BACKGROUND & AIMS: :In Taiwan, the authorities have spent years working on remedying polluted rivers. Generally, the remediation planning works are divided into two phases. During the first phase, the allowed pollution discharge quantity and abatement quantity of each drainage zone, including the assimilative capacity, are generated based on the total river basin. In the second phase, the abatement action plans for each pollution source in each drainage zone are respectively devised by the related organizations based on the strategies generated during the first phase. However, the effectiveness of linking the two phases is usually poor. Highly integrated performances are not always achieved because the separate two-phase method does not take system and management thinking into consideration in the planning stage. This study pioneers the use of the Managing for Results (MFR) method in planning strategies and action plans for river water quality management. A sustainable management framework is proposed based on the concept and method of MFR, Management Thinking, and System Analysis. The framework, consisting of planning, implementation, and controlling stages, systematically considers the relationships and interactions among four factors: environment, society, economy, and institution, based on the principles of sustainable development. Based on the framework, the Modified Bounded Implicit Enumeration algorithm, which is used as a solving method, is combined with Visual Basic software and MS Excel to develop a computer system for strategy planning. The Shetzu River, located in northern Taiwan, is applied as a case study. According to the theoretical, practical, and regulatory considerations, the result-oriented objectives are defined to first improve the pollution length of the Shetzu River in specific remediation periods to finally meet regulated water quality standards. The objectives are then addressed as some of the constraints for the strategy planning model. The model objective is to pursue the maximum assimilative capacity (environmental phase) subjected to the constraints of water quality standards (institutional phase), social equity (social phase), and proper available technology (economic phase). The pollution quantity abatement and allocation, which are named the top strategies, of each drainage zone for different scenarios can be obtained based on each water quality standard. The middle as well as lower strategies and action plans, which consist of pollution quantity abatement and allocation of each class (domestic, industrial, livestock, and non-point pollution sources) and their individual pollution sources in each drainage zone, are then generated based on the top strategies. The performance indicators and measure plans are proposed based on the action plans to promote the comprehensive effectiveness of river water quality management. The authorities have begun to develop a budget based on the strategies and action plans developed in this study. The analytical results indicate that the objectives, strategies, and action plans developed based on the sustainable management framework and strategy planning system can effectively help the related authorities to fulfill the tasks of water quality management for a river basin.

背景与目标： : 在台湾，当局花了数年时间对污染的河流进行补救。通常，补救计划工作分为两个阶段。在第一阶段，根据整个流域产生每个流域的允许排污量和减排量，包括同化能力。在第二阶段，相关组织根据第一阶段产生的策略，分别为每个排水区的每个污染源制定减排行动计划。然而，将这两个阶段联系起来的有效性通常很差。并非总是能够实现高度集成的性能，因为在计划阶段，单独的两阶段方法并未考虑系统和管理思想。这项研究率先在河流水质管理的规划策略和行动计划中使用了结果管理 (MFR) 方法。基于MFR的概念和方法，管理思想和系统分析，提出了可持续管理框架。该框架由规划，实施和控制阶段组成，根据可持续发展的原则，系统地考虑了环境，社会，经济和制度四个因素之间的关系和相互作用。基于该框架，将作为求解方法的改进的有界隐式枚举算法与Visual Basic软件和MS Excel相结合，开发了用于策略规划的计算机系统。以台湾北部的Shetzu河为例。根据理论，实践和法规方面的考虑，定义了以结果为导向的目标，以首先在特定的整治时期改善Shetzu河的污染长度，以最终达到规定的水质标准。然后将目标作为战略规划模型的一些约束条件来解决。模型目标是在水质标准 (制度阶段)，社会公平 (社会阶段) 和适当的可用技术 (经济阶段) 的约束下，追求最大的同化能力 (环境阶段)。根据每个水质标准，可以获得每个排水区针对不同情况的污染量减少和分配 (称为顶级策略)。然后生成中间和较低的策略和行动计划，其中包括减少和分配每一类 (家庭，工业，牲畜和面源污染源) 及其在每个排水区中的单个污染源根据顶级策略。根据促进河流水质管理综合成效的行动计划，提出了绩效指标和措施计划。当局已开始根据本研究中制定的战略和行动计划制定预算。分析结果表明，基于可持续管理框架和战略规划系统制定的目标，战略和行动计划可以有效地帮助相关当局完成流域水质管理的任务。

