血管紧张素转换酶基因及CD14基因多态性与变应性鼻炎的关系

目的：通过对血管紧张素转换酶（ACE）基因插入／缺失的多态性及CD14／-159C／T基因的多态性分析，探讨其在变应性鼻炎发病中的作用。方法：采用聚合酶链反应（PCR）扩增及限制性内切酶片段多态性（PCR—RFLP）分析方法测定60例变应性鼻炎患者和40例健康对照者的ACE基因型和CD14／-159C／T基因型的分布情况，并采用相关统计学方法对结果进行分析。结果：（1）ACE等位基因I、D频率在变应性鼻炎组和对照组的分布差异有统计学意义（xz=17．37，P〈0．01）。等位基因D与变应性鼻炎高度相关（OR=3．46，95％CI=1．92—6．23，P〈0．01）。（2）CD14／-159C／T等位基因C、T频率在变应性鼻炎组和对照组的分布差别具有统计学意义（xz=14．53，P〈0．01），等位基因C与变应性鼻炎高度相关（OR=3．1，95％CI=1．75—5．47，P〈0．01）。2组基因型（CC型、CT型、TT型）频率的分布比较差别也有统计学意义（x^2=11．77，P〈0．01）。结论：ACE基因多态性与CD14基因的多态性是影响变应性鼻炎的重要候选基因，其中ACE的D等位基因与CD14—159C／T的C等位基因与变应性鼻炎相关。     

白细胞介素-6基因多态性与高脂血症的关联性研究

目的：探讨高血脂患者白细胞介素-6（IL-6）启动子-634C／G基因在中国人群中的多态性,旨在了解其是否为高脂血症的遗传因素。方法：筛选高脂血症患者197例,健康志愿者200例。采用酚-氯仿法提取外周血DNA,聚合酶链反应-限制性片断长度多态性（PCR_RFLP）技术检测IL-6基因多态性。结果：高脂血症组CC、CG和GG基因型的频率分别为51．3％（101／197）,37.6％（74／197）和11.1％（22／197）,与正常对照组[CC：65％（130／200）：CG：28．5％（57／200）：GG：6．5％（13／200）]相比差异具有显著性（P〈0．05）。     

Gβ3基因C825T多态性与抗抑郁药的临床疗效

目的：研究中国南京地区人群中Gβ3基因C825T多态性与抗抑郁药的临床疗效是否存在相关性。方法：采用聚合酶链式反应－限制性片段长度多态性分析（PCR－RFLP）技术对154例抑郁症患者和100例健康志愿者进行基因型分析；用HAMD评定抗抑郁药的疗效。结果：抑郁症患者Gβ3基因基因型频率（CC22．7％，CT31．8％，TT44．8％）等位基因频率（C38．6％，T61．4％）；与正常对照组基因型频率（CC27．0％，CT51．0％，TT22．0％），等位基因频率（C52．5％，T47．5％）比较具有显著性差异（P＜0．001，P＜0．05）；140例抗抑郁药显效者Gβ3基因型频率（CC20．7％，CT31．4％，TT47．9％），等位基因频率（C364％，T63．6％）和14例药物无效者基因型频率（CC42．9％，CT35．7％，TT21．4％），等位基因频率（C60．7％，T39．3％）比较有显著性差异（P＜0．001，P＜0．001）；不同基因型抑郁症患者经4wk SSRI,SNRI类抗抑郁药治疗后，HAMD总分均显著下降，减分率有显著差异（CC与CT比较，P＞0．05；CC与TT比较，P＜0．01；CT与TT比较，P＜0．05）。结论：在中国南京地区人群中Gβ3基因C825T多态性与抑郁症及抗抑郁药疗效有关。     

