Endothelial NO and O2− production rates differentially regulate oxidative,nitroxidative, and nitrosative stress in the microcirculation

Endothelial dysfunction causes an imbalance in endothelial NO and O₂⁻ production rates and increased peroxynitrite formation. Peroxynitrite and its decomposition products cause multiple deleterious effects including tyrosine nitration of proteins, superoxide dismutase (SOD) inactivation, and tissue damage. Studies have shown that peroxynitrite formation during endothelial dysfunction is strongly dependent on the NO and O₂⁻ production rates. Previous experimental and modeling studies examining the role of NO and O₂⁻ production imbalance on peroxynitrite formation showed different results in biological and synthetic systems. However, there is a lack of quantitative information about the formation and biological relevance of peroxynitrite under oxidative, nitroxidative, and nitrosative stress conditions in the microcirculation. We developed a computational biotransport model to examine the role of endothelial NO and O₂⁻ production on the complex biochemical NO and O₂⁻ interactions in the microcirculation. We also modeled the effect of variability in SOD expression and activity during oxidative stress. The results showed that peroxynitrite concentration increased with increase in either O₂⁻ to NO or NO to O₂⁻ production rate ratio (Q_O2⁻/Q_NO or Q_NO/Q_O2⁻, respectively). The peroxynitrite concentrations were similar for both production rate ratios, indicating that peroxynitrite-related nitroxidative and nitrosative stresses may be similar in endothelial dysfunction or inducible NO synthase (iNOS)-induced NO production. The endothelial peroxynitrite concentration increased with increase in both Q_O2⁻/Q_NO and Q_NO/Q_O2⁻ ratios at SOD concentrations of 0.1–100 μM. The absence of SOD may not mitigate the extent of peroxynitrite-mediated toxicity, as we predicted an insignificant increase in peroxynitrite levels beyond Q_O2⁻/Q_NO and Q_NO/Q_O2⁻ ratios of 1. The results support the experimental observations of biological systems and show that peroxynitrite formation increases with increase in either NO or O₂⁻ production, and excess NO production from iNOS or from NO donors during oxidative stress conditions does not reduce the extent of peroxynitrite mediated toxicity.     

杀虫剂硫丹对中国虎纹蛙的毒性效应： 存活率、红细胞核异常及酶活性

农药的使用对水生动物有直接和间接的影响。本文研究了有机氯杀虫剂硫丹对中国虎纹蛙（Hoplobatrachus chinensis）蝌蚪的毒性效应。具体而言,首先检测了硫丹的安全浓度（SC）,并在急性毒性实验中评估了硫丹的毒性等级。然后检测了外周血液中红细胞核形态异常,并在慢性毒性实验中测定了酸性磷酸酶（ACP）、碱性磷酸酶（AKP）和乳酸脱氢酶（LDH）的活性。结果表明,在急性毒性中,随着硫丹溶液浓度的增加和染毒时间的延长,蝌蚪的平均死亡率显著增加,即蝌蚪存活率取决于农药剂量和染毒的时长。硫丹对中国虎纹蛙蝌蚪的96 h半致死浓度LC50值为23.38 μg/L,安全浓度为2.34 μg/L,为剧毒性农药。在血液红细胞核异常实验中,观察到5种不同类型的细胞核异常：核碎裂、双核、不等分裂、核凹陷和核空洞。血液红细胞核异常率与农药浓度呈正相关。在酶活性检测中,三种酶的活性均受硫丹浓度的影响。与对照组相比,酸性磷酸酶（ACP）和碱性磷酸酶（AKP）活性随硫丹浓度的增加而降低,乳酸脱氢酶（LDH）活性随着硫丹浓度的增加呈先升高后降低。研究结果表明,硫丹对中国虎纹蛙蝌蚪具有很高的毒性,并证明了血液红细胞核异常和特定的代谢酶可以作为环境监测的生物标志物。     

