BACKGROUND & AIMS: These experiments were designed to determine whether glycogenolysis was influenced by the glycogen concentration of vascular smooth muscle. Segments of hog carotid artery smooth muscle were allowed to synthesize variable amounts of 1-[13C]glucosyl units of glycogen. Artery segments were then isometrically contracted in the presence of 2-[13C]glucose. Prior to and after isometric contraction, measurements were made of tissue glycogen content and superfusate glucose and lactate concentrations. 2-[13C]Lactate and 3-[13C]lactate peak intensities in the superfusate were measured using 13C-NMR spectroscopy. The tissue glycogen content decreased exponentially during the 4.5 h of isometric contraction (R2 = 0.990), despite more than a 3-fold range of glycogen concentration prior to contraction. The extent of glycogen utilization during a 3 h isometric contraction varied linearly with the precontraction glycogen concentration (R2 = 0.727). Lactate production specifically from glycogen breakdown increased with an increase in precontraction glycogen concentration (R2 = 0.620). During a 3 h isometric contraction neither the glucose utilization (R2 = 0.007) nor lactate production specifically produced from glucose (R2 = 0.00002) varied with the precontraction glycogen concentration. It is concluded that the rate of glycogenolysis is determined by the content of glycogen during prolonged contractions. In addition, precontraction glycogen levels influence the pathway for glycogen utilization but not the pathway for glucose utilization. Therefore, glycolysis and glycogenolysis behave independently in vascular smooth muscle.

背景与目标： 这些实验旨在确定糖原分解是否受血管平滑肌糖原浓度的影响。允许猪颈动脉平滑肌段合成可变量的1-[13C] 糖原葡萄糖单元。然后在2-[13C] 葡萄糖存在下等距收缩动脉段。在等距收缩之前和之后，测量组织糖原含量和超融合物葡萄糖和乳酸浓度。使用13C-NMR光谱测量超融合物中的2-[13C] 乳酸和3-[13C] 乳酸峰强度。组织糖原含量在等距收缩的4.5小时内呈指数下降 (R2 = 0.990)，尽管收缩前糖原浓度超过3倍。在3 h等距收缩期间糖原利用的程度随收缩前糖原浓度线性变化 (R2 = 0.727)。糖原分解产生的乳酸产量随着收缩前糖原浓度的增加而增加 (R2 = 0.620)。3小时的等距收缩葡萄糖利用率 (R2 = 0.007) 和特别由葡萄糖产生的乳酸产量 (R2 = 0.00002) 都不随收缩前糖原浓度而变化。结论是糖原分解速率由长期收缩期间糖原含量决定。此外，收缩前糖原水平会影响糖原利用的途径，但不会影响葡萄糖利用的途径。因此，糖酵解和糖原分解在血管平滑肌中独立运作。

BACKGROUND & AIMS: :Go/Gi coupled G-protein receptor mediated transactivation is critical in the activation of receptor tyrosine kinases (RTK). Here we show that mu opioid receptor (MOR) transactivates Flk1 and platelet-derived growth factor-beta (PDGF-beta) receptors and its agonist morphine stimulates pro-angiogenic and survival-promoting signaling in mouse retinal endothelial cells (mREC). Morphine stimulates mREC proliferation in a dose dependent fashion and promotes survival to the same extent as vascular endothelial growth factor164 (VEGF164). Morphine stimulates mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and Akt phosphorylation in a time dependent manner like VEGF in mREC. Moreover, analogous to VEGF, morphine stimulates oncogenic signal transducer and activator of transcription 3 (STAT3) signaling. Morphine as well as VEGF-induced phospho-STAT3 and phospho-Flk1 immunoprecipitated with MOR-associated proteins. In addition morphine also stimulated MOR associated PDGF-beta receptor phosphorylation. Consistent with the relationship between VEGF and MOR we found that VEGF upregulates MOR protein and RNA expression in mREC. These data suggest that MOR associates and transactivates RTKs for Flk1 and PDGF-beta, which may have a compounding effect on angiogenic signaling in endothelium. Therefore, G-Protein coupled receptors including MOR provide novel targets to develop anti-angiogenic agents.

