BACKGROUND & AIMS: :Differentiation-inducing factor-1 [1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one (DIF-1)] is an important regulator of cell differentiation and chemotaxis in the development of the cellular slime mold Dictyostelium discoideum However, the entire signaling pathways downstream of DIF-1 remain to be elucidated. To characterize DIF-1 and its potential receptor(s), we synthesized two fluorescent derivatives of DIF-1, boron-dipyrromethene (BODIPY)-conjugated DIF-1 (DIF-1-BODIPY) and nitrobenzoxadiazole (NBD)-conjugated DIF-1 (DIF-1-NBD), and investigated their biological activities and cellular localization. DIF-1-BODIPY (5 µM) and DIF-1 (2 nM) induced stalk cell differentiation in the DIF-deficient strain HM44 in the presence of cyclic adenosine monosphosphate (cAMP), whereas DIF-1-NBD (5 µM) hardly induced stalk cell differentiation under the same conditions. Microscopic analyses revealed that the biologically active derivative, DIF-1-BODIPY, was incorporated by stalk cells at late stages of differentiation and was localized to mitochondria. The mitochondrial uncouplers carbonyl cyanide m-chlorophenylhydrazone (CCCP), at 25-50 nM, and dinitrophenol (DNP), at 2.5-5 µM, induced partial stalk cell differentiation in HM44 in the presence of cAMP. DIF-1-BODIPY (1-2 µM) and DIF-1 (10 nM), as well as CCCP and DNP, suppressed chemotaxis in the wild-type strain Ax2 in shallow cAMP gradients. These results suggest that DIF-1-BODIPY and DIF-1 induce stalk cell differentiation and modulate chemotaxis, at least in part, by disturbing mitochondrial activity.

背景与目标： : 分化诱导因子-1 [1-(3,5-二氯-2,6-二羟基-4-甲氧基苯基) hexan-1-one (DIF-1)] 是细胞黏菌发育过程中细胞分化和趋化性的重要调节剂DIF-1下游的整个信号通路仍有待阐明。为了表征DIF-1及其潜在受体，我们合成了两种DIF-1的荧光衍生物，硼-二吡咯亚甲基 (BODIPY)-共轭DIF-1 (DIF-1-BODIPY) 和硝基苯并恶二唑 (NBD)-共轭DIF-1 (DIF-1-NBD)，并研究了它们的生物学活性和细胞定位。在环腺苷单球 (cAMP) 存在下，DIF-1-BODIPY (5  µ m) 和DIF-1 (2  nM) 诱导DIF缺陷菌株HM44的茎细胞分化，而DIF-1-NBD (5 µm µ m) 在相同条件下几乎不诱导茎细胞分化。显微分析显示，生物活性衍生物DIF-1-BODIPY在分化后期被茎细胞掺入，并定位于线粒体。线粒体解偶联羰基氰化物间氯苯基腙 (CCCP)，在cAMP. DIF-1-BODIPY (1-2  µ m) 和DIF-1 (10  nM) 以及CCCP和DNP的存在下，HM44在25-50  nM和2.5-5  µ m诱导茎秆细胞部分分化，在浅cAMP梯度中抑制野生型菌株Ax2的趋化性。这些结果表明，DIF-1-BODIPY和DIF-1至少部分地通过干扰线粒体活性来诱导茎细胞分化并调节趋化性。

BACKGROUND & AIMS: :Previously reported propellane derivative KNT-42 preferred the κ receptor and functioned as a message part in the message-address concept, but its affinity for the κ receptor was not high. To improve affinity, we synthesized five pentacyclic propellane derivatives designed for the purpose of fixing the conformation of KNT-42. The etheno- and ethano-bridged derivatives SYK-347 and SYK-393 exhibited high affinity and selectivity for the κ receptor, whereas the other derivatives did not. These results would be due to the different ranges of movement of the basic nitrogens and less basicity of the nitrogens due to the electron withdrawing effect of the introduced hydroxy or keto group. SYK-347 and SYK-393 preferring the κ receptor were expected to be useful for designing selective ligands for opioid receptor types, especially the κ receptor.

