七氟醚预处理对冠心病人心血管功能的影响及机制作用研究

目的观察七氟醚预处理对于冠心病人心血管功能的影响,探讨其机制作用。方法选择2009年1月至2012年12月期间在本院接受治疗的冠心病患者80例,按随机数字表法分为研究组（4l例）和对照组（39例）,研究组进行七氟醚预处理,对照组给予异丙酚,于麻醉诱导前（T0）、手术进行30min时（T1）、切口缝合后（T2）,以及术后6h（T3）、术后12h（T4）、术后24h（T5）记录患者心率（HR）、中心静脉压（CVP）、平均动脉压（MAP）、每搏输出量（SV）、心排血量（CO）、心脏收缩时间比率（STR）及血清肌钙蛋白T（cTnT）。结果研究组患者的HR、CO、SV、CVP、MAP、STR、cTnT在术前、术中、术后及恢复过程中波动比对照组小,较为平稳。其中,研究组T,时点CO、SV、STR和cTnT分别为（3．48±0．40）L／min、（6．4±1．9）ml／（min·m^2）、（0．36±0．76）、（0．227±0．112）ng／ml,T2时点CO、SV、STR和cTnT分别为（3．58±0．52）L／min、（6．6±2．3）ml／（min·m^2）、（0．36±0．63）、（0．241±0．115）ng／ml,对照组T1时点CO、SV、STR和cTnT分别为（3．11±0．53）L／min、（5．2±2．1）ml／（min·m^2）、（O．46±0．81）、（0．351±0．106）ng／ml,T2时点CO、SV、STR和cTnT分别为（3．15±0．61）L／min、（5．7±1．5）ml／（min·m^2）、（0．44±0．90）、（0．311±0．112）ng／ml,研究组的CO、SV在Tl、T2时点高于对照组,STR在Tl、T2时点低于对照组,cTnT在T1、T2时点低于对照组,且以上组间差异均具有统计学意义（P＜0．05）。结论七氟醚预处理能使患者的血流动力学更加平稳,更适用于临床麻醉,其机制可能与调节肌钙蛋白T的改变有关。     

Survey of glycol ether use in Taiwan, 1991

Glycol ethers (including glycol ether esters) are a group of solvents with medium-high boiling points and low evaporation rates, possessing solvent characteristics of alcohol/ether functions (or ether/ester functions). They have been widely used in coatings and other industrial products for more than half a century. Recently, E-series glycol ethers have been found to show reproductive and teratogenic toxicity, and throughout much of the world they are being replaced by the so-called P-series glycol ethers. In responding to the impact of the worldwide transition from E- to P-series glycol ethers, the current status of glycol ether use in Taiwan was studied. This study focuses on the type and quantity of these solvents being used, worker and public knowledge about their hazards, and possible changes in government regulations being considered. In this study, we found that large quantities of E-series glycol ethers were imported and used in Taiwan. The best estimates are: 2-ME, 2,500 tons; 2-EE, 1,200 tons; 2-EEA, 5,000–8,000 tons; 2-BE, 8,000 tons annually in 1991. For P-series glycol ethers, only about 2,500 tons are being used. Lack of knowledge about the potential toxic effects of the E-series glycol ethers is very common among users, regulatory agencies, academic institutes, and the general public. It is hoped that the results of this study, along with educational efforts, government regulations, and provision of technical services, will help prevent Taiwan from becoming a dumping site for these toxic chemicals. © 1993 Wiley-Liss, Inc.     

Inhalation toxicokinetics of butoxyethanol and its metabolite butoxyacetic acid in the male Sprague-Dawley rat

A total of 16 male Sprague-Dawley rats were continuously exposed to 20 ppm or 100 ppm butoxyethanol (BE) vapor for 1, 2, 3, 4, 6, 8, 10, or 12 days. Urine was collected in 24-h intervals and stored at –70°C. At the end of the exposure the animals were euthanized by decapitation and tissue samples of blood, muscle, liver and were rapidly collected and frozen to –70°C. The samples were later derivatized and analyzed for BE and its major metabolite butoxyacetic acid (BAA) by electron capture gas chromatography. BE and BAA were rapidly distributed to the tissues examined. The concentration of BE in blood was slightly higher, and that of BAA markedly higher than in other tissues, indicating weak (BE) and pronounced (BAA) blood protein binding, respectively. BE was efficiently metabolized and the blood clearance averaged 2.6 l/h per kg, corresponding to a hepatic extraction ratio of about 0.75. The renal clearance of BAA (average 0.53 l/h per kg) corresponded to approximately 15% of the renal blood flow. The kinetics of BE and BAA were linear up to 100 ppm. There were no clear indications of changes in the toxicokinetics, such as metabolic induction or inhibition of metabolism or excretion, during the course of the exposure. The recovery of BAA in urine was 64% of the calculated inhaled amount of BE, on an equimolar basis. Received: 15 February 1994/Accepted: 3 May 1994     

