钛种植体－羟基磷灰石早期修复犬下颌骨缺损与骨结合的实验研究

本研究对钛种植体－羟基磷灰石（Ｔｉ－ＨＡ）在早期修复下颌骨缺损中与骨结合的界面形态进行了扫描电镜和Ｘ线能谱观察分析。通过对９只健康狗下颌骨缺损区植入Ｔｉ－ＨＡ２、６及１２周后Ｔｉ－ＨＡ／宿主骨界面及Ｔｉ／ＨＡ界面的扫描电镜观察和Ｘ线能谱分析，结果表明Ｔｉ－ＨＡ植入骨缺损区，不引起正常的骨矿化过程改变，与宿主骨形成骨性结合；Ｔｉ／ＨＡ界面有新骨形成；扫描电镜观察和Ｘ线能谱分析在研究骨缺损修复过程中不同阶段的组织成份的变化是一个重要手段。     

IL-1β诱导体外培养的大鼠中脑黑质神经元c-jun表达

应用细胞原位杂交技术，观察经重组小鼠白细胞介素-19（IL-1β）处理后的体外培养的新生1d大鼠中脑黑质神经元c－jun基因的表达．结果显示，培养的黑质细胞多为酪氨酸羟化酶阳性神经元，IL-1β可诱导体外培养的黑质神经元c－junmRNA表达，高水平的表达出现在IL-1β处理后2～4h。说明IL－1β有兴奋黑质神经元的作用，并提示黑质神经元上可能存在IL－1β受体．     

Amine Prodrugs Which Utilize Hydroxy Amide Lactonization. I. A Potential Redox-Sensitive Amide Prodrug

Several amides of 3-(3,6-dioxo-2,4-dimethylcyclohexa-l,4-diene)-3,3-diniethylpropionic acid (2) have been synthesized and tested as model redox-sensitive pro-prodrugs of amines. The reduction of these model pro-prodrugs generated hydroxy amide intermediates 4a-4h, the lactonization of which resulted in amine release. The rates of lactonization of 4a-4h were investigated at pH 7.4 and 37°C. The half-lives for appearance of the product lactone la from these intermediates were found to range from 1.4 to 3.4 min. With such rapid lactonization rates, it is believed that reduction will be the rate-limiting step in the two-step conversion of the pro-prodrug to the amine.     

Iodine-125 labeled phenylphosphonic acid: A new radiopharmaceutical for long-term investigations of the skeleton

A skeletal seeking radiopharmaceutical labeled with a long-lived radionuclide was developed to evaluate regional bone formation and its subsequent resorption. The agent is [phosphonate (phenylmethylene hydroxy) bis]-I-125 or I-125 PA. Tissue distribution studies in mice (N=16) showed approximately 40% of the administered dose to be retained by the skeleton up to 336 hours post IV injection. The percentage of the dose accumulated by the thyroid gland remained at less than 0.5%, indicating minimal deiodination of the I-125 PA. Whole body retention studies in the same species revealed a triexponential release pattern with the longest component comprising 33% of the dose with a biologic half-life of 962 days. A fractured rat tibia model was studied with I-125 PA and Tc-99^m MDP. Chronic loss of the I-125 PA relative to normal tibia was quantitated: five days (62.8%); 30 days (47.4%). Concomitant increased uptake of the Tc-99^m MDP was observed at the fracture site relative to normal: five days (186%); 30 days (1,041%). The above data suggest that I-125 PA can be utilized to measure acute bone formation and chronic resorption.     

Update on vitamin D and evaluation of vitamin D status

Knowledge about vitamin D has greatly improved during the last few years. Vitamin D cannot any more be considered as exclusively necessary to prevent ricket/osteomalacia. Its role in the prevention of some osteoporotic fractures in the elderly (in association with calcium nutrition) is now well demonstrated and many epidemiologic and laboratory data argue for a role in the prevention of several diseases or anomalies (cancer, auto-immune diseases, cardiovascular events, sarcopenia...). A few intervention studies confirming some of these effects also exist. Vitamin D status can easily be assessed by measuring serum 25 hydroxy vitamin D (25OHD) level. However, many experts have claimed that the population-based reference values for 25OHD are too low and that the cut-off value below which vitamin D insufficiency can be present is somewhere between 20 and 40 ng/mL with a clear tendency to target values above 30 ng/mL (75 nmol/L). The main consequences are that vitamin D insufficiency is highly frequent whereas the currently recommended supplementation doses are not sufficient.     

Correlations between Serum P2X7, Vitamin A, 25‐hydroxy Vitamin D,and Mycoplasma Pneumoniae Pneumonia

BackgroundIdentifying new molecular diagnostic markers for Mycoplasma Pneumoniae Pneumonia (MPP) has always been an essential topic since MPP cases have increased every year, especially among children. Here, we examined the correlation between serum level of Purinergic receptor P2X7, vitamin A, and 25‐hydroxy vitamin D (25(OH)D) and the severity of MPP, aiming to identify molecules that have the potential to become diagnostic markers.MethodsThis study was conducted on 186 cases aged 1–14 (136 MPP and 50 non‐MPP patients). Serum levels of Purinergic receptor P2X7, vitamin A, 25(OH)D, and multiple inflammatory and immune factors were measured, compared, and tested for statistical significance.ResultsSerum P2X7, tumor necrosis factor‐α (TNF‐α), and interleukin‐1β (IL‐1β) levels were significantly increased in severe MPP patients, while serum vitamin A, 25(OH)D, IgA, and IgG levels were significantly decreased.ConclusionOur results demonstrated a positive correlation between serum P2X7 level and the severity of MPP, and negative correlations between serum levels of vitamin A and 25(OH)D and the severity of MPP, suggesting that high serum levels of P2X7 and low serum levels of vitamin A and 25(OH)D may indicate relatively severer MPP.     