系统和四维超声对胎儿器质性异常筛检价值分析

摘要 目的：探究系统及四维超声在胎儿器质性异常筛选中的应用价值。方法：回顾性分析2018年3月至2019年3月于我院接受检查的887例中晚期产妇超声检测资料,所有产妇均行系统及四维超声检测,对比系统超声、四维超声和联合检测在胎儿器质性异常筛查中的特异性、敏感性和准确性,分析上述检查方式对不同胎儿器质性异常筛查的价值。结果：（1）887例产妇共娩出899例胎儿,其中87例存在器质性异常,异常率9.68 %（87/899）,联合检测对器质性异常检出率为94.25 %（82/87）,系统超声检出率为68.97 %（60/87）,四维超声检出率为79.31 %（69/87）,联合检测明显优于单独检测（P<0.05）;（2）系统超声检测一致性为96.05 %,灵敏度为70.59 %,特异度为98.54 %,四维超声一致性为96.47 %,灵敏度为75.40 %,特异度为98.54 %,联合检测一致性为99.57%,灵敏度为96.26 %,特异度为99.90 %,对比发现联合检测一致性、灵敏度均优于单独检测。结论：系统及四维超声对胎儿器质性异常具有较好的筛查效果,联合检测筛查效果优于单独检测。     

盘基网柄菌(Dictyostelium discoideum)突变型细胞allC细胞周期异常的研究

细胞计数和细胞倍增时间计算的结果表明allC细胞的倍增时间为2.36h,仅为KAx-3细胞倍增时间的1/3。为了探究allC细胞倍增时间大幅度缩短、细胞周期异常的原因我们采用流式细胞术测定两种细胞的细胞周期,并结合实时荧光定量PCR技术测定cycB1和cdk1基因的相对表达量的比值。结果表明,16h突变型allC细胞处于G2期的数目(1.51%)显著少于KAx-3细胞(16.61%)。allC细胞和KAx-3细胞的细胞周期素B1(cyclinB1)cycB1基因相对表达量分别是2.5和0.25,两者相差10倍。这些数据表明,两种类型细胞中G2期的差异十分明显,cyclinB1的相对表达量也存在显著差异。提示cyclinB1的过表达可能在一定程度上影响allC细胞的细胞周期正常的调控机制,与突变细胞的G2期异常有一定关系。     

高龄隐匿性冠心病患者围术期心血管功能异常研究

目的：探讨隐匿性冠心病（或无症状心肌缺血SMI）患者围术期的心血管功能异常及与年龄的相关性,探讨围术期心律失常的临床治疗和转归。方法：180例择期手术的无症状心肌缺血患者,年龄≥51岁者130例,按年龄将其分为51～60岁组、61～70岁组和71～80岁组,其余50例年龄≤50岁者为对照组。动态心电图连续记录患术前24h、术后24h、术后48h心电图信息,专业医师分析统计s11段下移及弓背样抬高的幅度、时间,各型心律失常、各时间段心律失常发生率等,同时记录临床治疗、效果及转归。结果：随年龄增加,ST段改变幅度及持续时间增大（P〈0．05,P〈0．01）;71～80岁组ST段弓背样抬高发生率大于对照组（P〈0．05）;61～70岁组ST段下移时间、71～80岁组ST段下移时间及弓背样抬高幅度大于51～60岁组（P〈0．05）。61～70岁组的加速性室性自主心率（A巩）发生率和71。80岁组的窦性的心动过缓（SB）、室性早搏（VPB）、室性心动过速（vT）发生率大于对照组（P〈0．05,P〈0．01）;61～70岁组的房颤（AF）发生率和71～80岁组的VP、VT及AF发生率大于51-60岁组（P〈0．05,P〈0．01）。各组术后24h心律失常发生率大于术后48h及术前24h（P〈0．01）;随年龄增加,排除诱因后可逆转的心律失常明显减少,需药物逆转和电学逆转者明显增加（P〈0．05）。结论：高龄SMI患者围术期心肌缺血及心律失常高发,且随着年龄的增加而增加,术后24h是心功能异常高发时段。     

