阿尔茨海默病相关影响因素的病例对照研究

目的研究高同型半胱氨酸血症、叶酸和维生素B_(12)对阿尔茨海默病(AD)的影响。方法选择89例AD患者及45例正常老年人,分为3组。AD1组(无心血管疾病)、AD2组(伴有心血管疾病)和对照组,分别应用高效液相色谱法和放射免疫法测定血浆同型半胱氨酸(Hcy)、叶酸和维生素B12的含量。结果 AD1组与对照组比较,Hcy、叶酸和维生素B_(12无显著性差异。AD2组Hcy、叶酸和维生素B_(12分别为(18.30±2.57)μmol/L、(14.30±1.18)nmol/L和(237.20±28.77)nmol/L,与其他两组比较,Hcy含量显著升高,叶酸含量显著降低,维生素B_(12含量无显著性差异。结论高同型半胱氨酸血症与AD的发病无关,与AD的严重程度有关。血清叶酸的降低是导致AD患者高同型半胱氨酸血症的重要因素。维生素B_(12与AD患者高同型半胱氨酸血症的发生无关。     

血浆同型半胱氨酸与叶酸、维生素B12在脑梗死病例中的水平及相互影响

目的：观察脑梗死患者的血清同型半胱氨酸、叶酸、维生素B12水平与健康人群的差异,探讨采用叶酸、维生素B12干预对于高同型半胱氨酸血症的脑梗死病例血清同型半胱氨酸水平的影响。方法：选择急性脑梗死住院患者90例,作为病例组,并选择中、老年志愿者70例。测定90例脑梗死患者及70例健康对照者的血清同型半胱氨酸、叶酸和维生素B12的浓度。对于高同型半胱氨酸的脑梗死患者进行补充叶酸和维生素B12的干预,干预4wk后复查血清同型半胱氨酸水平。结果：1）血清同型半胱氨酸浓度〉15umol／L的高同型半胱氨酸血症者,在病例组中占52．2％,极明显高于对照组中的12．9％（P〈0．001）;2）病例组血清同型半胱氨酸浓度为18．72±8．25umol／L,比对照组高;3）病例组血清叶酸和维生素B12的平均浓度分别为7．59±4．52ng／mL和359．15±186．72pg／mL,均比对照组的12．25±3．23ng／mL和498．32±256．23pg／mL降低（P〈0．01）;4）脑梗死组高同型半胱氨酸血症者经补充叶酸和维生素B。干预4wk后血清同型半胱氨酸浓度平均为17．86±4．6umol／L,较干预前27．45±7．36umol／L极显著降低（P〈0．01）。结论：脑梗死患者血清同型半胱氨酸水平升高,叶酸和维生素B12水平降低,补充叶酸、维生素B12可有效降低高同型半胱氨酸血症的脑梗死患者的血清同型半胱氨酸浓度。     

妊娠期高血压疾病患者血浆总同型半胱氨酸水平与叶酸和维生素B12的关系

目的 测定妊娠期高血压疾病患者血浆总同型半胱氨酸(tHCY)、血清叶酸和维生素B12水平,以探讨轻、重度患者3者之间的相互关系.方法 用荧光偏振免疫分析法测定血浆tHCY水平,离子捕捉免疫分析法测定血清叶酸水平,微粒子酶联免疫分析法测定血清维生素B12水平.结果 232例妊娠期高血压疾病患者血浆tHCY水平、血清叶酸和维生素B12水平分别为(12.46±3.98)μmol/L,(11.81±3.39)nmol/L和(352.35±97.67)pmol/L,232例正常同期妊娠妇女血浆tHCY水平、血清叶酸和维生素B12水平分别为(6.71±2.43)μmol/L,(15.65±4.77)nmol/L和(438.63±129.45)pmol/L,2组比较均有显著性差异(P<0.01).97例重度患者血浆tHCY水平、血清叶酸和维生素B12水平分别为(15.07±5.21)μmol/L,(9.52±2.66)nmol/L和(315.29±84.18)pmol/L,135例轻度患者tHCY水平、血清叶酸和维生素B12水平分别为(10.28±3.74)μmol/L,(13.16±4.83)nmol/L和(390.23±114.35)pmol/L,2组比较均有显著性差异(P<0.01).相关分析显示,2组血浆tHCY水平与血清叶酸、维生素B12水平均呈负相关性.结论 妊娠期高血压疾病患者血浆tHCY浓度显著上升,血清叶酸、维生素B12浓度显著下降.随着病情的加重,妊娠期高血压疾病患者血浆tHCY浓度呈逐渐上升趋势,血清叶酸、维生素B12浓度呈逐渐下降趋势.     

