Simultaneous quantification of 8-iso-prostaglandin-F2α and 11-dehydro thromboxane B2 in human urine by liquid chromatography-tandem mass spectrometry

Both F₂-isoprostanes (8-iso-PGF_2α), a well-known marker of oxidative stress, and thromboxanes A₂ (TXA₂) are involved in atherosclerosis through LDL oxidation and platelet activation. Different aspects of the pathology can be described by 8-iso-PGF_2α and TXA₂ so it is important to determine both their concentrations to monitor the disease progression and/or therapy effects. We developed a simple and sensitive method based on liquid chromatography-tandem mass spectrometry, using electrospray ionization in negative-ion mode, for the simultaneous measurement of the concentration of 8-iso-PGF_2α and 11-dehydro thromboxane B₂ (11-DH-TXB₂), a TXA₂ metabolite. This method was applied to analyze urine samples collected overnight from 15 atherosclerotic patients, with documented carotid artery sclerosis (CAS), and from 20 controls. The detection limit was 0.097 pg/μL for 8-iso-PGF_2α and 0.375 pg/μL for 11-DH-TXB₂, with a linear range of 0.78-25 pg/μL; the inter- and intraday imprecision was <5% for both metabolites. These analytes were higher in CAS (P < 0.005 vs controls) and were positively correlated in patients but not in controls, even after adjustment for age and gender (r = 0.60; P = 0.032). This highly sensitive, precise, and rapid method allows for the simultaneous determination of 8-iso-PGF_2α and 11-DH-TXB₂ in human urine samples in order to evaluate oxidative stress and platelet aggregation.     

慢性缺氧对大鼠颈动脉体中wnt-1和β-catenin表达的影响

目的：观察慢性缺氧对大鼠颈动脉体（carotidbody,CB）中Wnt-1和β—catenin蛋白表达量的影响。方法：雄性SD大鼠40只,随机分为5组：正常氧组、慢性低压性缺氧1周、2周、3周和4周组。处理后,立即取出大鼠双侧CB,提取总蛋白,用westernblot法检测各组大鼠CB中Wnt-1和β-catenin表达量。结果：缺氧3周组和缺氧4周组之间Wnt-1的表达量无明显区别（P〉0．05）,而其余各组之间Wnt．1的表达量均具有统计学差异（P〈0．05）;相对于正常氧组,缺氧3周组大鼠CB中β-catenin的含量明显增加,有统计学意义（P〈0．05）。结论：本研究提示Wnt／β-catenin信号通路可能参与了慢性缺氧引起的颈动脉体干细胞增殖分化的过程。     

Cryopreservation of carotid artery segments via vitrification subject to marginal thermal conditions: correlation of freezing visualization with functional recovery