三氧化二砷(As2O3)对雄性小鼠的遗传毒性的研究

本以清洁级ICR雄性小鼠为实验动物,研究As2O3对小鼠的遗传毒性。采用小鼠精子畸形实验法以及小鼠骨髓PCE微核实验法,对成年的小鼠腹腔注射0．25—6．0mg/kg/dAs2O3,染毒7d。结果表明,AsO3对小鼠的体重增长及睾丸的重量存在抑制作用,其中1．00mg/kg／d剂量AS2O3对小鼠体重增长及睾丸重量的抑制是最显的(P＜0.001);AS2O3使小鼠精子的畸形率明显增加(P＜0.001),且呈明显的剂量-效应关系;此外As2O3还使小鼠PCE微核率增加,且As2O3与PCE微核率之间也具有明显的剂量效应。结论是As2O3对雄性小鼠具有明显的遗传毒性。     

100WCO2激光心肌血管再造术的实验研究

本文给出了利用１００ＷＣＯ２激光心肌血管再造术动物实验研究结果。激光器采用１００ＷＣＯ２激光,经光关节臂传输和会聚,激光孔径０．２５～０．５ｍｍ,孔间距离５ｍｍ,照射时间０．３秒,利用附加“滤波器”激光打孔技术可减轻心脏的热损伤。结果表明,在正常心肌上打孔,孔周２７０μｍ以外的心肌基本上不受损伤;高功率密度的激光束心肌打孔能够改善心肌微循环,可以明显改善打孔区的心肌缺血程度。实验犬术后六个月铸型实验证实了激光孔道仍然存在,术后三年病理切片检查充分说明了激光孔道仍然保持畅通     

Oxygen transport in the rat brain cortex at normobaric hyperoxia

The distribution of oxygen tension (PO(2)) in microvessels and in the tissues of the rat brain cortex on inhaling air (normoxia) and pure oxygen at atmospheric pressure (normobaric hyperoxia) was studied with the aid of oxygen microelectrodes (diameter = 3-6 microm), under visual control using a contact optic system. At normoxia, the PO(2) of arterial blood was shown to decrease from [mean (SE)] 84.1 (1.3) mmHg in the aorta to about 60.9 (3.3) mmHg in the smallest arterioles, due to the permeability of the arteriole walls to oxygen. At normobaric hyperoxia, the PO(2) of the arterial blood decreased from 345 (6) mmHg in the aorta to 154 (11) mmHg in the smallest arterioles. In the blood of the smallest venules at normoxia and at normobaric hyperoxia, the differences between PO(2) values were smoothed out. Considerable differences between PO(2) values at normoxia and at normobaric hyperoxia were found in tissues at a distance of 10-50 microm from the arteriole walls (diameter = 10-30 microm). At hyperbaric hyperoxia these values were greater than at normoxia, by 100-150 mmHg. In the long-run, thorough measurements of PO(2) in the blood of the brain microvessels and in the tissues near to the microvessels allowed the elucidation of quantitative changes in the process of oxygen transport from the blood to the tissues after changing over from the inhalation of air to inhaling oxygen. The physiological, and possibly pathological significance of these changes requires further analysis.     

Substance P induces degranulation of mast cells and leukocyte adhesion to venular endothelium

Substance P (SP), one of the established neurotransmitters, evokes an immunoinflammatory response involving leukocyte adhesion to venular endothelium and the degranulation of mast cells. The pathogenetic relationship between these responses, however, remains unresolved. In this study, we propose to examine the changes associated with the activation of mast cells, as well as leukocyte adhesion to venular endothelium by in vivo observation of the rat mesentery. The use of an in vitro assay for intracellular Ca²⁺ mobilization and the degranulation of mast cells demonstrated the significant upper shift of concentration response to SP (10⁻⁴–10⁻⁵ M). In vivo experiments on the mesenteric microcirculation also showed that SP induced a significant increase in the number of degranulated mast cells as well as in the number of leukocytes adherent to the venular wall. Tranilast, a mast cell stabilizer, as well as SP antagonist (CP-96,345) significantly attenuated the extent of mast cell degranulation and leukocyte adhesion elicited by SP. Although an immunoneutralization against CD18 by WT-3 significantly attenuated the leukocyte adhesion, it had no influence on the mast cell degranulation after SP superfusion. These separate in vivo observations show that SP induces leukocyte adhesion to the venular endothelium, possibly through the degranulation of mast cells.