RANTES 基因多态性与结核性脓胸发病风险的关系

目的：探讨河北地区受激活调节正常 T 细胞表达和分泌因子（regulated upon activation normal T cell ex－pressed and secreted factor,RANTES）基因－403G／A 和－28C／G 单核苷酸多态性（SNP）与结核性脓胸的关系。方法采用聚合酶链反应－限制性片段长度多态性（PCR－RFLP）方法检测300例结核性脓胸患者和300例对照人群RANTES基因－403G／A 和－28C／G 的基因型。结果 RANTES 基因－403G／A SNP 基因型频率和等位基因频率在结核性脓胸组和正常组间差异有统计学意义（ P ＝0．004和 P ＝0．008）,与 GG 基因型相比,携带 AG ＋AA 基因型可增加结核性脓胸发病风险（OR ＝1．40395％,CI ＝1．015～1．939）。 RANTES 基因－28C／G SNP 基因型频率和等位基因频率在结核性脓胸组和正常组间差异无统计学意义（ P ＝0．128和 P ＝0．064）,与 CC 基因型相比,携带 CG ＋GG 基因型与结核性脓胸发病风险无关（OR ＝1．31495％,CI ＝0．891～1．936）。结论 RANTES 基因－403G／A SNP 可能与结核性脓胸的发病风险有关,即携带 AG ＋AA 基因型增加结核性脓胸发病风险;RANTES 基因－28C／G SNP 可能与结核性脓胸发病风险无关。     

育龄女性基因多态性对补充叶酸降低HCY的影响

目的阐明MTHFRC677T、A1298C和MTRRA66G多态性在河南汉族育龄女性中的分布特征及其对补充叶酸降低HCY的影响。方法选取2011年7月至2013年4月在郑州大学第三附属医院进行优生咨询的育龄女性425名。荧光定量PCR检测MTHFRC677T、A1298C和MTRRA66G的基因多态性;化学发光法测定血叶酸浓度;循环酶法测定血HCY浓度。结果①河南地区汉族育龄女性中MTHFR677T、1298C和MTRR66G等位基因频率分别为62．1％、13．1％、23．7％。②补充叶酸前MTHFRC677T基因型叶酸浓度Tr〈CT〈CC,TT基因型HCY浓度远高于CC和CT基因型（P〈0．001）。400μg／d补充后HCY浓度迅速下降（TT〉CT〉CC）,但6．3％CT、16．9％TT基因型HCY浓度没有降低至正常范围。结论河南地区汉族育龄女性具有其他省份不同的遗传特征,MTHFRC677T各基因型对补充叶酸降低HCY的反应不同。     

白细胞介素-18基因多态性与脑梗死相关性研究

目的探讨白细胞介素-18（IL-18）基因启动子区-137G／C与脑梗死关系及其对血脂、脂蛋白水平的影响。方法运用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法检测190例脑梗死患者及对照组210例的IL-18基因型,同时测定血浆脂质、脂蛋白水平。结果IL—18基因-137G／C多态性在两组人群中的分布差异具有统计学意义（P〈0．05）,等位基因频率的相对风险分析发现,C等位基因携带者患脑梗死的风险是G等位基因的1．624倍（OR=1．624,95％CI：1．134—2．324）;携带C等位基因的脑梗死个体血清TC水平显著高于不携带者（P〈0．05）。结论IL-18基因．137G／C多态性与脑梗死发病具有相关性,其中C等位基因可能是脑梗死的遗传易感基因。     

佛山市汉族人群HIFIA基因1790（G→A）多态性研究

目的研究低氧诱导因子-1α基因（HIF1A）第12外显子1790（G→A）单核苷酸多态性在广东佛山市汉族人群中的分布特征。方法随机选取佛山市汉族健康个体90人的血样,提取白细胞基因组DNA,利用限制性片段长度多态性-聚合酶链反应（restriction fragment length polymorphisrm-polymerase chain reaction, RFLP-PCR）技术检测HIF1A基因第12外显子1790（G＋A）的单核苷酸多态性基因型,并分析其基因多态性特征。结果HIF1A基因1790（G→A）单核苷酸多态性的GG、GA和AA基因型频率分别为75．56％、21．11％和3．33％,G、A等位基因频率分别为86．11％、13。89％。广东佛山汉族人群HIF1A基因1790（G→A）单核苷酸多态性等位基因分布频率与日本人群相比差异有显著意义（P〈0．05）。结论广东佛山汉族人群HIF1A基因1790（G→A）多态性以GG基因型分布频率高,具有一定的种族差异性。     

