.Experimental group D contained four overdenture support foundations:two free standing MDIs in the right canine region and the first premolar region,and two simulated tooth roots with MDIs screwed in at the same MDI position,but on the left side of the model.Each group was further divided into two subgroups according to attachment type used.Five samples were prepared for each group.Re-tention force (N) values were recorded initially (0 cycles) and after 360,720,1440 and 2880 insertion and removal cycles.During the tensile test a cross-head speed of 10 mm/min was applied.Values of ab-solute force (AF) and relative force (RF) were statistically analyzed by two-way ANOVA and multiple comparison Tukey’s tests between groups and cycles periods.The results of fatigue tests showed a 50% reduction in retention force in the subgroups with flexible attachments.A triangular design of overden-ture support foundations with O-Ring attachments revealed the lowest value of AF and a relatively high reduction in RF.The four overdenture support designs with flexible acrylic attachments improved the retention force and reduced the fatigue retention.Furthermore,the results of the investigation demon-strate that flexible acrylic attachments for both teeth and implant-supported overdentures offer a wide range of retention forces.     

Development of the foremost light-curable calcium-silicate MTA cement as root-end in oral surgery. Chemical-physical properties, bioactivity and biological behavior

Aim

An innovative light-curable calcium-silicate cement containing a HEMA-TEGDMA-based resin (lc-MTA) was designed to obtain a bioactive fast setting root-end filling and root repair material.

Methods

lc-MTA was tested for setting time, solubility, water absorption, calcium release, alkalinizing activity (pH of soaking water), bioactivity (apatite-forming ability) and cell growth-proliferation. The apatite-forming ability was investigated by micro-Raman, ATR-FTIR and ESEM/EDX after immersion at 37 °C for 1-28 days in DPBS or DMEM + FBS. The marginal adaptation of cement in root-end cavities of extracted teeth was assessed by ESEM/EDX, and the viability of Saos-2 cell on cements was evaluated.

Results

lc-MTA demonstrated a rapid setting time (2 min), low solubility, high calcium release (150-200 ppm) and alkalinizing power (pH 10-12). lc-MTA proved the formation of bone-like apatite spherulites just after 1 day. Apatite precipitates completely filled the interface porosities and created a perfect marginal adaptation. lc-MTA allowed Saos-2 cell viability and growth and no compromising toxicity was exerted.

Significance

HEMA-TEGDMA creates a polymeric network able to stabilize the outer surface of the cement and a hydrophilic matrix permeable enough to allow water absorption. SiO⁻/Si-OH groups from the mineral particles induce heterogeneous nucleation of apatite by sorption of calcium and phosphate ions. Oxygen-containing groups from poly-HEMA-TEGDMA provide additional apatite nucleating sites through the formation of calcium chelates. The strong novelty was that the combination of a hydraulic calcium-silicate powder and a poly-HEMA-TEGDMA hydrophilic resin creates the conditions (calcium release and functional groups able to chelate Ca ions) for a bioactive fast setting light-curable material for clinical applications in dental and maxillofacial surgery. The first and unique/exclusive light-curable calcium-silicate MTA cement for endodontics and root-end application was created, with a potential strong impact on surgical procedures.     

模拟微重力培养环境下牙周膜干细胞生长状态的研究

目的探讨模拟微重力培养体系下人牙周膜干细胞（human periodontal ligament stem cells,HPDLSCs）的生长特点。方法在体外用有限稀释法克隆化生长获得HPDLSCs,接种于葡聚糖微载体,观察在旋转微重力细胞培养环境下与普通重力环境下细胞生长状态的差异。结果利用克隆生长法成功获取具备多向分化潜能的HPDLSCs,在微重力环境下的微载体表面细胞多呈半球形,少数铺展为不规则扁平形或长梭形,与普通重力环境相比,细胞生长速度明显加快。结论三维微重力培养环境可以迅速获得大量的HPDLSCs,为构建工程化牙周组织奠定了实验基础。     

Brain development,environment and sex: what can we learn from studying graviperception,gravitransduction and the gravireaction of the developing CNS to altered gravity?

As man embarks on space exploration and contemplates space habitation, there is a critical need for basic understanding of the impact of the environmental factors of space, and in particular gravity, on human survival, health, reproduction and development. This review summarizes our present knowledge on the effect of altered gravity on the developing CNS with respect to the response of the developing CNS to altered gravity (gravireaction), the physiological changes associated with altered gravity that could contribute to this effect (gravitransduction), and the possible mechanisms involved in the detection of altered gravity (graviperception). Some of these findings transcend gravitational research and are relevant to our understanding of the impact of environmental factors on CNS development on Earth.     

Effectiveness of simulated presence therapy for individuals with dementia: A systematic review and meta-analysis

Objectives: To formally assess the strength of evidence for the efficacy of simulated presence therapy for challenging behaviours in dementia (playing an audio or videotape to an individual, personalized by a carer and containing positive experiences from the client's life and shared memories involving family and friends) using meta-analytic techniques.

Method: Systematic review and meta-analysis of k = 4 studies of simulated presence therapy for challenging behaviours in dementia.

Results: Meta-analysis indicated a significance effect (d = 0.70, 95% CI = 0.38–1.02), although this was reduced when the first published study was removed from the analysis.

Conclusion: These findings provide limited support for the use of simulated presence therapy with this population and stress the importance of assessing participants’ suitability for such an approach and monitoring their responses closely. Future adequately powered studies are necessary to confirm the efficacy of simulated presence therapy.