叶酸和复合维生素B对血液透析患者血浆同型半胱氨酸水平的影响

目的观察叶酸和复合维生素B联合用药对维持性血液透析(HD)患者血浆同型半胱氨酸(Hcy)水平的影响。方法对48例稳定HD超过三个月成年患者的血浆Hcy水平以及对叶酸和复合维生素B治疗的反应进行了前瞻性随机对照研究。所有患者口服叶酸5mg/d,3个月后随机分成联合治疗组(叶酸+复合维生素B)和对照组(叶酸+安慰剂),每次血液透析后联合治疗组静脉注射复合维生素B1支,对照组静脉注射等量的生理盐水,疗程3个月。观察治疗前后患者血浆Hcy水平的变化。结果HD患者的血浆Hcy水平明显增高[(33.25±4.54)μmol/L]并伴随维生素B12的不足[(320.7±25.2)pmol/L]。口服叶酸5mg/d3个月后,血浆Hcy降至(23.83±4.51)μmol/L(P<0.01);叶酸和复合维生素B联合治疗6个月,患者的血浆维生素B12水平明显高于对照组[(631.4±60.9)pmol/L与(317.6±49.2)pmol/L,P<0.001],血浆Hcy水平下降程度高于对照组[(18.69±3.91)μmol/L与(23.95±4.32)μmol/L,P<0.05]。结论HD患者普遍存在高Hcy血症,并伴随维生素B12水平的不足。补充叶酸能有效降低HD患者血浆Hcy水平;联合使用复合维生素B能更进一步地改善高Hcy血症。     

罗格列酮对糖尿病患者血浆同型半胱氨酸水平的影响

目的探讨罗格列酮对2型糖尿病患者血浆总同型半胱氨酸水平的影响。方法采用高效液相色谱法测定20名健康对照者、46例新诊断2型糖尿病患者血浆总同型半胱氨酸水平。对比口服罗格列酮治疗2个月前后血总同型半胱氨酸改变。结果2型糖尿病患者血浆总同型半胱氨酸水平(15±3)μmol/L高于对照组[(8±3)μmol/L,P<0.05],并且总同型半胱氨酸水平与年龄、体重指数(BMI)、空腹血糖(FBG)和空腹胰岛素水平(FINS)呈明显正相关(P<0.05),与尤岛素敏感指数呈负相关。罗格列酮治疗2个月后,血浆总同型半胱氨酸水平(12±5)μmol/L比治疗前降低(P<0.05)。结论2型糖尿病患者血浆总同型半胱氨酸水平增高,罗格列酮治疗后可降低其水平。     

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.     

测定急性冠状动脉综合征患者血浆同型半胱氨酸的意义

目的探讨冠心病(CHD)尤其是急性冠状动脉综合征(ACS)患者血浆同型半胱氨酸(Hcy)及影响因素叶酸、维生素B12等水平变化与冠状动脉病变严重性之间的关系。方法采用荧光偏振免疫分析法、离子捕获免疫分析法及非均相微粒子酶免疫分析法等测定302例CHD患者,包括ACS组202例(急性心肌梗死组132例和不稳定型心绞痛组70例),稳定型心绞痛(SAP)组100例和正常对照组120例的血浆Hcy、叶酸及维生素B12等水平。对冠心病患者的冠状动脉损害行Gensini评分,并比较各组间的差异。结果①ACS组、SAP组Hcy浓度显著高于对照组[(19±12)μmol/L vs (10±6)μmol/L(P<0.01)、(15±5)μmol/L vs (10±6)μmol/L(P<0.01)],而叶酸,维生素B12浓度显著低于对照组[(3.2±0.7)μg/L vs (7.1±1.8)μg/L(P<0.01),(5.3±0.6)μg/L vs (7.1±1.8)μg/L(P<0.01);(184±32)ng/L vs (283±56)ng/L(P<0.01),(228±45)ng/L vs (283±56)ng/L(P<0.01)。并且ACS组和SAP组的血浆同型半胱氨酸和血清叶酸、维生素B12浓度差异也有统计学意义。②血浆Hcy浓度与血浆叶酸、维生素B12浓度呈线性负相关。③随着冠状动脉病变Gensini评分的增加,Hcy浓度明显升高。结论冠心病尤其是ACS患者血浆Hcy显著升高,其升高严重程度与CHD的发生、病情严重性和冠状动脉病变程度有密切关系,检测CHD患者血浆Hcy水平可以预测冠状动脉病变程度,对于高Hcy者应用叶酸,维生素B12治疗,对于延缓CHD尤其是ACS病变发展可能有十分重要的临床意义。     

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.     

