Inhibitive effects of Fructus Psoraleae extract on dopamine transporter and noradrenaline transporter

A petroleum ether extract (FP) from Fructus Psoraleae, seeds of Psoralea corylifolia L. (Leguminosae), was found to strongly inhibit dopamine (DA) uptake by dopamine transporter (DAT) heterogeneously expressed cells (D8 cells) and noradrenaline (NE) uptake by noradrenaline transporter (NET) heterogeneously expressed cells, which, however, had no effect on gamma-aminobutyric acid transporter heterogeneously expressed cells and serotonin transporter heterogeneously expressed cells at the concentration up to 100 microg/ml. These inhibitory effects were also confirmed by experiments on SK-N-SH cell line and synaptosomes from rats' brains. In addition, FP showed a significantly mitigating effect on 1-methyl-4-pyridinium induced injury of D8 cells. Meanwhile, FP dose-dependently reduced the binding of tritium-labeled cocaine analog (-)-2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane to DAT of D8 cells, which suggests that FP may inhibit DAT activity in the same way as cocaine does. Behavioral study showed FP had a long-lasting stimulant effects on the activity of intact mice and reserpinized mice. So FP is proposed as a kind of DAT and NET inhibitor and may be involved in the process of regulating the DA and NE system, and FP or its unknown bioactive compounds may be developed into new medicines for disorders such as Parkinson's disease, depression, Attention Deficit Hyperactivity Disorder (ADHD) or cocaine addiction.     

Anthracycline treatment of the human monocytic leukemia cell line THP-1 increases phosphatidylserine exposure and tissue factor activity

Introduction

Cancer associated thrombosis is a well-recognized phenomenon that results in considerable patient morbidity and mortality. Malignancy conveys an increased risk for thrombosis and chemotherapy further elevates this risk. The pathophysiological mechanisms underlying this process remain poorly defined.

Materials and Methods

A human acute monocytic leukemia cell line (THP-1) was treated with commonly used anthracycline chemotherapeutics at concentrations similar to those found in the plasma of cancer patients. Cells were analyzed for tissue factor (TF) mRNA, protein, and activity. Microparticle (MP) TF activity was also measured. Phosphatidylserine (PS) exposure on cells and MPs was analyzed by flow cytometry. PS levels on MPs was also evaluated in an annexin V capture assay.

Results

Anthracycline treatment of THP-1 cells resulted in a concentration-dependent increase in cellular TF activity without a change in TF protein, which was associated with increased PS exposure on the cell surface and apoptosis. The increase in TF activity was abolished by annexin V or lactadherin indicating that PS exposure was required. Anthracycline treatment of THP-1 cells also increased the number of TF-positive MPs.

Conclusion

Treatment of THP-1 cells with anthracyclines induces apoptosis and increases cellular TF activity. The increased activity required an increase in exposure of PS. Additionally, anthracyclines increase the release of TF-positive MPs from THP-1 cells. We propose that the increase in cellular TF activity in circulating leukemic cells, combined with increased numbers of TF-positive MPs, may contribute to thrombosis in cancer patients receiving chemotherapy.     

Structural characterization of the Hepatitis C Virus NS3 protease from genotype 3a: The basis of the genotype 1b vs. 3a inhibitor potency shift

The first structural characterization of the genotype 3a Hepatitis C Virus NS3 protease is reported, providing insight into the differential susceptibility of 1b and 3a proteases to certain inhibitors. Interaction of the 3a NS3 protease with a P2-P4 macrocyclic and a linear phenethylamide inhibitor was investigated. In addition, the effect of the NS4A cofactor binding on the conformation of the protease was analyzed. Complexation of NS3 with the phenethylamide inhibitor significantly stabilizes the protease but binding does not involve residues 168 and 123, two key amino acids underlying the different inhibition of genotype 1b vs. 3a proteases by P2-P4 macrocycles. Therefore, we studied the dynamic behavior of these two residues in the phenethylamide complex, serving as a model of the situation in the apo 3a protein, in order to explore the structural basis of the inhibition potency shift between the proteases of the genotypes 1b and 3a.     

Induction of hepatic microsomal cytochrome P-448-mediated oxidases by 3,3′-Dichlorobenzidine in the rat

Intraperitoneal administratioin of the hepatocarcinogen 3,3′-dichlorobenzidine (4,4′-diamino, 3,3′-dichlorobiphenyl) to adult male rats caused the induction of hepatic microsomal ethoxycoumarin O-deethylase and p-nitrophenetole O-deethylase activities comparable in magnitudes to those induced by 3-methylcholanthrene; neither anilin hydroxylase nor aminopyrine N-demethylase activity was affected by the pretreatment. The induction was not accompanied by a significant increase in content of hepatic microsomal cytochrome P-450; however, a shift in the absorption maxium of the reduced + CO spectrum of the cytochrome to 448 nm and an increase in the ratio of the 455 nm : 430 nm peaks of the reduced + ethylisocyanide spectrum of the hemoprotein was affected. Arylhydrocarbon hydroxylase activitity was stimulated 5-fold by dichlorobenzidine pretreatment in comparison with a 12-fold stimulation following 3-methylcholanthrene pretreatment. However, enzymatically mediated covalent binding of benzo[a]pyrene to microsomal protein was greater in microsomes from dichlorobenzidine-pretreated rats than in those from methylcholanthrene-pretreated rats. All of the dichlorobenzidine-induced enzymic activities were inhibited by α-naphthoflavone but not by SKF-525A. Hepatic microsomes from dichlorobenzidine than those from untreated animalsl both sets of microsomes elicited the Type II spectral change on combination with the compound, albeit with different binding affinities and capacities. The results show that dichlorobenzidine, although only a dihalogenated biphenyl derivative, is a potent inducer of cytochrome P-448.     

