Graves病甲亢肝损害与CD40基因C/T单核苷酸多态性相关性的研究

目的：探讨CD40基因5’非翻译区域-1位点C／T多态性和中国天津地区汉族人Graves病（GD）甲亢肝损害发病的相关性。方法：采用序列特异性聚合酶链式反应一限制性内切酶酶切长度多态性（PCR-RFLP）方法分析60例GD甲亢患者，60例GD甲亢肝损害患者CD40基因5’非翻译区域-1位点C／T多态性，并和106例正常对照组比较。结果：天津地区汉族人CD40基因5’非翻译区域-1位点基因型、等位基因型在正常对照组、GD甲亢肝功正常患者、GD甲亢肝功异常患者差异有统计学意义（P〈0．05），但在GD甲亢肝功正常患者与GD甲亢肝功异常患者差异无统计学意义（P〉0．05）。结论：CD40基因可能是GD甲亢的一种易感基因，但并非GD甲亢肝损害的易感基因。     

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。     

Graves病甲亢白细胞减少与HLA-DQA1基因多态性的关联性

目的：研究天津地区汉族Graves病甲状腺功能亢进症（GD甲亢）白细胞减少与HLA-DQA1基因多态性的关联。方法：采用限制性片段长度多态性聚合酶链反应（PCR-RFLP）法检测60例GD甲亢白细胞减少患者、60例GD甲亢白细胞正常患者、100例正常对照者的HLA-DQA1基因型，计算和比较3组的HLA-DQA1等位基因频率。结果：（1）GD甲亢患者DQA1^＊0301频率高于对照组（P〈0．05，OR=1．528），而DQAI^＊0201频率和DQAI^＊0401频率低于对照组（P〈0．05，0R=0．474；P〈0．05，OR=0．333）。（2）GD甲亢白细胞减少组DAQI^＊0301高于对照组（P〈0．05，0R=1．737）。而DQAI^＊0201和DQAI^＊0401低于对照组（P〈0．05，OR=0．310；P〈0．05，OR=0．132）。GD甲亢白细胞正常组与对照组差别无统计学意义。结论：HLA-DQAI^＊0301等位基因可能是天津地区汉族人GD甲亢的易感基因，但并非GD甲亢白细胞减少的易感基因；HLA-DQAI^＊0201和HLA-DQAI^＊0401可能是天津地区汉族人GD甲亢的保护基因，但并非GD甲亢白细胞减少的保护基因。     

醛糖还原酶基因5''''端两种基因多态性与2型糖尿病肾病的相关性

目的：研究AR基因5＇-端（AC）n多态标记及启动子区C（-106）T多态标记与2型糖尿病肾病易感性之间的关系。方法：研究对象为421例中国北方汉族人，包括320例2型糖尿病（DM）患者，其中162例合并糖尿病肾病（DN），另101例为非糖尿病对照组（CON）。用PCR-变性聚丙烯酰胺凝胶-银染的方法检测AR基因5＇-端（AC）n串联重复序列多态标记，同时设计引物，PCR扩增含AR基因调控区多态标记的C（-106）T的目的片断，以限制性内切酶XspI行酶切RFLP分析。比较各组间等位基因频率和基因型频率。结果：在2型糖尿病和对照组中共发现AR基因（AC）n序列的10种等位基因，28种基因型（Z-10～Z＋8），C（-106）T多态标记的CC、CT和TT3种基因型及C、T两种等位基因；上述各种等位基因和基因型频率在DM组和CON组之间无显著性差异；2型糖尿病合并肾病者Z-2等位基因、含Z-2等位基因的基因型、T等位基因及CT＋TT基因型频率明显高于无肾病患者。结论：AR基因5’端（AC）n多态标记Z-2等位基因及C（-106）T多态标记T等位基因与2型糖尿病肾病易感性密切相关。     

GDF5基因5′端一功能性SNP与骨性关节炎易感性相关

目的 评估江苏汉族人群中转化生长因子5(GDF5)非翻译区域的一个单核苷酸基因多态性(+104T/C;rs143383)与膝关节骨性关节炎相关性.方法 对313例具有原发症状并有影像学证据的膝关节骨性关节炎患者及485名年龄相匹配的对照组进行+104T/C基因型测定,并检测+104T/C等位基因与膝关节骨性关节炎之间的关系.结果 江苏汉族人群中,GDF5基因5′非翻译区域的一个单核苷酸基因多态性(+104T/C;rs143383)与膝关节骨性关节炎显著相关(P<0.01),含有+104C的等位基因转录能力下降.结论 江苏汉族人群中GDF5基因5′非翻译区域+104T/C等位基因与膝关节骨性关节炎易感性呈显著相关.     