Disposable devices for the dispensing of oral drops. Study of photoprotectiveness and compatibility

in the first part of this article calorimetric studies on poly (hydroxy ethyl methacrylate) (PHEMA) are presented. In the past the irregular melting curves in this type of experiment have been interpreted as evidence for the existence of different types of water in these gels. The studies presented here demonstrate that the occurrence of a glass transition in the freezing hydrogels may be responsible for this irregular melting behavior, and that this behavior is not (necessarily) an indication for the existence of different types of water. In the second part results are shown of measurements of the mobility of water in hydrogels, made by relaxation NMR. These results indicate that very rapid interchange occurs between the water molecules, and they support the conclusion that the calorimetric data mentioned above are not indicative for the existence of different classes of water in hydrogels. These results are compared with data from other fields of science, especially from fundamental freeze drying studies, which support the alternative interpretation of the calorimetric measurements.     

Perampanel,a selective,noncompetitive α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor antagonist,as adjunctive therapy for refractory partial‐onset seizures: Interim results from phase III,extension study 307

Purpose: To evaluate safety, tolerability, and seizure outcome data during long‐term treatment with once‐daily adjunctive perampanel (up to 12 mg/day) in patients with refractory partial‐onset seizures. Methods: Study 307 was an extension study for patients completing the double‐blind phase of three pivotal phase III trials (studies 304, 305, and 306). The study consisted of two phases: an open‐label treatment phase (including a 16‐week blinded conversion period and a planned 256‐week maintenance period) and a 4‐week follow‐up phase. Patients were blindly titrated during the conversion period to their individual maximum tolerated dose (maximum 12 mg/day). Adverse events (AEs) were monitored throughout the study and seizure frequency recorded. The interim data cutoff date for analyses was December 1, 2010. Key Findings: In total, 1,218 patients were enrolled in the study. At the interim cutoff date, 1,186 patients were in the safety analysis set; 1,089 (91.8%) patients had >16 weeks of exposure to perampanel, 580 (48.9%) patients had >1 year of exposure, and 19 (1.6%) patients had >2 years of exposure. At the interim analysis, 840 (70.8%) patients remained on perampanel treatment. The large majority of patients (n = 1,084 [91%]) were titrated to 10 mg or 12 mg/day. Median (range) duration of exposure was 51.4 (1.1–128.1) weeks. Treatment‐emergent AEs were reported in 87.4% of patients. The most frequent were dizziness (43.9%), somnolence (20.2%), headache (16.7%), and fatigue (12.1%). Serious AEs were reported in 13.2% of patients. In the intent‐to‐treat analysis set (n = 1,207), the frequency of all seizures decreased over the first 26 weeks of perampanel treatment in patients with at least 26 weeks of exposure to perampanel (n = 1,006 [83.3%]); this reduction was maintained in patients with at least 1 year of exposure (n = 588 [48.7%]). The overall median percent changes in seizure frequency in patients included in each 13‐week interval of perampanel treatment were ?39.2% for weeks 14–26 (n = 1,114), ?46.5% for weeks 40–52 (n = 731), and ?58.1% for weeks 92–104 (n = 59). Overall responder rates in patients included in each 13‐week interval of perampanel treatment were 41.4% for weeks 14–26 (n = 1,114), 46.9% for weeks 40–52 (n = 731), and 62.7% for weeks 92–104 (n = 59). During the blinded conversion period, the reduction in seizure frequency in patients previously randomized to placebo (?42.4%, n = 369) was similar to that in patients previously randomized to perampanel (?41.5%, n = 817). Significance: Consistent with pivotal phase III trials, these interim results demonstrated that perampanel had a favorable tolerability profile in patients with refractory partial‐onset seizures over the longer term. The decrease in seizure frequency was consistent and maintained in those patients over at least 1 year of perampanel exposure.     

支气管哮喘患儿血清25-羟维生素D3水平及其与肺功能、呼出气一氧化氮的关系

目的：了解支气管哮喘（简称哮喘）患儿血清25-羟维生素D3[25（OH）D3]水平及其与肺功能、呼出气一氧化氮（ FeNO）的关系,为哮喘的治疗提供新的策略。方法选取门诊6~14岁初诊哮喘患儿112例为观察组,选取同期在儿童保健科体检的6~14岁健康儿童78例为对照组,通过电化学发光法检测两组患儿血清中25（ OH）D3的含量,检测哮喘患儿呼气峰流速（ PEF）、第1秒用力呼气容积（ FEV1）、呼气峰流速占预计值百分比（ PEF％ pred ）、第1秒用力呼气容积占预计值百分比（ FEV1％ pred）,对观察组患儿进行FeNO检测。对25（ OH）D3与PEF％ pred、FEV1％ pred、FeNO的相关性进行分析。结果观察组的维生素 D 缺乏、不足比例均高于对照组（χ2＝7.78,P ﹤0.01）;PEF％ pred、FEV1％ pred的值随血清25（OH）D3水平的下降而降低（F＝28.12、29.56,P均﹤0.05）, FeNO值随血清25（OH）D3水平的下降反而升高（F＝15.65,P﹤0.05）。结论维生素D缺乏或不足与儿童哮喘相关,与哮喘患儿肺功能下降有关,且可增加哮喘患儿气道炎症水平。