慢性肾衰竭患者血浆总同型半胱氨酸与心、脑血管并发症的关系

目的观察慢性肾衰竭(CRF)患者血浆总同型半胱氨酸(tHcy)的变化,探讨其与心、脑血管疾病的关系.方法选择CRF患者83例和健康对照组40例,采用荧光偏振免疫分析法(FPIA)测定血浆tHcy浓度,全自动生化分析仪测定甘油三酯(TG)、总胆固醇(ChoL)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白AI(ApoAI)、载脂蛋白B(ApoB)浓度,用多元逐步逻辑回归法分析慢性肾衰并发心、脑血管疾病的相关因子,比较血浆tHcy与血脂的相关性.结果以正常对照组血浆tHcyx 2s为95%可信度上限,CRF患者高同型半胱氨酸血症的发生率为85.54%;CRF患者血浆tHcy水平[(23.16±10.93)μmol·L-1,n=83]明显高于正常对照组[(7.97±2.89)μmol·L-1,n=40](P＜0.01);血液透析(HD)组血浆tHcy水平[(24.12±11.67)μmol·L-1,n=36]显著高于非透析治疗组[(19.53±8.92)μmol·L-1,n=31]和持续性非卧床腹膜透析(CAPD)组[(17.34±5.64)μmol·L-1,n=16](P＜0.05);83例CRF患者中伴有心、脑血管疾病者的血浆tHcy水平[(26.72±14.21)μmol·L-1,n=21]明显高于无此类并发症的患者[(20.51±9.07)μmol·L-1,n=62](P＜0.01).相关分析显示,CRF患者的血浆tHcy水平和部分血脂指标对心、脑血管疾病的发生有显著影响,但血浆tHcy水平与血脂各项指标均不存在相关关系(P均＞0.05).结论CRF患者普遍存在高同型半胱氨酸血症,其血浆tHcy水平与血脂无相关性,可能为心、脑血管疾病发生的独立危险因子.     

脑梗死患者血清同型半胱氨酸、叶酸、维生素B12水平的测定及临床意义

目的 探讨血清同型半胱氨酸(Hcy)、叶酸(FA)及VitB12与脑梗死的关系及临床意义.方法 采用酶循环法和电化学发光免疫分析法分别检测100例脑梗死患者血清Hcy、FA及VitB12水平,并与同期60例健康体检者进行比较.结果 脑梗死组患者血清Hcy水平(16.35±5.52)μmol/L,升高比例(22％),明显高于对照组[(8.62±3.45)μmol/L,6.7％,P<0.01];血清FA和VitB12降低的脑梗死组患者升高比例(19％和24％)显著高于健康对照组(5.0％,11.7％,P<0.01),而血清FA水平(13.62±5.98)nmol/L和VitB12水平(527.35±288.65)pmol/L显著低于对照组[(18.45±6.70)nmol/L,(565.24±282.72)pmol/L,P<0.01].脑梗死组患者血清FA和VitB12水平与Hcy水平均呈负相关(r1=-0.365,r2=-0.625,P<0.05).结论 Hcy血症为脑梗死的高危因素,与FA和VitB12水平下降有关,Hcy、FA、VitB12的检测在脑梗死患者的预防与治疗中有重要的临床价值.     

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.     

子痫前期患者血浆总同型半胱氨酸水平及其与叶酸、维生素B12的关系

目的：测定子痫前期患者血浆总同型半胱氨酸（tHcy）、血清叶酸、维生素B12水平,以探讨子痫前期患者血浆tHcy水平及其与叶酸、维生素B12的相互关系。方法：采用荧光偏振免疫分析法测定320例子痫前期患者（其中轻度236例,重度84例）和320例正常同期妊娠妇女血浆tHcy水平,同时用离子捕捉免疫分析法测定其血清叶酸水平,用微粒子酶联免疫分析法测定其血清维生素B12水平。结果：子痫前期组血浆tHcy水平为（11．65±3．54）μmol·L^-1,显著高于正常妊娠组[（6．73±2．58）μmol·L^-1]（P〈0．01）,且重度患者[（16．57±5．21）μmol·L^-1]显著高于轻度患者[（10．48±4．11）μmol·L^-1]（P〈0．01）;血清叶酸水平子痫前期组[（11．82±3．67）nmol·L^-1]显著低于正常妊娠组[（14．71±3．89）nmol·L^-1]（P〈0．01）;血清维生素B12水平子痫前期组[（338±91）pmol·L^-1]显著低于正常妊娠组[（406±88）pmol·L^-1]（P〈0．01）。结论：子痫前期患者血浆tHcy水平明显升高,且随着病情的加重血浆tHcy水平呈逐渐上升趋势,血浆tHcy水平与叶酸、维生素B12水平呈负相关。     

血浆同型半胱氨酸水平与脑梗死关系探讨

目的 研究空腹血浆总同型半胱氨酸(tHcy)水平与脑梗死的关系,并分析影响tHcy水平的因素,探讨预防tHcy升高的途径.方法 46例脑梗死患者(脑梗死组)与40例健康体检者(对照组)均晨起空腹抽取静脉血,并同步抽血测叶酸和维生素B12(VitB12)浓度.结果 脑梗死组tHcy水平明显高于对照组(P＜0.01),而叶酸、VitB12明显低于对照组(P＜0.01).结论 tHcy升高是脑梗死的独立危险因素,血清叶酸、VitB12均为tHcy的影响因素.     

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.