背景与目标： : 先前报道的推进烷衍生物KNT-42更喜欢 κ 受体，并在消息地址概念中充当消息部分，但其对 κ 受体的亲和力不高。为了提高亲和力，我们合成了五个五环推进烷衍生物，目的是固定KNT-42的构象。etheno和ethano桥接的衍生物SYK-347和SYK-393对 κ 受体表现出高亲和力和选择性，而其他衍生物则没有。这些结果是由于碱性氮的运动范围不同，而由于引入的羟基或酮基的吸电子效应，氮的碱度较低。优选 κ 受体的SYK-347和SYK-393被认为可用于设计阿片受体类型的选择性配体，尤其是 κ 受体。

BACKGROUND & AIMS: :Vitamin D hormone (1,25-dihydroxyvitamin D) is involved in innate immunity and induces host defense peptides in epithelial cells, suggesting its involvement in mucosal defense against infections. Chlamydia trachomatis is a major cause of bacterial sexually transmitted disease worldwide. We tested the hypothesis that the vitamin D endocrine system would attenuate chlamydial infection. Vitamin D receptor knock-out mice (VDR(-/-)) and wild-type mice (VDR(+/+)) were infected with 10(3) inclusion forming units of Chlamydia muridarum and cervical epithelial cells (HeLa cells) were infected with C. muridarum at multiplicity of infection 5:1 in the presence and absence of 1,25-dihydroxyvitamin D3. VDR(-/-) mice exhibited significantly higher bacterial loading than wild-type VDR(+/+) mice (P<0.01) and cleared the chlamydial infection in 39 days, compared with 18 days for VDR(+/+) mice. Monocytes and neutrophils were more numerous in the uterus and oviduct of VDR(-/-) mice than in VDR(+/+) mice (P<0.05) at d 45 after infection. Pre-treatment of HeLa cells with 10nM or 100nM 1,25-dihydroxyvitamin D3 decreased the infectivity of C. muridarum (P<0.001). Several differentially expressed protein spots were detected by proteomic analysis of chlamydial-infected HeLa cells pre-treated with 1,25-dihydroxyvitamin D3. Leukocyte elastase inhibitor (LEI), an anti-inflammatory protein, was up-regulated. Expression of LEI in the ovary and oviduct of infected VDR(+/+) mice was greater than that of infected VDR(-/-) mice. We conclude that the vitamin D endocrine system reduces the risk for prolonged chlamydial infections through regulation of several proteins and that LEI is involved in its anti-inflammatory activity.

背景与目标： : 维生素d激素 (1,25-二羟基维生素d) 参与先天免疫，并在上皮细胞中诱导宿主防御肽，表明其参与粘膜防御感染。沙眼衣原体是全球细菌性性传播疾病的主要原因。我们检验了维生素d内分泌系统会减轻衣原体感染的假设。维生素d受体敲除小鼠 (VDR(-/-)) 和野生型小鼠 (VDR (/)) 感染了10(3) 包涵体形成单位的衣原体和宫颈上皮细胞 (HeLa细胞) 感染多重性的C. muridarum 5:1在存在和不存在1的情况下，25-二羟基维生素d3。VDR(-/-) 小鼠表现出显著高于野生型VDR(+/+) 小鼠的细菌负荷 (P<0.01)，并且在39天内清除衣原体感染，而VDR(+/+) 小鼠为18天。在感染后第45天，VDR(-/-) 小鼠的子宫和输卵管中的单核细胞和中性粒细胞多于VDR (/+) 小鼠 (P<0.05)。用10nM或100nM 1,25-二羟基维生素D3预处理HeLa细胞会降低C. muridarum的感染性 (P<0.001)。通过用1,25-二羟基维生素d3预处理的衣原体感染的HeLa细胞的蛋白质组学分析，检测了几个差异表达的蛋白质斑点。抗炎蛋白白细胞弹性蛋白酶抑制剂 (LEI) 上调。感染的VDR (/) 小鼠的卵巢和输卵管中LEI的表达大于感染的VDR(-/-) 小鼠的表达。我们得出的结论是，维生素d内分泌系统通过调节多种蛋白质降低了长期衣原体感染的风险，并且LEI参与了其抗炎活性。

