Common Deficiencies of <Emphasis Type="Italic">in vitro</Emphasis> Binding Bioequivalence (BE) Studies Submitted in Abbreviated New Drug Applications (ANDAs)

There are several drug products that bind phosphate or bile acid in the gastrointestinal (GI) tract to exert their therapeutic efficacy. In vitro binding studies are used to assess bioequivalence (BE) of these products. The objective of this study is to identify the common deficiencies in Abbreviated New Drug Applications (ANDAs) for these products. Deficiencies were compiled from ANDAs containing in vitro binding BE studies. The deficiencies were classified into eight categories: Pre-Study Method Validation, During-Study Sample Analysis, Study Design, Study Procedure, Dissolution/Disintegration, Analytical Site Inspection, Data Submission, and Formulations. Within each category, additional subcategories were defined to characterize the deficiencies. A total of 712 deficiencies from 95 ANDAs for 11 drug products were identified and included in the analysis. The four categories with the most deficiencies were During-Study Sample Analysis (27.8%), Pre-Study Method Validation (17.3%), Data Submission (16.7%), and Study Design (15.7%). For the During-Study Sample Analysis category, failure to submit complete raw data or analytical runs ranked as the top deficiency (32.8%). For the Study Design category, using an unacceptable alternate study design (26.8%) was the most common deficiency. Within this category, other commonly occurring deficiencies included incorrect/insufficient number of absorbent concentrations, failure to pre-treat drug product with acid, insufficient number of replicates in study, incorrect calculation of k1 and k2 values, incorrect dosage form or pooled samples used in the study, and incorrect pH of study medium. The review and approval of these products may be accelerated if these common deficiencies are addressed in the original ANDA submissions.     

中医院信息化发展现状分析与对策

以甘肃省某中医医院为例,从信息系统硬软件、信息系统应用、信息化人才队伍等方面分析中医院信息化建设现状及问题,并提出解决问题的对策方法。     

自拟中药促卵泡汤治疗多囊卵巢不孕32例

目的探究自拟中药促卵泡汤治疗多囊卵巢不孕的临床效果。方法选取在我院接受治疗的患有多囊卵巢不孕的64例患者作为研究对象,严格按照随机原则将其分为对照组与观察组,每组患者均有32例。对照组患者采用枸橼酸氯米芬胶囊进行治疗,观察组患者采用自拟中药促卵泡汤进行治疗,观察并对比两组患者治疗前后的卵泡数目、卵巢大小、性激素水平以及临床治疗效果。结果观察组与对照组患者治疗后,卵泡数目均有所减少,卵巢均有所缩小,性激素水平得到改善,与治疗前相比,差异具有统计学意义(P0.05);与对照组患者治疗后相比,观察组患者的卵泡数目减少、卵巢缩小更为明显、性激素水平改善的效果更佳,差异具有统计学意义(P0.05);观察组患者的总有效率为93.75%,对照组患者的总有效率为75.00%,差异较大,具有统计学意义(P0.05)。结论自拟中药促卵泡汤可有效地减少卵泡数目,缩小卵巢,改善性激素水平,利于治疗多囊卵巢不孕,值得临床推广使用。     

Orthodontic re-treatment. A qualitative study of patients

A growing number of patients go to orthodontic practices to receive orthodontic re-treatment, but their reasons for seeking re-treatment are uncertain. By means of a standardized questionnaire this study investigates the patients'experiences with the initial orthodontic treatment, applied retention procedures, and the patients'expectations and motivational reasons for re-treatment. In total 100 patients were asked to complete the questionnaire, 88 of them actually filled it out. The study subjects showed an above average educational level, with a considerably higher percentage of females than males seeking re-treatment. Fixed appliances were used most frequently during the first course of treatment and most patients had been fitted with a removable retention plate or fixed retention wire at the conclusion of their first treatment; almost 40% of the patients did not receive any kind of retention appliance. Patients sought re-treatment mostly on their own initiative, as opposed to their initial treatment, when they were mostly referred by dentists or orthodontists. This revealed itself in patients' high levels of motivation for re-treatment. Moreover, patients appeared to have realistic impressions of the time and cost involved in re-treatment.     