Cryopreservation is a well-established technique for long-term storage of viable cells and tissues. However, in recent years, application of established cryobiological principles to the preservation of multicellular tissues and organs has demanded considerable attention to ways of circumventing the deleterious effects of ice and thermal stresses in bulky tissues. As part of a multidisciplinary research program designed to study the interactions of thermo-physical events with tissue preservation, we report here on the implementation of a slow cooling (3 °C/min) and slow warming (62 °C/min) regimen towards scale-up of vitreous preservation of large tissue samples. Specifically, the correlation of thermo-physical events during vitrification of carotid artery segments with function recovery is reported using marginal thermal conditions for achieving vitrification in bulky samples. Moreover, the outcome is compared with a similar study reported previously using a 3-fold higher rate of rewarming (186 ± 13 °C/min). Tissue vitrification using an 8.4 M cryoprotectant cocktail solution (VS55) was achieved in 1 ml samples by imposing a low (2.6 ± 0.1 °C/min) cooling rate, between −40 and −100 °C, and a low rewarming rate (62 ± 4 °C/min) between −100 and −40 °C. Following cryoprotectant removal, the artery segments were cut into 3-4 mm rings for function testing on a contractility apparatus by measuring isometric responses to four agonist and antagonists (norepinephrine, phenylepinephrine, calcium ionophore and sodium nitroprusside). In addition, non-specific metabolic function of the vessel rings was determined using the REDOX indicator alamarBlue. Contractile function, normalized to untreated control samples, in response to the agonists norepinephrine and phenylepinephrine was significantly better in the slowly rewarmed group of carotid segments (74 ± 9% and 62 ± 11%, respectively) than for the more rapidly warmed group 31 ± 7% and 45 ± 15%, respectively). However, EC₅₀ sensitivities were not significantly different between the groups. Thermo-physical events such as ice formation and fractures were monitored throughout the cooling and warming phases using cryomacroscopy with the aid of a purpose-built borescope device. This technique allowed a direct observation of the visual impact of ice formation on specific zones along the blood vessel segment where, in most cases, no ice formation or fractures were observed in the vicinity of the artery segments. However, in specific instances when some ice crystallization was observed to impact the artery segment, the subsequent testing of function revealed a total loss of contractility. The successful vitrification of blood vessel segments using marginal conditions of slow cooling and rewarming, provide essential information for the development of scale-up protocols that is necessary when clinically relevant size samples need to be cryopreserved in an essentially ice-free state. This information can further be integrated into computer simulations of heat transfer and thermo-mechanical stress, where the slowest cooling rate anywhere in the simulated domain must exceed the critical values identified in the current study.     

Racial differences in the burden of coronary artery calcium and carotid intima media thickness between Blacks and Whites

Background

Identification of racial differences in the burden and correlates of carotid intima media thickness (CIMT) and coronary artery calcium (CAC) may provide the basis for the development of race-specific cardiovascular disease (CVD) risk prediction algorithms.

Methods

In the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study, CIMT was measured by carotid ultrasonography in 792 individuals (35 % Black). CIMT >1 mm was considered significant. CAC was quantified by electron beam computed tomography in 776 individuals (46 % Black). CAC was considered significant if the Agatston score was >100. Cross-sectional associations between race, CIMT and CAC were assessed using logistic regression models.

Results

Blacks had greater CIMT (mean difference 0.033 mm, 95 % CI 0.005–0.06 mm; p = 0.02) and 1.5-fold (95 % CI 1.0–2.3) higher odds of having significant CIMT than Whites. Blacks had less CAC than Whites (mean Agatston score difference 66, [11–122]; p = 0.02) and 50 % lower odds of a significant CAC score compared with Whites (0.5 [0.3–0.7]). These associations were virtually unchanged after adjustment for CVD risk factors. Of the novel CVD risk markers assessed, small-dense low-density lipoprotein was independently associated with increased odds of significant CIMT, with the association being similar among Blacks and Whites (odds ratio [95 % CI]: 1.7 [1.2–2.5] and 1.4 [1.0–1.8] per 1-SD higher level, respectively). Interleukin-6 was significantly associated with CAC among Blacks (1.4 [1.0–2.0]).

Conclusion

Black race is independently associated with greater CIMT but less CAC than White race. CVD risk stratification strategies that incorporate these measures of subclinical atherosclerosis should consider race-specific algorithms.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-014-0610-4) contains supplementary material, which is available to authorized users.     

