重组腺病毒TRAIL基因联合抗EGFR靶向药物对肺癌细胞增殖的影响

目的:观察重组腺病毒TRAIL基因制剂联合抗EGFR靶向药物对H460肺癌细胞株及裸鼠移植瘤增殖的影响。方法:重组腺病毒TRAIL基因治疗制剂分别与EGFR信号通路靶向治疗药物Iressa、Tarceva、以及C225联合应用于H460肺腺癌细胞株,采用MTT法以及流式细胞仪检测不同用药方案的抗肿瘤作用;在裸鼠H460肺癌模型中验证重组腺病毒TRAIL制剂与C225的协同抗肿瘤作用。结果:在体外实验中发现Iressa和Tarceva可以增加重组腺病毒TRAIL基因制剂对H460肺癌细胞的抗肿瘤作用(P<0.05);重组腺病毒TRAIL基因制剂在体外实验中与C225并不存在协同效应(P>0.05),但在裸鼠H460肺癌模型中重组腺病毒TRAIL基因制剂与C225有明显的协同抗肿瘤作用(P<0.05)。结论:本研究初步探讨了基因治疗与靶向治疗的联合抗肿瘤作用,实验发现EGFR信号通路上的靶向治疗药物包括小分子酪氨酸激酶抑制剂以及EGFR单克隆抗体均可以增加重组腺病毒TRAIL基因制剂抗肺癌作用。     

Effects of acute and sub-chronic nicotine on impulsive choice in rats in a probabilistic delay-discounting task

Rationale

Cigarette smokers typically display impulsivity by preferring immediate rewards over larger, delayed rewards at shorter delays than do non-smokers. Suggesting causality, nicotine injections in rats increase the choice for an immediate reward over a larger, delayed reward.

Objectives

To examine the generality of this latter effect, the present study employed a delay-discounting task to determine if acute and sub-chronic nicotine will also increase impulsive choice when subjective reward value is manipulated by changes in the probability, rather than magnitude, of reward.

Materials and methods

Rats were presented with two levers, one of which delivered an immediate water reward on half of the trials, while the other lever delivered the same reward on every trial, but only after one of five increasing delays.

Results

Acute injections of 1.2 mg/kg, but not 0.8 mg/kg, of nicotine increased the preference for the immediate (but less certain) reward lever at intermediate delays. Moreover, twice-daily injections of 0.8 mg/kg of nicotine for 6 days progressively increased the preference for the immediate reward. Latency to make the first response on each trial was not affected by nicotine.

Conclusions

The similar increases in impulsive choice produced by both acute and sub-chronic nicotine in delay-discounting paradigms whether subjective reward value is manipulated by changes in reward magnitude or probability suggests that nicotine may be increasing what is common to these paradigms, namely delay discounting. Whatever the mechanism, these data indicate that both acute and sub-chronic nicotine may help develop and maintain an addiction by increasing impulsivity.     

Significance of Serum Uric Acid in Pregnancy Induced Hypertension

Background and objective

Hypertension is one of the common medical complications of pregnancy and contributes significantly to maternal and perinatal morbidity and mortality. Uric acid (UA) is filtered, reabsorbed and secreted by the kidney. Thus, this study was conducted to assess the serum UA levels in PIH and to evaluate the diagnostic value of serum UA level in PIH.

Teachers awareness and opinion about AIDS--a study from eastern Nepal

The potential for spread of HIV in Nepal is considered large because of the presence of extensive commercial sex workers, high rate of sexually transmitted disease, low condom use and many pockets of intravenous drug users. To prevent this disease from producing any public health problem in Nepal, strategies have been formulated by Government and non-government agencies in Nepal. School teachers' views and knowledge regarding HIV/AIDS are very important so that they can impart correct acknowledge about this dreaded disease AIDS to the school children who ultimately serve as catalytic agent to spread correct acknowledge in the community in long run. Teachers' awareness about HIV/AIDS in this study was fairly good. Majority of them were aware about established routes of HIV/AIDS transmission and various ways of preventing it. Various misconceptions regarding HIV transmission and its causes are the matter of concern. To impart education to the teachers and the community, more than 60% of the teachers expressed the radio to be the most effective medium. This can be suggested to the government to deliver more simple and attractive programmes about HIV/AIDS education through radio in suitable time for the community. The special AIDS education programme, for school teachers long term objective and with the support of government, non-government and social organizations will go a long way in dissemination of health knowledge to the school children.     

Risk Factors for Drug Abuse Among Nepalese Samples Selected from a Town of Eastern Nepal

The study focuses on the serious issue related to the adolescents’ and adults’ behavior and health. It aims to identify the risk factors for drug abuse from samples taken from a town of Eastern Nepal. This is a matched case-control study. The conditional logistic regression method was adopted for data analysis. The diagnosis cut off was determined by Receiver Operating Characteristic curve. A representative sample of 150 matched pairs was recruited from Dharan in 2006. The final model after adjusting 17 possible variables each other, detected some factors like education, occupation, short temper, depression, etc that were significantly associated with drug abuse, but shy behavior was not a significant predictor for drug abuse among the study sample. The level of education, occupation and depression were the strong predictors as identified by the model. The findings of the study may have implications to aware families and schools in developing countries like Nepal. The authors warrant that this research report entitled “Risk factors for drug abuse among Nepalese samples selected from a town of Eastern Nepal” is the original one and has not been published elsewhere. It is currently not under consideration for publication by any other journal (except in the form of an abstract; if applicable in such cases please quote the reference).     

Pressure-dissociable reversible assembly of intrinsically denatured lysozyme is a precursor for amyloid fibrils

Although a diversity of proteins is known to form amyloid fibers, their common mechanisms are not clear. Here, we show that an intrinsically unfolded protein (U), represented by a disulfide-deficient variant of hen lysozyme with no tertiary structure, forms an amyloid-like fibril after prolonged incubation. Using variable pressure NMR along with sedimentation velocity, circular dichroism, and fluorescence measurements, we show that, before the fibril formation, the protein forms a pressure-dissociable, soluble assemblage (U'(n)) with a sedimentation coefficient of 17 S and a rich intermolecular beta-sheet structure. The reversible assemblage is characterized with a Gibbs energy for association of -23.3 +/- 0.8 kJ.mol(-1) and a volume increase of 52.7 +/- 11.3 ml.mol(-1) per monomer unit, and involves preferential interaction of hydrophobic residues in the initial association step. These results indicate that amyloid fibril formation can proceed from an intrinsically denatured protein and suggest a scheme N <==>U <==>U'(n)-->fibril as a common mechanism of fibril formation in amyloidogenic proteins, where two-way arrows represent reversible processes, one-way arrow represents an irreversible process, and N, U, and U'(n)represent, respectively, the native conformer, the unfolded monomeric conformer, and the soluble assemblage of unfolded conformers.