Improved selectivity in the removal of the tert.-butyloxycarbonyl group

Removal of the tert.-butyloxycarbonyl group by trifluoroacetic acid in the presence of benzyloxycarbonyl groups, benzyl esters and benzyl ethers is rendered more selective by dilution with acetic acid. Trifluoroacetic acid-acetic acid mixtures, however, cause acetylation of hydroxyl groups and also some formation of tert.-butyl esters at free carboxyls. Hence, such mixtures are useful only for the deprotection of intermediates in which the hydroxyl and carboxyl groups are fully blocked. A search for a diluent without such inherent limitation led to the application of a mixture of phenol and p-cresol. Dilution of trifluoroacetic acid with phenols both improved the selectivity in the removal of the tert.-butyloxycarbonyl group and suppressed the alkylation of amino acid side chains as well. A 4:3:3 mixture of trifluoroacetic acid, phenol and p-cresol was found useful in the practical execution of partial deprotection.     

七氟醚预处理对心肌缺血再灌注大鼠心肌线粒体蛋白质组学双向凝胶电泳分析

[目的]研究七氟醚预处理对缺血再灌注心肌保护的线粒体相关蛋白的变化.[方法]采用双向凝胶电泳技术对七氟醚预处理（S组）与对照组（C组）大鼠心肌线粒体蛋白质进行分离和比较分析.[结果]S组与C组相比,有21个蛋白质表达发生了改变,其中表达增强的有17个蛋白,表达降低的有4个蛋白.[结论]这些差异表达的蛋白质可能参与了七氟醚预处理对心肌的保护作用.     

In vitro study of polyoxyethylene alkyl ether niosomes for delivery of insulin

In this study, niosomes of polyoxyethylene alkyl ethers (Brij) were prepared for encapsulation of insulin by film hydration method. Without cholesterol, brij 35 and brij 58 did not form niosomes, apparently because of relatively large polar head groups in comparison with their alkyl chains. The size of vesicles depended on the cholesterol content, charge incorporation or hydrophilicity of surfactants. Entrapment of insulin in bilayer structure of niosomes protected it against proteolytic activity of alpha-chymotrypsin, trypsin and pepsin in vitro. The maximum protection activity was seen in brij 92/cholesterol (7:3 molar ratios) in which only 26.3+/-3.98% of entrapped insulin was released during 24h in simulated intestinal fluid (SIF). The kinetic of drug release for most formulations could be best described by Baker and Lonsdale equation indicating diffusion based delivery mechanism. These results indicate that niosomes could be developed as sustained release oral dosage forms for delivery of peptides and proteins such as insulin.     

Effects of decabrominated diphenyl ether (PBDE 209) on voltage‐gated sodium channels in primary cultured rat hippocampal neurons

Polybrominated diphenyl ethers (PBDEs) are widely used as flame‐retardant additives. But the application of PBDEs has been challenged due to their toxicity, especially neurotoxicity. In this study, we investigated the effects of decabrominated diphenyl ether (PBDE 209), the major PBDEs product, on voltage‐gated sodium channels (VGSCs) in primary cultured rat hippocampal neurons. Employing the whole‐cell patch‐clamp technique, we found that PBDE 209 could irreversibly decrease voltage‐gated sodium channel currents (I_Na) in a very low dose and in a concentration‐dependent manner. We had systematically explored the effects of PBDE 209 on I_Na and found that PBDE 209 could shift the activation and inactivation of I_Na toward hyperpolarizing direction, slow down the recovery from inactivation of I_Na, and decrease the fraction of activated sodium channels. These results suggested that PBDE 209 could affect VGSCs, which may lead to changes in electrical activities and contribute to neurotoxicological damages. We also showed that ascorbic acid, as an antioxidant, was able to mitigate the inhibitory effects of PBDE 209 on VGSCs, which suggested that PBDE 209 might inhibit I_Na through peroxidation. Our findings provide new insights into the mechanism for the neurological symptoms caused by PBDE 209. © 2009 Wiley Periodicals, Inc. Environ Toxicol 25: 400–408, 2010.     