缬沙坦联合叶酸对老年高血压肾病患者降压及降同型半胱氨酸的临床研究

目的探讨老年高血压肾病患者血浆同型半胱氨酸、血清叶酸及维生素B12的浓度,同时加用缬沙坦联合叶酸,观察其对老年高血压肾病患者降压及降低高同型半胱氨酸血症(Hhcy),及对肾功能的保护作用。方法选2009年10月至2011年5月我院住院及门诊患者共75例原发性高血压伴蛋白尿或轻中度肾功能衰竭(eGFR 30～60 ml/min)患者。随机分为两组。对照组给予缬沙坦80 mg/d、观察组缬沙坦80 mg+叶酸0.8 mg/d,连续治疗8周。监测血压。测定给药前、给药后第4周和第8周3个不同时点的血浆同型半胱氨酸(Hcy)水平和尿白蛋白排泄率(UAE)、血清半胱氨酸蛋白酶抑制剂C(CysC)、血清叶酸、维生素B12的浓度,计算eGFR。结果两组治疗2、4、6、8周,收缩压(SBP)和舒张压(DBP)均有下降趋势,组间、不同时点、组间和不同时点的交互作用比较差异有统计学意义(均P<0.01)。两组患者均存在Hcy水平增高、叶酸水平降低、维生素B12水平降低。治疗8周后,观察组血浆Hcy、尿白蛋白排泄率(UAE)、血清叶酸、维生素B12、血清半胱氨酸蛋白酶抑制剂C(Cys C)、eGFR改善较对照组差异明显(均P<0.01),分别为(10.43±4.16)μmol/L vs(15.75±9.20)μmol/L,(110.93±56.32)μg/min vs(215.75±79.28)μg/min,(14.7±5.5)nmol/L vs(8.59±1.66)nmol/L,(784.56±111.49)nmol/L vs(421.52±167.75)nmol/L,(1.72±2.41)mg/L vs(3.47±1.99)mg/L,(74.53±21.33)ml/min vs(61.02±27.43)ml/min(P<0.01)。结论缬沙坦联合叶酸治疗老年高血压合并早中期肾损害患者,对于有效降压、延缓甚至阻止肾功能损伤和恶化意义重大。     

高同型半胱氨酸血症对帕金森病的影响

目的研究高同型半胱氨酸血症对帕金森病的发病与药物治疗的影响。方法选择正常老年组30例和未治疗帕金森病(PD)患者组30例,应用高效液相色谱法测定血浆同型半胱氨酸(hcy)水平。选择治疗中的PD患者60例,分为治疗组(应用美多巴)30例和对照组30例(应用其他抗震颤麻痹药物),同样方法测定其血浆中hcy水平。结果未治疗PD组、治疗组和对照组的hcy水平分别为:18.79±2.14、21.30±3.57和19.82±2.80,与正常老年组(12.31±1.26)比较显著升高(P<0.05),治疗组与未治疗PD组、对照组比较hcy水平无明显差异。结论高同型半胱氨酸血症是PD的危险因素,但对PD的治疗无明显影响。     

慢性肾功能衰竭患者血浆同型半胱氨酸水平和血清叶酸、维生素B12的关系

目的:研究慢性肾功能衰竭(CRF)患者血浆总同型半胱氨酸(tHcy)水平及其与血清叶酸、维生素B12(VitB12) 的关系.方法:采用荧光偏振免疫分析法检测45例CRF患者和40例正常对照组血浆tHcy浓度,并同时用离子捕捉免疫分析法检测其血清叶酸和微粒子酶联免疫分析法检测血清VitB12的含量.结果:CRF患者血浆tHcy浓度[(24±12)μmol·L-1]显著高于正常对照组[(8.0±2.9)μmol·L-1](P<0.01);CRF患者血清叶酸水平[(18±6.3)nmol·L-1]显著低于正常对照组[(21±8.3)nmol·L-1](P<0.01),VitB12水平[(423±154)pmol·L-1]显著低于正常对照组[(485±181)pmol·L-1](P<0.01).相关分析显示,两组血浆tHcy浓度与叶酸、VitB12水平均呈负相关性.结论:CRF患者普遍存在高同型半胱氨酸血症,叶酸、VitB12缺乏可能是诱发高同型半胱氨酸血症的重要因素之一.     