BACKGROUND & AIMS: BACKGROUND:Angiotensin-converting enzyme (ACE) inhibitors prevent the expansion and rupture of aortic aneurysms in animals. We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms. METHODS:We did a population-based case-control study of linked administrative databases in Ontario, Canada. The sample included consecutive patients older than 65 (n=15,326) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1, 1992, and April 1, 2002. FINDINGS:Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm (odds ratio [OR] 0.82, 95% CI 0.74-0.90) than those who did not receive ACE inhibitors. Adjustment for demographic characteristics, risk factors for rupture, comorbidities, contraindications to ACE inhibitors, measures of health-care use, and aneurysm screening yielded similar results (0.83, 0.73-0.95). Consistent findings were noted in subgroups at high risk of rupture, including patients older than 75 years and those with a history of hypertension. Conversely, such protective associations were not observed for beta blockers (1.02, 0.89-1.17), calcium channel blockers (1.01, 0.89-1.14), alpha blockers (1.15, 0.86-1.54), angiotensin receptor blockers (1.24, 0.71-2.18), or thiazide diuretics (0.91, 0.78-1.07). INTERPRETATION:ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm, unlike other antihypertensive agents. Randomised trials of ACE inhibitors for prevention of aortic rupture might be warranted.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:A detailed appreciation of left atrial/pulmonary vein (LA/PV) anatomy may be important in improving the safety and success of catheter ablation (CA) for atrial fibrillation (AF). OBJECTIVES:The aim of this nonrandomized study was to determine the impact of computerized tomography (CT) image integration into a 3-dimensional (3D) mapping system on the clinical outcome of patients undergoing CA for AF. METHODS:Ninety-four patients (age: 56 +/- 10 years) with AF (paroxysmal 46, persistent 48) underwent wide encirclement of ipsilateral PV pairs using irrigated radiofrequency ablation with the endpoint of electrical isolation. Ablation was guided by 3D mapping alone (electroanatomic 24, noncontact 23) in 47 (3DM group) patients and by CT image integration (Cartomerge) in 47 (CT group). In persistent AF, a combination of linear ablation and targeted ablation of complex fractionated electrograms was also performed. RESULTS:Successful PV electrical isolation did not differ between the two groups. A significant reduction in fluoroscopy times was demonstrated in the CT group (49 +/- 27 minutes vs 3DM group 62 +/- 26 minutes, P = 0.03). Arrhythmia recurrence was reduced in the CT group (32% vs 51% in the 3DM group, P < 0.01). In 30 symptomatic patients (12 CT and 18 3DM), repeat procedures for AF (13 in 3DM and 5 CT, P < or = 0.10) and AT (5 in 3DM and 7 CT, P = NS) were performed. Overall success on 7-day monitor off antiarrhythmic drugs was achieved in 60% in the 3DM group when compared with 83% in the CT group (P < 0.05) at a follow-up of 25 +/- 5 weeks. CONCLUSION:CA for AF guided by CT integration was associated with reduced fluoroscopy times, arrhythmia recurrence, and increased restoration of sinus rhythm. Improved visualization of complex LA geometries might improve the safety and success of CA for AF.

背景与目标：

BACKGROUND & AIMS: :A retroviral vector was constructed with an autoregulatory cassette to allow expression of the gene of interest in response to oral administration of doxycycline (Dox) in vivo. The cassette contains all the components of the reverse tetracycline-regulated (rtTA) system, a drug selectable marker with the internal ribosome entry site and the gene of interest (GFP). FACS analyses showed an induction of GFP-fluorescence of two orders of magnitude in retrovirus-infected 208F cells dependent on the amount of Dox in the medium. Furthermore, oral administration of Dox resulted in GFP expression in transplanted 208F cells in the peritoneal cavity of nude mice. Thus this reverse tetracycline-regulated retroviral vector (RTRV) system simplifies the delivery of controllable genes to cultured and implanted cells. It is hoped that this approach may pave the way to controlled gene expression during a particular window of time in gene therapy applications.

