Ameliorative effects of pycnogenol on carbon tetrachloride-induced hepatic oxidative damage in rats

This study evaluated the putative antioxidant activity of Pycnogenol (PYC) against CCl4-induced hepatic oxidative damage in Sprague-Dawley rats. A single oral dose of CCl4 (1.25 mL/kg) produced significantly increased levels of serum aminotransferase (AST) and alanine aminotransferase (ALT) activities. In addition, increased malondialdehyde (MDA) concentration, reduced glutathione (GSH) content, and decreased catalase, superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were observed in the hepatic tissues. However, concomitant administration with PYC (10 or 20 mg/kg) significantly improved CCl4-induced hepatic injury, as evidenced by the decline of serum AST and ALT activities in a dose dependent manner. Moreover, PYC reduced MDA concentration and increased GSH levels and catalase, SOD and GST activities in hepatic tissues, indicating that concomitant administration with PYC efficiently prevent the CCl4-induced oxidative damage in rats. The free radical scavenging assay showed that PYC has a dose-dependent scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals. These results indicate that PYC has an antioxidant effect against CCl4-induced hepatic oxidative damage and is useful as a hepatoprotective agent against various liver diseases induced by oxidative stress.     

国家最大容许浓度内二硫化碳暴露对血压和心电图的影响

目的 探讨国家最大容许浓度(MAC)内二硫化碳(CS_2)暴露对血压、心电图的影响及其相互之间的关系.方法 根据工种的不同,将化纤厂职工按CS_2接触浓度分为高浓度接触组(821人)、低浓度接触组(259人),工作场所CS_2浓度控制在MAC范围内.随机抽取同期来医院健康体检人员250人作为对照组.测量臂部收缩压、舒张压,计算脉压、平均动脉压,与常规同步12导联静息心电图描记结果 、性别、年龄、工龄、工种、甘油三酯、胆固醇、血糖结果 汇总,分析接触CS_2后血压升高和心电图异常的危险因素,以及它们之间的关系.结果 高、低浓度接触组间及高浓度接触组与对照组间收缩压、舒张压、平均动脉压均数及异常发生率的差异均有统计学意义(P<0.01);高、低浓度接触组工人舒张压异常发生率均高于收缩压异常发生率近2倍.工种因素在高收缩压、高舒张压组中是最大的危险因素,高浓度接触的危险度是低浓度接触的2倍多,OR值分别为2.086、2.331.高、低浓度接触组与对照组间心电图异常发生率的差异有统计学意义(P<0.01);在低浓度接触组中筛出高收缩压,在高浓度接触组中筛出高舒张压2个OR值(3.531,1.638)较高的危险因素和值得探究的血糖(OR=0.747)保护因素,而低浓度接触的高收缩压组、高浓度接触的高舒张压组又分别筛出工龄、胆固醇等危险因素.与血压相关的心电图左心室高电压诊断在高浓度接触组中仪筛出高舒张压一个危险因素(OR=4.140),在低浓度接触组中仅筛出高收缩压一个危险因素(OR=4.776);在低浓度接触组中高脉压是复极异常的唯一危险因素(OR值达20.417);血糖在起源异常方面是危险因素,而在左心室高电压方面却是保护因素(OR=0.633).结论 CS_2对心血管的损害是一个循序渐进的过程,接触CS_2的早期、或接触浓度很低都会损伤人们的循环系统,在国家MAC内CS_2对心血管的毒性作用仍然随接触时间、接触浓度的增加而增加.CS_2对舒张压的作用大于对收缩压的作用,间接说明CS_2对外周阻力血管的作用可能大于对大动脉的作用.心电网结果 的异常不仅有血压异常后作用于心脏的结果 ,还有CS_2作用于心脏及外周血管的共同表现.     

纳米炭在腹腔镜中低位直肠癌根治术中的应用价值

巴结转移率上(纳米炭组60/277、21.66%比对照组15/218、6.88%)差异有统计学意义(P＜0.01).在术后病理分期上的差异有统计学意义(P＜0.05).纳米炭组有3例术中可见侧方髂内血管旁淋巴结黑染,行黑染淋巴结切除活检快速冰冻检查,1例结果为癌疑,随对该例加行侧方淋巴结清扫,术后病理证实为淋巴结转移.结论 纳米炭对于指导腹腔镜直肠癌根治术术中的选择性侧方淋巴结清扫具有潜在价值;纳米碳的应用能够增加术后转移淋巴结的检出,精确术后病理分期.     