转化生长因子β1基因T869C多态性与类风湿关节炎的相关性

目的 研究转化生长因子β1（TGFβ1）基因T869C多态性与江苏地区汉族人群类风湿关节炎（RA）的相关性。方法 76例随访2年的RA患者及100例健康对照组,PCR-RFLP方法检测TG即1基因T869C多态性,比较两组间基因型及等位基因频率,并分析RA组不同基因型间临床及实验室指标的差异。结果 RA组CC基因型频率较对照组显著下降,而CT及TT基因型频率则显著升高（P〈0．05）,与对照组相比,RA组C等位基因频率下降,而T等位基因频率升高（P〈0．01）,与CC基因型相比,CT、TT基因型的RA危险度分别为2．62倍（P〈0．05）和3．60倍（P〈0．01）;RA组携带T等位基因的基因型（CT＋TT）发病年龄显著低于、CC基因型（P〈0．05）,在X线≥Ⅲ期改变比例也显著高于CC基因型（P〈0．01）。结论 TGFβ1基因多态性与RA相关,T等位基因是RA的遗传易患因子,并且与RA起病及严重程度呈正相关。     

海洛因依赖和μ阿片受体A118G多态性的关联：Meta分析

目的：探讨汉族人群中海洛因依赖和μ阿片受体基因（OPRM1）A118G多态性的关联。方法：检索PubMed，CNKI，维普等数据库，搜集有关汉族人群海洛因依赖和A118G多态性关联研究的相关文献，然后进行Meta分析。结果：A118G基因型G／G在海洛因依赖组和对照组之间的比较中，异质性检验无显著性差异（P=O．49），遂选用固定效应模型，合并OR=0．90（95％CI，0．64—1．25），效应检验结果提示没有显著性差异（P=0．51）；A118G等位基因G在海洛因依赖组和对照组之间的比较中，异质性检验存在显著性差异（P=0．03），则选用随机效应模型，合并OR=0．94（95％CI，0．71—1．23），效应检验结果提示不存在显著性差异（P=0．63）。结论：汉族人群海洛因依赖与A118G多态性的基因型和等位基因不存在关联性。     

转化生长因子β1基因多态性与广东汉族糖尿病肾病的相关性研究

目的研究转化生长因子β1（TGF-β1）＋869T／C、＋915G／C基因多态性与广东汉族糖尿病肾病（DN）的相关性。方法采用病例-对照方法进行研究,即以DN患者为病例组,糖尿病不伴肾病患者与健康对照者两组人群分别构成两个对照组进行比较研究。采用序列特异性引物聚合酶链反应（PCR—SSP）技术检测糖尿病肾病患者45例,糖尿病不伴肾病患者53例,健康对照组50例的TGF-β1第1号外显子＋869T／C及＋915G／C位点等位基因及基因型分布,并对该基因多态性与广东汉族糖尿病肾病的相关性进行分析。结果TGF-β1＋869T／C、＋915G／C基因多态性可区分为3种类型,分别为TT、TC、CC3种和GG、GC、CC3种;＋869T／C中T、C等位基因的分布,DN组分别为0．414、0．586,糖尿病非肾病组分别为0．455、0．545,对照组分别为0．596、0．404;＋915G／C中G、C等位基因的分布,DN组分别为0．714、0．286,糖尿病非肾病组分别为0．700、0．300,对照组分别为0．768、0．232;三组数据总体比较,＋869T／C基因类型TT、TC、CC这一组数据总体上差异有显著性（P〈0．05）,说明DN组、非肾病组和对照组这三组的TT、TC、CC3种基因类型总体分布存在差异,＋915G／C基因类型差异无显著性（P〉0．05）;三组数据两两比较,差异均无显著性（P〉0．05）。结论TGF—β1＋869T／C及＋915G／C位点基因多态性与广东汉族糖尿病肾病可能无关。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

---

Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.