Study of the Effect of Two New Types of IUDs,TCu380A and GyneFix on the Positive Rate of Chlamydia Trahmatis

Among the agents causing sexually transmitted disease( STD) in the urogeniteltract,Chlamydia Trahmatis( CT) is the most common one. About three fourths ofpatients contracted by CT show no symptoms and it is just this character thatleadsto its persistent infection,covert spreading and the association with many kinds ofdiseases such as urethritis,cervicitis,perihepatitis,ectopic pregnancy and infertili-ty.In the recent years,researchers in the world have made an advance in investigating the r…     

Exploring the impact of climate on human longevity

The purpose of this study was to examine the impact of physical geographic factors and climate conditions on human longevity. The centenarian rate (CR) in 2005 was computed for Japan's 47 prefectures, whose geography and climate vary greatly. Several pathways, such as excess winter mortality, land use and agricultural production, possibly linking physical and climate factors with extreme longevity, were explored. The probability of becoming a centenarian varies significantly among the Japanese prefectures. In particular, the computation of CR(70) demonstrated that the actual probability for individuals 70years old in 1975 of becoming centenarians in 2005 was 3 times higher, on average, in Okinawa, both for males and females, than in Japan as a whole. About three quarters of the variance in CR(70) for females and half for males is explained by the physical environment and land use, even when variations in the level of socio-economic status between prefectures are controlled. Our analysis highlighted two features which might have played an important role in the longevity observed in Okinawa. First, there is virtually no winter in Okinawa. For instance, the mean winter temperature observed in 2005 was 17.2°C. Second, today, there is almost no rice production in Okinawa compared to other parts of Japan. In the past, however, production was higher in Okinawa. If we consider that long term effects of harsh winters can contribute to the mortality differential in old age and if we consider that food availability in the first part of the 20th century was mainly dependent on local production, early 20th century birth cohorts in Okinawa clearly had different experiences in terms of winter conditions and in terms of food availability compared to their counterparts in other parts of Japan. This work confirms the impact of climate conditions on human longevity, but it fails to demonstrate a strong association between longevity and mountainous regions and/or air quality.     

High immunogenicity of nicotine vaccines obtained by intradermal delivery with safe adjuvants

Immunotherapy for tobacco addiction may offer a safe, alternative treatment if the immunogenicity of the current nicotine vaccines can be improved. We show here that intradermal (ID) immunization induces the production of antibody directed against nicotine (NicAb) at a much higher level than conventional intramuscular (IM) immunization. The magnitude and duration of NicAb production was further increased robustly by non-inflammatory laser vaccine adjuvant (LVA), slightly inflammatory monophosphoryl lipid A (MPL) or a combination of MPL and CpG adjuvants. Consequently, significantly fewer vaccination doses were required to attain a high level of NicAb production for an extended period of time and reduce nicotine entry into the brain in the presence of LVA, MPL or MPL/CpG adjuvant, respectively. Yet, the potency of these adjuvants to augment ID nicotine vaccine immunogenicity came at the expense of local skin reactogenicity, with LVA causing little skin reaction and MPL/CpG stimulating overt skin irritation. These observations underscore a necessity of a balance between optimal adjuvant potency and undesired local reactogenicity. In summary, our study presents a novel approach to significantly improve nicotine vaccine immunogenicity by a combination of safe cutaneous vaccine adjuvants with ID immunization.     

绿脓杆菌对6种抗生素的耐药分析

目的了解绿脓杆菌（铜绿假单胞菌）的耐药谱,给临床正确合理选用抗生素提供依据。方法分离鉴定100例患者标本中的绿脓杆菌,并用纸片扩散法（K-B法）检测该菌对6种常用抗菌素的耐药性,计算耐药率。结果绿脓杆菌对庆大霉素、头孢噻甲羧肟、哌拉西林、环丙沙星、头孢三嗪、阿米卡星的耐药率分别为69%、39%、24%、24%、16%和12%。结论绿脓杆菌对一线药物如庆大霉素,哌拉西林,头孢噻甲羧肟等均有一定耐药性。     

整体护理和人文关怀在子宫内膜癌患者围手术期中的应用观察

目的：通过对23例子宫内膜癌患者进行围手术期的整体护理和人文关怀,探讨更有利于子宫内膜癌患者的护理措施。方法：随机抽取我科2008年1月至2009年12月份进行手术治疗的患者46例,把其中的23例分为实验组,23例分为对照组,对照组的患者采取常规的术前术后护理,而实验组在围手术期中进行常规护理外,更注重患者的心理干预,对其实行整体护理和全程的人文关怀,并进行跟踪分析和问卷调查,总结患者的护理效果和术后的生活质量。结果：实验组患者手术后生活质量佳,夫妻关系好,对前途充满信心。结论：整体护理以人为本,注重人文关怀,注重人的生理、心理、社会、文化、精神多层次的需要,能提供给子宫内膜癌患者手术前后更优质护理服务,使疾病对患者的生活影响不大,降低疾病的复发率。     

247例不同胎龄胎儿的外形测量

正常引产胎儿247例(胎龄4～9月),各月龄胎儿的身长、“顶骨长、体重、手长、足长、枕额径、双顶径、头、胸 腹围与胎龄呈正相关关系,并随胎龄的增长而增加。胎龄6个月后,手、足长与身长的比值分别为0.12,0.15。各月龄胎儿的枕额径约为双顶径的1.2倍。胸、腹围与头围的比值约为0.86及0.75。