背景与目标： : Go/Gi偶联的g蛋白受体介导的反式激活在受体酪氨酸激酶 (RTK) 的激活中至关重要。在这里，我们显示mu阿片受体 (MOR) 反式激活Flk1和血小板衍生的生长因子-β (pdgf-β) 受体及其激动剂吗啡刺激小鼠视网膜内皮细胞 (mREC) 中的促血管生成和促进存活的信号。吗啡以剂量依赖性方式刺激mREC增殖，并以与血管内皮生长因子164 (VEGF164) 相同的程度促进存活。吗啡以时间依赖性方式刺激丝裂原激活的蛋白激酶/细胞外信号调节激酶 (MAPK/ERK) 和Akt磷酸化，如mREC中的VEGF。此外，与VEGF类似，吗啡刺激致癌信号转导和转录激活因子3 (STAT3) 信号传导。吗啡以及VEGF诱导的phospho-STAT3和phospho-Flk1用MOR相关蛋白免疫沉淀。此外，吗啡还刺激MOR相关的PDGF-β 受体磷酸化。与VEGF和MOR之间的关系一致，我们发现VEGF上调了MOR蛋白和RNA在mREC中的表达。这些数据表明，MOR关联并反式激活了Flk1和PDGF-β 的RTKs，这可能对内皮中的血管生成信号传导具有复合作用。因此，包括MOR在内的g蛋白偶联受体为开发抗血管生成剂提供了新的靶标。

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: :Thrombosis is the main cause of failure of small-diameter synthetic vascular grafts when used for by-pass procedures. The development of bioresorbable vascular scaffolds with localized and sustained intra-luminal antithrombotic drug release could be considered a desirable improvement towards a valuable solution for this relevant clinical need. For this aim, we present the fabrication and characterization of aspirin-loaded electrospun poly(ε-caprolactone) tubular scaffolds as a vascular drug-delivery graft. Three different drug concentrations were considered (i.e., 1, 5 or 10 % w/w). Although a fibrous structure was clearly observed for all the collected scaffolds, aspirin content was directly implied in the final microstructure leading to a bimodal fiber diameter distribution and fused fibers at crossing-points (5 or 10 % w/w). Mechanical response highlighted a direct relationship for modulus and stress at break with the aspirin content, while the elongation at break was not remarkably different for the investigated cases. The temporal drug release was strongly dependent from the amount of loaded aspirin, reaching a steady state release after about 50 h. Finally, the adhesion assay confirmed the capability of the electrospun scaffolds to reduce platelet adhesion/aggregation onto aspirin loaded polymeric fibers. Aspirin-loaded electrospun tubular scaffold could represent a feasible candidate to develop a novel bioresorbable drug-releasing graft for small-diameter vessel replacements.

背景与目标： : 血栓形成是用于旁路手术时小直径合成血管移植物失败的主要原因。开发具有局部和持续的腔内抗血栓药物释放的生物可吸收血管支架可被认为是针对此相关临床需求的有价值解决方案的理想改进。为此，我们介绍了负载阿司匹林的电纺聚 (ε-己内酯) 管状支架作为血管药物递送移植物的制备和表征。考虑三种不同的药物浓度 (即1、5或10% w/w)。尽管对于所有收集的支架都清楚地观察到纤维结构，但在最终微结构中直接隐含阿司匹林含量，导致双峰纤维直径分布和在交叉点处的融合纤维 (5或10% w/w)。机械响应强调了模量和断裂应力与阿司匹林含量的直接关系，而断裂伸长率在所研究的情况下没有显着差异。暂时的药物释放强烈依赖于阿司匹林的载量，约50小时后达到稳定状态释放。最后，粘附试验证实了电纺支架减少血小板粘附/聚集在阿司匹林负载的聚合物纤维上的能力。阿司匹林负载的电纺管状支架可能是开发用于小直径血管置换的新型生物可吸收药物释放移植物的可行候选者。