背景与目标： : 用自动调节盒构建逆转录病毒载体，以响应体内口服强力霉素 (Dox) 的目的基因表达。该盒包含反向四环素调节 (rtTA) 系统的所有成分，该系统是具有内部核糖体进入位点和目标基因 (GFP) 的药物选择标记。FACS分析显示，在逆转录病毒感染的208F细胞中，取决于培养基中Dox的量，诱导了两个数量级的GFP荧光。此外，口服Dox导致裸鼠腹膜腔中移植的208F细胞中GFP表达。因此，这种反向四环素调节的逆转录病毒载体 (RTRV) 系统简化了可控基因向培养和植入细胞的传递。希望这种方法可以为在基因治疗应用中的特定时间窗口内控制基因表达铺平道路。

BACKGROUND & AIMS: :Angiostensin II (Ang II) regulates the migration and proliferation of vascular smooth muscle cells. Recent studies indicate that intermediate-conductance Ca2+ -activated K+ (IKca) channels have an important role in cell migration and proliferation. It is not known, however, whether the action of Ang II is linked to IKca channel regulation. Here, we investigated the modulation of IKca channels by Ang II in artery smooth muscle cells. Functional IKca channel expression in cultured embryonic rat aorta smooth muscle (A10) cells was studied using the patch-clamp technique. These cells predominantly express IKca channels. In contrast, large-conductance Ca2+ -activated K+ (BKca) currents were rarely observed in excised patches. Ang II increased the IKca current in a contration-dependent manner. Losartan (1.0 microM), an AT1 selective antagonist, abolished the activation of IKca channels by Ang II. Pretreatment with 100 microM myristoylated protein kinase C inhibitor peptide 20-28 or 10 microM GF109203X completely abolished the AngII-induced activation of IKca currents, whereas the action of Ang II was not prevented in the presence of 100 microM Rp-cyclic 3', 5'-hydrogen phosphotiate adenosine triethylammonium, a protein kinase A inhibitor, or 1.0 microM KT-5823, a protein kinase G inhibitor. A membrane permeant analogue of diacylglycerol 1, 2-dioctanoyl-sn-glycerol (10 microM) induced the activation of IKca currents. These data suggest that Ang II activates IKca channels through the activation of protein kinase C, and the AT1 receptor is involved in the regulation of these channels.

背景与目标： : Angiostensin II (Ang II) 调节血管平滑肌细胞的迁移和增殖。最近的研究表明，中间电导Ca2激活的K (IKca) 通道在细胞迁移和增殖中起重要作用。但是，尚不清楚Ang II的作用是否与IKca通道调节有关。在这里，我们研究了Ang II对动脉平滑肌细胞中IKca通道的调节。使用膜片钳技术研究了培养的胚胎大鼠主动脉平滑肌 (A10) 细胞中功能性IKca通道的表达。这些细胞主要表达IKca通道。相反，在切除的贴片中很少观察到大电导Ca2激活的K (BKca) 电流。Ang II以依赖于收缩的方式增加了IKca电流。氯沙坦 (1.0 microM)，一种AT1选择性拮抗剂，通过Ang II消除了IKca通道的激活。用100 microM肉豆蔻酰化蛋白激酶C抑制剂肽20-28或10 microM GF109203X进行预处理完全消除了AngII诱导的IKca电流的激活，而在存在100 microM Rp-环状3 '，5'-磷酸氢腺苷三乙基铵的情况下，Ang II的作用没有被阻止，蛋白激酶a抑制剂，或1.0 microM KT-5823，蛋白激酶G抑制剂。二酰基甘油1,2-二酰基-sn-甘油 (10 microM) 的膜渗透类似物诱导了IKca电流的激活。这些数据表明Ang II通过激活蛋白激酶C激活IKca通道，AT1受体参与了这些通道的调节。

BACKGROUND & AIMS: :The tachykinin family of vasoactive peptides comprises the neuropeptides substance P, neurokinin A and neurokinin B, and the newly discovered endokinins and hemokinins. Their cardiovascular effects are predominantly mediated by the family of neurokinin receptors. This review summarises the most recent advances in understanding the effects of tachykinins on the vasculature, and summarises their therapeutic potential. Tachykinins stimulate plasma extravasation, particularly acting through neurokinin-1 receptors in an endothelium-dependent manner. They therefore play prominent roles in tissue oedema and inflammation (called neurogenic inflammation). Pro-inflammatory effects of tachykinins are enhanced by their capacity to stimulate inflammatory cell recruitment, and to initiate angiogenesis. Tachykinins also regulate vascular tone and blood flow, although differences between species and between different vascular beds make this a highly complex area of research. They may relax vessels in some scenarios whilst inducing vasoconstriction in other situations, the state of the endothelium appearing to be of key importance. Tachykinins also modulate blood pressure and heart rate, acting both peripherally, and on the central nervous system. Cardiovascular effects of tachykinins and neurokinin receptors may be important therapeutic targets in diverse disorders such as pulmonary oedema, hypertension, pre-eclampsia, complex regional pain syndrome type 2, stroke and chronic inflammatory diseases such as arthritis. Sophisticated modelling of human disease is required to enable neurokinin receptor antagonists to achieve this therapeutic potential.