降脂通脉胶囊联合瑞舒伐他汀治疗冠心病合并颈动脉粥样硬化斑块的临床研究

摘要 目的：探讨降脂通脉胶囊联合瑞舒伐他汀治疗冠心病合并颈动脉粥样硬化斑块的临床疗效。方法：选取2018年2月~2019年10月期间我院收治的冠心病合并颈动脉粥样硬化斑块患者80例,根据随机数字表法分为对照组（n=40）和研究组（n=40）,对照组患者予以瑞舒伐他汀治疗,研究组在对照组的基础上予以降脂通脉胶囊治疗,比较两组患者疗效、血脂、心功能、颈动脉内膜中层厚度（IMT）、颈动脉斑块积分及不良反应。结果：研究组治疗6个月后的临床总有效率为90.00%（36/40）,高于对照组的70.00%（28/40）（P<0.05）。两组治疗6个月后心排血量（CO）、射血分数（LVEF）均较治疗前升高,且研究组高于对照组（P<0.05）;左室舒张末内径（LVEDD）较治疗前降低,且研究组低于对照组（P<0.05）。两组治疗6个月后总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、甘油三酯（TG）均较治疗前下降,且研究组低于对照组（P<0.05）;高密度脂蛋白胆固醇（HDL-C）较治疗前升高,且研究组高于对照组（P<0.05）。两组治疗6个月后IMT、颈动脉斑块积分均较治疗前下降,且研究组低于对照组（P<0.05）。两组均未见明显不良反应发生。结论：降脂通脉胶囊联合瑞舒伐他汀治疗冠心病合并颈动脉粥样硬化斑块,疗效显著,可有效改善患者血脂、心功能及颈动脉斑块病变,且安全可靠。     

健康体检人群幽门螺杆菌感染的影响因素分析及其与胃蛋白酶原和颈动脉粥样硬化的关系研究

摘要 目的：分析健康体检人群幽门螺杆菌（Hp）感染的影响因素,并进一步探讨健康体检人群Hp感染与胃蛋白酶原（PG）和颈动脉粥样硬化（CAS）的关系。方法：选取2021年3月～2022年3月在我院体检的146例接受Hp筛查的健康体检者,根据碳13尿素呼气试验结果分为Hp阳性组（n=62）和Hp阴性组（n=84）。采用单因素和多因素Logistic回归分析健康体检人群Hp感染的影响因素,比较两组血清PGⅠ、PGⅡ、PGⅠ/PGⅡ水平和CAS比例。Spearman相关系数分析Hp阳性组DOB值与血清PGⅠ、PGⅡ、PGⅠ/PGⅡ和颈动脉内中膜厚度（CIMT）的相关性。结果：单因素分析显示,与Hp阴性组比较,Hp阳性组年龄更大,家族Hp感染史、吸烟、饮酒、饮食口味辛辣、经常摄入腌制食品、共用餐具比例更高,经常喝茶、经常摄入水果/蔬菜比例更低（均P＜0.05）。多因素Logistic回归分析显示,年龄增加、家族Hp感染史、吸烟、饮食口味辛辣、经常摄入腌制食品、共用餐具为健康体检人群Hp感染的独立危险因素,经常喝茶、经常摄入水果/蔬菜为独立保护因素（均P＜0.05）。Hp阳性组血清PGⅠ、PGⅡ水平和CAS比例高于Hp阴性组,PGⅠ/PGⅡ低于Hp阴性组（均P＜0.05）。Spearman相关系数显示,Hp阳性组DOB值与血清PGⅠ、PGⅡ和CIMT呈正相关,与PGⅠ/PGⅡ呈负相关。结论：年龄增加、家族Hp感染史、吸烟、饮食口味辛辣、经常摄入腌制食品、共用餐具是健康体检人群Hp感染的危险因素,而经常喝茶、经常摄入水果/蔬菜为健康体检人群Hp感染的保护因素,Hp感染与血清PG水平变化和CAS密切相关。     

不同性别间颈动脉粥样硬化相关危险因素差异的研究

目的:探讨中年人群中不同性别间颈动脉粥样硬化相关危险因素的差异。方法:将104例中年颈动脉粥样硬化患者作为研究对象,其中男53例,女51例,比较两组体质量指数(BMI)、收缩压(SBP)、舒张压(DBP)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、脂蛋白(a)[Lp(a)]、空腹血糖(FBG)、血尿酸(UA)、超敏CRP(hs-CRP)的差异。结果:男性组BMI、TG、UA较女性组高,HDL-C、Lp(a)较女性组低,差异有统计学意义(P<0.05)。结论:有些颈动脉粥样硬化相关危险因素在不同性别中年人群中具有差异。     