BACKGROUND & AIMS: :Spontaneous intracranial hemorrhage is a debilitating form of stroke, often leading to death or permanent cognitive impairment. Many of the causative genes and the underlying mechanisms implicated in developmental cerebral-vascular malformations are unknown. Recent in vitro and in vivo studies in mice have shown inhibition of the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) pathway to be effective in stabilizing cranial vessels. Using a combination of pharmacological and genetic approaches to specifically inhibit the HMGCR pathway in zebrafish (Danio rerio), we demonstrate a requirement for this metabolic pathway in developmental vascular stability. Here we report that inhibition of HMGCR function perturbs cerebral-vascular stability, resulting in progressive dilation of blood vessels, followed by vessel rupture, mimicking cerebral cavernous malformation (CCM)-like lesions in humans and murine models. The hemorrhages in the brain are rescued by prior exogenous supplementation with geranylgeranyl pyrophosphate (GGPP), a 20-carbon metabolite of the HMGCR pathway, required for the membrane localization and activation of Rho GTPases. Consistent with this observation, morpholino-induced depletion of the β-subunit of geranylgeranyltransferase I (GGTase I), an enzyme that facilitates the post-translational transfer of the GGPP moiety to the C-terminus of Rho family of GTPases, mimics the cerebral hemorrhaging induced by the pharmacological and genetic ablation of HMGCR. In embryos with cerebral hemorrhage, the endothelial-specific expression of cdc42, a Rho GTPase involved in the regulation of vascular permeability, was significantly reduced. Taken together, our data reveal a metabolic contribution to the stabilization of nascent cranial vessels, requiring protein geranylgeranylation acting downstream of the HMGCR pathway.

背景与目标： 自发性颅内出血是中风的一种衰弱形式，通常导致死亡或永久性认知障碍。与发育性脑血管畸形有关的许多致病基因和潜在机制尚不清楚。最近在小鼠中进行的体外和体内研究表明，抑制3-羟基-3-甲基戊二酰-coa还原酶 (HMGCR) 途径可有效稳定颅骨血管。使用药理学和遗传学方法相结合的方法来特异性抑制斑马鱼 (Danio rerio) 中的HMGCR途径，我们证明了这种代谢途径在发育血管稳定性中的需求。在这里，我们报告了HMGCR功能的抑制会干扰脑血管的稳定性，导致血管进行性扩张，然后血管破裂，模仿人和鼠模型中的脑海绵状畸形 (CCM) 样病变。通过事先补充香叶基焦磷酸 (GGPP) (HMGCR途径的20碳代谢产物) 来挽救脑部出血，这是Rho GTPases膜定位和激活所必需的。与该观察结果一致，吗啉代诱导的香叶基转移酶I (GGTase I) 的 β 亚基耗竭，该酶促进了GGPP部分翻译后转移到Rho gtp酶家族的C末端，模拟了HMGCR的药理和遗传消融引起的脑出血。在脑出血的胚胎中，参与调节血管通透性的Rho GTPase cdc42的内皮特异性表达显着降低。总之，我们的数据揭示了对新生颅骨血管稳定的代谢贡献，需要在HMGCR途径下游起作用的蛋白质香叶基。

BACKGROUND & AIMS: INTRODUCTION:Databases are useful tools in clinical settings. The authors review the benefits and challenges associated with the development and implementation of an efficient electronic database for the multidisciplinary Vascular Birthmark Clinic at the Alberta Children's Hospital, Calgary, Alberta. METHODS:The content and structure of the database were designed using the technical expertise of a data analyst from the Calgary Health Region. Relevant clinical and demographic data fields were included with the goal of documenting ongoing care of individual patients, and facilitating future epidemiological studies of this patient population. After completion of this database, 10 challenges encountered during development were retrospectively identified. Practical solutions for these challenges are presented. RESULTS:THE CHALLENGES IDENTIFIED DURING THE DATABASE DEVELOPMENT PROCESS INCLUDED: identification of relevant data fields; balancing simplicity and user-friendliness with complexity and comprehensive data storage; database expertise versus clinical expertise; software platform selection; linkage of data from the previous spreadsheet to a new data management system; ethics approval for the development of the database and its utilization for research studies; ensuring privacy and limited access to the database; integration of digital photographs into the database; adoption of the database by support staff in the clinic; and maintaining up-to-date entries in the database. CONCLUSIONS:There are several challenges involved in the development of a useful and efficient clinical database. Awareness of these potential obstacles, in advance, may simplify the development of clinical databases by others in various surgical settings.

