Cationic Polymer Based Gene Delivery Systems

Gene transfer to humans requires carriers for the plasmid DNA which canefficiently and safely carrythe gene into the nucleus of the desired cells. A series of chemically differentcationic polymers arecurrently being investigated for these purposes. Although many cationic polymersindeed condense DNAspontaneously, which is a requirement for gene transfer in most types of cells,the physicochemical andbiopharmaceutical behavior of the current generation of polyplexes severelylimits an efficient genetransfer in vitro and especially in vivo. This papersummarizes recent physicochemical and biologicalinformation on polyplexes and aims to provide new insights with respect to thistype of gene deliverysystem. Firstly, the chemical structure of frequently studied cationic polymersis represented. Secondly,the parameters influencing condensation of DNA by cationic polymers aredescribed. Thirdly, the surfaceproperties, solubility, aggregration behavior, degradation and dissociation ofpolyplexes are considered.The review ends by describing the in vitro and in vivo genetransfection behavior of polyplexes.     

Functional evidence for anti-oxidant action of fluvastatin on low-density lipoprotein using isolated macrophages and aorta

1. Fluvastatin has been reported to have not only a hypocholesterolaemic effect, but also a protective effect on low-density lipoprotein (LDL) from oxidation. We functionally evaluated the anti-oxidant effect of fluvastatin on oxidation of LDL by copper ions in vitro using mouse macrophages and rabbit aorta preparations. 2. After native LDL (N-LDL) from rabbit plasma had been pre-incubated in the presence or absence of fluvastatin (10 micromol/L) for 4 h, the N-LDL was mildly oxidized by incubation with 5 micromol/L CuCl2 for 5 h and two oxidized LDL, fluvastatin-pretreated (Flu-OxLDL) and -non-treated (OxLDL), were prepared. The level of thiobarbituric acid-reactive substances (TBARS) in Flu-OxLDL and OxLDL markedly increased compared with N-LDL. The degree of increment was significantly less in Flu-OxLDL than OxLDL. 3. When macrophages were incubated with Flu-OxLDL or OxLDL, the amount of cholesteryl ester that accumulated in the macrophages markedly increased compared with N-LDL. The degree of increment was significantly less in Flu-OxLDL than OxLDL. 4. Acetylcholine-induced endothelium-dependent relaxations in rabbit aortic rings were impaired in the presence of either Flu-OxLDL or OxLDL. The degree of impairment was significantly less in Flu-OxLDL. 5. The increased TBARS level, facilitated cholesteryl ester accumulation in macrophages and impaired endothelium-dependent relaxation elicited by OxLDL were not affected by simultaneous treatment with fluvastatin (10 micromol/L). 6. These findings indicate that fluvastatin can protect plasma LDL from oxidative modification and, thereby, prevent cholesterol accumulation in macrophages and endothelial dysfunction in blood vessels. This additional anti-oxidative effect of fluvastatin may be beneficial for preventing the progression of atherosclerosis.     

Electrophysiological characteristics of the Ca2+-activated Cl- channel family of anion transport proteins

1. A protein isolated from the bovine tracheal epithelium behaves as a Ca2+-activated Cl- channel (CaCC) when incorporated into planar lipid bilayers. 2. An antibody raised against this protein was used to screen a cDNA expression library and resulted in the isolation of a cDNA clone that exhibited nearly identical electrophysiological characteristics to the isolated endogenous protein when expressed. 3. Recent cloning of several related proteins has revealed that the cloned bovine CaCC is one of a large and growing family. All new family members so far examined are associated with the appearance of a novel Ca2+-mediated Cl- conductance when heterologously expressed. 4. This new group of proteins may underlie the Ca2+-mediated Cl- conductance upregulated in the cystic fibrosis (CF) knockout mouse and thought to be responsible for the escape from the significant airway pathology associated with CF.     

Association of first-trimester maternal lipid profiles and triglyceride-glucose index with the risk of gestational diabetes mellitus and large for gestational age newborn

Objective: To evaluate the association of maternal first-trimester plasma lipid profiles, fasting plasma glucose (FPG), and triglyceride (TyG) index with the risk of gestational diabetes mellitus (GDM) and large for gestational age (LGA) infant in Iranian mothers.

Methods: Nine hundred and fifty-four healthy pregnant women were prospectively followed till after delivery. Maternal fasting lipids and glucose concentration were measured at nine-week gestation on average. We used generalized linear models to calculate the relative risks and 95% confidence intervals.

Results: The incidence of GDM and LGA infants among our participants was 18.4% and 26.1%, respectively. There was a significant correlation between the increase in FPG, triglyceride, TG/HDL-C ratio, as well as TyG index with the risk of GDM and LGA infant. After adjusting for potential confounders, the relative risk of GDM in women in the top tertile of FPG, triglyceride (TG), triglyceride/high-density lipoprotein-cholesterol (TG/HDL-C) and TyG index was 4.2-, 4.2-, 3.9-, and 4.9-folds of its risk in women in the bottom tertile, respectively. Also after adjusting for GDM, the relative risk of LGA infants in women in the top tertile of FPG, TG, TG/HDL-C ratio and TyG index was 3.9-, 4.3-, 4.8-, and 5.3-folds of its risk in women in the bottom tertile, respectively.

Conclusions: Based on our findings, TyG index is more robust early predictors of GDM and LGA in Iranian women.     