BACKGROUND & AIMS: :The neuropeptide calcitonin gene-related peptide (CGRP) plays a critical role in the pathophysiology of migraine. We have focused on the role of CGRP in photophobia, which is a common migraine symptom. We previously used an operant-based assay to show that CGRP-sensitized transgenic (nestin/hRAMP1), but not control, mice exhibited light aversion in response to an intracerebroventricular CGRP injection. A key question was whether the transgenic phenotype was due to overexpression of the CGRP receptor at endogenous or novel expression sites. We reasoned that if endogenous receptor sites were sufficient for light-aversive behavior, then wild-type mice should also show the phenotype when given a sufficiently strong stimulus. In this study, we report that mice with normal levels of endogenous CGRP receptors demonstrate light avoidance following CGRP administration. This phenotype required the combination of two factors: higher light intensity and habituation to the testing chamber. Control tests confirmed that light aversion was dependent on coincident exposure to CGRP and light and cannot be fully explained by increased anxiety. Furthermore, CGRP reduced locomotion only in the dark, not in the light. Coadministration of rizatriptan, a 5-HT(1B/D) agonist anti-migraine drug, attenuated the effects of exogenous CGRP on light aversion and motility. This suggests that triptans can act by mechanisms that are distinct from inhibition of CGRP release. Thus, we demonstrate that activation of endogenous CGRP receptors is sufficient to elicit light aversion in mice, which can be modulated by a drug commonly used to treat migraine.

背景与目标： : 神经肽降钙素基因相关肽 (CGRP) 在偏头痛的病理生理中起关键作用。我们关注CGRP在畏光中的作用，这是一种常见的偏头痛症状。我们以前使用基于操作的测定法来显示CGRP致敏的转基因 (nestin/hRAMP1)，但不是对照，小鼠对脑室内CGRP注射表现出光厌恶。一个关键问题是转基因表型是否归因于CGRP受体在内源性或新型表达位点的过表达。我们认为，如果内源性受体位点足以引起光厌恶行为，那么当给予足够强的刺激时，野生型小鼠也应显示出表型。在这项研究中，我们报告了具有正常水平的内源性CGRP受体的小鼠在CGRP给药后表现出避免光的作用。这种表型需要两个因素的结合: 更高的光强度和测试室的习惯。对照测试证实，光厌恶取决于同时暴露于CGRP和光，不能用焦虑增加来完全解释。此外，CGRP仅在黑暗中而不是在光线中减少运动。利扎曲普坦是一种5-HT(1B/D) 激动剂抗偏头痛药物，可减轻外源性CGRP对光厌恶和运动的影响。这表明曲坦类药物可以通过不同于抑制CGRP释放的机制起作用。因此，我们证明内源性CGRP受体的激活足以引起小鼠的光厌恶，这可以通过通常用于治疗偏头痛的药物来调节。

BACKGROUND & AIMS: :Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple combinations towards a Mycobacterium tuberculosis Beijing genotype strain and drug resistance was assessed. Streptomycin, rifampicin and isoniazid were most active against fast-growing M. tuberculosis. Isoniazid with rifampicin or high dose ethambutol were the only synergistic drug combinations. The addition of rifampicin or streptomycin to isoniazid prevented isoniazid resistance. In vitro ranking showed agreement with early bactericidal activity in tuberculosis patients for some but not all anti-tuberculosis drugs. The time-kill kinetics assay provides important information on the mycobacterial killing dynamics of anti-tuberculosis drugs during the early phase of drug exposure. As such, this assay is a valuable component of the preclinical modeling framework.

背景与目标： 迫切需要新的结核病治疗策略。有许多不同的评估抗结核药物活性的临床前模型，但尚不清楚哪种模型组合最能预测临床治疗效果。这项研究的目的是确定我们的体外时间杀伤动力学测定法作为评估抗结核药物活性的预测性临床前建模框架的资产的作用。在暴露于结核分枝杆菌北京基因型菌株的过程中，确定了六种抗结核药物的浓度和时间依赖性的分枝杆菌杀伤能力，并评估了耐药性。链霉素，利福平和异烟肼对快速生长的结核分枝杆菌最有效。异烟肼与利福平或高剂量乙胺丁醇是唯一的协同药物组合。在异烟肼中添加利福平或链霉素可防止异烟肼耐药性。体外排名显示，对于某些 (但不是所有) 抗结核药物，结核病患者的早期杀菌活性一致。时间杀伤动力学测定法提供了有关药物暴露早期抗结核药物的分枝杆菌杀伤动力学的重要信息。因此，该测定是临床前建模框架的有价值的组成部分。