背景与目标：

BACKGROUND & AIMS: :This article describes the effects of dexmedetomidine (DEX) - the active ingredient of medetomidine, which is the latest popular sedative for functional magnetic resonance imaging (fMRI) in rodents - on multiple unit activity, local field potential (LFP), cerebral blood flow (CBF), pial vessel diameter [indicative of cerebral blood volume (CBV)], and blood oxygenation level-dependent (BOLD) fMRI. These measurements were obtained from the rat somatosensory cortex during 10 s of forepaw stimulation. We found that the continuous intravascular systemic infusion of DEX (50 μg/kg/h, doses typically used in fMRI studies) caused epileptic activities, and that supplemental isoflurane (ISO) administration of ~0.3% helped to suppress the development of epileptic activities and maintained robust neuronal and hemodynamic responses for up to 3 h. Supplemental administration of N(2)O in addition to DEX nearly abolished hemodynamic responses even if neuronal activity remained. Under DEX + ISO anesthesia, spike firing rate and the delta power of LFP increased, whereas beta and gamma power decreased, as compared with ISO-only anesthesia. DEX administration caused pial arteries and veins to constrict nearly equally, resulting in decreases in baseline CBF and CBV. Evoked LFP and CBF responses to forepaw stimulation were largest at a frequency of 8-10 Hz, and a non-linear relationship was observed. Similarly, BOLD fMRI responses measured at 9.4 T were largest at a frequency of 10 Hz. Both pial arteries and veins dilated rapidly (artery, 32.2%; vein, 5.8%), and venous diameter returned to baseline slower than arterial diameter. These results will be useful for designing, conducting and interpreting fMRI experiments under DEX sedation.

背景与目标： : 本文介绍了右美托咪定 (DEX) -美托咪定的有效成分，美托咪定是啮齿动物功能磁共振成像 (fMRI) 的最新流行镇静剂-对多单位活动，局部场电位 (LFP)，脑血流 (CBF)，血管直径 [指示脑血容量 (CBV)] 和血氧水平依赖性 (BOLD) fMRI。这些测量值是在前爪刺激10 s期间从大鼠体感皮层获得的。我们发现，连续血管内全身输注DEX (50 μ g/kg/h，通常用于fMRI研究的剂量) 引起癫痫活动，并且〜0.3% 的补充异氟烷 (ISO) 给药有助于抑制癫痫活动的发展，并在长达3小时的时间内保持强大的神经元和血液动力学反应。除DEX外，补充施用N(2)O几乎消除了血液动力学反应，即使神经元活性仍然存在。在DEX ISO麻醉下，与仅ISO麻醉相比，尖峰放电速率和LFP的 δ 功率增加，而 β 和 γ 功率降低。DEX给药导致腰肌动脉和静脉几乎相等地收缩，导致基线CBF和CBV降低。诱发的LFP和CBF对前爪刺激的反应在8-10Hz的频率下最大，并且观察到非线性关系。类似地，在9.4 T处测量的BOLD fMRI响应在10 hz的频率下最大。腰肌动脉和静脉均迅速扩张 (动脉，32.2%; 静脉，5.8%)，并且静脉直径恢复到基线的速度比动脉直径慢。这些结果将有助于在DEX镇静下设计，进行和解释fMRI实验。

BACKGROUND & AIMS: :Menopausal hormone treatment (MHT) may limit progression of cardiovascular disease (CVD) but poses a thrombosis risk. To test targeted candidate gene variation for association with subclinical CVD defined by carotid artery intima-media thickness (CIMT) and coronary artery calcification (CAC), 610 women participating in the Kronos Early Estrogen Prevention Study (KEEPS), a clinical trial of MHT to prevent progression of CVD, were genotyped for 13,229 single nucleotide polymorphisms (SNPs) within 764 genes from anticoagulant, procoagulant, fibrinolytic, or innate immunity pathways. According to linear regression, proportion of European ancestry correlated negatively, but age at enrollment and pulse pressure correlated positively with CIMT. Adjusting for these variables, two SNPs, one on chromosome 2 for MAP4K4 gene (rs2236935, β = 0.037, P value = 2.36 × 10(-06)) and one on chromosome 5 for IL5 gene (rs739318, β = 0.051, P value = 5.02 × 10(-05)), associated positively with CIMT; two SNPs on chromosome 17 for CCL5 (rs4796119, β = -0.043, P value = 3.59 × 10(-05); rs2291299, β = -0.032, P value = 5.59 × 10(-05)) correlated negatively with CIMT; only rs2236935 remained significant after correcting for multiple testing. Using logistic regression, when we adjusted for waist circumference, two SNPs (rs11465886, IRAK2, chromosome 3, OR = 3.91, P value = 1.10 × 10(-04); and rs17751769, SERPINA1, chromosome 14, OR = 1.96, P value = 2.42 × 10(-04)) associated positively with a CAC score of >0 Agatston unit; one SNP (rs630014, ABO, OR = 0.51, P value = 2.51 × 10(-04)) associated negatively; none remained significant after correcting for multiple testing. Whether these SNPs associate with CIMT and CAC in women randomized to MHT remains to be determined.

