Urinary hypoxanthine and xanthine levels in acute coronary syndromes

Ischemia leads to impaired ATP metabolism, with increased production of purine degradation products, such as hypoxanthine and xanthine, which are useful markers of tissue hypoxia. These extracellular markers of ischemia have been studied extensively in many clinical conditions of oxidative stress, including perinatal asphyxia, acute respiratory distress syndrome, cerebral ischemia, and preeclampsia. The aim of this study was to explore the usefulness of urinary hypoxanthine and xanthine as ischemia markers in acute coronary syndromes. Urinary excretion of hypoxanthine and xanthine was assessed by high-performance liquid chromatography in 30 patients with acute coronary syndromes and in 30 age- and sex-matched controls. Serum and urine uric acid, creatinine, and urea concentrations were also determined. Hypoxanthine excretion was significantly elevated in patients compared with healthy controls (84.37+/-8.63 and 42.70+/-3.97 nmol/mg creatinine, mean+/-SEM, P<0.0001). Urinary xanthine levels were also increased in patients with acute coronary syndromes (100.13+/-12.14 and 34.74+/-4.07 nmol/mg creatinine patients and controls, respectively; P<0.0001). Hypoxanthine and xanthine excretion showed a strong positive correlation in both groups. Significant negative correlations between urinary hypoxanthine and uric acid and xanthine and uric acid were observed in the patients, but not in controls. In conclusion, increased levels of ATP degradation products hypoxanthine and xanthine are observed in various hypoxic clinical conditions. This study suggests that these parameters may be useful markers of ischemia in patients with acute coronary syndromes.     

Value of the D-dimer test in diagnosing deep vein thrombosis in rehabilitation inpatients

OBJECTIVE: To assess the utility of the D-dimer test-a widely available, less costly, and less time-consuming test than others used to diagnose or exclude deep vein thrombosis (DVT) and pulmonary embolism. DESIGN: Blind comparison. SETTING: An inpatient rehabilitation facility in Turkey. PARTICIPANTS: Sixty-eight consecutive inpatients being rehabilitated after stroke, spinal cord injury, hip arthroplasty, or traumatic brain injury. INTERVENTIONS: A latex D-dimer assay was performed on each patient at admission and then weekly throughout the hospital stay. Color Doppler ultrasonography of the lower limbs was also done for each patient at admission and was repeated when indicated by clinical signs and symptoms of DVT or by elevated D-dimer levels.Main outcome measures Patients' clinical findings, D-dimer test results, and ultrasonography results were recorded. Sensitivity, specificity, and positive and negative predictive values were calculated for the D-dimer test, each clinical finding, and combinations of D-dimer results and clinical findings in relation to DVT diagnosis. RESULTS: The sensitivity and negative predictive value of the D-dimer test were high, at 95.2% and 96.2%, respectively. The specificity and positive predictive value were low, at 55.3% and 48.7%, respectively. No single clinical finding was reliably diagnostic for DVT. CONCLUSIONS: The D-dimer assay is a reliable method for ruling out DVT. In the rehabilitation setting, it can be used as a routine screening test or to assess cases of suspected DVT. D-dimer testing may reduce the need for sophisticated, time-consuming, and expensive diagnostic workup of rehabilitation inpatients, a group that is at increased risk for DVT.     

多通道微流控芯片的设计、仿真及细胞迁移应用研究

细胞迁移是指细胞朝着特定的化学浓度梯度发生定向迁移运动,其在胚胎发育、伤口愈合、肿瘤转移中发挥着至关重要的作用。当前研究手段大多通量低,难以综合考虑不同浓度梯度条件对细胞迁移行为的影响。针对上述问题,本文首先设计了一款四通道微流控芯片,其特征如下:借助层流和扩散机制在细胞迁移主通道中建立和维持浓度梯度;可在单一显微镜视野下同时观测四组细胞迁移现象;集成了宽度为20μm的细胞隔离带,可校准细胞初始位置,保证实验结果的准确性。随后,借助Comsol Multiphysics有限元分析软件完成了微流控芯片的仿真分析,证明了芯片上设计S型微通道和水平压力平衡通道有助于在细胞迁移主通道中形成稳定的浓度梯度。最后,采用不同浓度(0、0.2、0.5、1.0μmol·L^-1)与糖尿病及其并发症密切相关的晚期糖基化终末产物(AGEs)孵育中性粒细胞,研究了其在100 nmol·L^-1趋化因子fMLP浓度梯度环境中的迁移行为。结果表明,AGEs抑制了中性粒细胞的迁移能力,证明了四通道微流控芯片的可靠性和实用性。     