背景与目标： : 血管活性肽的速激肽家族包括神经肽p物质，神经激肽A和神经激肽B，以及新发现的内收缩素和血收缩素。它们的心血管作用主要由神经激肽受体家族介导。这篇综述总结了了解速激肽对脉管系统影响的最新进展，并总结了它们的治疗潜力。速激肽刺激血浆外渗，特别是通过neurokinin-1受体以内皮依赖性方式起作用。因此，它们在组织水肿和炎症 (称为神经源性炎症) 中起着重要作用。速激肽的促炎作用通过刺激炎性细胞募集和启动血管生成的能力而增强。速激肽还调节血管张力和血流，尽管物种之间以及不同血管床之间的差异使这成为一个高度复杂的研究领域。在某些情况下，它们可能会放松血管，而在其他情况下会引起血管收缩，内皮状态似乎至关重要。速激肽还调节血压和心率，既作用于外周，又作用于中枢神经系统。速激肽和神经激肽受体的心血管作用可能是多种疾病 (例如肺水肿，高血压，先兆子痫，2型复杂区域疼痛综合征，中风和慢性炎症性疾病 (例如关节炎) 的重要治疗靶标。需要对人类疾病进行复杂的建模，以使神经激肽受体拮抗剂能够实现这种治疗潜力。

BACKGROUND & AIMS: Magnetic resonance has assumed a preeminent role in the imaging evaluation of the spine. Owing to its multiplanar capability and superior soft tissue contrast, magnetic resonance imaging is the procedure of choice for a host of spinal disorders including degenerative disc disease, tumor evaluation, trauma, and spinal deformities. It represents the most accurate means of distinguishing between recurrent disc herniation and epidural fibrosis, and it excels at the assessment of many postoperative abnormalities such as infection, adjacent segment disc degeneration, and arachnoiditis. Magnetic resonance imaging is also helpful in the evaluation of numerous diagnostic challenges that are less well resolved by other means. This includes the distinction between disc herniation and epidural hematoma, synovial cyst from nonspecific fibrous thickening of a facet capsule, and the evaluation of numerous other soft tissue abnormalities. Computed tomography, computed tomography myelography, and scintigraphy continue to be useful for numerous specific disorders and in those patients with metal hardware or contraindications to magnetic resonance scanning. Overall, however, magnetic resonance is the imaging procedure preferred for many spinal disorders. This article is the first installment of a 3-part series discussing the role of magnetic resonance imaging of spinal disorders. Section 1 will describe the varying imaging modalities available and their relative advantages and disadvantages. A consideration of magnetic resonance imaging techniques will follow, followed by a discussion of the imaging manifestations of early degenerative disc disease. Section 2 will be devoted to an in depth discussion of specific pathologic processes encountered in patients with degenerative disc disease. Section 3 will end the series with a consideration of postoperative imaging followed by a discussion of spinal deformities, trauma, and neoplasms.

背景与目标： 磁共振在脊柱的成像评估中发挥了重要作用。由于其多平面能力和出色的软组织对比度，磁共振成像是许多脊柱疾病 (包括退行性椎间盘疾病，肿瘤评估，创伤和脊柱畸形) 的首选方法。它代表了区分复发性椎间盘突出症和硬膜外纤维化的最准确方法，并且擅长评估许多术后异常，例如感染，相邻节段椎间盘退变和蛛网膜炎。磁共振成像也有助于评估许多诊断难题，而其他方法无法很好地解决这些难题。这包括椎间盘突出症和硬膜外血肿之间的区别，关节突囊的非特异性纤维增厚引起的滑膜囊肿，以及对许多其他软组织异常的评估。计算机断层扫描，计算机断层扫描脊髓造影和闪烁显像对于许多特定疾病以及那些具有金属硬件或磁共振扫描禁忌症的患者仍然有用。然而，总的来说，磁共振是许多脊柱疾病首选的成像程序。本文是由3部分组成的系列文章的第一部分，讨论了脊柱疾病的磁共振成像的作用。第1节将描述可用的各种成像方式及其相对的优缺点。随后将考虑磁共振成像技术，然后讨论早期退行性椎间盘疾病的成像表现。第2节将致力于深入讨论退行性椎间盘疾病患者遇到的特定病理过程。第3节将在系列结束时考虑术后影像学，然后讨论脊柱畸形，创伤和肿瘤。