背景与目标： : 更年期激素治疗 (MHT) 可能会限制心血管疾病 (CVD) 的进展，但会带来血栓形成的风险。为了测试与颈动脉内膜中层厚度 (CIMT) 和冠状动脉钙化 (CAC) 定义的亚临床CVD相关的靶向候选基因变异，610参加Kronos早期雌激素预防研究 (KEEPS) 的妇女，MHT预防CVD进展的临床试验，在抗凝剂，促凝剂，纤溶或先天免疫途径的764基因内对13,229单核苷酸多态性 (snp) 进行基因分型。根据线性回归，欧洲血统的比例呈负相关，但入学年龄和脉压与CIMT呈正相关。调整这些变量，两个snp，一个在2号染色体上的MAP4K4基因 (rs2236935，β = 0.037，p值 = 2.36 × 10(-06))，一个在5号染色体上的IL5基因 (rs739318，β = 0.051，p值 = 5.02 × 10(-05))，与CIMT呈正相关; CCL5 17号染色体上的两个snp (rs4796119，β = -0.043，p值 = 3.59 × 10(-05); rs2291299，β = -0.032，p值 = 5.59 × 10(-05)) 与CIMT呈负相关; 校正多重测试后，只有rs2236935仍然显著。使用逻辑回归，当我们调整腰围时，两个snp (rs11465886，IRAK2，3号染色体，OR = 3.91，p值 = 1.10 × 10(-04); 和rs17751769，SERPINA1，14号染色体，OR = 1.96，p值 = 2.42 × 10(-04)) 与> 0 Agatston单位的CAC评分呈正相关; 1个SNP (rs630014，ABO，OR = 0.51，p值 = 2.51 × 10(-04)) 呈负相关; 校正多重测试后无显著。这些snp是否与CIMT和CAC相关，在随机分配到MHT的女性中仍有待确定。

BACKGROUND & AIMS: :We are developing biocompatible small-calibre vascular substitutes based on polymeric scaffolds that incorporate cell-matrix signals to enhance vascular cell attachment and function. Our graft scaffold comprises an outer electrostatically spun porous polyurethane layer seeded with smooth muscle cells, and a luminal polycaprolactone layer for endothelial cell attachment. Vascular cell adhesion properties of three vascular elastic fibre molecules, tropoelastin, fibrillin-1 and fibulin-5, have been defined, and adhesion fragments optimized. These fragments are being used to coat the scaffolds to enhance luminal endothelial cell attachment, and to regulate smooth muscle cell attachment and function. Tropoelastin-based cell seeding materials are also being developed. In this way, vascular cell-matrix biology is enhancing graft design.

背景与目标： : 我们正在开发基于聚合物支架的生物相容性小口径血管替代物，该支架结合了细胞基质信号以增强血管细胞附着和功能。我们的移植支架包括一个外部静电纺丝多孔聚氨酯层，该层接种有平滑肌细胞，以及一个用于内皮细胞附着的内腔聚己内酯层。已经定义了三种血管弹性纤维分子 (原弹性蛋白，fibrillin-1和fibulin-5) 的血管细胞粘附特性，并优化了粘附片段。这些片段被用于涂覆支架，以增强管腔内皮细胞的附着，并调节平滑肌细胞的附着和功能。基于原弹性蛋白的细胞播种材料也正在开发中。通过这种方式，血管细胞基质生物学正在增强移植物的设计。