彩色多普勒超声检查评估老年退行性心脏瓣膜病与颈动脉粥样硬化的相关性研究

目的:应用彩色多普勒超声评估老年退行性心脏瓣膜病(SDHVD)与颈动脉粥样硬化相关性。方法:选择2016年5月-2018年7月中国医科大学航空总医院收治的老年SDHVD患者240例作为观察组,根据心瓣膜钙化程度分级标准将所有患者分为1级组61例、2级组84例以及3级组95例。另取同期于我院住院治疗的非SDHVD患者100例作为对照组。所有患者均接受彩色多普勒超声检查,比较观察组与对照组患者的基础疾病合并情况,对比不同组别患者颈动脉内膜中层厚度(IMT)、颈动脉斑块积分以及颈动脉管腔狭窄程度情况,分析SDHVD与颈动脉粥样硬化相关性。结果:观察组冠心病、糖尿病、高血压以及高脂血症发生率分别为47.08%、50.42%、93.75%、81.67%,均分别高于对照组的24.00%、29.00%、68.00%、52.00%(P0.05)。对照组、1级组、2级组、3级组的IMT以及颈动脉斑块积分比较存在统计学差异,且随着心瓣膜钙化程度分级的逐渐提高,IMT以及颈动脉斑块积分呈逐渐上升趋势(P0.05)。随着心瓣膜钙化程度分级的逐渐升高,颈动脉管腔狭窄程度在50%-70%以及71%-99%中的发生率呈逐渐升高趋势(P0.05)。经Pearson相关性分析显示:SDHVD严重程度与IMT、颈动脉斑块积分以及颈动脉管腔狭窄程度均呈正相关(P0.05)。结论:彩色多普勒超声检查可有效评估SDHVD与颈动脉粥样硬化的严重程度,且SDHVD患者多并发基础疾病,临床应积极预防。     

Substituted imidazole derivatives as novel cardiovascular agents

A series of novel substituted imidazole derivatives were synthesized and have been screened in vivo for their hypotensive and acute toxicity activities. Out of seventeen compounds eight compounds (2b, 2c, 3b, 3c, 3f, 4a, 4b and 4c) have shown good hypotensive and bradycardiac responses. Compounds 3b, 3c, 3f and 4c have shown better activity than reference drug clonidine. All the compounds have shown ALD50 >1000 mg/kg with maximum in 2e and 4c (>1200 mg/kg).     

Ontogeny of the carotid body and glomus cells distributed in the wall of the common carotid artery and its branches in the chicken

Summary Developmental patterns of immunoreactivity for serotonin and neuropeptide Y were investigated immunohistochemically in the carotid body and glomus cells in the wall of the common carotid artery and around its branches of chickens at various developmental ages. The development of peptidergic nerve fibers was also studied. Serotonin immunoreactivity began to appear in the glomus cells of the carotid body and around arteries at 10 days of incubation and became very intense from 12 days onwards. Neuropeptide Y immunoreactivity also appeared in these cells at 10 days, became intense at 14 days, and was sustained until 20 days. After hatching, neuropeptide Y immunoreactivity in the carotid body rapidly decreased with age and almost cisappeared at posnatal day 10. However, it persisted for life in the glomus cells distributed in the wall of the common carotid artery. Substance P- and calcitonin gene-related peptide (CGRP)-immunoreactive fibers first penetrated into the carotid body parenchyma at 12 days of incubation. These peptidergic nerve fibers in the carotid body and glomus cell groups in and around arteries gradually increased with age, and approached the adult state at 18 days of incubation. Only a few galanin-and vasoactive intestinal peptide (VIP)-immunoreactive fibers were observed in the late embryonic carotid bodies. They rapidly developed after hatching and reached adult numbers at postnatal day 10. During late embryonic and neonatal development, considerable numbers of met-enkephalin-immunoreactive fibers were detected in the connective tissue encircling the carotid body.