叶酸、维生素B_6和维生素B_（12）治疗冠心病并高同型半胱氨酸血症患者40例临床观察

目的：评价叶酸、维生素B6和维生素B12对治疗高同型半胱氨酸（Hcy）血症及冠心病的临床疗效。方法：将冠心病伴高同型半胱氨酸血症患者78例随机分为两组,对照组给予常规治疗,治疗组在常规治疗基础上加用叶酸、维生素B6和维生素B12片,1个疗程1个月,对治疗前后血清同型半胱氨酸水平、临床表现及心电图进行观察。结果：治疗后两组空腹血清同型半胱氨酸水平分别为（25.9±8.1）μmol/L和（17.8±7.6）μmol/L,两组比较差异有统计学意义（P〈0.01）,且治疗组总有效率达90.0%,优于对照组的55.3%,两组比较差异有统计学意义（P〈0.05）。结论：口服叶酸片、维生素B6和维生素B12片可以有效降低血清同型半胱氨酸浓度,且对冠心病有显著疗效。     

同型半胱氨酸、叶酸、维生素B12水平在冠心病早期和慢性心力衰竭患者中的差异分析

目的 观察冠心病(CHD)早期患者和慢性心力衰竭(CHF)患者体内血清同型半胱氨酸、叶酸、维生素B₁₂水平的差异。方法 选择28例冠心病早期但尚未出现心力衰竭症状的患者作为冠心病早期组, 26例非冠心病引起的慢性心力衰竭患者作为慢性心力衰竭组,同期健康体检者20例作为对照组。入院时空腹状态下测定三组的血清同型半胱氨酸、叶酸及维生素B₁₂水平并进行比较。结果 对照组同型半胱氨酸水平为(9.5±1.7)μmol/L,叶酸水平为(14.2±3.5)ng/ml,维生素B₁₂水平为(399.2±104.5)pg/ml。冠心病早期组患者同型半胱氨酸水平为(17.7±8.6)μmol/L,叶酸水平为(8.8±4.8)ng/ml,维生素B₁₂水平为(267.8±103.3)pg/ml。慢性心力衰竭组患者同型半胱氨酸水平为(17.3±8.6)μmol/L,叶酸水平为(9.7±5.4)ng/ml,维生素B₁₂水平为(322.2±117.3)pg/ml。三组同型半胱氨酸、叶酸、维生素B_12...     

叶酸和甲钴胺对高同型半胱氨酸血症缺血性脑卒中复发的影响

目的 探讨叶酸和甲钴胺(维生素B12)对高同型半胱氨酸血症(Hhcy)患者缺血性脑卒中(ICS)复发的影响.方法 伴有Hhcy的ICS患者195例,分为治疗组112例和对照组83例.两组均给予常规治疗;治疗组加用叶酸片2 mg/d、维生素B6 25mg/d及维生素B12 500μg/d.随访2年,比较治疗前后同型半胱氨酸(Hcy)水平,评价ICS患者的再发性脑血管事件发生率.结果 2年后,对照组血浆Hcy水平与常规治疗前相仿[(16.6±5.2)μmol/L vs.(16.1±4.7)μmol/L](P>0.05),而治疗组血浆Hcy水平明显较治疗前降低[(8.2±4.7)μmol/L vs.(17.6±5.9)μmol/L](P<0.05).治疗组脑血管事件复发率低于对照组(6.3%vs.8.4%)(P<0.05).结论 口服叶酸加维生素B6和维生素B12可降低Hhcy,改善ICS患者的远期预后.     

冠心病患者同型半胱氨酸和叶酸及维生素B12水平的初步观察

目的探讨血清同型半胱氨酸、叶酸和维生素B12水平变化与冠心病的关系。方法经冠状动脉造影检查确诊为冠心病的患者90例作为冠心病组,90例健康受试者作为对照组,应用循环酶法测定同型半胱氨酸水平,用化学发光微粒子免疫检测法检测叶酸及维生素B12水平,观察冠心病组治疗前后同型半胱氨酸、叶酸和维生素B12的浓度变化。结果冠心病组中同型半胱氨酸升高82例,占91.1%;对照组中同型半胱氨酸升高4例,占4.4%,两组比较差异有统计学意义(P<0.05);两组血浆同型半胱氨酸、叶酸和维生素B12水平比较差异有统计学意义(P<0.05)。冠心病组患者治疗前后同型半胱氨酸、叶酸、维生素B12比较,冠心病患者治疗后血浆同型半胱氨酸明显下降,维生素B12明显升高(P<0.05);叶酸水平无明显变化(P>0.05)。结论同型半胱氨酸、维生素B12参与了冠心病的发生和发展过程,针对冠心病人群定期行同型半胱氨酸检测,预防性服用B族维生素,可能一定程度上对减少冠心病事件的发生和发展有益。     

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.     

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.