BACKGROUND & AIMS: OBJECTIVE:Ossification/calcification around the medial femoral condyle has been known as Pellegrini-Stieda (PS) disease for almost 100 years. Little attention has been given to magnetic resonance (MR) imaging characteristics. Our purpose is to demonstrate the anatomy in the medial femoral compartment and imaging findings of PS disease, determining the sites and patterns of ossification. DESIGN AND PATIENTS:In a cadaveric study seven specimens were dissected to show the anatomic relations of the tibial collateral ligament (TCL) and the tendon of the ischiocondylar part of the adductor magnus muscle, in the medial femoral epicondyle. In order to determine the nature of ossification/calcification in PS disease, MR imaging and radiographic findings in nine patients were analyzed by two observers with attention to the specific site, shape, and orientation of the ossification and its relationship to the tibial collateral ligament (TCL) and adductor magnus tendon. Available clinical history was recorded. A classification system addressing different sites and patterns of ossification was developed. RESULTS:The anatomic study showed that the TCL and the adductor magnus tendon insert at different sites in the medial femoral condyle and there is no continuation; however, some fibers of the posterior bundle of the TCL overlap the anterior aspect of the adductor magnus tendon. The imaging study showed that shape, orientation, and location of the abnormal calcification and ossification were similar on radiographic and MR imaging analysis. Ossification had an inferior orientation in six cases, a superior orientation in two cases, and both in one case. Four patterns of ossification were noted: (I) a beak-like appearance with an inferior orientation and femoral attachment was present in five cases; (II) a drop-like appearance with an inferior orientation, parallel to the femur, was evident in one case; (III) an elongated appearance with a superior orientation, parallel to the femur, was seen in two cases; and (IV) a beak-like appearance with an inferior and superior orientation, attached to the femur, was seen in one case. The ossification was present in the TCL in six cases, in the adductor magnus tendon in two cases, and in both in one case. The coronal plane was best in detecting and categorizing the ossification. CONCLUSION:Our data indicate that ossification in PS disease is not confined to the TCL but may also involve the adductor magnus tendon. In some cases, it can be related to the anatomic proximity (overlap) of the fibers of these two structures. PS disease should not be regarded as synonymous with ossification of the TCL. The ossification may be classified into four types. No clinical differences among these types appear to exist.

背景与目标：

BACKGROUND & AIMS: :We described seven patients with Streptococcus milleri group aortic (six patients) or vena cava (one patient) graft infection secondary to a vasculo-digestive fistula. Time between vascular graft setting and first clinical signs varied from eight months to more than thirteen years. Six patients had fever. Three patients presented with recurrent fever for more than nine months and in two of these cases, delay before diagnosis was long because repeated blood cultures were sterile. Three patients had abdominal pain and/or digestive haemorrhage. Abdominal CT-scan S. milleri was not contributive for the diagnosis in four patients. Streptococcus anginosus was isolated in four patients, Streptococcus constellatus in three patients. One patient died before surgical management. The other six patients were cured by a surgical management associated with a prolonged antibiotic (lactams) treatment. S. milleri group graft infections are rare (or misdiagnosed) while we found only 4 similar cases in the English medical literature. We conclude that a peri-prosthetic infection secondary to a digestive fistula must be insistently searched (and blood cultures must be repeated many times) in any patient with an aortic (or any other vascular) graft presenting prolonged or recurrent fever or acute digestive symptoms.

背景与目标： : 我们描述了7例继发于血管消化瘘的链球菌组主动脉 (6例) 或腔静脉 (1例) 移植物感染的患者。血管移植与首次临床体征之间的时间从8个月到13年以上不等。六名患者发热。三名患者出现反复发热超过9个月，其中两名患者由于反复的血液培养是无菌的，因此在诊断之前的延迟时间很长。三名患者患有腹痛和/或消化道出血。腹部ct扫描S. milleri对四名患者的诊断没有帮助。在4例患者中分离出aninosus链球菌，在3例患者中分离出constellatus链球菌。一名患者在手术治疗前死亡。其他六名患者通过长期抗生素 (lacams) 治疗的外科手术治愈。S. milleri组移植物感染很少见 (或误诊)，而我们在英国医学文献中仅发现4例类似病例。我们得出的结论是，对于任何主动脉 (或任何其他血管) 移植物出现长期或反复发烧或急性消化症状的患者，必须坚持检查继发于消化瘘的假体周围感染 (并且必须重复多次血液培养)。

BACKGROUND & AIMS: BACKGROUND:An impairment of cerebral microvessels is reported both in normal ageing and in senescence-associated processes, as well as in Alzheimer's disease (AD) and vascular dementia (VaD). The aim of this study was to explore cerebral hemodynamics by transcranial Doppler in VaD and AD, compared with age-matched control subjects. METHODS:Transcranial Doppler was investigated in all patients in the basal condition. Cerebral vasoreactivity to hyper- and hypocapnia was evaluated with CO2 mixture inhalation followed by hyperventilation. RESULTS:We studied 60 AD and 58 VaD patients and 62 nondemented controls. Both AD and VaD subjects showed lower flow velocities (FV) and higher pulsatility indices (PI) as compared with controls. Lower total vasomotor reactivity and lower response to hypercapnia were observed in the AD and VaD groups as compared with controls. AD and VaD patients did not show significant differences in FV, PI values or cerebral vasoreactivity. CONCLUSIONS:Reduced FV and increased PI with a significant vasoreactivity reduction in VaD and AD patients are indicators of impairment of cerebral microvasculature circulation in both diseases. The identification of vascular function impairment in all kinds of dementia could be of help in identifying patients who would thus benefit more from specific therapeutic approaches.

