Cortical and trabecular bone adaptation to incremental load magnitudes using the mouse tibial axial compression loading model

The mouse tibial axial compression loading model has recently been described to allow simultaneous exploration of cortical and trabecular bone adaptation within the same loaded element. However, the model frequently induces cortical woven bone formation and has produced inconsistent results with regards to trabecular bone adaptation. The aim of this study was to investigate bone adaptation to incremental load magnitudes using the mouse tibial axial compression loading model, with the ultimate goal of revealing a load that simultaneously induced lamellar cortical and trabecular bone adaptation. Adult (16 weeks old) female C57BL/6 mice were randomly divided into three load magnitude groups (5, 7 and 9 N), and had their right tibia axially loaded using a continuous 2-Hz haversine waveform for 360 cycles/day, 3 days/week for 4 consecutive weeks. In vivo peripheral quantitative computed tomography was used to longitudinally assess midshaft tibia cortical bone adaptation, while ex vivo micro-computed tomography and histomorphometry were used to assess both midshaft tibia cortical and proximal tibia trabecular bone adaptation. A dose response to loading magnitude was observed within cortical bone, with increasing load magnitude inducing increasing levels of lamellar cortical bone adaptation within the upper two thirds of the tibial diaphysis. Greatest cortical bone adaptation was observed at the midshaft where there was a 42% increase in estimated mechanical properties (polar moment of inertia) in the highest (9 N) load group. A dose response to load magnitude was not clearly evident within trabecular bone, with only the highest load (9 N) being able to induce measureable adaptation (31% increase in trabecular bone volume fraction at the proximal tibia). The ultimate finding was that a load of 9 N (engendering a tensile strain of 1833 με on medial surface of the midshaft tibia) was able to simultaneously induce measurable lamellar cortical and trabecular bone adaptation when using the mouse tibial axial compression loading model in 16 week old female C57BL/6 mice. This finding will help plan future studies aimed at exploring simultaneous lamellar cortical and trabecular bone adaptation within the same loaded element.     

Psychotherapy provision,socioeconomic deprivation,and the inverse care law

Abstract

In this study of routine service data and census data, the authors explore the influence of socioeconomic status on patients entering an integrated psychotherapy service. Between January 1, 2000, and September 30, 725 patients were assessed and had their Townsend Index of Material Deprivation (TIMD) scores derived from postcodes. Results showed no correlation between TIMD score and those attending their assessment and no significant difference in TIMD score between those allocated to psychoanalytic psychotherapy (PAP) or cognitive–behavioral psychotherapy (CBP) and between those accepted and not accepted for each treatment. No correlation was found between Townsend score and numbers presenting to the service, suggesting that the inverse care law applies. Deprivation is not a predictor of patient allocation to or acceptance for PAP or CBP.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

巨噬细胞迁移抑制因子通过CC趋化因子配体2诱导巨噬细胞聚集

巨噬细胞迁移抑制因子最初是由于能抑制体外巨噬细胞随机迁移而被发现,现在它作为一种重要的调节因子参与一系列炎症性疾病过程.我们最近发现,巨噬细胞迁移抑制因子的缺失使一些由炎症介质诱发的白细胞-内皮细胞相互作用减弱,提示巨噬细胞迁移抑制因子在炎症反应中起作用的机制之一是促进白细胞聚集.……     

Piecemeal degranulation of mast cells in the inflammatory eyelid lesions of interleukin-4 transgenic mice. Evidence of mast cell histamine release in vivo by diamine oxidase-gold enzyme-affinity ultrastructural cytochemistry

We used light and electron microscopy to analyze the eyelid inflammation that develops in transgenic mice that overexpress interleukin-4 (IL-4; Tepper et al, Cell 62:457, 1990). Analysis of alkaline Giemsa-stained plastic sections examined by light microscopy (Dvorak et al, J Exp Med 132:558, 1970), as well as by routine transmission electron microscopy, indicated that the mast cells in the inflammatory eyelid lesions were undergoing piecemeal degranulation, a form of secretion in which the cells' cytoplasmic granules exhibit characteristic morphologic changes that are thought to be associated with the prolonged, vesicle-mediated release of the granules' constituents. Moreover, by using a newly reported enzyme affinity-gold method, which stains histamine based on binding to diamine oxidase-gold (Dvorak et al, J Histochem Cytochem 41:787, 1993), we show that these activated mast cells had released much of their histamine content. The eyelid lesions also exhibited increased numbers of mast cells; interstitial fibrosis, particularly around cutaneous nerves and blood vessels; activated fibroblasts; focal axonal damage; venules with endothelial cells containing numerous vesiculo-vacuolar organelles; and infiltrates of neutrophils and eosinophils. Our findings illustrate that overexpression of the IL-4 gene in vivo can result in eyelid lesions associated with piecemeal degranulation of mast cells, as well as tissue fibrosis and a variety of other pathologic changes. These results also represent the first direct morphologic evidence for histamine secretion by mast cells in vivo.     

差速贴壁技术对大鼠脑皮质星形胶质细胞纯化率的影响

目的:观察差速贴壁技术对星形胶质细胞纯化率的影响,旨在建立一套可靠的大鼠脑皮质星形胶质细胞的取材分离、纯化培养技术。方法:实验于2006-06/08在泰山医学院生命科学研究所完成。实验材料:出生2～3d的Wistar大鼠,雌雄不拘,由泰山医学院生命科学研究所实验动物中心提供。实验方法:选用出生二三天的Wistar大鼠进行脑皮质星形胶质细胞原代培养。实验分两组培养:常规培养组和差速贴壁培养组。差速贴壁培养组分别于15,30min取出,轻轻翻转培养瓶,将上清液移至另一培养瓶中,放入培养箱中继续培养。7～10d后传代,待细胞分层生长后,置于37℃摇床中250r/min振荡18h,倒掉上清液,D-Hank’s液洗3次后,加入0.25%胰酶消化,倒置显微镜下观察,待细胞突起回缩后加入含血清的培养基终止消化,用吸管反复吹打使细胞从瓶壁上脱落,细胞悬液1000r/min离心5min后,弃上清液,加入含体积分数为0.2血清的DMEM培养基混悬沉淀,接种入预先涂有L-多聚赖氨酸的培养瓶中继续培养。采用双重免疫荧光法鉴定星形胶质细胞纯度,测定积分吸光度值判断星形胶质细胞的生长状况。结果:①应用差速贴壁技术培养星形胶质细胞可明显提高星形胶质细胞纯度[常规培养组:(82±3)%,差速贴壁培养组15min:(94±2)%,差速贴壁培养组30min:(95±2)%,P<0.01]。差速贴壁需要充分的时间,15min组和30min组在提高星形胶质细胞纯度方面无明显差别。②差速贴壁培养组星形胶质细胞积分吸光度值高于常规培养组(常规培养组:528±25,差速贴壁培养组15min:972±17,差速贴壁培养组30min:996±35,P<0.05)。结论:①差速贴壁技术可明显提高星形胶质细胞纯化度,并且星形胶质细胞生长状态明显优于常规培养方法。②最佳差速贴壁时间为15min,过长差速贴壁时间对提高星形胶质细胞纯度无明显影响。