单磷酸类脂A预处理对大鼠肝缺血再灌注损伤的保护作用及其机制

目的研究单磷酸类脂A（MPLA）是否通过血红素氧合酶-1-一氧化碳-环磷酸鸟苷（HO-1-CO-cGMP）途径促进降钙素基因相关肽（CGRP）释放,发挥其对大鼠肝缺血再灌注损伤的保护作用。方法健康雄性SD大鼠分为对照组、假手术组、肝脏缺血再灌注组、MPLA低、中、高剂量组（肝脏缺血再灌注＋MPLA0．2、0．5、1．0mg／kg）,复制肝缺血再灌注模型,随后电子显微镜观察细胞超微结构;多功能生化分析仪测定血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、乳酸脱氢酶（LDH）和肝组织CO水平;免疫组化检测肝组织HO-1表达;放射免疫分析法测定肝组织CGRP、cGMP浓度。结果和缺血再灌注组比较,MPLA低、中、高剂量组细胞损害相对较轻;各项肝功能指标显著降低;HO-1、CO、cGMP、CGRP含量升高（P〈0．05）,且HO—1与CO、CO与cGMP、cGMP与CGRP两两者之间存在明显的正相关关系（P〈0．05）。结论MPLA通过HO—1—CO-cGMP途径促进肝脏缺血／再灌注期间CGRP的合成和释放,这可能是MPLA减轻大鼠肝缺血再灌注损伤作用机制之一。     

The relationship between smoking machine derived tar yields and biomarkers of exposure in adult cigarette smokers in the US

Comprehensive data on human exposure to smoke constituents from different machine-measured tar yield cigarettes is limited. Methods: This study used a stratified, cross-sectional, multi-center design to estimate biomarkers of exposure (BOE) from nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), pyrene, CO, acrolein, and 1,3-butadiene and their relationship to tar yield categories of cigarette in adult smokers in the U.S. 3625 adults smokers were enrolled into four tar categories 2.9 mg (T1), 3.0–6.9 mg (T2), 7.0–12.9 mg (T3), and 13.0 mg (T4). Biomarkers were measured in blood (carboxyhemoglobin, 4-aminobiphenyl-hemoglobin (4-ABP-Hb)-adducts, serum cotinine) and 24 h urine (nicotine and five metabolites, calculated as nicotine equivalents (NE), NNAL, 1-OH-pyrene, 3-HPMA, MHBMA and DHBMA). Data were analyzed using analysis of covariance (ANCOVA). Results: Tar was a significant factor for most biomarkers in the ANCOVA models. The largest least square mean differences between tar categories was 35% for NE per day, 28% for NE per cigarette, 36% for serum cotinine, 42% for NNAL per day, 29% for NNAL per cigarette, 26% for 1-OHP, 24% for COHb, 14% for 3-HPMA and 40% for 4-ABP-Hb. Variability in BOE ranged from 41% to 154% CV. Conclusions: There was a statistically significant effect of machine-measured tar yield on most BOE, which were generally lower with lower tar yield.     

Oxidative stress and proinflammatory effects of carbon black and titanium dioxide nanoparticles: Role of particle surface area and internalized amount

The ubiquitous presence of nanoparticles (NPs) together with increasing evidence linking them to negative health effects points towards the need to develop the understanding of mechanisms by which they exert toxic effects. This study was designed to investigate the role of surface area and oxidative stress in the cellular effects of two chemically distinct NPs, carbon black (CB) and titanium dioxide (TiO₂), on the bronchial epithelial cell line (16HBE14o-). CB and TiO₂ NPs were taken up by 16HBE cells in a dose-dependent manner and were localized within the endosomes or free in the cytoplasm. Oxidative stress produced inside the cell by NPs was well correlated to the BET surface area and endocytosis of NPs. Contrary to intracellular conditions only CB NPs produced reactive oxygen species (ROS) under abiotic conditions. Exposure of cells to NPs resulted in an increased granulocyte macrophage colony stimulating factor (GM-CSF) mRNA expression and secretion. Inflammatory effects of NPs were dependent on the surface area and were mediated through oxidative stress as they were inhibited by catalase. It can be concluded that NP induced oxidative stress and pro-inflammatory responses are well correlated not only with the BET (Brunauer, Emmett and Teller) surface of the individual NPs but also with the internalized amount of NPs. Differences of even few nanometers in primary particle size lead to significant changes in inflammatory and oxidative stress responses.     