背景与目标：

BACKGROUND & AIMS: :Although the involvement of Rho proteins in the pathogenesis of vascular diseases is well studied, little is known about the role of their upstream regulators, the Rho guanine nucleotide exchange factors (RhoGEFs). Here, we sought to identify the RhoGEFs involved in monocyte chemotactic protein 1 (MCP1)-induced vascular wall remodeling. We found that, among the RhoGEFs tested, MCP1 induced tyrosine phosphorylation of p115 RhoGEF but not of PDZ RhoGEF or leukemia-associated RhoGEF in human aortic smooth muscle cells (HASMCs). Moreover, p115 RhoGEF inhibition suppressed MCP1-induced HASMC migration and proliferation. Consistent with these observations, balloon injury (BI) induced p115 RhoGEF tyrosine phosphorylation in rat common carotid arteries, and siRNA-mediated down-regulation of its levels substantially attenuated BI-induced smooth muscle cell migration and proliferation, resulting in reduced neointima formation. Furthermore, depletion of p115 RhoGEF levels also abrogated MCP1- or BI-induced Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling, which, as we reported previously, is involved in vascular wall remodeling. Our findings also show that protein kinase N1 (PKN1) downstream of Rac1-cyclin D1/CDK6 and upstream of CDK4-PAK1 in the p115 RhoGEF-Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling axis is involved in the modulation of vascular wall remodeling. Of note, we also observed that CCR2-Gi/o-Fyn signaling mediates MCP1-induced p115 RhoGEF and Rac1 GTPase activation. These findings suggest that p115 RhoGEF is critical for MCP1-induced HASMC migration and proliferation in vitro and for injury-induced neointima formation in vivo by modulating Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling.

背景与目标： : 尽管对Rho蛋白参与血管疾病的发病机理进行了很好的研究，但对其上游调节剂Rho鸟嘌呤核苷酸交换因子 (rhoiefs) 的作用知之甚少。在这里，我们试图鉴定参与单核细胞趋化蛋白1 (MCP1) 诱导的血管壁重塑的RhoGEFs。我们发现，在测试的RhoGEFs中，MCP1诱导人主动脉平滑肌细胞 (HASMCs) 中p115 RhoGEF的酪氨酸磷酸化，但不诱导PDZ RhoGEF或与白血病相关的RhoGEF的酪氨酸磷酸化。此外，p115 rhoge抑制抑制了MCP1-induced HASMC的迁移和增殖。与这些观察结果一致，球囊损伤 (BI) 在大鼠颈总动脉中诱导了p115 RhoGEF酪氨酸磷酸化，而siRNA介导的其水平下调大大减弱了BI诱导的平滑肌细胞迁移和增殖，从而减少了新内膜的形成。此外，p115 RhoGEF水平的耗竭也消除了MCP1或BI诱导的Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1信号传导，正如我们先前报道的那样，这与血管壁重塑有关。我们的发现还表明，Rac1-cyclin D1/CDK6下游和p115 RhoGEF-Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1信号轴CDK4-PAK1上游的蛋白激酶N1 (PKN1) 参与了血管壁重塑的调节。值得注意的是，我们还观察到CCR2-Gi/o-Fyn信号介导MCP1-induced p115 rhoge和rac1gtpase激活。这些发现表明，p115 RhoGEF对于MCP1-induced HASMC在体外迁移和增殖以及通过调节Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1信号传导在体内损伤诱导的新内膜形成至关重要。