The involvement of liquid crystals in multichannel implanted neurostimulators,hearing and ENT infections,and cancers

Liquid crystals (LCs) consist of assemblies of molecules, between one and tens of nanometers, grouped in identifiable cohorts according to orientation and structure, which is often lamellar with varying chirality. The term Lo phase designates certain such mesophases. This variety in geometry corresponds to a variety of functions. Some molecules, both organic and inorganic, used in applied engineering, and association with LCs confer new properties. Applying these aspects of LCs in manufacturing implantable material is a growing technology, especially in the interfaces of differentiated multichannel electro-neurostimulation. We highlight the involvement of LCs in the head and neck region, and the role mesophases play in outer hair cell electromotility (mechanotransduction). We summarize implications of LCs this for multichannel electroneurostimulation implant engineering, and highlight their role importance of LCs in early oncogenic process, HPV, and latency in Epstein-Barr and other pathogens. Our approach should help give rise to new therapeutic perspectives. Focusing on upstream nanometric phenomena needs to take on board classic determinism, quantum probability, and statistical complexity.     

活血化瘀类方对动脉粥样硬化家兔血脂、血液流变学变化的影响

目的 探讨活血化瘀类方对动脉粥样硬化（AS）家兔血脂，血液流变学的影响，比较其作用的异同。方法 采用高脂喂饲复制家兔动脉粥样硬化模型，观察各组家兔血脂，血液流变学改变。结果 血府逐瘀汤能显著降低家兔血清TC，TG，LDL－C含量，亦能降低家兔全血粘度（低切，高切），血浆粘度，红细胞比容（P＜0．01）；活络效灵丹能明显降低血清TC，LDL－CW含量（P＜0．01），亦能降低家兔全血粘度（低切）（P＜0．01），红细胞比容（P＜0．05），失笑散能降低家兔血清TC，TG，LDL－C含量以及红细胞比容（P＜0．05）；桃红四物汤明显降低血清TG含量以及全血粘度（低切）（P＜0．01），亦能降低家兔全血粘度（高切）（P＜0．05）；丹参饮能明显降低全血粘度（低切，高切），红细胞比容（P＜0．01），亦能降低血清TC，LDL－C含量（P＜0．05）；结论 5首活血化瘀方均有不同程度地调节血脂代谢，改善血液流变学，抑制高脂喂饲家兔动脉粥样硬化形成的作用，其中以血府逐瘀汤，洛络效灵丹的作用较强。     

Early sympathetic hyperactivity in Huntington''s disease

To investigate whether Huntington's disease (HD) affects autonomic nervous system (ANS) functioning 33 subjects with positive genetic test results were studied. The subjects were classified according to Shoulson and Fahn (S&F) HD disability scale into three subgroups: subgroup 1 (eight asymptomatic gene carriers), subgroup 2 (13 mildly disabled HD patients) and subgroup 3 (eight moderately and four severely disabled HD patients). A battery of cardiovascular autonomic tests (Valsalva maneuver, deep breathing test, sustained handgrip test, orthostatic test) and the spectral analysis of heart rate variability (HRV) were performed. The results were compared with a group of matched controls. In subgroup 1, there was a higher power of low-frequency band (LFB) (P < 0.05). In subgroup 2 a higher power of LFB was detected, LFB/high-frequency band (HFB) coefficient was increased and the blood pressure response to sustained handgrip was elevated (P < 0.05). Subgroup 3 showed significantly lower blood pressure response to sustained handgrip, lower respiratory (P < 0.05) and orthostatic ratio (P < 0.01). Our results suggest that sympathetic hyperfunction is present in asymptomatic gene carriers and mildly disabled HD patients. Contrary to that, ANS hypofunction was found in advanced HD patients.     

冠心病合并糖尿病患者脂蛋白谱颈动脉彩超和冠脉造影的相关性研究

目的 探讨冠心病合并糖尿病患者的脂蛋白谱、颈动脉彩超和冠脉造影的相关关系。方法 纳入冠脉造影冠状动脉狭窄≥75％为冠心病(CAD)的患者共193例，均查胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、空腹血糖(FBG)、餐后2h血糖(2hBG)，并作颈动脉彩超和评分。冠状动脉的狭窄程度用造影图像处理系统测量评分。用统计学方法分析脂蛋白谱、颈动脉彩超和冠脉造影的相关关系。结果 发现合并糖尿病的CAD患者，脂蛋白谱、颈动脉病变均与冠状动脉病变的严重程度有显著相关关系。结论 结合脂蛋白谱，颈动脉病变的严重程度可作为预测合并糖尿病的CAD患者严重程度的参考指标之一。颈动脉彩超无创、快速、准确，适宜临床广泛应用。     

微量元素硒缺乏对大鼠眼晶体的影响

本文测定了微量元素硒缺乏大鼠眼晶体某些酶活性、自由基以及过氧化物含量,结果表明缺硒使大鼠晶体谷胱甘肽过氧化物酶活性显著下降,晶体谷胱甘肽过氧化物酶活性与红细胞硒水平呈显著的正相关。缺硒使晶体丙二醛含量显著升高。缺硒组及对照组大鼠晶体中均有g=2.0015的自由基存在,但缺硒组自由基含量显著高于对照组,晶体自由基含量与红细胞硒水平以及晶体谷胱甘肽过氧化物酶活性呈显著的负相关。短暂的短波紫外线照射离体晶体,诱发晶体产生g=2.0097的自由基,缺硒组自由基的增加量也显著地高于对照组。因此硒缺乏导致大鼠晶体抗氧化能力下降,脂质过氧化作用加强,自由基产生增加。