BACKGROUND & AIMS: OBJECTIVE:To assess whether interindividual variation in renal plasma flow or in its response to angiotensin II infusion is associated with interindividual differences in blood pressure in a population-based sample of 287 non-Hispanic whites (143 women and 144 men), aged 20-49.9 years.

METHODS:After seven days of eating a high-sodium diet (260 mmol/day), the renal plasma flow was determined by measuring the clearance of p-aminohippurate before and after infusion of 3 ng/kg per min angiotensin II. Multiple linear regression methods were used to assess whether measures of the renal plasma flow and of its response to angiotensin II infusion were predictive of systolic or diastolic blood pressures measured prior to administration of the high-sodium diet, on day 6 of the high-sodium diet, or during the renal clearance procedure on day 7 prior to angiotensin II infusion.

RESULTS:There was some evidence that measures of the renal plasma flow and of its response to angiotensin II infusion during the high-sodium diet were statistically significant predictors of measures of blood pressure in women; there was less evidence for this for blood pressures in men. Interindividual variation in measures of the renal plasma flow and of its response to angiotensin II infusion explained less than 10% of the interindividual variation in any measure of the blood pressure in both sexes.

CONCLUSION:These results suggest that interindividual variation in renal plasma flow ad in its response to angiotensin II infusion during a high-sodium diet will be of limited utility in elucidating the basis for interindividual differences in blood pressure.

背景与目标： 目的 : 在基于人群的287非西班牙裔白人 (143名女性和144名男性) 样本中，评估肾血浆流量或对血管紧张素II输注的反应的个体差异是否与血压的个体差异相关，年龄在20-49.9岁之间。
方法 : 在食用高钠饮食 (260 mmol/天) 7天后，通过在每分钟输注3 ng/kg血管紧张素II之前和之后测量对氨基马尿酸盐的清除率来确定肾血浆流量。使用多元线性回归方法来评估肾血浆流量及其对血管紧张素II输注的反应的测量是否可以预测高钠饮食第6天在给予高钠饮食之前测得的收缩压或舒张压。钠饮食，或在输注血管紧张素II之前第7天的肾脏清除过程中。
结果 : 有证据表明，高钠饮食期间肾脏血浆流量的测量及其对血管紧张素II输注的反应是女性血压测量的统计学显着预测指标; 男性血压的证据较少。肾血浆流量测量及其对血管紧张素II输注的反应的个体差异解释了男女血压测量中个体间差异的10%。
结论 : 这些结果表明，在高钠饮食中对血管紧张素II输注的反应中，肾血浆流量ad的个体差异在阐明血压个体差异的基础方面将是有限的。

BACKGROUND & AIMS: :Evidence suggests that gender differences exist in renin-angiotensin system (RAS) function. It was hypothesized that women may differ also in their response to RAS blockade. The renal and peripheral hemodynamic responses to incremental dosages of an angiotensin receptor blocker and the degree of angiotensin II (AngII) insensitivity achieved during 8 wk were examined in men and women. Participants were 30 young healthy men (n = 15; mean age 27 +/- 2) and women (n = 15; mean age 28 +/- 2) who were on a controlled sodium and protein diet for 1 wk before each study. The humoral, renal, and systemic response to incremental dosages of irbesartan (75 mg for 4 wk, then 150 mg for 4 wk) was assessed, as was the pressor response to AngII (3 ng/kg per min), at 2-wk intervals. AngII type 1 receptor expression in skin biopsies was assessed at baseline and after 8 wk by a real-time PCR protocol. Men and women both exhibited significant declines in BP. Women achieved significantly reduced AngII sensitivity compared with men at lower dosages, showing no pressor response at 4 wk of 75 mg/d irbesartan, whereas men continued to exhibit a pressor response at 4 wk of 150 mg/d. Receptor expression at baseline did not differ between men and women but by 8 wk was significantly decreased in women and unchanged in men. Our findings indicate that men may require larger dosages of angiotensin receptor blocker than do women and that the BP response cannot be used as a surrogate marker for adequate RAS blockade of the renal microvasculature.