BACKGROUND & AIMS: Context:Vitamin D deficiency patients have an increased cardiovascular (CV) morbidity and mortality. Carotid intima-media thickness (IMT) and carotid plaques are markers of subclinical atherosclerosis and predictors of CV events. Objective:To perform a meta-analysis of studies evaluating the impact of Vitamin D deficiency on common carotid artery IMT (CCA-IMT) and on the prevalence of carotid plaques. Data Sources:Studies were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Results:Twenty-one studies (3,777 Vitamin D deficiency patients and 4,792 controls) with data on CCA-IMT and 6 studies (1,889 Vitamin D deficiency patients and 2,883 controls) on the prevalence of carotid plaques were included. Compared to controls, Vitamin D deficiency patients showed a significantly higher CCA-IMT (mean difference [MD]: 0.043 mm; 95%CI: 0.030, 0.056; P<0.001), and an increased prevalence of carotid plaques (Odds Ratio [OR]: 2.29, 95%CI: 1.03-5.11; P=0.043) with an attributable risk of 35.9%. When selecting studies specifically including patients with diabetes, the prevalence of carotid plaques in Vitamin D deficiency patients than in controls resulted higher (OR: 3.27; 95%CI: 1,62-6.62; P=0.001). A significant difference in CCA-IMT was confirmed when comparing patients with Vitamin D insufficiency to controls (MD: 0.011; 95%CI: 0.010-0.012, P<0.001). Sensitivity analyses substantially confirmed results and regression models showed that with the exception of LDL-cholesterol, HDL-cholesterol, triglycerides and the prevalence of hypercholesterolemia, all the other clinical and demographic co-variates significantly impacted on the difference in CCA-IMT between Vitamin D deficiency patients and controls. Conclusions:Both Vitamin D deficiency and Vitamin D insufficiency are associated with subclinical atherosclerosis, potentially suggesting an increased CV risk in these clinical settings.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Left atrial enlargement, a sensitive integrator of left ventricular diastolic function, is associated with increased cardiovascular morbidity and mortality. Vitamin D is linked to lower cardiovascular morbidity, possibly modifying cardiac structure and function; however, firm evidence is lacking. We assessed the effect of an activated vitamin D analog on left atrial volume index (LAVi) in a post hoc analysis of the PRIMO trial (clinicaltrials.gov: NCT00497146). METHODS AND RESULTS:One hundred ninety-six patients with chronic kidney disease (estimated glomerular filtration rate 15-60 mL/min per 1.73 m(2)), mild to moderate left ventricular hypertrophy, and preserved ejection fraction were randomly assigned to 2 μg of oral paricalcitol or matching placebo for 48 weeks. Two-dimensional echocardiography was obtained at baseline and at 24 and 48 weeks after initiation of therapy. Over the study period, there was a significant decrease in LAVi (-2.79 mL/m(2), 95% CI -4.00 to -1.59 mL/m(2)) in the paricalcitol group compared with the placebo group (-0.70 mL/m(2) [95% CI -1.93 to 0.53 mL/m(2)], P = .002). Paricalcitol also attenuated the rise in levels of brain natriuretic peptide (10.8% in paricalcitol vs 21.3% in placebo, P = .02). For the entire population, the change in brain natriuretic peptide correlated with change in LAVi (r = 0.17, P = .03). CONCLUSIONS:Forty-eight weeks of therapy with an active vitamin D analog reduces LAVi and attenuates the rise of BNP. In a population where only few therapies alter cardiovascular related morbidity and mortality, these post hoc results warrant further confirmation.