下调晚期糖基化终末产物受体对乳腺癌细胞 增殖、凋亡、侵袭、迁移能力的影响*

目的：研究下调晚期糖基化终末产物受体（RAGE）对乳腺癌细胞增殖、凋亡、侵袭、迁移能力的影响。 方法：培养乳腺癌BT474 细胞,分为对照组（ 不做任何处理的乳腺癌BT474 细胞）、上调组（ 乳腺癌BT474 细 胞+RAGE阴性对照）、下调组（ 乳腺癌BT474 细胞+RAGE siRNA）。用四甲基偶氮唑盐法检测乳腺癌细胞增 殖、凋亡水平;用Transwell 法检测乳腺癌细胞迁移、侵袭水平;用免疫印迹法检测细胞PI3K/Akt 信号通路蛋白 PI3K、p-PI3K、Akt、p-Akt、caspase 3、Bcl-2、Bax 表达量。结果：下调组细胞不同时间点增殖率均显著低于 上调组、对照组。下调组细胞不同时间点凋亡率均显著高于上调组、对照组。下调组细胞迁移、侵袭数均显著 低于上调组、对照组。下调组p-PI3K、PI3K、Akt、p-Akt、Bcl-2 蛋白表达量低于上调组、对照组,caspase 3、 Bax 蛋白表达量高于上调组、对照组。结论：经下调RAGE作用于PI3K/Akt 信号通路,其可抑制p-PI3K、PI3K、 Akt、p-Akt、Bcl-2 表达,促进caspase 3、Bax 表达,致乳腺癌细胞凋亡,抑制乳腺癌细胞增殖、侵袭、迁移。     

胃癌组织中RAGE和配体HMGB1表达的临床研究

目的：分析胃癌及相应癌旁组织中的晚期糖基化终产物受体（receptor for advanced glycation end product,RAGE）及其配体高迁移率族蛋白B1 （high mobility group box-1,HMGB1）的表达情况,探讨RAGE、HMGB1表达与胃癌患者临床病理因素的关系以及两者对预后的影响.方法：应用免疫组织化学的方法检测1 09例胃癌组织和30例癌旁组织中RAGE和HMGB1的表达,运用美国Media Cybernetics公司Image-Pro？ Plus 6.2软件分析每张切片的阳性着色的积分吸光度值.结果：相对于癌旁组织,胃癌组织内RAGE和HMGB1的表达升高（P＜ 0.001）.RAGE的表达情况与肿瘤浸润深度、淋巴结转移及TNM分期显著相关（P值均＜0.05）; HMGB1的表达情况与肿瘤组织分化程度和肿瘤转移相关（P=0.023）; RAGE的表达与患者无病生存期相关（P＜0.001）,而HMGB1的表达与患者术后的无病生存期无关.结论：HMGB1-RAGE信号偶联与胃癌的侵袭和转移相关,患者胃癌标本中RAGE的表达影响患者预后,HMGB1-RAGE信号偶联是胃癌治疗的可能靶点之一.     

Advanced oxidation protein products (AOPPs) in juvenile overweight and obesity prior to and following weight reduction

Objectives

To evaluate the formation of advanced oxidation protein products (AOPPs) in juvenile overweight/obesity and obesity-related disorders and to investigate the effect of weight reduction on AOPPs.

Design and methods

AOPPs were determined in 114 overweight/obese children and adolescents without/with insulin resistance and metabolic syndrome and compared with 53 lean controls. Measurements were repeated following weight reduction program (diet/exercise, bran-enriched diet/exercise, and diet/exercise plus metformin).

Results

Overweight/obese subjects had higher AOPPs than lean controls, more elevated in patients with co-occurring metabolic syndrome. AOPPs positively correlated with central obesity, triglycerides, lipid peroxidation and insulin, and negatively with glucose to insulin ratio. AOPPs decreased following obesity intervention and ΔAOPPs correlated with ΔBMI%. AOPPs reduction was more pronounced in subjects on bran-enriched diet. Baseline AOPPs were a better predictor of clinically significant weight reduction than BMI%.