背景与目标： : 证据表明，肾素-血管紧张素系统 (RAS) 功能存在性别差异。据推测，女性对RAS封锁的反应也可能有所不同。在男性和女性中检查了对血管紧张素受体阻滞剂增量剂量的肾脏和外周血液动力学反应以及在8周期间实现的血管紧张素II (AngII) 不敏感性程度。参与者是30名年轻的健康男性 (n = 15; 平均年龄27/- 2) 和女性 (n = 15; 平均年龄28/- 2)，他们在每次研究前接受钠和蛋白质饮食控制1周。评估了对递增剂量的厄贝沙坦 (75 mg，4 wk，然后150 mg，4 wk) 的体液，肾脏和全身反应，以及对AngII的升压反应 (3 ng/kg/min) 间隔2-wk。通过实时PCR方案在基线和8周后评估皮肤活检中的AngII 1型受体表达。男性和女性的血压都明显下降。与较低剂量的男性相比，女性的AngII敏感性显着降低，在4 wk 75 mg/d厄贝沙坦时没有升压反应，而男性在4 wk 150 mg/d时继续表现出升压反应。基线时，男女之间的受体表达没有差异，但到8周时，女性显着降低，而男性则没有变化。我们的发现表明，男性可能比女性需要更大剂量的血管紧张素受体阻滞剂，并且BP反应不能用作适当的RAS阻断肾微血管的替代指标。

BACKGROUND & AIMS: Development of methodologies for gene transfer into the central nervous system (CNS) is important for fundamental research as well as clinical studies for gene therapy. Cationic liposomes (CL) are attractive vectors because of their safety and ease of use. However, to date only low rates of success have been reported. We succeeded in obtaining high transfection efficiencies into the newborn mouse brain in vivo by CL and a cytoplasmic gene expression system based on T7 RNA polymerase and T7 RNA polymerase- and the luciferase-gene with the T7 promoter sequence. This system showed an efficiency rate 2 orders of magnitude higher than the standard system, which used CL and luciferase genes with a Rous sarcoma virus promoter, pRSVL. In addition, in vitro experiments using LLCMK2 cells showed that cytoplasmic gene expression occurred rapidly (within 6 h) after transfection. In contrast, pRSVL required 24-48 h for induction of luciferase expression. Our results suggest that the cytoplasmic gene expression system is useful for gene delivery into the CNS.

背景与目标： 开发将基因转移到中枢神经系统 (CNS) 的方法对于基因治疗的基础研究和临床研究至关重要。阳离子脂质体 (CL) 是有吸引力的载体，因为它们的安全性和易用性。然而，迄今为止，只有低成功率的报道。我们成功地通过CL和基于T7 RNA聚合酶和T7 RNA聚合酶以及具有T7启动子序列的荧光素酶基因的细胞质基因表达系统在体内获得了高转染效率。该系统的效率比标准系统高2个数量级，标准系统使用具有Rous肉瘤病毒启动子pRSVL的CL和荧光素酶基因。此外，使用LLCMK2细胞的体外实验表明，转染后细胞质基因表达迅速 (在6小时内) 发生。相反，pRSVL需要24-48小时才能诱导荧光素酶表达。我们的结果表明，细胞质基因表达系统可用于将基因传递到CNS中。

BACKGROUND & AIMS: Pseudomonas putida U does not degrade D-glucose through the glycolytic pathway but requires (i) its oxidation to D-gluconic acid by a peripherally located constitutive glucose dehydrogenase (insensitive to osmotic shock), (ii) accumulation of D-gluconic acid in the extracellular medium, and (iii) the induction of a specific energy-dependent transport system responsible for the uptake of D-gluconic acid. This uptake system showed maximal rates of transport at 30 degrees C in 50 mM potassium phosphate buffer, pH 7.0. Under these conditions the K(m) calculated for D-gluconic acid was 6.7 microM. Furthermore, a different transport system, specific for the uptake of glucose, was also identified. It is active and shows maximal uptake rates at 35 degrees C in 50 mM potassium phosphate buffer, pH 6.0, with a K(m) value of 8.3 microM.