Mouse mandible contains distinctive mesenchymal stem cells

Although human orofacial bone-marrow-derived mesenchymal stem cells showed differentiation traits distinctly different from those of mesenchymal stem cells (MSCs) derived from long bone marrow (BMMSCs), mouse MSCs derived from orofacial bone have not been isolated due to technical difficulties, which in turn precludes the use of mouse models to study and cure orofacial diseases. In this study, we developed techniques to isolate and expand mouse orofacial bone/bone-marrow-derived MSCs (OMSCs) from mandibles and verified their MSC characteristics by single-colony formation, multi-lineage differentiation, and in vivo tissue regeneration. Activated T-lymphocytes impaired OMSCs via the Fas/Fas ligand pathway, as occurs in BMMSCs. Furthermore, we found that OMSCs are distinct from BMMSCs with respect to regulating T-lymphocyte survival and proliferation. Analysis of our data suggests that OMSCs are a unique population of MSCs and play an important role in systemic immunity. Abbreviations: BMMSC, bone marrow mesenchymal stem cell; HA/TCP, hydroxyapatite/tricalcium phosphate; OMSC, orofacial mesenchymal stem cell; OVX, ovariectomized.     

Sliding contact fatigue of graded zirconia with external esthetic glass

Veneer chipping and fracture are common failure modes for porcelain-veneered zirconia dental restorations. We hypothesized that the graded glass/zirconia/glass with external esthetic glass (e-GZG) can increase the lifetime and improve resistance to veneer chipping and fracture relative to porcelain-veneered zirconia, while providing necessary esthetics. Previously, we have demonstrated that a graded glass-zirconia surface possesses excellent resistance to occlusal-like sliding contact fatigue. Here, we investigated the sliding contact fatigue response of this graded glass-zirconia surface with external esthetic glass. This external glass is essential for shade options, for preventing excessive wear of opposing dentition, and for protecting Y-TZP from hydrothermal degradation. e-GZG plates were bonded to composite blocks and subjected to prolonged sliding contact up to 10 million cycles at 200 N in water. The resistance to sliding contact fatigue of e-GZG matches that of monolithic Y-TZP, and both of these materials demonstrated lifetimes that were orders of magnitude longer than that of porcelain-veneered zirconia. Graded e-GZG is a promising restorative material.     

激光照射对牙髓细胞形态的影响

不同的激光能量可以产生不同的生物效应．本文应用扫描电镜、倒置显微镜观察不同能量、不同频率的激光能量设置对牙髓细胞形态的影响，结果表明：１００ｍｊ２０Ｈｚ、６０ｍｊ４０Ｈｚ、４０ｍｊ５０Ｈｚ以上的能量设置可使牙髓细胞产生裂纹、结构模糊．结论：Ｎｄ：ＹＡＧ激光的能量、频率均可影响牙髓细胞形态     

Optimum force magnitude for orthodontic tooth movement: a mathematic model.

The aim of this study was to develop a mathematic model to describe the relationship between magnitude of applied force and rate of orthodontic tooth movement. Initially, data were extracted from experimental studies in dogs (beagles), in which controlled, standardized forces were used to move mandibular second premolars distally. Curve-fitting by nonlinear regression analysis provided an equation describing the relationship between force magnitude and rate of tooth movement in beagles. A similar equation was subsequently used to analyze the limited available data from the literature on human canine retraction. The maximum rates of tooth movement in humans and dogs are very similar. A threshold for force magnitude that would switch on tooth movement could not be defined. The model showed that a wide range of forces can be identified, all of which lead to a maximum rate of tooth movement.     

Paxillin phosphorylation and integrin expression in osteoblasts infected by Porphyromonas gingivalis

OBJECTIVE: We investigated early biological events initiated by Porphyromonas gingivalis infection of human osteoblasts, focusing on tyrosine-phosphorylation and the expression of key components in focal adhesion and cell signalling. DESIGN: Human primary osteoblasts were challenged for 1h with Porphyromonas gingivalis. Tyrosine-phosphorylation of paxillin and focal adhesion kinase (FAK) was examined by Western blotting. Changes in alpha3- and beta1-integrin mRNA expression were quantified by RT-PCR. RESULTS: Tyrosine-phosphorylation of paxillin was proportional to the size of the Porphyromonas gingivalis inoculum. FAK, a potential kinase for paxillin, was not activated. The amount of alpha3- and beta1-integrins, determined by Western blotting, did not vary significantly, while the corresponding mRNA levels fell significantly when a large bacterial inoculum was used. CONCLUSIONS: These results indicate that Porphyromonas gingivalis infection of osteoblasts in vitro triggers tyrosine-phosphorylation of paxillin but not FAK and modify alpha3- and beta1-integrin mRNA expression. This infection thus appears to have different effects on components with essential roles in focal adhesion (paxillin) and cell signalling (FAK and integrins).