甲状腺激素及sTSH和B超在甲亢鉴别诊断中的意义

目的：探讨利用T3/T4、T3、敏感促甲状腺激素（sTSH）和甲状腺血流指标区别Graves’病（GD）甲状腺功能亢进（甲亢）和吸^131I率低性甲亢（非GD甲亢）的价值。方法：分别检测50例GD患者和35例非GD甲亢患者（亚急性甲状腺炎11例、桥本氏甲状腺炎20例、产后甲状腺炎3例、药物性甲亢l例）的吸^131I率和T3、T4、T3/T4、FT3，FT4、FT3/FT4、sTSH，并用彩色多普勒血流显像（CDFI）测定舒张期甲状腺上动脉（STA）内径（D）和STA的收缩期最高血流速度（Vmax）、舒张末期血流速度（Vmin）以及阻力指数（RI）。结果：GD组的T3/T4、T3、FT4、FT3和STA的D、Vmax和Vmin明显高于非GD组，GD组中sTSH〈0．005mIU/L者占36％（18／50）；而非GD组只占2．86％（1／35）。以非GD组的T3/T4、T3、Vmax和D的平均值＋2个标准差以及sTSH=0．005mIU／L为分界点．诊断GD甲亢的敏感性约为33％～47％，特异性达93％～100％。结论：与非GD组比较，GD患者的甲状腺分泌的T3更多。TSH更低。甲状腺血流更丰富。选取T3/T4、T3、sTSH、Vmax和D的特定数值对区别两类甲亢很有帮助。     

急性冠脉综合征患者血栓调节蛋白Ala455Val(C1 418T)多态性的研究

目的：探讨血栓调节蛋白（thrombomodulin，TM）Ala455Val（C1418T）多态性以及血浆中可溶性血栓调节蛋白（sTM）水平在急性冠脉综合征（ACS）发病中的作用。方法：PCR特异性扩增产物用非变性聚丙烯酰胺凝胶电泳法（SSCP）及内切酶法测定TM的1418位C/T多态性并进行测序，酶联免疫吸附试验测定sTM的水平。结果：ACS组中C／C基因型81例（96％），T／C基因型3例（4％），无T／T基因型；健康对照组C／C基因型80例（100％），无T／C与T／T基因型；ACS组sTM水平低于对照组（P〈0．01），其中AMI组sTM水平高于UAP组，但差异无统计学意义（P〉0．05）。结论：在ACS患者中TM存在Ala455Val（C1418T）多态性；TMAla455Val（C1418T）突变与血浆中sTM的水平无相关性；sTM水平是反映ACS患者内皮细胞损伤的良好标志。     

SUR1基因多态性与2型糖尿病的相关性研究

目的：探讨2型糖尿病（T2DM）与磺脲类药物受体1（SUR1）基因多态性的关系。方法：随机抽取正常人136例（正常组）及2型DM患者173例（T2DM组）外周血白细胞基因组DNA，PCR扩增SUR1基因31号外显子多态性位点的区域．用限制性酶切片段长度多态性分析其基因型，并用测序证实不同酶切图形基因型的准确性。结果：T2DM组和正常组SUR1基因31号外显子基因型及等位基因分布差别有统计学意义（P〈0．05）。结论：SUR1基因可能是中国天津地区2型糖尿病发生的易感基因。     

醛糖还原酶基因5′端两种基因多态性与2型糖尿病肾病的相关性

目的:研究AR基因5′-端(AC)n多态标记及启动子区C(-106)T多态标记与2型糖尿病肾病易感性之间的关系。方法:研究对象为421例中国北方汉族人,包括320例2型糖尿病(DM)患者,其中162例合并糖尿病肾病(DN),另101例为非糖尿病对照组(CON)。用PCR-变性聚丙烯酰胺凝胶-银染的方法检测AR基因5′-端(AC)n串联重复序列多态标记,同时设计引物,PCR扩增含AR基因调控区多态标记的C(-106)T的目的片断,以限制性内切酶XspI行酶切RFLP分析。比较各组间等位基因频率和基因型频率。结果:在2型糖尿病和对照组中共发现AR基因(AC)n序列的10种等位基因,28种基因型(Z-10￣Z 8),C(-106)T多态标记的CC、CT和TT3种基因型及C、T两种等位基因;上述各种等位基因和基因型频率在DM组和CON组之间无显著性差异;2型糖尿病合并肾病者Z-2等位基因、含Z-2等位基因的基因型、T等位基因及CT TT基因型频率明显高于无肾病患者。结论:AR基因5′端(AC)n多态标记Z-2等位基因及C(-106)T多态标记T等位基因与2型糖尿病肾病易感性密切相关。     

基因多态性背景下糖尿病肾病同型半胱氨酸水平研究

目的探讨载脂蛋白A5基因（APOA5）-1131T/C基因多态性与糖尿病肾病患者同型半胱氨酸（Hcy）水平的相关性。方法用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）技术检测40例健康人及45例糖尿病肾病患者APOA5-1131T/C基因型,并统计等位基因频率分布情况;用Olympus2700型全自动生化分析仪检测同型半胱氨酸水平。结果糖尿病肾病组APOA5-1131T/C基因频率、等位基因频率与对照组差异无统计学意义（P〉0.05）。糖尿病肾病组C等位基因携带者同型半胱氨酸水平显著高于非C等位基因携带者（P〈0.05）。结论 APOA5-1131T/C基因多态性影响糖尿病肾病患者同型半胱氨酸水平,C等位基因与糖尿病肾病同型半胱氨酸水平增高有密切关系。     

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.

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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.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.