The postural reduction in middle cerebral artery blood velocity is not explained by PaCO2

In the normocapnic range, middle cerebral artery mean velocity (MCA V _mean) changes ∼ 3.5% per mmHg carbon-dioxide tension in arterial blood (PaCO₂) and a decrease in PaCO₂ will reduce the cerebral blood flow by vasoconstriction (the CO₂ reactivity of the brain). When standing up MCA V _mean and the end-tidal carbon-dioxide tension (PETCO₂) decrease, suggesting that PaCO₂ contributes to the reduction in MCA V _mean. In a fixed body position, PETCO₂ tracks changes in the PaCO₂ but when assuming the upright position, cardiac output decreases and its distribution over the lung changes, while ventilation increases suggesting that PETCO₂ decreases more than PaCO₂. This study evaluated whether the postural reduction in PaCO₂ accounts for the postural decline in MCA V _mean. From the supine to the upright position, PETCO₂, PaCO₂, MCA V _mean, and the near-infrared spectrophotometry determined cerebral tissue oxygenation (CO₂Hb) were followed in seven subjects. When standing up, MCA V _mean (from 65.3±3.8 to 54.6±3.3 cm s⁻¹ ; mean ± SEM; P<0.05) and cO₂Hb (−7.2±2.2 μmol l⁻¹ ; P<0.05) decreased. At the same time, the ratio increased 49±14% (P<0.05) with the postural reduction in PETCO₂ overestimating the decline in PaCO₂ (−4.8±0.9 mmHg vs. −3.0±1.1 mmHg; P<0.05). When assuming the upright position, the postural decrease in MCA V _mean seems to be explained by the reduction in PETCO₂ but the small decrease in PaCO₂ makes it unlikely that the postural decrease in MCA V _mean can be accounted for by the cerebral CO₂ reactivity alone.     

Protective effects of silica hydride against carbon tetrachloride-induced hepatotoxicity in mice

The protective effects of MegaHydrate™ silica hydride against liver damage were evaluated by its attenuation of carbon tetrachloride (CCl₄)-induced hepatotoxicity in mice. Male ICR mice were orally treated with silica hydride (104, 208 and 520 mg/kg) or silymarin (200 mg/kg) daily, with administration of CCl₄ (1 mL/kg, 20% CCl4 in olive oil) twice a week for eight weeks. The results showed that oral administration of silica hydride significantly reduced the elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), and cholesterol and the level of malondialdehyde (MDA) in the liver that were induced by CCl₄ in mice. Moreover, the silica-hydride treatment was also found to significantly increase the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px), as well as increase the GSH content, in the liver. Liver histopathology also showed that silica hydride reduced the incidence of liver lesions induced by CCl₄. The results suggest that silica hydride exhibits potent hepatoprotective effects on CCl₄-induced liver damage in mice, likely due to both the increase of antioxidant-defense system activity and the inhibition of lipid peroxidation.     

Nanoparticle-based theranostic agents

Theranostic nanomedicine is emerging as a promising therapeutic paradigm. It takes advantage of the high capacity of nanoplatforms to ferry cargo and loads onto them both imaging and therapeutic functions. The resulting nanosystems, capable of diagnosis, drug delivery and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine, and much research effort has been devoted toward that goal. A convenience in constructing such function-integrated agents is that many nanoplatforms are already, themselves, imaging agents. Their well-developed surface chemistry makes it easy to load them with pharmaceutics and promote them to be theranostic nanosystems. Iron oxide nanoparticles, quantum dots, carbon nanotubes, gold nanoparticles and silica nanoparticles, have been previously well investigated in the imaging setting and are candidate nanoplatforms for building up nanoparticle-based theranostics. In the current article, we will outline the progress along this line, organized by the category of the core materials. We will focus on construction strategies and will discuss the challenges and opportunities associated with this emerging technology.