Conclusions

Juvenile overweight/obesity was associated with AOPPs accumulation, more pronounced in metabolic syndrome. Body mass reduction decreased oxidative stress, with bran-enriched diet being more effective than diet/exercise alone.     

HIV-1 integrase inhibitors: 2003-2004 update

The integration of viral cDNA into the host genome is an essential step in the HIV-1-life cycle and is mediated by the virally encoded enzyme, integrase (IN). Inhibition of this process provides an attractive strategy for antiviral drug design. The discovery of beta-diketo acid inhibitors played a major role in validating IN as a legitimate antiretroviral drug target. Over a decade of research, a plethora of IN inhibitors have been discovered and some showed antiviral activity consistent with their effect on IN. To date, at least two compounds have been tested in human but none are close to the FDA approval. In this review, we provide a comprehensive report of all small-molecule IN inhibitors discovered during the years 2003 and 2004. Compilation of such data will prove beneficial in developing QSAR, virtual screening, pharmacophore hypothesis generation, and validation.     

芳香聚酮类化合物产生菌的分子筛选及其代谢产物的研究

目的 建立一种芳香聚酮类化合物产生菌的基因筛选方法并获得相应结构类型的化合物.方法 依据芳香聚酮类化合物生物合成途径所用的Ⅱ型酮基合酶的同源性设计简并引物,通过PCR方法扩增出约0.6kb目的基因片段,同时通过同源进化和抗菌活性分析对海洋放线菌是否产生芳香聚酮类化合物进行早期评估,并最终从阳性菌中分离得到相应结构类型的化合物.结果 利用建立的芳香聚酮类化合物产生菌基因筛选体系对100株海洋放线菌进行筛选,获得了18株携带Ⅱ型酮基合酶基因的阳性菌株,通过同源进化和抗菌活性分析后从中筛选到1株与多环氧杂蒽酮类化合物lysolipin和xantholipin的酮基合酶基因同源的野野村菌(Nonomuraea sp.)FIM02-765,并最终从该菌中分离得到多环氧杂葸酮类化合物simaomicin α.结论 本研究通过聚酮合酶编码基因的同源进化分析以及建立起来的Ⅱ型酮基合酶基因与化合物之间的联系,验证了芳香聚酮类化合物产生菌的基因筛选方法的可行性,同时本文还首次从野野村菌(Nonomuraea sp.)中分离得到多环氧杂葸酮类化合物simaomicin α,这些都为高效利用海洋放线菌资源和基因资源奠定了一定的基础.     

VCAM-1和AOPP在GDM中的检测水平及相关性研究

目的：探讨血管细胞黏附分子1(VCAM-1)、晚期氧化蛋白产物(AOPP)在妊娠期糖尿病(GDM)中的表达水平并进行相关性研究。方法选取2010年1月至2012年12期间40例GDM患者为研究对象( GDM组),另选择正常妊娠孕妇40名为对照组(正常妊娠组)。检测受试者母血及脐血 VCAM-1、AOPP、空腹血糖( FBG)和糖化血红蛋白( HbA1c)、载脂蛋白 A (APOA)、载脂蛋白B(APOB)水平,对两组相关指标进行统计分析。结果 GDM组母血VCAM-1、AOPP、APOB、FBG和HbA1c水平均高于正常妊娠组,差异均有统计学意义(t值分别为37.64、27.19、7.98、8.79、7.53,均P<0.05),GDM组APOA水平低于正常妊娠组,差异有统计学意义(t=14.16,P<0.05);GDM组脐血VCAM-1、AOPP水平高于正常妊娠组,差异均有统计学意义(t值分别为19.37、12.56,均P<0.01);母血清VCAM-1、AOPP表达与APOB、FBG、HbA1c、脐血VCAM-1、脐血AOPP的表达均呈正相关(r值分别为0.468~0.551、0.498~0.598,均P<0.05),与APOA的表达呈负相关(r值分别为-0.459、-0.462,均P<0.05);母血清VCAM-1与AOPP表达呈正相关(r=0.572,P<0.05)。结论 GDM患者母血清及脐血中VCAM-1、AOPP明显高表达,VCAM-1和AOPP的高表达与GDM发病、进展密切相关,VCAM-1和AOPP可作为监测GDM病情及进展的指标。