背景与目标：

BACKGROUND & AIMS: :Rat brain synaptosomal membranes that are depleted of endogenous excitatory amino acids cannot bind [(+)-5-methyl-10, 11-dihydro-5H-dibenzo(a,d]cyclohept-5,10-imine maleate] ([3H]MK-801). However, they do so upon the restoration of excitatory amino acid agonists such as L-glutamate. [3H]MK-801 provides a molecular probe which is specific for a binding site located within the ionophore of the N-methyl-D-aspartate-type excitatory amino acid receptor, [3H]MK-801 does not bind to non-N-methyl-D-aspartate excitatory amino acid receptors. Exploiting [3H]MK-801 binding as a quantitative measure of agonist activity with respect to ability of inducing the open channel conformation, the present study demonstrates that L-homocysteate is an agonist almost equivalent to L-glutamate in terms of efficacy (maximal N-methyl-D-aspartate response) as well as potency (EC50). The effect of L-homocysteate was dose-dependent, stereospecific (L-homocysteate greater than DL-homocysteate greater than D-homocysteate), suppressible by the N-methyl-D-aspartate-selective competitive antagonist (+/-)-3(2-carboxy-piperazine-4-yl)propyl-l-phosphonate, and potentiated by the N-methyl-D-aspartate-selective "allosteric" modulator glycine. The demonstrated inactivity of L-homocysteine (and virtually all naturally occurring, non-acidic amino acids) implies that the omega-sulphonic acid moiety is an acceptable substitute for the omega carboxyl group for activating the N-methyl-D-aspartate receptor. While the potency of L-homocysteate at N-methyl-D-aspartate receptors was by a factor of only 1.6 smaller than that of L-glutamate, the affinity of L-homocysteate for kainate-type excitatory amino acid receptors was approximately four-fold lower than that of L-glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： : 消耗内源性兴奋性氨基酸的大鼠脑突触体膜不能结合 [(+)-5-甲基-10,11-dihydro-5H-dibenzo(a，d]cyclohept-5，马来酸10-亚胺] ([3H]MK-801)。它们是在兴奋性氨基酸激动剂如L-谷氨酸恢复时这样做的。[3H]MK-801提供了一种分子探针，该探针对位于N-甲基-D-天冬氨酸型兴奋性氨基酸受体的离子载体内的结合位点具有特异性，[3H]MK-801不结合非N-甲基-D-天冬氨酸兴奋性氨基酸受体。利用 [3H]MK-801结合作为关于诱导开放通道构象能力的激动剂活性的定量测量，本研究表明，L-同型半胱氨酸在功效 (最大N-甲基-D-天冬氨酸反应) 和效力 (EC50) 方面几乎等同于L-谷氨酸。L-同型半胱氨酸的作用是剂量依赖性的，立体特异性 (L-高半胱氨酸大于DL-高半胱氨酸大于D-高半胱氨酸)，可被N-甲基-D-天冬氨酸选择性竞争性拮抗剂 (/-)-3(2-羧基哌嗪-4-基) 丙基-l-膦酸酯抑制，并由N-甲基-D-天冬氨酸选择性 “变构” 调节剂甘氨酸增强。已证明L-高半胱氨酸 (几乎所有天然存在的，非酸性氨基酸) 意味着 ω-磺酸部分是激活N-甲基-D-天冬氨酸受体的 ω 羧基的可接受替代品。而L-同型半胱氨酸在N-甲基-D-天冬氨酸受体上的效力仅比1.6小L-谷氨酸，L-同型半胱氨酸对红藻氨酸型兴奋性氨基酸受体的亲和力大约比L-谷氨酸低4倍。(摘要截短于250字)

BACKGROUND & AIMS: INTRODUCTION:This project addresses the validation study design of a test system using a telemetered non-human primate model for cardiovascular safety pharmacology evaluation. METHODS:The validation provided by the supplier evaluated installation (IQ) and operation (OQ) qualifications. This protocol was completed with tests evaluating electronic data management and accuracy and precision of transmitter (n=4) measurements for temperature and pressure criteria with a series of tested values. As part of performance qualification, physical activity (for 24 h) as well as cardiovascular, ECG (20 complexes for each animal) and systemic arterial blood pressure (SAP, 10 different measures), data were recorded simultaneously from the same animals (n=4) using certified equipment and the telemetry system. Reliability was evaluated over 60 days. RESULTS:The IQ and OQ were completed successfully. The electronic data management was performed successfully. The ex-vivo evaluation for temperature and pressure showed high correlation (R(2)>0.99) but with a slight pressure shift, as expected, with this transmitter model. For physical activity, the correlation coefficients were good to excellent with high activity counts but the comparison demonstrated a limited sensitivity of the telemetry system with animal presenting low activity levels. ECG interval measurement using the telemetry software was considered at least equivalent to manual measurement, but with some limitations in the reading of the ECG. The comparison between both methods of SAP measurement showed adequate precision (R(2)=0.969) but no accuracy. DISCUSSION:Reference monitoring methods are important to ensure proper test system validation. Monitoring with a reference methodology and the telemetry system is important in order to evaluate precision and accuracy of the test system. Computerized analysis may lack the capability to analyze ECG complexes with abnormal morphologies. This reinforces the need to have ECG evaluation prior to telemetry implantation along with visual evaluation of ECG tracing at standard speed (e.g. 50 mm/s) at all time points.