背景与目标： 恶臭假单胞菌U不会通过糖酵解途径降解D-葡萄糖，但需要 (i) 通过位于外周的组成型葡萄糖脱氢酶将其氧化为D-葡萄糖酸 (对渗透休克不敏感)，(ii) D-葡萄糖酸在细胞外培养基中的积累，(iii) 诱导负责吸收D-葡萄糖酸的特定能量依赖性转运系统。该吸收系统在50 mM磷酸钾缓冲液 (pH 7.0) 中显示了在30 ℃ 下的最大转运速率。在这些条件下，计算的D-葡萄糖酸的K(m) 为6.7微米。此外，还确定了特定于葡萄糖摄取的不同转运系统。它具有活性，并在50 mM磷酸钾缓冲液 (pH 6.0) 中的35摄氏度下显示出最大的吸收速率，K(m) 值为8.3微米。

BACKGROUND & AIMS: BACKGROUND:Angiotensin II (Ang II) is a well-known activator of smooth muscle in the vasculature but has been little explored with regard to intestinal wall muscular activity. This study investigates pharmacological properties of Ang II and expression of its receptors in small-intestinal smooth muscle from rats and humans. METHODS:Isometric recordings were performed in vitro on small intestinal longitudinal muscle strips. Protein expressions of Ang II typ 1 (AT1R) and typ 2 (AT2R) receptors were assessed by Western blot. RESULTS:Ang II elicited concentration-dependent contractions of rat jejunal and ileal muscle preparations. The concentration-response curve (rat ileum, EC(50): 1.5 +/- 0.9 x 10(-8) M) was shifted to the right by the AT1R receptor antagonist losartan (10(-7) M) but was unaffected by the AT2R antagonist PD123319 (10(-7) M) as well as by the adrenolytic guanethidine (3 x 10(-6) M) and the anticholinergic atropine (10(-6) M). Human duodenal, jejunal and ileal longitudinal muscle preparations all contracted concentration-dependently in response to Ang II. The concentration-response curve (human jejunum, EC(50): 1.5 +/- 0.8 x 10(-8) M) was shifted to the right by losartan (10(-7) M) but was unaffected by PD123319 (10(-7) M). Both AT1R and AT2R were detected in all segments of the rat small intestinal wall musculature, whereas only AT1R was readily detectable in the human samples. CONCLUSION:Ang II elicits contractions of small-intestinal longitudinal muscle preparations from the small intestine of rats and man. The pharmacological pattern and protein expression analyses indicate mediation via the AT1R.

背景与目标：

BACKGROUND & AIMS: :Peroxisome proliferator-activated receptors (PPARs) are expressed on vascular tissue. To investigate the direct vasoprotective effects of PPARgamma and PPARalpha ligands, pioglitazone (3 mg/kg/day) and bezafibrate (10 mg/kg/day) were given by gavage to streptozotocin-induced diabetic rats for 4 weeks. Streptozotocin (65 mg/kg, i.p.) significantly increased NADPH oxidase, vascular call adhesion molecule-1 (VCAM-1), and osteopontin mRNA levels in the aorta, as determined by reverse transcription (RT)-polymerase chain reaction (PCR). Immunohistochemical analysis revealed that the expression of osteopontin protein was also enhanced in the streptozotocin-injected rat aorta. Pioglitazone or bezafibrate attenuated the streptozotocin-induced increase in the expression of NADPH oxidase and VCAM-1 mRNA. The enhanced expression of osteopontin gene and protein induced by streptozotocin was suppressed by pioglitazone, whereas treatment with bezafibrate had no effect on the expression of osteopontin. We also demonstrated that pioglitazone or bezafibrate prevented the streptozotocin-induced increase in angiotensin converting enzyme (ACE) gene and protein content, by the means of RT-PCR and Western blotting. On the other hand, the treatment of pioglitazone or bezafibrate in the present study did not affect glucose tolerance, serum insulin or lipid level in streptozotocin-induced diabetic rats. These results suggest that the direct anti-oxidant and anti-inflammatory effects of PPARs ligands in the aorta of streptozotocin-induced diabetic rats were not likely to have been mediated by the normalization of glucose or lipid metabolism, but instead these salutary effects appear to have been associated with the inhibition of the expression of ACE. In addition, pioglitazone appeared to be more effective on the suppression of osteopontin expression compared with bezafibrate.