BACKGROUND & AIMS: BACKGROUND/AIMS:Cardiovascular disease (CVD) is increased in chronic kidney disease (CKD), and contributed to by the CKD-mineral bone disorder (CKD-MBD). CKD-MBD begins in early CKD and its vascular manifestations begin with vascular stiffness proceeding to increased carotid artery intima-media thickness (cIMT) and vascular calcification (VC). Phosphorus is associated with this progression and is considered a CVD risk factor in CKD. We hypothesized that modifying phosphorus balance with lanthanum carbonate (LaCO3) in early CKD would not produce hypophosphatemia and may affect vascular manifestations of CKD-MBD. METHODS:We randomized 38 subjects with normophosphatemic stage 3 CKD to a fixed dose of LaCO3 or matching placebo without adjusting dietary phosphorus in a 12-month randomized, double-blind, pilot and feasibility study. The primary outcome was the change in serum phosphorus. Secondary outcomes were changes in measures of phosphate homeostasis and vascular stiffness assessed by carotid-femoral pulse wave velocity (PWV), cIMT and VC over 12 months. RESULTS:There were no statistically significant differences between LaCO3 and placebo with respect to the change in serum phosphorus, urinary phosphorus, tubular reabsorption of phosphorus, PWV, cIMT, or VC. Biomarkers of the early CKD-MBD such as plasma fibroblast growth factor-23, Dickkopf-related protein 1 (DKK1), and sclerostin were increased 2- to 3-fold at baseline, but were not affected by LaCO3. CONCLUSION:Twelve months of LaCO3 had no effect on serum phosphorus and did not alter phosphate homeostasis, PWV, cIMT, VC, or biomarkers of CKD-MBD.

背景与目标：

BACKGROUND & AIMS: :This study investigates whether salivary tumours with different morphology and evolution also differ in terms of neovascularization and VEGF expression and the prognostic value of the results. Surgical specimens from 45 patients - 8 pleomorphic adenomas (PA), 7 Warthin tumours (WT), 5 basal cell adenomas (BA), 6 carcinomas ex-pleomorphic adenoma (CEPA), 6 mucoepidermoid carcinomas (MEC), 5 acinic cell carcinomas (AC), 4 adenoid cystic carcinomas (ACC) and 4 adenocarcinomas not otherwise specified (ADK NOS) - were immunostained. In malignant salivary tumours, the following mean microvascular density (MVD) values were recorded (± SD = Standard Deviation): 27.61 (SD ± 2.27) in cases with CEPA, 27.08 (DS ± 7.81) in AC and 32.93 (SD ± 7.76) in ADK NOS, with lower values for MEC 24.31(SD ± 2.88) and for ACC 22.13 (SD ± 5.44). For benign tumours, an MVD of 35.71 (SD ± 2.09) was recorded in WT and lower average values in PA (MVD = 14.84; SD ± 4.86) and in BA (MVD = 23.96; SD ± 9.13). MVD did not correlate with the investigated clinicopathological parameters. The VEGF expression is significantly more important (p = 0.001) in malignant salivary tumours as compared with benign ones. The VEGF expression and the microvascularization in salivary gland tumours are important elements to be considered when formulating a diagnosis and assessing case evolutions in patients with such tumours.

背景与目标： : 本研究调查了具有不同形态和演变的唾液肿瘤在新生血管形成和VEGF表达以及结果的预后价值方面是否也存在差异。45例患者的手术标本-8例多形性腺瘤 (PA)，7例Warthin肿瘤 (WT)，5例基底细胞腺瘤 (BA)，6例非多形性腺瘤 (CEPA)，6例粘液表皮样癌 (MEC)，5例腺泡细胞癌 (AC)，免疫染色了4例腺样囊性癌 (ACC) 和4例未指明的腺癌 (ADK NOS)。在恶性唾液肿瘤中，记录了以下平均微血管密度 (MVD) 值 (± SD = 标准差): CEPA病例为27.61 (SD ± 2.27)，AC为27.08 (DS ± 7.81)，ADK NOS为32.93 (SD ± 7.76)，MEC 24.31(SD ± 2.88) 和ACC 22.13 (SD ± 5.44) 的值较低。对于良性肿瘤，在WT中记录了35.71的MVD (SD ± 2.09)，在PA (MVD = 14.84; SD ± 4.86) 和BA (MVD = 23.96; SD ± 9.13) 中记录了较低的平均值。MVD与所研究的临床病理参数无关。与良性唾液肿瘤相比，恶性唾液肿瘤中VEGF表达明显更重要 (p = 0.001)。涎腺肿瘤中的VEGF表达和微血管形成是制定诊断和评估此类肿瘤患者病例演变时要考虑的重要因素。