背景与目标：

BACKGROUND & AIMS: :A scar flap is formed with the pedicle at the lateral part of the columella base at the cleft side, that is, in the center of the affected region. It enables flap placement according to individual need. A prospective evaluation was performed in a group of 76 patients with cleft lip and palate, all operated on by the same plastic surgeon. The flap was used to improve the height of the columella and the extent of nasal mucosa on the frontal septum and on the nostril base in the vestibule. In the lip, the flap raised its height and improved proportionality. The average area of flap used in a unilateral deformity was 42 mm. Both flaps in a bilateral deformity were 77 mm. The average follow-up was 22.4 months. Neither local nor general complications were noted apart from a recurrence of the deformity of the nasal septum in 7.9% of patients. The nasal passage was improved in 59.9% of patients and normalized in 19.6% upon follow-up rhinomanometry, but nevertheless, only one third of patients overcame their dynamic stereotype of breathing by the mouth. Anthropometric measurements showed an absence of statistically significant differences between patients after surgery and healthy individuals in crucial parameters (nasal tip projection, length of columella, nasolabial angle, nasal angle, and lip angle). The loss of the stigmatizing deformity is based on rotation of the nasolabial angle in relation to the aesthetic axis of the face. Direct examination proved aesthetic and functional improvement as statistically significant in 92.1% of patients.

背景与目标： : 疤痕皮瓣在裂隙侧的小柱基部的外侧部分 (即在受影响区域的中心) 形成。它可以根据个人需要放置襟翼。对76例唇腭裂患者进行了前瞻性评估，所有患者均由同一位整形外科医生进行手术。皮瓣用于改善前庭额隔和鼻孔基部的小柱高度和鼻粘膜的程度。在嘴唇上，皮瓣提高了高度并提高了比例。用于单侧畸形的皮瓣的平均面积为42毫米。双侧畸形的两个皮瓣均77毫米。平均随访22.4个月。除了7.9% 患者的鼻中隔畸形复发外，均未发现局部或一般并发症。59.9% 患者的鼻腔通道得到改善，并在随访的鼻腔测量后在19.6% 中恢复正常，但是，只有3分之1的患者克服了通过口腔呼吸的动态刻板印象。人体测量显示，手术后患者与健康个体之间在关键参数 (鼻尖投影，小柱长度，鼻唇角，鼻角和唇角) 上没有统计学上的显着差异。污名化畸形的丧失是基于鼻唇角相对于面部美学轴的旋转。直接检查证明在患者92.1% 中具有统计学意义的美学和功能改善。

BACKGROUND & AIMS: Using a melt-pressing technique, we produced a small solid cylinder containing cisplatin (CDDP) embedded in poly-d, l-lactic acid (CDDP-PLA). The in vitro release of CDDP from the polymer was examined in an immersion system. CDDP was released continuously for more than four weeks with no initial burst. Drug distribution for CDDP-PLA was compared with CDDP solution (CDDP-SOL) by subcutaneous administration into the back of rats. In the CDDP-PLA group, a high concentration of CDDP was maintained in the subcutaneous tissues near the implants for 20 days. However, in the CDDP-SOL group, the concentration of CDDP was low by 10 days after drug administration. CDDP-PLA may become a useful tool in locoregional chemotherapy as a solid type of drug delivery system with longlasting release.