背景与目标： : 过氧化物酶体增殖物激活受体 (ppar) 在血管组织上表达。为研究PPARgamma和PPARalpha配体的直接血管保护作用，将吡格列酮 (3 mg/kg/天) 和苯扎贝特 (10 mg/kg/天) 灌胃给链脲佐菌素诱导的糖尿病大鼠4周。通过逆转录 (RT)-聚合酶链反应 (PCR) 测定，链脲佐菌素 (65 mg/kg，i.p.) 显着增加主动脉中的NADPH氧化酶，血管呼叫粘附分子-1 (VCAM-1) 和骨桥蛋白mRNA水平。免疫组织化学分析显示，在注射链脲佐菌素的大鼠主动脉中，骨桥蛋白的表达也得到了增强。吡格列酮或苯扎贝特减弱了链脲佐菌素诱导的NADPH氧化酶和VCAM-1 mRNA表达的增加。吡格列酮抑制了链脲佐菌素诱导的骨桥蛋白基因和蛋白的增强表达，而苯扎贝特治疗对骨桥蛋白的表达没有影响。我们还证明，吡格列酮或苯扎贝特通过rt-pcr和Western印迹阻止了链脲佐菌素诱导的血管紧张素转化酶 (ACE) 基因和蛋白质含量的增加。另一方面，本研究中吡格列酮或苯扎贝特的治疗不会影响链脲佐菌素诱导的糖尿病大鼠的葡萄糖耐量，血清胰岛素或脂质水平。这些结果表明，链脲佐菌素诱导的糖尿病大鼠主动脉中ppar配体的直接抗氧化和抗炎作用不太可能由葡萄糖或脂质代谢的正常化介导。但是，这些有益的作用似乎与抑制ACE的表达有关。此外，与苯扎贝特相比，吡格列酮似乎对抑制骨桥蛋白表达更有效。

BACKGROUND & AIMS: OBJECTIVE:To compare prostate carcinoma, with and with no lymph node metastasis, to benign prostatic hyperplasia (BPH) tissue for lymphatic vessel density (LVD) and the expression of the lymph-endothelial specific growth factor, vascular endothelial growth factor C (VEGF-C), to determine their role in lymphogenic metastasis. PATIENTS, MATERIALS AND METHODS:Lymphatic vessels were stained using lymphatic vessel endothelial hyaluronan receptor 1 and assessed in standard areas. The expression of VEGF-C was assessed by the number of positive epithelial cells. The data were compared with the clinical staging. RESULTS:The lowest LVD was found in tumorous areas as opposed to periphery and nontumorous tissue (P = 0.007; P < 0.001). The highest LVD was in BPH tissue (P < 0.001). There was no correlation with clinical staging. There was more VEGF-C staining in pN1 than in pN0 and in BPH specimens (P = 0.002). CONCLUSION:LVD is not a prognostic variable for the process of lymphogenic metastasis in prostate cancer. VEGF-C is up-regulated in prostate cancer and its correlation with lymph node status suggests a role for the development of lymph node metastasis, e.g. via an increased permeability of lymphatic vessels.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:P21-activated kinase 1 (PAK1) stimulates growth and metastasis of colorectal cancer (CRC) through activation of multiple signalling pathways. Up-regulation of CRC stem cell markers by PAK1 also contributes to the resistance of CRC to 5-fluorouracil. The aim of this study was to investigate the effect of PAK1 depletion and inhibition on the immune system and on intestinal tumour formation in APC∆14/+ mice. METHODS:The PAK1 KO APC∆14/+ mice were generated by cross-breeding of PAK1 KO mice with APC∆14/+ mice. Splenic lymphocytes were analysed by flow cytometry, and immunohistochemical staining. The numbers of intestinal tumours were counted. Blood cells were also counted. RESULTS:Compared to APC+/+ mice, the numbers of both T- and B- lymphocytes were reduced in the spleen of APC∆14/+ mice. Depletion of PAK1 in APC∆14/+ mice increased the numbers of splenic T- and B- lymphocytes and decreased the numbers of intestinal tumours. Treatment of APC∆14/+ mice with PF-3758309, a PAK inhibitor reduced the numbers of intestinal tumours and increased the numbers of blood lymphocytes. CONCLUSION:Depletion of active PAK1 up-regulates the immune system of APC∆14/+ mice and suppresses intestinal tumour development. These observations suggest an important role for PAK1 in the immune response to tumours.

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