Genotoxicity studies of organically grown broccoli (Brassica oleracea var. italica) and its interactions with urethane,methyl methanesulfonate and 4-nitroquinoline-1-oxide genotoxicity in the wing spot test of Drosophila melanogaster

Broccoli (Brassica oleracea var. italica) has been defined as a cancer preventive food. Nevertheless, broccoli contains potentially genotoxic compounds as well. We performed the wing spot test of Drosophila melanogaster in treatments with organically grown broccoli (OGB) and co-treatments with the promutagen urethane (URE), the direct alkylating agent methyl methanesulfonate (MMS) and the carcinogen 4-nitroquinoline-1-oxide (4-NQO) in the standard (ST) and high bioactivation (HB) crosses with inducible and high levels of cytochrome P450s (CYPs), respectively. Larvae of both crosses were chronically fed with OGB or fresh market broccoli (FMB) as a non-organically grown control, added with solvents or mutagens solutions. In both crosses, the OGB added with Tween–ethanol yielded the expected reduction in the genotoxicity spontaneous rate. OGB co-treatments did not affect the URE effect, MMS showed synergy and 4-NQO damage was modulated in both crosses. In contrast, FMB controls produced damage increase; co-treatments modulated URE genotoxicity, diminished MMS damage, and did not change the 4-NQO damage. The high dietary consumption of both types of broccoli and its protective effects in D. melanogaster are discussed.     

Developmental exposure to decabrominated diphenyl ether (BDE‐209): Effects on sperm oxidative stress and chromatin dna damage in mouse offspring

Polybrominated diphenyl ethers (PBDEs) are used as brominated flame retardants and have been found in human milk in recent years. This study investigates whether prenatal exposure to decabrominated diphenyl ether (BDE‐209) induces sperm dysfunction in male offspring. Pregnant CD‐1 mice were gavaged once daily with corn oil (control), 10, 500, and 1500 mg kg^?1 body weight of BDE‐209 from day 0 of gestation to day 17. The outcomes of male reproductive parameters were assessed on postnatal day 71. Anogenital distance, sperm‐head abnormalities, and testicular histopathology were significantly affected in male offspring prenatally exposed to 1500 mg kg^?1. Significant increases in the tendency for sperm DNA denaturation (αT) induction and the DNA fragmentation index (DFI) were found in those exposed to 10, 500, and 1500 mg kg^?1 (P < 0.05). We observed a significant increase of sperm hydrogen peroxide (H₂O₂) generation in the 10 and 1500 mg/kg/day groups compared to the control group (P < 0.05). Although our findings suggested that the mechanisms underlying BDE‐209‐induced sperm DNA damage and H₂O₂ generation might not be represented as a dose‐response relationship, we found that the greater the excess production of sperm H₂O₂, the greater the sperm αT (r = 0.65, P = 0.0155) and DFI (r = 0.53, P = 0.002). In conclusion, developmental exposure to BDE‐209 induced sperm‐head abnormality, oxidative stress, chromatin DNA damage, and testicular histopathological changes. These findings suggest that BDE‐209‐induced male reproductive effects might involve the formation of sperm H₂O₂ which attacks nucleic acids via H₂O₂ generation. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.     

Potential neurotoxic effect of ethylene glycol ethers mixtures

BackgroundEthylene glycol ethers (EGEs) are widely used as mixtures in various industrial processes and in many household products. 2-Methoxyethanol and 2-ethoxyethanol primarily exert gonadotoxic effect, while 2-butoxyethanol and 2-isopropoxyethanol have potent hemolytic activity. EGEs can cross the blood-brain barrier, but their potential neurodegenerative action in vivo has not been investigated, yet. In the present work, we examined potential adverse effects of EGEs on some selected brain structures.MethodsA mixture of two compounds: one with stronger hydrophilic properties (2-methoxyethanol or 2-ethoxyethanol) and the second more lipophilic (2-butoxyethanol or 2-isopropoxyethanol) were administered sc for 4 weeks. Total antioxidant capacity, lipid peroxidation and caspase-3 activity were determined in the frontal cortex and hippocampus.ResultsIt has been found that 4-week administration of a mixture of two EGEs, with various intensity, decreased total antioxidant capacity, enhanced lipid peroxidation and increased caspase-3 activity in the frontal cortex and hippocampus of Wistar rat.ConclusionThe obtained results suggested that EGEs exerted adverse effects on the CNS cells and may contribute in pathogenesis of neurodegenerative disorders.