背景与目标： 使用熔融压制技术，我们生产了一个小的固体圆柱体，其中包含嵌入聚d，l-乳酸 (CDDP-PLA) 中的顺铂 (CDDP)。在浸没系统中检查了CDDP从聚合物中的体外释放。CDDP连续发布超过四个星期，没有初始爆发。通过皮下给药到大鼠背部，将CDDP-PLA的药物分布与CDDP溶液 (CDDP-SOL) 进行比较。在cddp-pla组中，在植入物附近的皮下组织中维持高浓度的CDDP 20天。然而，在CDDP-SOL组中，给药后10天CDDP的浓度较低。Cddp-pla作为一种具有持久释放的固体药物输送系统，可能成为局部化疗的有用工具。

BACKGROUND & AIMS: :Maxillofacial injuries are often seen in the emergency department. Fractures of the facial skeleton are commonly seen after assault, road traffic accidents, falls, and sporting injuries in a ratio mandibular:zygoma:maxillary of 6:2:1. Clinicians must be familiar with their management so that appropriate treatment may be used.

背景与目标： : 急诊科经常看到颌面受伤。在袭击，道路交通事故，跌倒和运动伤害后，通常会出现面部骨骼骨折，其比例为下颌: 骨瘤: 6:2:1上颌。临床医生必须熟悉其管理，以便可以使用适当的治疗方法。

BACKGROUND & AIMS: :Vitamin D and its analogues exhibit potent antitumor effects in many tissues, including the pancreas. Normal and malignant pancreatic tissues were recently shown to express high levels of vitamin D 1-alpha-hydroxylase, which converts circulating 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D. We examined associations between dietary intake of vitamin D, calcium, and retinol and subsequent risk for pancreatic cancer. We conducted prospective studies in cohorts of 46,771 men ages 40 to 75 years as of 1986 (the Health Professionals Follow-up Study), and 75,427 women ages 38 to 65 years as of 1984 (the Nurses' Health Study), documenting incident pancreatic cancer through the year 2000. Diet was ascertained by semiquantitative food-frequency questionnaire. We identified 365 incident cases of pancreatic cancer over 16 years of follow-up. Compared with participants in the lowest category of total vitamin D intake (<150 IU/d), pooled multivariate relative risks for pancreatic cancer were 0.78 [95% confidence interval (95% CI), 0.59-1.01] for 150 to 299 IU/d, 0.57 (95% CI, 0.40-0.83) for 300 to 449 IU/d, 0.56 (95% CI, 0.36-0.87) for 450 to 599 IU/d, and 0.59 (95% CI, 0.40-0.88) for >/=600 IU/d (P(trend) = 0.01). These associations may be stronger in men than women. After adjusting for vitamin D intake, calcium and retinol intakes were not associated with pancreatic cancer risk. In two U.S. cohorts, higher intakes of vitamin D were associated with lower risks for pancreatic cancer. Our results point to a potential role for vitamin D in the pathogenesis and prevention of pancreatic cancer.

背景与目标： : 维生素d及其类似物在包括胰腺在内的许多组织中表现出有效的抗肿瘤作用。最近显示正常和恶性胰腺组织表达高水平的维生素d 1-α-羟化酶，可将循环中的25-羟基维生素d转化为活性的1,25-二羟基维生素d。我们研究了饮食中维生素d，钙和视黄醇的摄入量与胰腺癌后续风险之间的关联。我们对46,771名年龄在40 ~ 75岁的男性作为1986年 (健康专业人员随访研究) 和75,427名年龄在38 ~ 65岁的女性作为1984年 (护士健康研究) 进行了前瞻性研究，记录了通过2000年发生的胰腺癌。通过半定量食物频率问卷确定饮食。在16年的随访中，我们确定了365例胰腺癌事件。与维生素d总摄入量最低类别 (<150 IU/D) 的参与者相比，胰腺癌的合并多变量相对风险被0.78 [95% 置信区间 (95% CI)，0.59-1.01] 150至299 IU/d，0.57 (95% CI，0.40-0.83) 300至449 IU/d，0.56 (95% CI，0.36-0.87) 450至599 IU/d，0.59 (95% CI，0.40-0.88)>/= 600 IU/d (P (趋势) = 0.01)。这些联想在男性中可能比女性更强。调整维生素d摄入量后，钙和视黄醇的摄入量与胰腺癌风险无关。在两个美国队列中，较高的维生素d摄入量与较低的胰腺癌风险相关。我们的结果指出维生素d在胰腺癌的发病机理和预防中的潜在作用。

BACKGROUND & AIMS: STUDY DESIGN:A descriptive cadaveric study incorporating a novel nerve root marking technique. OBJECTIVES:To describe the displacement and strain of the lumbosacral nerve roots in the lateral recess during straight leg raise (SLR) without disrupting the foraminal ligaments. SUMMARY OF BACKGROUND DATA:Previous studies document 2 to 8 mm of lumbosacral nerve root displacement during SLR. Prior dissection methods incorporated laminectomy and facetectomy. METHODS:Lower limbs and associated nerve roots of 5 unembalmed cadavers (n = 10) were studied. Metal markers were inserted intraneurally within the lateral recess of L4, L5, and S1 with a modified spinal needle. Fluoroscopic images were digitized to evaluate displacement and strain during SLR. RESULTS:The lumbosacral nerve roots in the lateral recess moved less and experienced less strain during SLR than described in previously published reports. Statistically significant distal displacement occurred at hip positions greater than 60 degrees of flexion at all nerve root levels (P < 0.01). CONCLUSIONS:The lumbosacral nerve roots (L4, L5, S1) moved less and underwent less strain during SLR testing than previously reported and may require hip motion greater than 60 degrees to produce substantive displacement in the lateral recess. Additional research is needed to examine the effects of prepositioning during SLR.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:The present study evaluates the efficiency of software-generated white blood cell (WBC) "suspect flags" of the hematology analyzers Sysmex SE-9000, Sysmex NE-8000, and Coulter STKS.

DESIGN:Automated WBC differential counts were considered positive if they contained any suspect WBC flag indicating the presence of blasts, myeloid precursor cells, or abnormal lymphocytes. Reference differential counts were performed by microscopic examination of 400 WBCs per sample. After comparison to the reference method, automated differential counts were classified as true-positive, true-negative, false-positive, and false-negative. The flagging efficiency of analyzers was expressed as a percentage of subjects correctly classified.

SPECIMENS:Four hundred sixty-seven blood samples were randomly chosen for comparison analysis from various inpatient and outpatient departments of the Vienna university hospital, Austria.

RESULTS:The efficiency rates of flagging for the presence of > or = 1% abnormal WBCs were 78% (SE-9000), 77% (NE-8000), and 72% (Coulter STKS). The flagging efficiencies were best for samples with normal WBC counts. With regard to the specific suspect flags, the flagging of blast cells was most efficient on all analyzers.

CONCLUSIONS:Our results demonstrate the comparable overall performance of three analyzers, SE-9000, NE-8000, and Coulter STKS. They further underscore the importance of critical interpretation of automated differential counts, because at a detection limit of > or = 1% abnormal WBCs > 20% of samples were not correctly flagged by either analyzer.

背景与目标： 目的 : 本研究评估了血液分析仪Sysmex SE-9000，Sysmex NE-8000和Coulter STKS的软件生成的白细胞 (WBC) “可疑标志” 的效率。
设计 : 如果自动WBC差异计数包含任何可疑的WBC标志，表明存在原始细胞，髓样前体细胞或异常淋巴细胞，则被认为是阳性。参考差异计数通过每个样品400 wbc的显微镜检查进行。与参考方法比较后，自动差异计数分为真阳性，真阴性，假阳性和假阴性。分析仪的标记效率表示为正确分类的受试者的百分比。
标本 : 从维也纳大学医院的各个住院和门诊部门随机选择了467个血液样本进行比较分析，奥地利。
结果 : 标记存在> 或 = 1% 个异常wbc的效率为78% (SE-9000)，77% (NE-8000) 和72% (Coulter STKS)。标记效率对于WBC计数正常的样品最好。关于特定的可疑标志，在所有分析仪上标记原始细胞是最有效的。
结论 : 我们的结果证明了SE-9000，NE-8000和库尔特STKS这三种分析仪的总体性能相当。他们进一步强调了对自动差异计数进行严格解释的重要性，因为在> 或 = 1% 的检测极限下，任何一种分析仪均未正确标记样本的异常wbc> 20%。